277 results on '"Joaquim M. Oliveira"'
Search Results
2. Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications
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Hajer Radhouani, Cristiana Gonçalves, F. Raquel Maia, Eduarda P. Oliveira, Rui L. Reis, and Joaquim M. Oliveira
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biomedical device ,carbodiimide-mediated coupling ,characterization ,chondroitin sulfate ,cryogelation technique ,kefiran ,Pharmacy and materia medica ,RS1-441 - Abstract
Hydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysaccharide-chondroitin sulfate (CS) conjugate via carbodiimide-mediated coupling to overcome these drawbacks. The freeze-thawing procedure of cryogel preparation followed by lyophilization is a promising route to fabricate polymer-based scaffolds with countless and valuable biomedical applications. The novel graft macromolecular compound (kefiran-CS conjugate) was characterized through 1H-NMR and FTIR spectroscopy—which confirmed the structure of the conjugate, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)—which mirrored good thermal stability (degradation temperature of about 215 °C) and, finally, gel permeation chromatography–size exclusion chromatography (GPC-SEC)—which proved an increased molecular weight due to chemical coupling of kefiran with CS. At the same time, the corresponding cryogels physically crosslinked after the freeze-thawing procedure were investigated by scanning electron microscopy (SEM), Micro-CT, and dynamic rheology. The results revealed a prevalent contribution of elastic/storage component to the viscoelastic behavior of cryogels in swollen state, a micromorphology with micrometer-sized open pores fully interconnected, and high porosity (ca. 90%) observed for freeze-dried cryogels. Furthermore, the metabolic activity and proliferation of human adipose stem cells (hASCs), when cultured onto the developed kefiran-CS cryogel, was maintained at a satisfactory level over 72 h. Based on the results obtained, it can be inferred that the newly freeze-dried kefiran-CS cryogels possess a host of unique properties that render them highly suitable for use in tissue engineering, regenerative medicine, drug delivery, and other biomedical applications where robust mechanical properties and biocompatibility are crucial. more...
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- 2023
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3. Engineering of Extracellular Matrix‐Like Biomaterials at Nano‐ and Macroscale toward Fabrication of Hierarchical Scaffolds for Bone Tissue Engineering
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Rafael Lemos, F. Raquel Maia, Rui L. Reis, and Joaquim M. Oliveira
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biomaterials ,bone ,microparticles ,nanocomposites ,nanoparticles ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
The increasing rate of musculoskeletal pathologies has compelled the development of improved and novel treatment strategies in order to address unmet clinical needs. Tissue engineering approaches comprising the use of scaffolds for bone regeneration have been showing to be a promising alternative to conventional bone repair/substitution approaches. In particular, hierarchical scaffolds as methods of structural support and osteogenic differentiation promoters are among the most used tools in bone tissue engineering (BTE). In this reasoning, hierarchical scaffolds have sparked the field, striving toward mimicking the natural bone tissue in both, its complex 3D structure and composition. A recent and promising trend has been the merging of nanotechnology and tissue engineering concepts. As such the incorporation of nanoparticles and nanocomposites into micro‐ or macroscaffold systems can result in an improvement of scaffolds’ biofunctionality at different levels. These tools are versatile in nature and can be used for multiple purposes such as drug delivery, thermal conductors, and mechanical reinforcement. Taking into consideration multidisciplinary approaches, several strategies have been pursued. The recent reports dealing with the approaches pursued in the hierarchical scaffolds production and enhancement, ranging from the nanoscale to the macroscale, are overviewed herein. more...
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- 2022
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4. Special Issue: Tissue Engineered Biomaterials and Drug Delivery Systems
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Viviana P. Ribeiro, Joaquim M. Oliveira, and Rui L. Reis
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n/a ,Pharmacy and materia medica ,RS1-441 - Abstract
Current advances in biomaterials processing and engineering for drug delivery have allowed interesting progressed in biomedical field [...]
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- 2022
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5. Glial Cell Line-Derived Neurotrophic Factor-Loaded CMCht/PAMAM Dendrimer Nanoparticles for Peripheral Nerve Repair
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Ane Escobar, Mariana R. Carvalho, F. Raquel Maia, Rui L. Reis, Tiago H. Silva, and Joaquim M. Oliveira
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peripheral nerve injury ,peripheral nerve repair ,nanoparticles ,neurotrophic factor ,dendrimers ,Pharmacy and materia medica ,RS1-441 - Abstract
(1) Background: Peripheral nerve injuries represent a major clinical challenge. If nerve ends retract, there is no spontaneous regeneration and grafts are required to proximate the nerve ends and give continuity to the nerve. (2) Methods: GDNF-loaded NPs were characterized physicochemically. For that, NPs stability at different pH’s was assessed, and GDNF release was studied through ELISA. In vitro studies are performed with Schwann cells, and the NPs are labeled with fluorescein-5(6)-isothiocyanate for uptake experiments with SH-SY5Y neural cells. (3) Results: GDNF-loaded NPs are stable in physiological conditions, releasing GDNF in a two-step profile, which is beneficial for nerve repair. Cell viability is improved after 1 day of culture, and the uptake is near 99.97% after 3 days of incubation. (4) Conclusions: The present work shows the efficiency of using CMCht/PAMAM NPs as a GDNF-release system to act on peripheral nerve regeneration. more...
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- 2022
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6. PARP1 Inhibitor Combined With Oxaliplatin Efficiently Suppresses Oxaliplatin Resistance in Gastric Cancer-Derived Organoids via Homologous Recombination and the Base Excision Repair Pathway
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Huafu Li, Chunming Wang, Linxiang Lan, Wenhui Wu, Ian Evans, E. Josue Ruiz, Leping Yan, Zhijun Zhou, Joaquim M. Oliveira, Rui L. Reis, Zhenran Hu, Wei Chen, Axel Behrens, Yulong He, and Changhua Zhang more...
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gastric cancer ,L-OHP resistance ,homologous recombination ,PARP1 inhibitors ,organoid ,Biology (General) ,QH301-705.5 - Abstract
Oxaliplatin (OXA) resistance in the treatment of different types of cancer is an important and complex problem. The culture of tumor organoids derived from gastric cancer can help us to provide a deeper understanding of the underlying mechanisms that lead to OXA resistance. In this study, our purpose was to understand the mechanisms that lead to OXA resistance, and to provide survival benefits to patients with OXA through targeted combination therapies. Using sequence analysis of OXA-resistant and non-OXA-resistant organoids, we found that PARP1 is an important gene that mediates OXA resistance. Through the patients’ follow-up data, it was observed that the expression level of PARP1 was significantly correlated with OXA resistance. This was confirmed by genetic manipulation of PARP1 expression in OXA-resistant organoids used in subcutaneous tumor formation. Results further showed that PARP1 mediated OXA resistance by inhibiting the base excision repair pathway. OXA also inhibited homologous recombination by CDK1 activity and importantly made cancers with normal BRCA1 function sensitive to PARP inhibition. As a result, combination of OXA and Olaparib (PARP-1/2/3 inhibitor), inhibited in vivo and in vitro OXA resistant organoid growth and viability. more...
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- 2021
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7. Impact of Kefiran Exopolysaccharide Extraction on Its Applicability for Tissue Engineering and Regenerative Medicine
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Susana Correia, Cristiana Gonçalves, Joaquim M. Oliveira, Hajer Radhouani, and Rui L. Reis
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characterization ,extraction ,kefiran ,regenerative medicine ,scaffolds ,tissue engineering ,Pharmacy and materia medica ,RS1-441 - Abstract
Kefiran is an exopolysaccharide produced by the microflora of kefir grains used to produce the fermented milk beverage kefir. The health-promoting and physicochemical properties of kefiran led to its exploration for a range of applications, mainly in the food industry and biomedical fields. Aiming to explore its potential for tissue engineering and regenerative medicine (TERM) applications, the kefiran biopolymer obtained through three different extraction methodologies was fully characterized and compared. High-quality kefiran polysaccharides were recovered with suitable yield through different extraction protocols. The methods consisted of heating the kefir grains prior to recovering kefiran by centrifugation and differed mainly in the precipitation steps included before lyophilization. Then, kefiran scaffolds were successfully produced from each extract by cryogelation and freeze-drying. In all extracts, it was possible to identify the molecular structure of the kefiran polysaccharide through 1H-NMR and FTIR spectra. The kefiran from extraction 1 showed the highest molecular weight (~3000 kDa) and the best rheological properties, showing a pseudoplastic behavior; its scaffold presented the highest value of porosity (93.2% ± 2), and wall thickness (85.8 µm ± 16.3). All extracts showed thermal stability, good injectability and desirable viscoelastic properties; the developed scaffolds demonstrated mechanical stability, elastic behavior, and pore size comprised between 98–94 µm. Additionally, all kefiran products proved to be non-cytotoxic over L929 cells. The interesting structural, physicochemical, and biological properties showed by the kefiran extracts and cryogels revealed their biomedical potential and suitability for TERM applications. more...
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- 2022
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8. Hierarchical HRP-Crosslinked Silk Fibroin/ZnSr-TCP Scaffolds for Osteochondral Tissue Regeneration: Assessment of the Mechanical and Antibacterial Properties
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Viviana P. Ribeiro, Sandra Pina, Sabina Gheduzzi, Ana C. Araújo, Rui L. Reis, and Joaquim M. Oliveira
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silk fibroin ,horseradish peroxidase ,ZnSr-tricalcium phosphate ,hierarchical scaffolds ,mechanical strength ,antibacterial adhesion ,Technology - Abstract
The biomaterials requirements for osteochondral (OC) defects restoration simultaneously include adequate mechanical behavior, and the prevention of bacterial adherence and biofilm formation, without impairing local tissue integration. Bilayered and hierarchical scaffolds combining a cartilage-like layer interconnected to an underlying subchondral bone-like layer appeared as innovative technological solutions able to mimic the native OC tissue hierarchical architecture. This study is focused on the assessment of the combined compression-shear stresses and possible bacterial biofilm formation of hierarchical scaffolds prepared from a horseradish peroxidase-crosslinking reaction of silk fibroin (SF) combined with zinc (Zn) and strontium (Sr)-doped β-tricalcium phosphate (β-TCP) for OC tissue regeneration. Scaffolds with undoped-β-TCP incorporation were used as control. Results showed that the bilayered scaffolds presented suitable aptitude to support compression and shear loading for OC tissue, with better mechanical properties for the ZnSr-containing structures. Young and shear moduli presented values close to 0.01 MPa in the region 10–20% strain. The investigation of biomaterials surface ability to prevent biofilm formation showed reduced bacterial adhesion of Escherichia coli (E. coli, gram-negative) and Staphylococcus aureus (S. aureus, gram-positive) on both scaffolds, thus suggesting that the proposed hierarchical scaffolds have a positive effect in preventing gram-positive and gram-negative bacteria proliferation. more...
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- 2020
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9. Bioinspired Silk Fibroin-Based Composite Grafts as Bone Tunnel Fillers for Anterior Cruciate Ligament Reconstruction
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Viviana P. Ribeiro, João B. Costa, Sofia M. Carneiro, Sandra Pina, Ana C. A. Veloso, Rui L. Reis, and Joaquim M. Oliveira
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anterior cruciate ligament ,tissue engineering ,silk fibroin ,osteointegration ,Pharmacy and materia medica ,RS1-441 - Abstract
Anterior cruciate ligament (ACL) replacement is still a big challenge in orthopedics due to the need to develop bioinspired implants that can mimic the complexity of bone-ligament interface. In this study, we propose biomimetic composite tubular grafts (CTGs) made of horseradish peroxidase (HRP)-cross-linked silk fibroin (SF) hydrogels containing ZnSr-doped β-tricalcium phosphate (ZnSr-β-TCP) particles, as promising bone tunnel fillers to be used in ACL grafts (ACLGs) implantation. For comparative purposes, plain HRP-cross-linked SF hydrogels (PTGs) were fabricated. Sonication and freeze-drying methodologies capable of inducing crystalline β-sheet conformation were carried out to produce both the CTGs and PTGs. A homogeneous microstructure was achieved from microporous to nanoporous scales. The mechanical properties were dependent on the inorganic powder’s incorporation, with a superior tensile modulus observed on the CTGs (12.05 ± 1.03 MPa) as compared to the PTGs (5.30 ± 0.93 MPa). The CTGs presented adequate swelling properties to fill the space in the bone structure after bone tunnel enlargement and provide a stable degradation profile under low concentration of protease XIV. The in vitro studies revealed that SaOs-2 cells adhered, proliferated and remained viable when cultured into the CTGs. In addition, the bioactive CTGs supported the osteogenic activity of cells in terms of alkaline phosphatase (ALP) production, activity, and relative gene expression of osteogenic-related markers. Therefore, this study is the first evidence that the developed CTGs hold adequate structural, chemical, and biological properties to be used as bone tunnel fillers capable of connecting to the ACL tissue while stimulating bone tissue regeneration for a faster osteointegration. more...
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- 2022
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10. Supporting shared hypothesis testing in the biomedical domain
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Asan Agibetov, Ernesto Jiménez-Ruiz, Marta Ondrésik, Alessandro Solimando, Imon Banerjee, Giovanna Guerrini, Chiara E. Catalano, Joaquim M. Oliveira, Giuseppe Patanè, Rui L. Reis, and Michela Spagnuolo more...
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Biomedical ontology ,Ontology mapings ,Network analysis ,Hypothesis testing ,Incomplete knowledge ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Background Pathogenesis of inflammatory diseases can be tracked by studying the causality relationships among the factors contributing to its development. We could, for instance, hypothesize on the connections of the pathogenesis outcomes to the observed conditions. And to prove such causal hypotheses we would need to have the full understanding of the causal relationships, and we would have to provide all the necessary evidences to support our claims. In practice, however, we might not possess all the background knowledge on the causality relationships, and we might be unable to collect all the evidence to prove our hypotheses. Results In this work we propose a methodology for the translation of biological knowledge on causality relationships of biological processes and their effects on conditions to a computational framework for hypothesis testing. The methodology consists of two main points: hypothesis graph construction from the formalization of the background knowledge on causality relationships, and confidence measurement in a causality hypothesis as a normalized weighted path computation in the hypothesis graph. In this framework, we can simulate collection of evidences and assess confidence in a causality hypothesis by measuring it proportionally to the amount of available knowledge and collected evidences. Conclusions We evaluate our methodology on a hypothesis graph that represents both contributing factors which may cause cartilage degradation and the factors which might be caused by the cartilage degradation during osteoarthritis. Hypothesis graph construction has proven to be robust to the addition of potentially contradictory information on the simultaneously positive and negative effects. The obtained confidence measures for the specific causality hypotheses have been validated by our domain experts, and, correspond closely to their subjective assessments of confidences in investigated hypotheses. Overall, our methodology for a shared hypothesis testing framework exhibits important properties that researchers will find useful in literature review for their experimental studies, planning and prioritizing evidence collection acquisition procedures, and testing their hypotheses with different depths of knowledge on causal dependencies of biological processes and their effects on the observed conditions. more...
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- 2018
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11. Towards the Development of a Female Animal Model of T1DM Using Hyaluronic Acid Nanocoated Cell Transplantation: Refinements and Considerations for Future Protocols
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Fernanda Zamboni, Ibrahim F. Cengiz, Ana M. Barbosa, Antonio G. Castro, Rui L. Reis, Joaquim M. Oliveira, and Maurice N. Collins
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diabetes induction ,female animal model ,transplantation ,Pharmacy and materia medica ,RS1-441 - Abstract
Female mice (Black 6 strain) (C57BL/6) aged 6 weeks were subject to low dose streptozotocin (STZ) treatment for five consecutive days to mimic type 1 diabetes mellitus (T1DM) with insulitis. At two weeks after STZ injections, evaluation of the elevated glucose levels was used to confirm diabetes. The diabetic mice were then subject to the transplantation of pancreatic β-cells (MIN-6 line). Four groups of mice were studied. The first group was injected with saline-only acting as the placebo surgery control, also known as SHAM group, the second and third groups were injected with MIN-6 single cells and polyethylene glycol-modified dipalmitoyl-glycerol-phosphatidyl ethanolamine (PEG-DPPE) modified MIN-6 single cells (500 µg per 1.106 cells), respectively, while the fourth group was injected with hyaluronic acid (HA)-coated MIN-6 single cells (5 bilayers). At seven- and fourteen-days following transplantation, the mice were euthanised. The renal and pancreatic tissues were then collected and histologically analysed. The induction of diabetes in female mice, through five-consecutive daily STZ injections resulted in inconsistent glycaemic levels. Interestingly, this shows an incomplete diabetes induction in female mice, of which we attribute to sex dimorphism and hormonal interferences. Transplantation failure of free-floating encapsulated cells was unable to decrease blood glucose hyperglycaemia to physiological ranges. The result is attributed to deprived cell–cell interactions, leading to decreased β-cells functionality. Overall, we highlight the necessity of refining T1DM disease models in female subjects when using multiple low-dose STZ injections together with transplantation protocols. Considerations need to be made regarding the different developmental stages of female mice and oestrogen load interfering with pancreatic β-cells susceptibility to STZ. The use of pseudo islets, cell aggregates and spheroids are sought to improve transplantation outcome in comparison to free-floating single cells. more...
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- 2021
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12. Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit
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Cristiana R. Carvalho, Joaquim M. Oliveira, and Rui L. Reis
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peripheral nerve ,tissue engineering ,biomaterials ,nerve guidance conduit ,luminal fillers ,Biotechnology ,TP248.13-248.65 - Abstract
Peripheral nerve repair and regeneration remains among the greatest challenges in tissue engineering and regenerative medicine. Even though peripheral nerve injuries (PNIs) are capable of some degree of regeneration, frail recovery is seen even when the best microsurgical technique is applied. PNIs are known to be very incapacitating for the patient, due to the deprivation of motor and sensory abilities. Since there is no optimal solution for tackling this problem up to this day, the evolution in the field is constant, with innovative designs of advanced nerve guidance conduits (NGCs) being reported every day. As a basic concept, a NGC should act as a physical barrier from the external environment, concomitantly acting as physical guidance for the regenerative axons across the gap lesion. NGCs should also be able to retain the naturally released nerve growth factors secreted by the damaged nerve stumps, as well as reducing the invasion of scar tissue-forming fibroblasts to the injury site. Based on the neurobiological knowledge related to the events that succeed after a nerve injury, neuronal subsistence is subjected to the existence of an ideal environment of growth factors, hormones, cytokines, and extracellular matrix (ECM) factors. Therefore, it is known that multifunctional NGCs fabricated through combinatorial approaches are needed to improve the functional and clinical outcomes after PNIs. The present work overviews the current reports dealing with the several features that can be used to improve peripheral nerve regeneration (PNR), ranging from the simple use of hollow NGCs to tissue engineered intraluminal fillers, or to even more advanced strategies, comprising the molecular and gene therapies as well as cell-based therapies. more...
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- 2019
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13. Tuning Enzymatically Crosslinked Silk Fibroin Hydrogel Properties for the Development of a Colorectal Cancer Extravasation 3D Model on a Chip
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Mariana R. Carvalho, Fátima Raquel Maia, Sílvia Vieira, Rui L. Reis, and Joaquim M. Oliveira
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3D model ,colorectal cancer ,extravasion ,microfluidics ,silk ,Technology ,Environmental sciences ,GE1-350 - Abstract
Abstract Microfluidic devices are now the most promising tool to mimic in vivo like scenarios such as tumorigenesis and metastasis due to its ability to more closely mimic cell's natural microenvironment (such as 3D environment and continuous perfusion of nutrients). In this study, the ability of 2% and 3% enzymatically crosslinked silk fibroin hydrogels with different mechanical properties are tested in terms of colorectal cancer cell migration, under different microenvironments in a 3D dynamic model. Matrigel is used as control. Moreover, a comprehensive comparison between the traditional Boyden chamber assay and the 3D dynamic microfluidic model in terms of colorectal cancer cell migration is presented. The results show profound differences between the two used biomaterials and the two migration models, which are explored in terms of mechanical properties of the hydrogels as well as the intrinsic characteristics of the models. Moreover, the developed 3D dynamic model is validated by demonstrating that hVCAM‐1 plays a major role in the extravasation process, influencing extravasation rate and traveled distance. Furthermore, the developed model enables precise visualization of cancer cell migration within a 3D matrix in response to microenvironmental cues, shedding light on the importance of biophysical properties in cell behavior. more...
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- 2018
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14. Synergistic Effect of Co‐Culturing Breast Cancer Cells and Fibroblasts in the Formation of Tumoroid Clusters and Design of In Vitro 3D Models for the Testing of Anticancer Agents (Adv. Biology 4/2023)
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Lara Pierantoni, Virginia Brancato, João B. Costa, Subhas C. Kundu, Rui L. Reis, Joana Silva‐Correia, and Joaquim M. Oliveira
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Biomaterials ,Biomedical Engineering ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
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15. Integration of polyurethane meniscus scaffold during ACL revision is not reliable at 5 years despite favourable clinical outcome
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Hélder Pereira, Ibrahim Fatih Cengiz, Joana Silva-Correia, Joaquim M. Oliveira, José C. Vasconcelos, Sérgio Gomes, Pedro L. Ripoll, Jón Karlsson, Rui L. Reis, and João Espregueira-Mendes
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Treatment Outcome ,Anterior Cruciate Ligament Reconstruction ,Anterior Cruciate Ligament Injuries ,Polyurethanes ,Humans ,Meniscus ,Orthopedics and Sports Medicine ,Surgery ,Lysholm Knee Score ,Menisci, Tibial ,Follow-Up Studies ,Meniscectomy - Abstract
The aim of this study was to evaluate the clinical outcome at 5-year follow-up of a one-step procedure combining anterior cruciate ligament (ACL) reconstruction and partial meniscus replacement using a polyurethane scaffold for the treatment of symptomatic patients with previously failed ACL reconstruction and partial medial meniscectomy. Moreover, the implanted scaffolds have been evaluated by MRI protocol in terms of morphology, volume, and signal intensity.Twenty patients with symptomatic knee laxity after failed ACL reconstruction and partial medial meniscectomy underwent ACL revision combined with polyurethane-based meniscal scaffold implant. Clinical assessment at 2- and 5-year follow-ups included VAS, Tegner Activity Score, International Knee Documentation Committee (IKDC), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lysholm Score. MRI evaluation of the scaffold was performed according to the Genovese scale with quantification of the scaffold's volume at 1- and 5-year follow-ups.All scores revealed clinical improvement as compared with the preoperative values at the 2- and 5-year follow-ups. However, a slight, but significant reduction of scores was observed between 2 and 5 years. Concerning the MRI assessment, a significant reduction of the scaffold's volume was observed between 1 and 5 years. Genovese Morphology classification at 5 years included two complete resorptions (Type 3) and all the remaining patients had irregular morphology (Type 2). With regard to the Genovese Signal at the 5-year follow-up, three were classified as markedly hyperintense (Type 1), 15 as slightly hyperintense (Type 2), and two as isointense (Type 1).Simultaneous ACL reconstruction and partial meniscus replacement using a polyurethane scaffold provides favourable clinical outcomes in the treatment of symptomatic patients with previously failed ACL reconstruction and partial medial meniscectomy at 5 years. However, MRI evaluation suggests that integration of the scaffold is not consistent.Level IV. more...
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- 2022
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16. Emerging scaffold- and cellular-based strategies for brain tissue regeneration and imaging
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Maurice N. Collins, Fernanda Zamboni, Aleksandra Serafin, Ane Escobar, Romain Stepanian, Mario Culebras, Rui L. Reis, and Joaquim M. Oliveira
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Stimulating brain tissue regeneration is a major challenge after central nervous system (CNS) injury, such as those observed from trauma or cerebrovascular accidents. Full regeneration is difficult even when a neurogenesis-associated repair response may occur. Currently, there are no effective treatments to stimulate brain tissue regeneration. However, biomaterial scaffolds are showing promising results, where hydrogels are the materials of choice to develop these supportive scaffolds for cell carriers. Their combination with growth factors, such as brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), or vascular endothelial growth factor (VEGF), together with other cell therapy strategies allows the prevention of further neuronal death and can potentially lead to the direct stimulation of neurogenesis and vascularisation at the injured site. Imaging of the injured site is particularly critical to study the reestablishment of neural cell functionality after brain tissue injury. This review outlines the latest key advances associated with different strategies aiming to promote the neuroregeneration, imaging, and functional recovery of brain tissue. Graphical abstract more...
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- 2022
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17. Contributors
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Elaheh Dalir Abdolahinia, Mohamed Abdul-Al, Khosro Adibkia, Aram-Sevag Afarian, Nima Ahmadkhani, Jawaria Ahmed, Zineb Ajji, Saeideh Allahyari, Zohreh Arabpour, Igbal Awad, Mahmoud Azami, Alireza Badiei, Zohreh Bagher, Nima Beheshtizadeh, Somayeh Ebrahimi-Barough, Asrin Emami, Gholamali Farzi, Ali Farzin, Leyla Fath-Bayati, Marziyeh Fathi, Narges Forouzideh, Maedeh Gheysipour, Mahdieh Ghiasi, Zoe Hancox, Nastaran Hashemzadeh, Mahshid Hosseini, Arman Jafari, Shehpara Kausar, Saeed Heidari Keshel, Mehdi Khanmohammadi, Zahra Khosrowpour, Nasrin Lotfibakhshaiesh, Kanchan Maji, Soheyl Mirzababaei, Fatemeh Mohajer, Ghodsi Mohammadi Ziarani, Ali Mousavi, Amir Nahanmoghadam, Haideh Namdari, Mojdeh Salehi Namini, Samira Nasirizadeh, Mona Navaei-Nigjeha, Aina Nisar, Eduarda P. Oliveira, Joaquim M. Oliveira, Farzad Parvizpour, Parth Nayanbhai Patel, Zahra Pazhouhnia, Xenos Petridis, Zahra Pirdel, Krishna Pramanik, Heather Price, Nasim Rashedi, Sina Rashedi, Rui L. Reis, Haleemah Sa’diyah Hussain, Morvarid Saeinasab, Mohammad Samiei, Houman Savoji, Mahsa Sedighi, Farshid Sefat, Rukhsar Shah, Tasbeeya Shah, Hajrah Siddique, Joana Silva-Correia, Paniz Siminzar, Cristina Tuinea-Bobe, Ahmad Vaez, Mohammad Varzandeh, Li Yifan, and Elmira Zolali more...
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- 2023
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18. List of contributors
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Dana Akilbekova, Michele Bertolini, Pablo Bordón, Ben Bowles, Harshavardhan Budharaju, Claudio Capelli, Miguel Castilho, Gerardo Cedillo-Servin, Wenqing Chen, Angela Daly, Carmen Salvadores Fernandez, Stephen Hilton, Shervanthi Homer-Vanniasinkam, Andrei Hrynevich, Deepak M. Kalaskar, Ruchi Pathak Kaul, Yang Li, F. Raquel Maia, Jos Malda, Mario D. Monzón, Ali Mousavi, Zaid Muwaffak, Amy Nommeots-Nomm, Joaquim M. Oliveira, Rubén Paz, Gowsihan Poologasundarampillai, Elena Provaggi, Subha N. Rath, Rui L. Reis, Uday Kiran Roopavath, Sharanya Sankar, Patricia Santos Beato, Houman Savoji, Silvia Schievano, Muthu Parkkavi Sekar, Swaminathan Sethuraman, Dhakshinamoorthy Sundaramurthi, Manish K Tiwari, Amanzhol Turlybekuly, Eirini Velliou, Lulu Xu, and Allen Zennifer more...
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- 2023
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19. Contributors
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Muhammad Aamir, Shuja Ahmed, Javeed Akhtar, Muhammad Awais Aslam, Amol C. Badgujar, V. Belessi, Neha Bisht, Sivasambu Böhm, Liliana P.T. Carneiro, Pritam Kishore Chakraborty, Silvia Colella, Carola Esposito Corcione, Olivier Degryse, Felipe M. de Souza, Sanjay R. Dhage, Steven John DiGregorio, Eleonora Ferraris, Nádia S. Ferreira, Octavio Garate, Snehraj Gaur, V. Georgakilas, Mehak Ghafoor, Sujit Kumar Ghosh, Gustavo Giménez, Antonella Giuri, Ram K. Gupta, Ritu Gupta, Owen James Hildreth, Žiga Jelen, Muhammad Kaleem Shabbir, Humaira Rashid Khan, Fahd Sikandar Khan, Muhammad Ejaz Khan, Pawan Kumar Khanna, S. Kiruthika, A. Koutsioukis, Andrea Listorti, F. Raquel Maia, Peter Majerič, Manab Mallik, Rocío Martínez-Flores, Dibakar Mondal, Leandro N. Monsalve, Sania Naseer, Gayatri Natu, Joaquim M. Oliveira, Gerko Oskam, Ayan Pal, Sudip Kumar Pal, Alexandra M.F.R. Pinto, Dena Pourjafari, Mallar Ray, Rui L. Reis, Aurora Rizzo, Geonel Rodríguez-Gattorno, Rebeka Rudolf, Miguel A. Ruiz-Gómez, Mainak Saha, M. Goreti F. Sales, Angel Samos-Puerto, Miriam Seiti, Abu Bakar Siddique, Rina Singh, Ahmed Shuja Syed, Amit Tewari, Khalid Hussain Thebo, Hanuma Reddy Tiyyagura, Ajay B. Urgunde, Lionel S. Veiga, Akash Verma, Maria Rosaria Vetrano, Thomas L. Willett, Brijesh Singh Yadav, and Gabriel Ybarra more...
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- 2023
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20. Repairing Annulus Fibrosus Fissures Using Methacrylated Gellan Gum Combined with Novel Silk
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Andreas S. Croft, Slavko Ćorluka, Janine Fuhrer, Michael Wöltje, Joana Silva-Correia, Joaquim M. Oliveira, Georg F. Erbach, Rui L. Reis, Benjamin Gantenbein, and Universidade do Minho
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Organ culture ,Methacrylated gellan gum ,intervertebral disc herniation ,methacrylated gellan gum ,silk fibroin ,annulus fibrosus repair ,organ culture ,complex dynamic loading ,540 Chemistry ,Intervertebral disc herniation ,Silk fibroin ,570 Life sciences ,biology ,610 Medicine & health ,Annulus fibrosus repair ,General Materials Science ,Complex dynamic loading ,620 Engineering - Abstract
Intervertebral disc (IVD) herniation often causes severe pain and is frequently associated with the degeneration of the IVD. As the IVD degenerates, more fissures with increasing size appear within the outer region of the IVD, the annulus fibrosus (AF), favoring the initiation and progression of IVD herniation. For this reason, we propose an AF repair approach based on methacrylated gellan gum (GG-MA) and silk fibroin. Therefore, coccygeal bovine IVDs were injured using a biopsy puncher (â 2 mm) and then repaired with 2% GG-MA as a filler material and sealed with an embroidered silk yarn fabric. Then, the IVDs were cultured for 14 days either without any load, static loading, or complex dynamic loading. After 14 days of culture, no significant differences were found between the damaged and repaired IVDs, except for a significant decrease in the IVDsâ relative height under dynamic loading. Based on our findings combined with the current literature that focuses on ex vivo AF repair approaches, we conclude that it is likely that the repair approach did not fail but rather insufficient harm was done to the IVD., DFG -Deutsche Forschungsgemeinschaft(437213841) more...
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- 2023
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21. Nano inks for tissue engineering
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F. Raquel Maia, Rui L. Reis, and Joaquim M. Oliveira
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- 2023
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22. Synergistic Effect of Co-Culturing Breast Cancer Cells and Fibroblasts in the Formation of Tumoroid Clusters and Design of In Vitro 3D Models for the Testing of Anticancer Agents
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Lara Pierantoni, Virginia Brancato, João B. Costa, Subhas C. Kundu, Rui L. Reis, Joana Silva‐Correia, Joaquim M. Oliveira, Pierantoni, L, Brancato, V, Costa, J, Kundu, S, Reis, R, Silva-Correia, J, and Oliveira, J more...
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Biomaterials ,3D tumor model ,breast cancer ,silk fibroin ,Biomedical Engineering ,hydrogel ,drug testing ,General Biochemistry, Genetics and Molecular Biology - Abstract
Breast cancer is still the leading cause of women's death due to relapse and metastasis. In vitro tumor models are considered reliable tools for drug screening and understanding cancer-driving mechanisms due to the possibility of mimicking tumor heterogeneity. Herein, a 3D breast cancer model (3D-BCM) is developed based on enzymatically-crosslinked silk fibroin (eSF) hydrogels. Human MCF7 breast cancer cells are encapsulated into eSF hydrogels, with and without human mammary fibroblasts. The spontaneously occurring conformational change from random coil to β-sheet is correlated with increased eSF hydrogels’ stiffness over time. Moreover, mechanical properties analysis confirms that the cells can modify the stiffness of the hydrogels, mimicking the microenvironment stiffening occurring in vivo. Fibroblasts support cancer cells growth and assembly in the eSF hydrogels up to 14 days of culture. Co-cultured 3D-BCM exhibits an upregulated expression of genes related to extracellular matrix remodeling and fibroblast activation. The 3D-BCM is subjected to doxorubicin and paclitaxel treatments, showing differential drug response. Overall, these results suggest that the co-culture of breast cancer cells and fibroblasts in eSF hydrogels allow the development of a mimetic in vitro platform to study cancer progression. This opens up new research avenues to investigate novel molecular targets for anti-cancer therapy. more...
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- 2023
23. Adaptable hydrogel with reversible linkages for regenerative medicine: Dynamic mechanical microenvironment for cells
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Qi Zhong, Rui L. Reis, Zhengwei Mao, Zongrui Tong, Lulu Jin, Joaquim M. Oliveira, and Changyou Gao
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Matrix remodeling ,Future studies ,Computer science ,0206 medical engineering ,Biomedical Engineering ,Nanotechnology ,macromolecular substances ,02 engineering and technology ,Yes-associated protein ,complex mixtures ,Regenerative medicine ,Article ,Biomaterials ,lcsh:TA401-492 ,Adaptable hydrogel ,lcsh:QH301-705.5 ,Flexibility (engineering) ,Mechanism (biology) ,technology, industry, and agriculture ,Dynamic covalent chemistry ,021001 nanoscience & nanotechnology ,Dynamic mechanical microenvironment ,020601 biomedical engineering ,3. Good health ,lcsh:Biology (General) ,Self-healing hydrogels ,lcsh:Materials of engineering and construction. Mechanics of materials ,Supramolecular chemistry ,0210 nano-technology ,Biotechnology - Abstract
Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix. These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility. It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues. Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix. The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows. First, we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry. Next, we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate, including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling. Finally, we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine. We conclude by discussing the limitations and challenges for adaptable hydrogel, and we present perspectives for future studies., Graphical abstract Image 1, Highlights • Introduction of adaptable hydrogels with dynamic mechanical properties as 3D extracellular matrix. • Summary of reversible linkages based on supramolecular interactions and dynamic covalent bonds. • Discussion of how adaptable hydrogels provide dynamic mechanical microenvironment and influence cell behaviors and fate. • Overview of applications of adaptable hydrogel in regenerative medicine. more...
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- 2021
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24. Microphysiological systems to study colorectal cancer: state-of-the-art
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Pedro Ramos, Mariana R Carvalho, Wei Chen, Le-Ping Yan, Chang-Hua Zhang, Yu-long He, Rui L Reis, and Joaquim M Oliveira
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Biomaterials ,Biomedical Engineering ,Bioengineering ,General Medicine ,Biochemistry ,Biotechnology - Abstract
Basic pre-clinical research based on 2D cultures have been very valuable in colorectal cancer (CRC) research but still have failed to improve patient prognostic outcomes. This is because they simply do not replicate what happens in vivo, i.e. 2D cultured cells system cannot replicate the diffusion constraints usually found in the body. Importantly, they also do not mimic the dimensionality of the human body and of a CRC tumour (3D). Moreover, 2D cultures lack the cellular heterogeneity and the tumour microenvironment (TME) such as stromal components, blood vessels, fibroblasts, and cells of the immune system. Cells behave differently whether in 2D and 3D, in particular their different genetic and protein expression panels are very different and therefore we cannot fully rely on drug tests done in 2D. A growing field of research based on microphysiological systems involving organoids/spheroids or patient-derived tumour cells has become a solid base for a better understanding of the TME and as a result is a step towards personalized medicine. Furthermore, microfluidic approaches have also started to open possibilities of research, with tumour-on-chips and body-on-chips being used in order to decipher complex inter-organ signalling and the prevalence of metastasis, as well as CRC early-diagnosis through liquid biopsies. Herein, we focus on the state-of-the-art of CRC research with emphasis on 3D microfluidic in vitro cultures—organoids, spheroids—drug resistance, circulating tumour cells and microbiome-on-a-chip technology. more...
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- 2023
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25. 3D Bioprinted Highly Elastic Hybrid Constructs for Advanced Fibrocartilaginous Tissue Regeneration
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Adam M. Jorgensen, Ji Hoon Park, João B. Costa, Joana Silva-Correia, Anthony Atala, Joaquim M. Oliveira, Rui L. Reis, James J. Yoo, Sang Jin Lee, and Universidade do Minho
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Materials science ,General Chemical Engineering ,Medicina Básica [Ciências Médicas] ,Fibroin ,02 engineering and technology ,Meniscus (anatomy) ,010402 general chemistry ,01 natural sciences ,Article ,law.invention ,chemistry.chemical_compound ,law ,Materials Chemistry ,medicine ,3D bioprinting ,Science & Technology ,Regeneration (biology) ,Bioprinting ,Structural integrity ,General Chemistry ,021001 nanoscience & nanotechnology ,Hybrid ,Gellan gum ,0104 chemical sciences ,medicine.anatomical_structure ,fibrocartilage ,chemistry ,Ciências Médicas::Medicina Básica ,Subcutaneous implantation ,Fibrocartilage ,0210 nano-technology ,Biomedical engineering - Abstract
Advanced strategies to bioengineer a fibrocartilaginous tissue to restore the function of the meniscus are necessary. Currently, 3D bioprinting technologies have been employed to fabricate clinically relevant patient-specific complex constructs to address unmet clinical needs. In this study, a highly elastic hybrid construct for fibrocartilaginous regeneration is produced by coprinting a cell-laden gellan gum/fibrinogen (GG/FB) composite bioink together with a silk fibroin methacrylate (Sil-MA) bioink in an interleaved crosshatch pattern. We characterize each bioink formulation by measuring the rheological properties, swelling ratio, and compressive mechanical behavior. For in vitro biological evaluations, porcine primary meniscus cells (pMCs) are isolated and suspended in the GG/FB bioink for the printing process. The results show that the GG/FB bioink provides a proper cellular microenvironment for maintaining the cell viability and proliferation capacity, as well as the maturation of the pMCs in the bioprinted constructs, while the Sil-MA bioink offers excellent biomechanical behavior and structural integrity. More importantly, this bioprinted hybrid system shows the fibrocartilaginous tissue formation without a dimensional change in a mouse subcutaneous implantation model during the 10-week postimplantation. Especially, the alignment of collagen fibers is achieved in the bioprinted hybrid constructs. The results demonstrate this bioprinted mechanically reinforced hybrid construct offers a versatile and promising alternative for the production of advanced fibrocartilaginous tissue., United States National Institutes of Health (1P41EB023833-346 01) and the Portuguese Foundation for Science and Technology (PTDC/BBB-ECT/2690/2014 and PTDC/EMD-EMD/ 31367/2017). FCT/MCTES is acknowledged for the Ph.D. scholarship attributed to J.B.C. (PD/BD/113803/2015) and the financial support provided to J.S.-C. (IF/00115/2015) and J.M.O. (IF/01285/2015) under the program “Investigador FCT” more...
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- 2020
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26. Marine‐origin Polysaccharides for Tissue Engineering and Regenerative Medicine
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Nuno M. Neves, Simone S. Silva, L. L. Reys, Catarina Oliveira, Joaquim M. Oliveira, Albino Martins, Rita López-Cebral, Rui L. Reis, and Tiago H. Silva
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chemistry.chemical_classification ,0303 health sciences ,Fucoidan ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Polysaccharide ,Regenerative medicine ,Chitosan ,03 medical and health sciences ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Chitin ,Tissue engineering ,0210 nano-technology ,030304 developmental biology - Published
- 2020
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27. Ionic Liquid-Mediated Processing of SAIB-Chitin Scaffolds
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Joana Gomes, F. Raquel Maia, Isabel Matos Oliveira, Raphaël F. Canadas, Hajer Radhouani, Joaquim M. Oliveira, Rui L. Reis, Cristiana Gonçalves, and Simone S. Silva
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Renewable Energy, Sustainability and the Environment ,General Chemical Engineering ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Chitin ,Tissue engineering ,Chemical engineering ,Solubilization ,Ionic liquid ,Environmental Chemistry ,0210 nano-technology ,Sucrose acetate isobutyrate - Abstract
This study proposes a green and innovative ionic liquid (IL) methodology for processing sucrose acetate isobutyrate (SAIB) porous structures for tissue engineering. The solubilization of SAIB in an... more...
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- 2020
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28. Kefiran in Tissue Engineering and Regenerative Medicine
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Rui L. Reis, Susana Correia, Hajer Radhouani, and Joaquim M. Oliveira
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Tissue engineering ,Chemistry ,Kefiran ,Regenerative medicine ,Biomedical engineering - Published
- 2022
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29. Engineering of extracellular matrix-like biomaterials at nano- and macroscale toward fabrication of hierarchical scaffolds for bone tissue engineering
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F. Raquel Maia, Rafael Lemos, Joaquim M. Oliveira, Rui L. Reis, and Universidade do Minho
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Materials science ,Fabrication ,Nanoparticle ,Nanotechnology ,02 engineering and technology ,Microparticles ,Bone tissue engineering ,Nanocomposites ,Extracellular matrix ,Biomaterials ,03 medical and health sciences ,Nano ,Medical technology ,R855-855.5 ,Bone ,030304 developmental biology ,General Environmental Science ,0303 health sciences ,Nanocomposite ,Science & Technology ,021001 nanoscience & nanotechnology ,General Earth and Planetary Sciences ,Nanoparticles ,0210 nano-technology ,TP248.13-248.65 ,Biotechnology - Abstract
The increasing rate of musculoskeletal pathologies has compelled the development of improved and novel treatment strategies in order to address unmet clinical needs. Tissue engineering approaches comprising the use of scaffolds for bone regeneration have been showing to be a promising alternative to conventional bone repair/substitution approaches. In particular, hierarchical scaffolds as methods of structural support and osteogenic differentiation promoters are among the most used tools in bone tissue engineering (BTE). In this reasoning, hierarchical scaffolds have sparked the field, striving toward mimicking the natural bone tissue in both, its complex 3D structure and composition. A recent and promising trend has been the merging of nanotechnology and tissue engineering concepts. As such the incorporation of nanoparticles and nanocomposites into micro- or macroscaffold systems can result in an improvement of scaffoldsâ biofunctionality at different levels. These tools are versatile in nature and can be used for multiple purposes such as drug delivery, thermal conductors, and mechanical reinforcement. Taking into consideration multidisciplinary approaches, several strategies have been pursued. The recent reports dealing with the approaches pursued in the hierarchical scaffolds production and enhancement, ranging from the nanoscale to the macroscale, are overviewed herein., The authors thank the funds provided by the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), the project 3BioMeD (FCT/4773/ 4/5/2017/S) supported by Fundação para a Ciência e a Tecnologia (FCT) and the R&D Project KOAT PTDC/BTMMAT/29760/2017 (POCI 01-0145-FEDER-029760) financed by FCT and cofinanced by FEDER and POCI. F.R.M. acknowledges FCT for her contract under the Transitional Rule DL 57/2016 (CTTI-57/18-I3BS (5)). more...
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- 2022
30. Macromolecular modulation of a 3D hydrogel construct differentially regulates human stem cell tissue-to-tissue interface
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Diana R. Pereira, Joana Silva-Correia, Joaquim M. Oliveira, Rui L. Reis, Abhay Pandit, and Universidade do Minho
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Biomedical Engineering ,Bioengineering ,02 engineering and technology ,Stem cells ,3D hydrogels ,Biomaterials ,03 medical and health sciences ,Humans ,Tissue engineering ,Hyaluronic Acid ,030304 developmental biology ,0303 health sciences ,Science & Technology ,Tissue Engineering ,Stem Cells ,Interface tissue engineering ,Hydrogels ,Mesenchymal Stem Cells ,3D hydrogels stem cells ,021001 nanoscience & nanotechnology ,3. Good health ,Extracellular Matrix ,INTERFACE ,Immune regeneration ,0210 nano-technology - Abstract
The simultaneous generation of multiple tissues and their functional assembly into complex tissues remains a critical challenge for regenerative medicine. The tissue-to-tissue interface connecting two adjacent tissues is vital in effective tissue function. The presented worked hypothesize that differential functional property can be engineered by modulating the macromolecular composition of a 3D hydrogel construct and distinctively endow stem cell fate. Hence, it was possible to successfully generate macromolecular constructs by using the extracellular matrix (ECM)-based materials; type I collagen (Col I) and hyaluronic acid (HA); and natural-derived biomaterials as methacrylated gellan-gum (GGMA). The 3D hydrogel constructs consisted of two dissimilar layers: 1) Col I: HA hydrogel and 2) GGMA hydrogel. The tissue-to-tissue interface was created by seeding human mesenchymal stem cells (MSCs) between the two layers. Differential functional rheological and mechanical properties characterized the acellular 3D gradient hydrogel constructs. The cell-based 3D hydrogel constructs were assessed for MSCs viability by live/dead staining. Assessing apoptosis by flow cytometry, data showed the feasibility of the 3D hydrogel constructs in maintaining cell viability with no apoptosis induction onto MSCs. A homogeneous distribution was achieved in a successful cellular tissue-to-tissue interface. Human MSCs low proliferative rate and low ECM deposition were seen for all constructs; however, lower proliferative rate within the ECM microenvironment highlights controlled self-renewal of MSCs. The 3D hydrogel constructs maintained the human MSCs phenotype, yet the macromolecular modulation allowed tuning the human MSCs morphology from round to spindle-shaped phenotype. The intrinsic properties of the 3D cell-based hydrogel construct induced differential inflammatory and angiogenic paracrine secretory profiles owing to the dissimilar engineered biophysical milieu. Human MSCs sense the nearby macromolecular environment adjusting the cell-ECM interactions, which influence cell behaviour and fate. Beyond multi-tissue regeneration, the engineered cellular 3D hydrogel constructs may simultaneously address immune regeneration., This material is based on works supported by the European Union funding under the 7th Framework Programme under Grant Agreement Number 317304 and supported in part by a research grant from Science Foundation Ireland (SFI) and co-funded under the European Regional De-velopment Fund under Grant Number 13/RC/2073_P2. D.R. Pereira ac-knowledges the Foundation for Science and Technology (FCT) , Portugal, for an individual grant (SFRH/BD/81356/2011) . J. Silva-Correia and J.M. Oliveira also acknowledges the FCT for the funds provided under the prestigious program Investigator FCT 2015 (IF/00115/2015 and IF/01285/2015, respectively).The authors acknowledge the scientific and technical assistance of the Electron Microscopy unit within the Centre for Microscopy & Imaging, the flow cytometry core facility and histology core facility at the National University of Ireland (NUI)Galway. All facilities are funded by NUI Galway and the Irish Government's Programme for Research in Third Level Institutions (PRTLI), Cycles 4 and 5, National Development Plan 2007-2013. The authors would like to also acknowledge the Centre for Microscopy & Imaging funded by the National University of Ireland Galway and MSSI in the University of Limerick for the rheometer facilities, both funded by the Programme for Research in Third-Level Institutions (PRTLI), Cycles 4 and 5, National Development Plan 2007-2013. more...
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- 2021
31. Towards the development of a female animal model of T1DM using hyaluronic acid nanocoated cell transplantation: refinements and considerations for future protocols
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Ibrahim Fatih Cengiz, Joaquim M. Oliveira, António G. Castro, Maurice N. Collins, Rui L. Reis, Fernanda Zamboni, Ana Margarida Barbosa, and Universidade do Minho
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medicine.medical_specialty ,female animal model ,Pharmaceutical Science ,030209 endocrinology & metabolism ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacy and materia medica ,Diabetes mellitus ,Internal medicine ,Hyaluronic acid ,medicine ,Outras Ciências Médicas [Ciências Médicas] ,Ciências Médicas::Outras Ciências Médicas ,030304 developmental biology ,0303 health sciences ,Type 1 diabetes ,geography ,geography.geographical_feature_category ,Science & Technology ,business.industry ,medicine.disease ,Streptozotocin ,Islet ,3. Good health ,Transplantation ,RS1-441 ,Endocrinology ,chemistry ,diabetes induction ,business ,Insulitis ,Hormone ,medicine.drug ,transplantation - Abstract
Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/pharmaceutics13111925/s1. Figure S1 (A) Intraperitoneal injection of STZ. (B) Mice are kept in cages with ad libitum fed regimen. Figure S2 MIN-6 cell transplantation. A) Abdominal viscera of female mice. (B) Intramuscular administration of anaesthetics. (C) Topical application of Vaseline to protect eyes from drying during surgery, lateral hair removal for incision. (D) Graft injection inside the kidney capsule. (E–F) Suture and stiches. (G) Post-operation recovery., Female mice (Black 6 strain) (C57BL/6) aged 6 weeks were subject to low dose streptozotocin (STZ) treatment for five consecutive days to mimic type 1 diabetes mellitus (T1DM) with insulitis. At two weeks after STZ injections, evaluation of the elevated glucose levels was used to confirm diabetes. The diabetic mice were then subject to the transplantation of pancreatic β-cells (MIN-6 line). Four groups of mice were studied. The first group was injected with saline-only acting as the placebo surgery control, also known as SHAM group, the second and third groups were injected with MIN-6 single cells and polyethylene glycol-modified dipalmitoyl-glycerol-phosphatidyl ethanolamine (PEG-DPPE) modified MIN-6 single cells (500 µg per 1.106 cells), respectively, while the fourth group was injected with hyaluronic acid (HA)-coated MIN-6 single cells (5 bilayers). At seven- and fourteen-days following transplantation, the mice were euthanised. The renal and pancreatic tissues were then collected and histologically analysed. The induction of diabetes in female mice, through five-consecutive daily STZ injections resulted in inconsistent glycaemic levels. Interestingly, this shows an incomplete diabetes induction in female mice, of which we attribute to sex dimorphism and hormonal interferences. Transplantation failure of free-floating encapsulated cells was unable to decrease blood glucose hyperglycaemia to physiological ranges. The result is attributed to deprived cell–cell interactions, leading to decreased β-cells functionality. Overall, we highlight the necessity of refining T1DM disease models in female subjects when using multiple low-dose STZ injections together with transplantation protocols. Considerations need to be made regarding the different developmental stages of female mice and oestrogen load interfering with pancreatic β-cells susceptibility to STZ. The use of pseudo islets, cell aggregates and spheroids are sought to improve transplantation outcome in comparison to free-floating single cells., Irish Research Council Postgraduate Scholarship (GOIPG/2015/3577) and ERASMUS+ grant student mobility placement (University of Limerick/Erasmus+ 1920) for F.Z. The authors also thank the financial support under the FRONTHERA (NORTE-01-0145-FEDER-000023) project (J.M.O. and I.F.C.), and the project 2IQBIONEURO (ref. 0624_2IQBIONEURO_6_E) (J.M.O. and I.F.C.), and TERM RES-Hub, Tissue Engineering and Regenerative Medicine Infrastructure project, funded by the Portuguese Foundation for Science and Technology (FCT) (I.F.C.). more...
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- 2021
32. A Microfludic Platform as An In Vitro Model for Biomedical Experimentation - A Cell Migration Study
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Nevena Milivojevic, David Caballero, Mariana R Carvalho, Mihajlo Kokanovic, Marko Zivanovic, Nenad Filipovic, Rui L Reis, and Joaquim M Oliveira
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- 2021
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33. Combining experiments and in silico modeling to infer the role of adhesion and proliferation on the collective dynamics of cells
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Nuno A. M. Araújo, Hygor P. M. Melo, Joaquim M. Oliveira, André S. Nunes, Rui L. Reis, F. Raquel Maia, and Universidade do Minho
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Engineering ,Cell division ,Engenharia e Tecnologia::Biotecnologia Industrial ,Science ,In silico ,Morphogenesis ,Motility ,Computational biology ,Models, Biological ,Article ,Cell Line ,Cell Physiological Phenomena ,03 medical and health sciences ,Cell growth ,0302 clinical medicine ,Surfaces, interfaces and thin films ,Tissue engineering ,Cell Movement ,Biotecnologia Industrial [Engenharia e Tecnologia] ,Cell Line, Tumor ,Humans ,Collective dynamics ,Statistical physics, thermodynamics and nonlinear dynamics ,Cell adhesion ,Cells, Cultured ,Cell proliferation ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,In silico modeling ,Science & Technology ,Chemistry ,Mechanism (biology) ,business.industry ,Adhesion ,030220 oncology & carcinogenesis ,Cancer cell ,Biophysics ,Medicine ,business ,Cell collective dynamics ,030217 neurology & neurosurgery ,Algorithms - Abstract
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-021-99390-x., The collective dynamics of cells on surfaces and interfaces poses technological and theoretical challenges in the study of morphogenesis, tissue engineering, and cancer. Different mechanisms are at play, including, cellâ cell adhesion, cell motility, and proliferation. However, the relative importance of each one is elusive. Here, experiments with a culture of glioblastoma multiforme cells on a substrate are combined with in silico modeling to infer the rate of each mechanism. By parametrizing these rates, the time-dependence of the spatial correlation observed experimentally is reproduced. The obtained results suggest a reduction in cellâ cell adhesion with the density of cells. The reason for such reduction and possible implications for the collective dynamics of cancer cells are discussed., The authors acknowledge fnancial support from the Portuguese Foundation for Science and Technology (FCT) under Contracts no. PTDC/FIS-MAC/28146/2017 (LISBOA-01-0145-FEDER-028146), UIDB/00618/2020, and UIDP/00618/2020. F.R.M. also acknowledges FCT for her contract under the Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)). more...
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- 2021
34. Complex in vitro 3D models of digestive system tumors to advance precision medicine and drug testing: Progress, challenges, and trends
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Sheng-Lei Song, Bo Li, Mariana R. Carvalho, Hui-Jin Wang, De-Li Mao, Ji-Tao Wei, Wei Chen, Zhi-Hui Weng, Yang-Chao Chen, Chu-Xia Deng, Rui L. Reis, Joaquim M. Oliveira, Yu-Long He, Le-Ping Yan, Chang-Hua Zhang, and Universidade do Minho more...
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Pharmacology ,Digestive system cancer ,Science & Technology ,tumour ,cancer-on-a-chip ,Digestive System Neoplasms ,Digestive system ,Organoids ,Mice ,Tumor Microenvironment ,Humans ,Animals ,Pharmacology (medical) ,In vitro 3D models ,Precision Medicine ,in vitro models ,Gastrointestinal Neoplasms - Abstract
Digestive system cancers account for nearly half of all cancers around the world and have a high mortality rate. Cell culture and animal models represent cornerstones of digestive cancer research. However, their ability to en- able cancer precision medicine is limited. Cell culture models cannot retain the genetic and phenotypic heteroge- neity of tumors and lack tumor microenvironment (TME). Patient-derived xenograft mouse models are not suitable for immune-oncology research. While humanized mouse models are time- and cost-consuming. Suitable preclinical models, which can facilitate the understanding of mechanisms of tumor progression and develop new therapeutic strategies, are in high demand. This review article summarizes the recent progress on the establish- ment of TME by using tumor organoid models and microfluidic systems. The main challenges regarding the translation of organoid models from bench to bedside are discussed. The integration of organoids and a microflu- idic platform is the emerging trend in drug screening and precision medicine. A future prospective on this field is also provided., This study was supported by the National Natural Science Foundation of China (Grant No.82073148), the Guangdong Provincial Key Laboratory of Digestive Cancer Research (No. 2021B1212040006), the Sanming Project of Medicine in Shenzhen (SZSM201911010), the Shenzhen Key Medical Discipline Construction Fund (SZXK016), the Shenzhen Sustainable Project (KCXFZ202002011010593), and the Shenzhen-Hong Kong-Macau Technology Research Programme (Type C) (Grant No. SGDX2020110309260100). more...
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- 2022
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35. METTL3 promotes oxaliplatin resistance of gastric cancer CD133+ stem cells by promoting PARP1 mRNA stability
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Huafu Li, Chunming Wang, Linxiang Lan, Leping Yan, Wuguo Li, Ian Evans, E. Josue Ruiz, Qiao Su, Guangying Zhao, Wenhui Wu, Haiyong Zhang, Zhijun Zhou, Zhenran Hu, Wei Chen, Joaquim M. Oliveira, Axel Behrens, Rui L. Reis, Changhua Zhang, and Universidade do Minho more...
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RNA Stability ,Poly (ADP-Ribose) Polymerase-1 ,DNA repair ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,PARP1 mRNA ,Cellular and Molecular Neuroscience ,Mice ,Stomach Neoplasms ,Tumor Cells, Cultured ,Animals ,Humans ,Digestive system tumors ,AC133 Antigen ,RNA, Messenger ,Child ,Molecular Biology ,Cell Proliferation ,Pharmacology ,Mice, Inbred BALB C ,Gene Expression Profiling ,Cell Biology ,Methyltransferases ,Prognosis ,Xenograft Model Antitumor Assays ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Oxaliplatin ,Drug Resistance, Neoplasm ,Neoplastic Stem Cells ,Molecular Medicine ,METTL3 ,Epigenetic modulation ,Gastric cancer ,Chemotherapy resistance - Abstract
Oxaliplatin is the first-line regime for advanced gastric cancer treatment, while its resistance is a major problem that leads to the failure of clinical treatments. Tumor cell heterogeneity has been considered as one of the main causes for drug resistance in cancer. In this study, the mechanism of oxaliplatin resistance was investigated through in vitro human gastric cancer organoids and gastric cancer oxaliplatin-resistant cell lines and in vivo subcutaneous tumorigenicity experiments. The in vitro and in vivo results indicated that CD133+â stem cell-like cells are the main subpopulation and PARP1 is the central gene mediating oxaliplatin resistance in gastric cancer. It was found that PARP1 can effectively repair DNA damage caused by oxaliplatin by means of mediating the opening of base excision repair pathway, leading to the occurrence of drug resistance. The CD133+â stem cells also exhibited upregulated expression of N6-methyladenosine (m6A) mRNA and its writer METTL3 as showed by immunoprecipitation followed by sequencing and transcriptome analysis. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3â ²-untranslated Region (3â ²-UTR) of PARP1 mRNA. The CD133+â tumor stem cells can regulate the stability and expression of m6A to PARP1 through METTL3, and thus exerting the PARP1-mediated DNA damage repair ability. Therefore, our study demonstrated that m6A Methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+â gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity., NSFC -National Natural Science Foundation of China(2021B1212040006) more...
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- 2021
36. Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells
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Piotr Walczak, Kamila Milewska, Miroslaw Janowski, Lukasz Kalkowski, Joanna Kwiatkowska, Piotr Holak, Dominika Golubczyk, Izabela Malysz-Cymborska, Joaquim M. Oliveira, and Universidade do Minho
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Biocompatibility ,MRI contrast agent ,Pharmaceutical Science ,Intrathecal ,02 engineering and technology ,Article ,Cell therapy ,03 medical and health sciences ,0302 clinical medicine ,Pharmacy and materia medica ,Viability assay ,Large animals ,Manganese ,Science & Technology ,Chemistry ,Biomaterial ,021001 nanoscience & nanotechnology ,In vitro ,RS1-441 ,Hydrogel ,Contrast agent ,Self-healing hydrogels ,Stem cell ,0210 nano-technology ,030217 neurology & neurosurgery ,Biomedical engineering - Abstract
Cell therapy is a promising tool for treating central nervous system (CNS) disorders; though, the translational efforts are plagued by ineffective delivery methods. Due to the large contact surface with CNS and relatively easy access, the intrathecal route of administration is attractive in extensive or global diseases such as stroke or amyotrophic lateral sclerosis (ALS). However, the precision and efficacy of this approach are still a challenge. Hydrogels were introduced to minimize cell sedimentation and improve cell viability. At the same time, contrast agents were integrated to allow image-guided injection. Here, we report using manganese ions (Mn2+) as a dual agent for cross-linking alginate-based hydrogels and magnetic resonance imaging (MRI). We performed in vitro studies to test the Mn2+ alginate hydrogel formulations for biocompatibility, injectability, MRI signal retention time, and effect on cell viability. The selected formulation was injected intrathecally into pigs under MRI control. The biocompatibility test showed a lack of immune response, and cells suspended in the hydrogel showed greater viability than monolayer culture. Moreover, Mn2+-labeled hydrogel produced a strong T1 MRI signal, which enabled MRI-guided procedure. We confirmed the utility of Mn2+ alginate hydrogel as a carrier for cells in large animals and a contrast agent at the same time., This research was funded by The National Centre for Research and Development, grant number 12/EuroNanoMed/2016. more...
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- 2021
37. An efficient and user-friendly method for cytohistological analysis of organoids
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Yu-Hong Liu, Wei Chen, Zheng Yang, Le-Ping Yan, Shi-Wei Zhang, Changhua Zhang, Zhang Wen, Rui L. Reis, Joaquim M. Oliveira, Xiao-Fang Lu, Qiao Su, Lei Hu, Ling Xue, and Yulong He
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0303 health sciences ,Paraffin Embedding ,Tissue Fixation ,Computer science ,Cytological Techniques ,Biomedical Engineering ,Medicine (miscellaneous) ,Paraffin embedded ,Fluorescence ,Biomaterials ,Organoids ,03 medical and health sciences ,General pathology ,0302 clinical medicine ,Tissue engineering ,030220 oncology & carcinogenesis ,Formaldehyde ,Organoid ,Frozen Sections ,Humans ,Colorectal Neoplasms ,030304 developmental biology ,Biomedical engineering - Abstract
Organoid culture is a recently developed in-vitro three-dimensional (3D) cell culture technology. It has wide applications in tissue engineering studies. However, histological analysis of organoid is quite complex and tedious for researchers. This study proposes a user-friendly, affordable and efficient method for making formalin-fixed paraffin embedded (FFPE) organoid blocks and Optimal Cutting Temperature compound (OCT) embedded frozen organoid blocks. This method implements a key pre-embedding step for preparing paraffin embedded organoid blocks, which could concentrate organoid togethor without damaging or loss of samples. This method could be used to process even a small number of organoids with high efficiency. In addition, with minor modifications, the method is readily applied for OCT embedded organoid blocks. The slides generated were ready for H&E staining, immunohistochemistry staining and immunofluorescent staining. The method described in this study can be easily used for routine histological analysis of organoid, and could be performed in general pathology labs and requires no dedicated equipment and reagent. This article is protected by copyright. All rights reserved. more...
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- 2021
38. Cytocompatible manganese dioxide-based hydrogel nanoreactors for MRI imaging
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Soraia V. Lopes, Piotr Walczak, Miroslaw Janowski, Rui L. Reis, Joana Silva-Correia, Joaquim M. Oliveira, and Universidade do Minho
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Biomedical Engineering ,Manganese dioxide ,Contrast Media ,Bioengineering ,010402 general chemistry ,01 natural sciences ,Biomaterials ,03 medical and health sciences ,Magnetic resonance imaging ,Animals ,Nanotechnology ,Hyaluronic Acid ,Methacrylated Gellan-gum ,030304 developmental biology ,0303 health sciences ,Manganese ,Science & Technology ,Hydrogels ,Oxides ,Magnetic Resonance Imaging ,0104 chemical sciences ,Rats ,Manganese Compounds ,Nanoparticles ,Reactive oxygen species ,Reactive Oxygen Species - Abstract
The application of nanoparticles in magnetic resonance imaging (MRI) has been greatly increasing, due to their advantageous properties such as nanoscale dimension and tuneability. In this context, manganese (Mn2+)-based nanoparticles have been greatly investigated, due to their valuable use as a contrast agent, improving signal intensity and specificity in MRI (manganese-enhanced MRI, MEMRI). Additionally, Mn2+ can act as scavengers of reactive oxygen species (ROS), commonly present in the inflammatory processes of neurodegenerative diseases. The aim of the present study was to develop nanoreactors, which can be used as contrast-agent in MEMRI. Several blends of methacrylated gellan gum (GG-MA) and hyaluronic acid (HA) were embedded with different types of manganese dioxide (MnO2) nanoparticles and further physico-chemically characterized. Dynamic light scattering, scanning electron microscopy, water uptake and degradation studies were performed. In vitro cytotoxicity of the different formulations was also evaluated using an immortalized rat fibroblast cell line L929, up to 72 h of culturing. Synthesized nanoparticles were obtained with an average size of 70 nm and round-shaped morphology. The stability of the different formulations of hydrogels was not affected by nanoparticles' concentration or HA ratio. The presence of synthesized MnO2 (MnO2_S) nanoparticles reduced hydrogels' cytocompatibility, whereas the commercially available type 1 (MnO2_C1) nanoparticles were less toxic to cells. Additionally, cell proliferation and viability were enhanced when a lower content of HA was present. Higher concentrations (75 and 100 ng/mL) of MnO2_S and MnO2_C1 nanoparticles did not negatively affected cell viability, whereas the opposite effect was observed for the commercial type 2 (MnO2_C2) nanoparticles. Further studies are required to evaluate the potential application of the most promising nanoreactors' formulations for combined application in MEMRI and as ROS scavengers., The authors would like to acknowledge the financial support pro vided through the EC Funded project NanoTech4ALS (ENMed/0008/ 2015) and the funding provided under the projects FROnTHERA (No. NORTE-01-0145-FEDER-000023) and JUSThera (No. NORTE-01-0145- FEDER-000055), supported by Norte Portugal Regional Operational Programme (No. NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The authors also thank the funding through the project 2IQBIONEURO (ref. 0624_2IQBIONEURO_6_E). S.V. Lopes thanks to the Portuguese Foundation for Science and Technology (FCT) for the PhD grant (SFRH/ BD/143954/2019). The FCT distinction to J. Silva-Correia (IF/00115/ 2015) under the Investigator FCT program is also greatly acknowledged. more...
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- 2021
39. Tumor-Associated protrusion fluctuations as a signature of cancer invasiveness
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Nuno M. Neves, Vitor M. Correlo, Ana Catarina Lima, Joaquim M. Oliveira, Subhas C. Kundu, David Caballero, Catarina M. Abreu, Rui L. Reis, Virginia Brancato, Universidade do Minho, Caballero, D, Brancato, V, Lima, A, Abreu, C, Neves, N, Correlo, V, Oliveira, J, Reis, R, and Kundu, S more...
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micro-spheroids ,fluctuations ,tumors invasion ,Biomedical Engineering ,Biophysics ,Tumor cells ,Astrophysics::Cosmology and Extragalactic Astrophysics ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Physics::Geophysics ,Biomaterials ,Cancer invasiveness ,biophysical signatures ,03 medical and health sciences ,protrusion ,0302 clinical medicine ,Invasion ,Biotecnologia Médica [Ciências Médicas] ,medicine ,Humans ,Neoplasm Invasiveness ,030304 developmental biology ,Cancer ,0303 health sciences ,Protrusions ,micro-spheroid ,Science & Technology ,fluctuation ,Tumor Cell Invasion ,Astrophysics::Instrumentation and Methods for Astrophysics ,biophysical signature ,medicine.disease ,Physics::History of Physics ,3. Good health ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Ciências Médicas::Biotecnologia Médica ,Prediction - Abstract
uncorrected proof version, The generation of invasive fluctuating protrusions is a distinctive feature of tumor dissemination. During the invasion, individual cancer cells modulate the morphodynamics of protrusions to optimize their migration efficiency. However, it remains unclear how protrusion fluctuations govern the invasion of more complex multi-cellular structures, such as tumors, and their correlation with the tumor metastatic potential. Herein, a reductionist approach based on 3D tumor cell micro-spheroids with different invasion capabilities is used as a model to decipher the role of tumor-associated fluctuating protrusions in cancer progression. To quantify fluctuations, a set of key biophysical parameters that precisely correlate with the invasive potential of tumors is defined. It is shown that different pharmacological drugs and cytokines are capable of modulating protrusion activity, significantly altering protrusion fluctuations, and tumor invasiveness. This correlation is used to define a novel quantitative invasion index encoding the key biophysical parameters of fluctuations and the relative levels of cell-cell/matrix interactions, which is capable of assessing the tumor's metastatic capability solely based on its magnitude. Overall, this study provides new insights into how protrusion fluctuations regulate tumor cell invasion, suggesting that they may be employed as a novel early indicator, or biophysical signature, of the metastatic potential of tumors., Portuguese Foundation for Science and Technology (FCT) under the program CEEC Individual 2017 (CEECIND/00352/2017). D.C., V.B., A.C.L., C.M.A., and S.C.K. also thank the support from the FCT under the scope of the projects 2MATCH (PTDC/BTM-ORG/28070/2017) and BREAST-IT (PTDC/ BTM-ORG/28168/2017) funded by the Programa Operacional Regional do Norte supported by European Regional Development Funds (ERDF). The authors also thank the financial support from the European Union Framework Program for Research and Innovation Horizon 2020 on FoReCaST project under (Grant Number: 668983), and the Institution of Engineering and Technology (IET) for the funding provided under the ENG ThE CANCER project (Grant Number: IET Harvey Engineering Research Award 2018). J.M.O. is grateful for the FCT distinctions (IF/00423/2012 and IF/01285/2015) more...
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- 2021
40. Nanotechnology in peripheral nerve repair and reconstruction
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Cristiana R. Carvalho, Joana Silva-Correia, Joaquim M. Oliveira, Rui L. Reis, and Universidade do Minho
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Bioactive molecules ,Nanofibers ,Pharmaceutical Science ,Nanotechnology ,02 engineering and technology ,03 medical and health sciences ,Peripheral Nerve Injuries ,Peripheral nerve ,Humans ,Medicine ,Degree of precision ,Peripheral Nerves ,Carbon nanomaterials ,030304 developmental biology ,Tubular conduits ,0303 health sciences ,Science & Technology ,nanotechnology ,Nanoimaging ,business.industry ,Regeneration (biology) ,021001 nanoscience & nanotechnology ,Nerve Regeneration ,3. Good health ,Nanomedicine ,Neuroprotective Agents ,Peripheral Nerve Regeneration ,Nanoparticles ,0210 nano-technology ,business ,Repair - Abstract
The recent progress in biomaterials science and development of tubular conduits (TCs) still fails in solving the current challenges in the treatment of peripheral nerve injuries (PNIs), in particular when disease-related and long-gap defects need to be addressed. Nanotechnology-based therapies that seemed unreachable in the past are now being considered for the repair and reconstruction of PNIs, having the power to deliver bioactive molecules in a controlled manner, to tune cellular behavior, and ultimately guide tissue regeneration in an effective manner. It also offers opportunities in the imaging field, with a degree of precision never achieved before, which is useful for diagnosis, surgery and in the patientâ s follow-up. Nanotechnology approaches applied in PNI regeneration and theranostics, emphasizing the ones that are moving from the lab bench to the clinics, are herein overviewed., The authors acknowledge the Portuguese Foundation for Science and Technology (FCT) for the financial support provided to Joaquim M. Oliveira (IF/01285/2015) and Joana Silva-Correia (IF/00115/2015) under the program “Investigador FCT”., info:eu-repo/semantics/publishedVersion more...
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- 2019
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41. The Clinical Use of Biologics in the Knee Lesions: Does the Patient Benefit?
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Joaquim M. Oliveira, João Espregueira-Mendes, Rui L. Reis, Ibrahim Fatih Cengiz, Hélder Pereira, and Universidade do Minho
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medicine.medical_specialty ,Sports medicine ,animal diseases ,Osteoarthritis ,Biologics ,Meniscus (anatomy) ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Outcomes Research in Orthopedics (O Ayeni, Section Editor) ,Medicine ,Knee ,Meniscus ,Orthopedics and Sports Medicine ,Ligament ,Intensive care medicine ,030222 orthopedics ,Science & Technology ,Platelet-Rich Plasma ,business.industry ,030229 sport sciences ,medicine.disease ,nervous system diseases ,3. Good health ,Clinical trial ,medicine.anatomical_structure ,Concomitant ,Platelet-rich plasma ,Orthopedic surgery ,medicine.symptom ,business - Abstract
 Purpose of Review Overview the outcomes of the latest use of platelet-rich plasma (PRP) for the treatment of knee lesions in the clinics and discuss the challenges and limitations. Recent Findings Recent clinical studies mainly indicate there may be benefit of PRP usage for the treatment of knee lesions. As an autologous source of bioactive components, PRP has been shown to be typically safe, free of major adverse outcomes. The use of PRP has been continuously increasing, and some well-designed, double-blinded, placebo-controlled clinical trials have been published. Summary Clinical outcomes relating to PRP usage are multifactorial and depend on the severity of the lesion and patient characteristics. Although PRP is safe to use and it can be easily applied in the clinics, case-specific considerations are needed to determine whether PRP could be beneficial or not. If the use of PRP is favored, then, the configuration/optimization of the preparation and administration/delivery strategy with or without a concomitant treatment may further enhance the clinical outcomes and patients experience., The authors would like to thank the Portuguese Foundation for Science and Technology (FCT) project M-ERA-NET/0001/2014 project. This work is also a result of the project FROnTHERA(NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). IFC thanks the FCT for the grant SFRH/BD/99555/2014. JMO also thanks the FCT for the funds provided under the program Investigador FCT 2015 (IF/01285/2015). more...
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- 2019
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42. A soft 3D polyacrylate hydrogel recapitulates the cartilage niche and allows growth-factor free tissue engineering of human articular cartilage
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Gema Jiménez, Raphaël F. Canadas, Mark Bradley, Esmeralda Carrillo, Elena López-Ruiz, Joaquim M. Oliveira, Macarena Perán, Seshasailam Venkateswaran, Anthony Callanan, Elvira Montañez, Juan José Diaz-Monchon, Juan A. Marchal, Robert Walllace, Rui L. Reis, Salvatore Pernagallo, and Cristina Antich more...
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Cartilage, Articular ,0206 medical engineering ,Acrylic Resins ,Biomedical Engineering ,Mice, SCID ,02 engineering and technology ,Biochemistry ,Chondrocyte ,Biomaterials ,Extracellular matrix ,Mice ,Chondrocytes ,Tissue engineering ,Mice, Inbred NOD ,medicine ,Animals ,Humans ,Molecular Biology ,Aggrecan ,Tissue Engineering ,Tissue Scaffolds ,Hyaline cartilage ,Chemistry ,Cartilage ,Hydrogels ,General Medicine ,021001 nanoscience & nanotechnology ,Chondrogenesis ,020601 biomedical engineering ,Extracellular Matrix ,Cell biology ,medicine.anatomical_structure ,Self-healing hydrogels ,0210 nano-technology ,Biotechnology - Abstract
Cartilage degeneration or damage treatment is still a challenge, but, tissue engineering strategies, which combine cell therapy strategies, which combine cell therapy and scaffolds, and have emerged as a promising new approach. In this regard, polyurethanes and polyacrylates polymers have been shown to have clinical potential to treat osteochondral injuries. Here, we have used polymer microarrays technology to screen 380 different polyurethanes and polyacrylates polymers. The top polymers with potential to maintain chondrocyte viability were selected, with scale-up studies performed to evaluate their ability to support chondrocyte proliferation during long-term culture, while maintaining their characteristic phenotype. Among the selected polymers, poly (methylmethacrylate-co-methacrylic acid), showed the highest level of chondrogenic potential and was used to create a 3D hydrogel. Ultrastructural morphology, microstructure and mechanical testing of this novel hydrogel revealed robust characteristics to support chondrocyte growth. Furthermore, in vitro and in vivo biological assays demonstrated that chondrocytes cultured on the hydrogel had the capacity to produce extracellular matrix similar to hyaline cartilage, as shown by increased expression of collagen type II, aggrecan and Sox9, and the reduced expression of the fibrotic marker's collagen type I. In conclusion, hydrogels generated from poly (methylmethacrylate-co-methacrylic acid) created the appropriate niche for chondrocyte growth and phenotype maintenance and might be an optimal candidate for cartilage tissue-engineering applications. SIGNIFICANCE STATEMENT: Articular cartilage has limited self-repair ability due to its avascular nature, therefore tissue engineering strategies have emerged as a promising new approach. Synthetic polymers displaygreat potential and are widely used in the clinical setting. In our study, using the polymer microarray technique a novel type of synthetic polyacrylate was identified, that was converted into hydrogels for articular cartilage regeneration studies. The hydrogel based on poly (methylmethacrylate-co-methacrylic acid-co-PEG-diacrylate) had a controlable ultrastructural morphology, microstructure (porosity) and mechanical properties (stiffness) appropriate for cartilage engineering. Our hydrogel created the optimal niche for chondrocyte growth and phenotype maintenance for long-term culture, producing a hyaline-like cartilage extracellular matrix. We propose that this novel polyacrylate hydrogel could be an appropriate support to help in the treatment efficient cartilage regeneration. more...
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- 2019
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43. Thermal annealed silk fibroin membranes for periodontal guided tissue regeneration
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Ana Oliveira, Cassilda Cunha-Reis, Joaquim M. Oliveira, Silvia Regina Rios Vieira, Ana R. Costa-Pinto, Catarina Geão, Viviana P. Ribeiro, Rui L. Reis, and Veritati - Repositório Institucional da Universidade Católica Portuguesa more...
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Glycerol ,Materials science ,Hot Temperature ,Cell Survival ,Periodontal Ligament ,Surface Properties ,0206 medical engineering ,Biomedical Engineering ,Biophysics ,Fibroin ,Connective tissue ,Bioengineering ,02 engineering and technology ,Polyvinyl alcohol ,Cell Line ,Biomaterials ,chemistry.chemical_compound ,Tensile Strength ,medicine ,Cell Adhesion ,Periodontal fiber ,Animals ,Humans ,Regeneration ,Cell Proliferation ,Tissue Scaffolds ,Regeneration (biology) ,Membranes, Artificial ,Adhesion ,Fibroblasts ,021001 nanoscience & nanotechnology ,Bombyx ,020601 biomedical engineering ,Membrane ,medicine.anatomical_structure ,chemistry ,Polyvinyl Alcohol ,Guided Tissue Regeneration, Periodontal ,Stress, Mechanical ,Swelling ,medicine.symptom ,0210 nano-technology ,Fibroins ,Biomedical engineering - Abstract
Guided tissue regeneration (GTR) is a surgical procedure applied in the reconstruction of periodontal defects, where an occlusive membrane is used to prevent the fast-growing connective tissue from migrating into the defect. In this work, silk fibroin (SF) membranes were developed for periodontal guided tissue regeneration. Solutions of SF with glycerol (GLY) or polyvinyl alcohol (PVA) where prepared at several weight ratios up to 30%, followed by solvent casting and thermal annealing at 85 °C for periods of 6 and 12 h to produce high flexible and stable membranes. These were characterized in terms of their morphology, physical integrity, chemical structure, mechanical and thermal properties, swelling capability and in vitro degradation behavior. The developed blended membranes exhibited high ductility, which is particular relevant considering the need for physical handling and adaptability to the defect. Moreover, the membranes were cultured with human periodontal ligament fibroblast cells (hPDLs) up to 7 days. Also, the higher hydrophilicity and consequent in vitro proteolytic degradability of these blends was superior to pure silk fibroin membranes. In particular SF/GLY blends demonstrated to support high cell adhesion and viability with an adequate hPDLs’ morphology, make them excellent candidates for applications in periodontal regeneration. more...
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- 2019
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44. Enhanced performance of chitosan/keratin membranes with potential application in peripheral nerve repair
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Cristiana R. Carvalho, Joaquim M. Oliveira, Zi Kuang Moay, João B. Costa, Rui L. Reis, Joana Silva-Correia, Lígia Costa, Kee Woei Ng, Universidade do Minho, School of Materials Science and Engineering, Skin Research Institute of Singapore, Nanyang Environment and Water Research Institute, and Environmental Chemistry and Materials Centre more...
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Cell Survival ,Biomedical Engineering ,Neovascularization, Physiologic ,Chick Embryo ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Cell Line ,Biomaterials ,Chitosan ,Mice ,chemistry.chemical_compound ,Chitin ,Tissue engineering ,Keratin ,Cell Adhesion ,Animals ,Humans ,General Materials Science ,Peripheral nerves ,Cytoskeleton ,chemistry.chemical_classification ,Membranes ,Science & Technology ,Materials [Engineering] ,Regeneration (biology) ,Biomaterial ,Membranes, Artificial ,Adhesion ,021001 nanoscience & nanotechnology ,Nerve Regeneration ,0104 chemical sciences ,Membrane ,chemistry ,Hair Keratin Hydrogel ,Biophysics ,Keratins ,Cellular-response ,0210 nano-technology - Abstract
Although surgical management of peripheral nerve injuries (PNIs) has improved over time, autographs are still the current â gold standardâ treatment for PNIs, which presents numerous limitations. In an attempt to improve natural biomaterial-based nerve guidance conduits (NGCs), chitosan (CHT), a derivative of the naturally occurring biopolymer chitin, has been explored for peripheral nerve regeneration (PNR). In addition to CHT, keratin has gained enormous attention as a biomaterial and tissue engineering scaffolding. In this study, biomimetic CHT/keratin membranes were produced using solvent casting technique. These membranes were broadly characterized in terms of surface topography and physicochemical properties, with techniques such as Fourier Transform Infrared Spectroscopy (FTIR), Differencial Scanning Calorimetry (DSC), contact angle measurments, weight loss and water uptake, as well as Scanning Electron Microscopy (SEM) and Atomic force microscopy (AFM). Biological in vitro assays were also performed, where a preliminary cytotoxicity screening with L929 fibroblast cell line revealed that the membranes and respective materials are suitable for cell culture. In addition, Schwann cells, fibroblasts and endothelial cells were directly seeded in the membranes. Quantitative and qualitative assays revealed that the addition of keratin enchanced cell viablity and adhesion. Based on the in vitro encouraging results, the in vivo angiogenic/antiangiogenic potential of CHT and CHT/keratin membranes was assessed, using an optimized chick embryo chorioallantoic membrane assay, where higher angiogenic responses were seen in keratin-enriched materials. Overall, the obtained results indicate the higher potential of CHT/keratin membranes for guided tissue regeneration applications in the field of PNR., This study was also supported by the European Community’s Seventh Framework Programme (FP7-HEALTH-2011) under grant agreement no. 278612 (BIOHYBRID). The authors acknowledge the Portuguese Foundation for Science and Technology (FCT) for the financial support provided to Joaquim M. Oliveira (IF/ 00423/2012 and IF/01285/2015) and Joana Silva-Correia (IF/ 00115/2015) under the program “Investigador FCT”. more...
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- 2019
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45. AdipoSIGHT in therapeutic response: consequences in osteosarcoma treatment
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Joaquim M. Oliveira, Subhas C. Kundu, Rui L. Reis, Virginia Brancato, Vitor M. Correlo, Banani Kundu, Kundu, B, Brancato, V, Oliveira, J, Correlo, V, Reis, R, Kundu, S, and Universidade do Minho
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Technology ,QH301-705.5 ,Cell ,drug response ,Drug response ,Bioengineering ,Article ,Nonadherent surface ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,SOX2 ,osteosarcoma ,Heterotypic tumorspheres ,Heterotypic tumorsphere ,Human adipose-derived stem cell ,Medicine ,Biology (General) ,Human adipose-derived stem cells ,030304 developmental biology ,0303 health sciences ,Osteosarcoma ,Science & Technology ,heterotypic tumorspheres ,biology ,business.industry ,CD44 ,Cancer ,medicine.disease ,3. Good health ,medicine.anatomical_structure ,human adipose-derived stem cells ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,biology.protein ,nonadherent surface ,Stem cell ,business - Abstract
Chemotherapeutic resistance is a major problem in effective cancer treatment. Cancer cells engage various cells or mechanisms to resist anti-cancer therapeutics, which results in metastasis and the recurrence of disease. Considering the cellular heterogeneity of cancer stroma, the involvement of stem cells is reported to affect the proliferation and metastasis of osteosarcoma. Hence, the duo (osteosarcoma: Saos 2 and human adipose-derived stem cells: ASCs) is co-cultured in present study to investigate the therapeutic response using a nonadherent, concave surface. Staining with a cell tracker allows real-time microscopic monitoring of the cell arrangement within the sphere. Cell–cell interaction is investigated by means of E-cadherin expression. Comparatively high expression of E-cadherin and compact organization is observed in heterotypic tumorspheres (Saos 2–ASCs) compared to homotypic ones (ASCs), limiting the infiltration of chemotherapeutic compound doxorubicin into the heterotypic tumorsphere, which in turn protects cells from the toxic effect of the chemotherapeutic. In addition, genes known to be associated with drug resistance, such as SOX2, OCT4, and CD44 are overexpressed in heterotypic tumorspheres post-chemotherapy, indicating that the duo collectively repels the effect of doxorubicin. The interaction between ASCs and Saos 2 in the present study points toward the growing oncological risk of using ASC-based regenerative therapy in cancer patients and warrants further investigation., This work is supported by the European Union Framework Programme for Research and Innovation Horizon 2020 (nº 668983 — FoReCaST; FROnTHERA—NORTE-01-0145-FEDER-000023), Investigator FCT program (IF/01214/2014—V.M.), FCT2015 (IF/01285/2015—J.M.O.) and PTDC/BTMORG/28168/2017 (V.B. and S.C.K.). more...
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- 2021
46. Hydrogels in the treatment of rheumatoid arthritis: drug delivery systems and artificial matrices for dynamic in vitro models
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Ibrahim Fatih Cengiz, Joaquim M. Oliveira, Isabel Maria Oliveira, Diogo Castro Fernandes, Rui L. Reis, and Universidade do Minho
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Cartilage, Articular ,Materials science ,Polymers ,Biomedical Engineering ,Biophysics ,Dynamic In Vitro Models ,Bioengineering ,Inflammation ,02 engineering and technology ,In Vitro Techniques ,Bone tissue ,Bioinformatics ,Bone and Bones ,Biomaterials ,Arthritis, Rheumatoid ,03 medical and health sciences ,Drug Delivery Systems ,Biotecnologia Médica [Ciências Médicas] ,Drug Development ,medicine ,Animals ,Humans ,Animal testing ,Rheumatoid arthritis ,030304 developmental biology ,0303 health sciences ,Science & Technology ,Cartilage ,Hydrogels ,021001 nanoscience & nanotechnology ,medicine.disease ,In vitro ,3. Good health ,Delivery Systems ,Extracellular Matrix ,Disease Models, Animal ,medicine.anatomical_structure ,Drug delivery ,Self-healing hydrogels ,Ciências Médicas::Biotecnologia Médica ,medicine.symptom ,0210 nano-technology ,Porosity - Abstract
Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disorder that mostly affects the synovial joints and can promote both cartilage and bone tissue destruction. Several conservative treatments are available to relieve pain and control the inflammation; however, traditional drugs administration are not fully effective and present severe undesired side effects. Hydrogels are a very attractive platform as a drug delivery system to guarantee these handicaps are reduced, and the therapeutic effect from the drugs is maximized. Furthermore, hydrogels can mimic the physiological microenvironment and have the mechanical behavior needed for use as cartilage in vitro model. The testing of these advanced delivery systems is still bound to animal disease models that have shown low predictability. Alternatively, hydrogel-based human dynamic in vitro systems can be used to model diseases, bypassing some of the animal testing problems. RA dynamic disease models are still in an embryonary stage since advances regarding healthy and inflamed cartilage models are currently giving the first steps regarding complexity increase. Herein, recent studies using hydrogels in the treatment of RA, featuring different hydrogel formulations are discussed. Besides, their use as artificial extracellular matrices in dynamic in vitro articular cartilage is also reviewed., Norte2020 project (NORTE-08-5369-FSE000044) and the Portuguese Foundation for Science and Technology (FCT) program (PD/BD/143081/2018). IFC thanks the TERM RES-Hub, Tissue Engineering and Regenerative Medicine Infrastructure project, funded by FCT. The FCT distinction attributed to JMO under the Investigator FCT program (number IF/01285/2015) is also greatly acknowledged more...
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- 2021
47. Synthesis and Characterization of Biocompatible Methacrylated Kefiran Hydrogels: Towards Tissue Engineering Applications
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Joaquim M. Oliveira, Hajer Radhouani, Rui L. Reis, Susana Correia, Cristiana Gonçalves, and Universidade do Minho
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biomedical applications ,Materials science ,Polymers and Plastics ,Organic chemistry ,Methacrylic anhydride ,02 engineering and technology ,Methacrylate ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,QD241-441 ,methacrylation ,Tissue engineering ,Fourier transform infrared spectroscopy ,030304 developmental biology ,0303 health sciences ,Science & Technology ,Chemical modification ,Kefiran ,General Chemistry ,021001 nanoscience & nanotechnology ,chemical cross-linking ,3. Good health ,Biomedical applications ,Hydrogel ,chemistry ,Chemical engineering ,Chemical cross-linking ,Self-healing hydrogels ,Extrusion ,Methacrylation ,hydrogel ,0210 nano-technology - Abstract
Hydrogel application feasibility is still limited mainly due to their low mechanical strength and fragile nature. Therefore, several physical and chemical cross-linking modifications are being used to improve their properties. In this research, methacrylated Kefiran was synthesized by reacting Kefiran with methacrylic anhydride (MA). The developed MA-Kefiran was physicochemically characterized, and its biological properties evaluated by different techniques. Chemical modification of MA-Kefiran was confirmed by 1H-NMR and FTIR and GPC-SEC showed an average Mw of 793 kDa (PDI 1.3). The mechanical data obtained revealed MA-Kefiran to be a pseudoplastic fluid with an extrusion force of 11.21 ± 2.87 N. Moreover, MA-Kefiran 3D cryogels were successfully developed and fully characterized. Through micro-CT and SEM, the scaffolds revealed high porosity (85.53 ± 0.15%) and pore size (33.67 ± 3.13 μm), thick pore walls (11.92 ± 0.44 μm) and a homogeneous structure. Finally, MA-Kefiran revealed to be biocompatible by presenting no hemolytic activity and an improved cellular function of L929 cells observed through the AlamarBlue® assay. By incorporating methacrylate groups in the Kefiran polysaccharide chain, a MA-Kefiran product was developed with remarkable physical, mechanical, and biological properties, resulting in a promising hydrogel to be used in tissue engineering and regenerative medicine applications., H. Radhouani and C. Goncalveswere supported by the Foundation for Science and Technology (FCT) fromPortugal, with references CEECIND/00111/2017 and SFRH/BPD/94277/2013, respectively. S. Correia and this work were funded by the R&D Project KOAT-Kefiran Exopolysaccharide: Promising Biopolymer for Use in Regenerative Medicine and Tissue Engineering, with reference PTDC/BTMMAT/29760/2017 (POCI-01-0145-FEDER-029760), financed by FCT and co-financed by FEDER and POCI. We also thank Duarte N. Carvalho for input on the schematic representation of the process. more...
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- 2021
48. Vascularization approaches in tissue engineering: recent developments on evaluation tests and modulation
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Soraia V. Lopes, Joana Silva-Correia, Rui L. Reis, Joaquim M. Oliveira, Maurice N. Collins, and Universidade do Minho
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Angiogenesis ,Biomedical Engineering ,Neovascularization, Physiologic ,Biocompatible Materials ,02 engineering and technology ,Biomaterials ,03 medical and health sciences ,Tissue scaffolds ,Tissue engineering ,Materials Testing ,Medicine ,Humans ,Particle Size ,030304 developmental biology ,In vitro/in vivo assays ,0303 health sciences ,Science & Technology ,business.industry ,Biochemistry (medical) ,Vascularization ,General Chemistry ,021001 nanoscience & nanotechnology ,Modulation ,0210 nano-technology ,business ,Biomedical engineering - Abstract
This review focuses on vascularization and strategies involved in its evaluation and modulation. Clinical issues associated with engineered tissues of an atomically relevant size that require a vascular network to supply their cells with nutrients and oxygen are analyzed in terms of vascular network formation within scaffolds, which can be produced from varying biomaterials, with the capability of connecting to the vasculature of the patient. Developing angiogenesis techniques and monitoring of angiogenesis development as well as how these methods can be further utilized to tailor vascularization within large tissue engineered constructs are also discussed. Finally, we offer a glimpse toward the future by providing an outlook for vascularization and associated emerging bioprinting concepts in tissue engineering applications., The authors acknowledge the financial support provided through the projects B-FABULUS (PTDC/BBB-ECT/2690/2014) and Fun4TE (PTDC/EMD-EMD/31367/2017), financed by the Portuguese Foundation for Science and Technology (FCT) and cofinanced by European Regional Development Fund (FEDER) and Operational Programme for Competitiveness and Internationalisation (POCI). This work was also partly supported by H2020-MSCA-RISE BAMOS project, funded from the European Union's Horizon 2020 research and innovation program under Grant Agreement No. 734156. S.V.L. acknowledges FCT for the PhD grant (SFRH/BD/143954/2019). The FCT distinction attributed to J.S.-C. (IF/00115/2015) under the Investigator FCT program is also greatly acknowledged. more...
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- 2021
49. Deep learning in bioengineering and biofabrication: a powerful technology boosting translation from research to clinics
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Joaquim M. Oliveira, Rui L. Reis, João B. Costa, Joana Silva-Correia, and Universidade do Minho
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0303 health sciences ,3D bioprinting ,Artificial intelligence ,Boosting (machine learning) ,Computer science ,business.industry ,Deep learning ,Bioengineering ,02 engineering and technology ,Biofabrication ,021001 nanoscience & nanotechnology ,Machine learning ,computer.software_genre ,03 medical and health sciences ,0210 nano-technology ,business ,computer ,030304 developmental biology - Abstract
Bioengineering has been revolutionizing the production of biofunctional tissues for tackling unmet clinical needs. Bioengineers have been focusing their research in biofabrication, especially 3D bioprinting, providing cutting-edge approaches and biomimetic solutions with more reliability and cost–effectiveness. However, these emerging technologies are still far from the clinical setting and deep learning, as a subset of artificial intelligence, can be widely explored to close this gap. Thus, deep-learning technology is capable to autonomously deal with massive datasets and produce valuable outputs. The application of deep learning in bioengineering and how the synergy of this technology with biofabrication can help (more efficiently) bring 3D bioprinting to clinics, are overviewed herein., The authors acknowledge financial support provided through projects B-FABULUS (PTDC/BBB-ECT/2690/2014), Fun4TE (PTDC/EMD-EMD/31367/2017) and JUSThera (ref: NORTE-01-0145-FEDER-000055), financed by the Portuguese Foundation for Science and Technology (FCT) and co-financed by European Regional Development Fund (FEDER) and Operational Program for Competitiveness and Internationalization (POCI). JB Costa acknowledges the Junior Researcher contract (POCI-01-0145-FEDER 031367) attributed by FCT to Fun4TE. The FCT distinction attributed to J Silva-Correia (IF/00115/2015) under the Investigator FCT program is also greatly acknowledged. more...
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- 2021
50. Current Concepts and Challenges in Osteochondral Tissue Engineering and Regenerative Medicine
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Joaquim M. Oliveira, Ana Oliveira, Rui L. Reis, Le-Ping Yan, Universidade do Minho, and Veritati - Repositório Institucional da Universidade Católica Portuguesa
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0206 medical engineering ,Biomedical Engineering ,02 engineering and technology ,Regenerative medicine ,Biomaterials ,Tissue engineering ,Pluripotent stem cells ,Medicine ,Autologous chondrocyte implantation ,Induced pluripotent stem cell ,Science & Technology ,business.industry ,Cartilage ,Layered scaffold ,021001 nanoscience & nanotechnology ,Chondrogenesis ,020601 biomedical engineering ,Osteochondral tissue engineering ,3. Good health ,Clinical trial ,Stem cell fate ,medicine.anatomical_structure ,Interface engineering ,Biomimetic ,Stem cell ,0210 nano-technology ,business ,Biomedical engineering - Abstract
"Publication Date (Web): February 20, 2015", In the last few years, great progress has been made to validate tissue engineering strategies in preclinical studies and clinical trials on the regeneration of osteochondral defects. In the preclinical studies, one of the dominant strategies comprises the development of biomimetic/bioactive scaffolds, which are used alone or incorporated with growth factors and/or stem cells. Many new trends are emerging for modulation of stem cell fate towards osteogenic and chondrogenic differentiations, but bone/cartilage interface regeneration and physical stimulus have been showing great promise. Besides the matrix-associated autologous chondrocyte implantation (MACI) procedure, the matrix-associated stem cells implantation (MASI) and layered scaffolds in acellular or cellular strategy are also applied in clinic. This review outlines the progresses at preclinical and clinical levels, and identifies the new challenges in osteochondral tissue engineering. Future perspectives are provided, e.g., the applications of extracellular matrix-like biomaterials, computer-aided design/manufacture of osteochondral implant and reprogrammed cells for osteochondral regeneration., The authors thank the Portuguese Foundation for Science and Technology (FCT) through the projects TISSUE2TISSUE (PTDC/CTM/105703/2008) and OsteoCart (PTDC/CTM-BPC/115977/2009). We also acknowledge European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement REGPOT-CT2012-316331-POLARIS. L-P.Y. acknowledges the PhD scholarship from FCT (SFRH/BD/64717/2009). The FCT distinction attributed to J.M.O. and A.L.O. under the Investigator FCT program (IF/00423/2012) and (IF/00411/2013) are also greatly acknowledged. more...
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- 2021
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