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Despite the growing significance of generating highly porous, high‐precision 3D printed scaffolds using melt electrowriting (MEW), the absence of easy‐to‐use and robust design and g‐code generation tools hinders its effectiveness and widespread adoption. This article introduces a versatile scaffold design workflow for MEW fabrication, drawing on learnings in scaffold design and fabrication optimization from pioneers in the field and unifies innovative approaches into one user‐friendly platform. The application contains a library of validated flat and tubular patterns, as well as incorporating automated solutions to common challenges such as scaffold dimension fitting and toolpath corrections previously reported in the literature and historically challenging to deploy into new g‐codes. Available to users via GitHub, this application readily generates a g‐code that compensates for MEW fiber lag across diverse geometries on a variety of flat and cylindrical collectors. The application's capabilities are demonstrated through proof‐of‐concept prints, including layer‐shifting strategies, and their effects on scaffold mechanical properties. By integrating design flexibility, layer‐shifting strategies, and advanced visualization, this application streamlines the MEW scaffold design process, offering a valuable tool for researchers and promises to both advance the field and enable greater access to tools required to produce high‐quality, reproducible scaffolds. [ABSTRACT FROM AUTHOR]

Owing to their native extracellular matrix-like features, magnetic hydrogels have been proven to be promising biomaterials as tissue engineering templates In the present work, magnetic hydrogels scaffold based on chitosan, gelatin, hyaluronic acid, containing Fe3O4 as magnetic nanoparticles (IONPs) were prepared. The prepared hydrogels were loaded with ciprofloxacin hydrochloride as a model drug. The magnetic hydrogel was prepared using different volumes of chitosan, 1%, gelatin, 10%, and hyaluronic acid, 1% in glutaraldehyde as the crosslinking agent and Fe3O4 as magnetic nanoparticles. The hydrogel scaffold and magnetic scaffold hydrogel samples were characterized by scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), and Fourier-transform infrared spectroscopy (FTIR). The porosity, mechanical properties, swelling degree, and antibacterial activity of the hydrogel scaffold were also determined as well as the drug release profiles of the hydrogels. SEM imaging revealed that the magnetic hydrogel scaffold showed a relatively rough morphology with an irregular surface. The data obtained indicated that the hydrogel surface has three-dimensional porous microstructures and the porosity varied depending on the hydrogel formulation. The breaking load of the hydrogel scaffold increased from 1.361 Kgf to 4.98 Kgf by increasing the glutaraldehyde concentration from 0.2 mL to 0.8 mL. Swelling degree values in water were from 250 to 2000% after 24 h. The antibacterial activity of the hydrogel scaffold ranged from 54% to about 97% for Gram-positive bacteria (S. aureus) and from about 26–92% for Gram-negative bacteria (E. coli). The ciprofloxacin hydrochloride loaded hydrogel has a sustained release of ciprofloxacin hydrochloride over 10 h. The presence of IONPs gave a faster release of ciprofloxacin hydrochloride. [ABSTRACT FROM AUTHOR]

Since wound healing is one of the most important medical challenges and common dressings have not been able to manage this challenge well today, efforts have been increased to achieve an advanced dressing. Mesenchymal stem cells and exosomes derived from them have shown high potential in healing and regenerating wounds due to their immunomodulatory, anti-inflammatory, immunosuppressive, and high regenerative capacities. However, challenges such as the short life of these cells, the low durability of these cells in the wound area, and the low stability of exosomes derived from them have resulted in limitations in their use for wound healing. Nowadays, different scaffolds are considered suitable biomaterials for wound healing. These scaffolds are made of natural or synthetic polymers and have shown promising potential for an ideal dressing that does not have the disadvantages of common dressings. One of the strategies that has attracted much attention today is using these scaffolds for seeding and delivering MSCs and their exosomes. This combined strategy has shown a high potential in enhancing the shelf life of cells and increasing the stability of exosomes. In this review, the combination of different scaffolds with different MSCs or their exosomes for wound healing has been comprehensively discussed. [ABSTRACT FROM AUTHOR]

In this work, five new peptides derived from natural resources and two peptide bolaamphiphiles were designed. The self-assembling ability of the peptides and the bolaamphiphiles, as well as their predicted antioxidant activity was examined computationally. In particular, replica modeling molecular dynamics studies were carried out at three different temperatures. Results showed that the bolaamphiphiles as well as three of the peptides efficiently formed spherical or fibrous assemblies, particularly at physiological temperatures. In addition, stacking interactions and hydrogen bonds played a critical role in assembly formation. Furthermore, molecular docking studies with extracellular matrix proteins such as the triple helix motif of collagen and the fibronectin (III) motif of tenascin-X displayed binding interactions with the peptides and the bolaamphiphiles. The most optimal peptide bolaamphiphile WMYGGGWMY-CO-NH-(CH2)4-YMWGGGYMW was then synthesized in the laboratory and its ability to form functional scaffolds upon binding to collagen and tenascin-X was examined. The scaffolds were bioprinted with co-cultures of fibroblasts and keratinocytes. The cells not only proliferated over time but also showed strong adherence and spreading within the matrix. Thus, the peptides and the bolaamphiphiles studied in this work, may be potentially developed as scaffold components for tissue regeneration applications. [ABSTRACT FROM AUTHOR]

Polymer technology has rapidly advanced across diverse domains, particularly in biomedical applications. Among various polymers, polyurethane (PU) hold great potential in developing biomaterials such as biomedical scaffold and drug delivery. In this study, we have innovatively engineered eco‐friendly polyurethane using lignin, a sustainable bio‐polyol derived from oil palm empty fruit bunches. To enhance the physicochemical properties of the PU, we have incorporated hydroxyapatite (HA) into the composites. The inclusion of HA has led to notable improvements in crucial properties such as density, porosity, and water absorption, making these composites ideal candidates for tissue regeneration scaffolds. Furthermore, to assess their biomedical applicability in drug delivery and cell scaffolding, we have employed the quercetin drug model. The results revealed a sustained kinetic release behavior within the polyurethane/hydroxyapatite (PU/HA) composites, showcasing their potential for controlled drug delivery applications. Moreover, cytotoxicity assays conducted using neuro‐2a cell models demonstrated the non‐cytotoxic nature of both PU and PU/HA composites. This finding holds significant implications for biomedical applications, indicating that these composites offer biocompatible platforms for tissue engineering and regenerative medicine endeavors. The ability of these composites to support cell viability underscores their potential for a wide range of biomedical applications, including neural tissue engineering and drug delivery systems targeting brain diseases. These findings pave the way for the development of innovative and sustainable biomaterials with diverse biomedical applications. Highlights: An eco‐friendly polyurethane has been engineered by harnessing liginin‐derived oil palm empty fruit bunches.Incorporation of hydroxyapaptite enhance the physical properties of polyurethane.Controlled kinetic drug release is one of polyurethane/hydroxyapatite (PU/HA) composites features.The PU/HA composites has low cytotoxicity against neuro‐2a cells. [ABSTRACT FROM AUTHOR]

This review explores core‐shell scaffolds in bone tissue engineering, highlighting their osteoconductive and osteoinductive properties critical for bone growth and regeneration. Key design factors include material selection, porosity, mechanical strength, biodegradation kinetics, and bioactivity. Electrospun core‐shell nanofibrous scaffolds demonstrate potential in delivering therapeutic agents and enhancing bone regeneration. Critical characterization techniques include structural, surface, chemical composition, mechanical, and degradation analyses. Scaling up production poses challenges, addressed by innovative electrospinning techniques. Future research focuses on regulatory and commercial considerations, while exploring advanced materials and fabrication methods to optimize scaffold performance for improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Interest in self-cleaning coatings is rising due to their potential to enhance comfort and quality of life in polluted urban environments, driving the search for materials with optimal physical properties. Convergent with this goal, this study investigates the wetting properties and photo-catalytic efficiency of reticulated TiO 2 layers. It shows that these properties are significantly influenced by the topographical characteristics of the TiO 2 surface, which can be precisely controlled through variations in pulverization pressure and low-temperature post-annealing treatments. Post-deposition annealing of the TiO 2 layers achieves 100 % self-cleaning efficiency for both thick and thin films, with optical transmission ranging from approximately 60 %–80 % in the visible spectrum. Additionally, the TiO 2 layers exhibited promising capabilities for eliminating pathogenic microorganisms and disinfecting surfaces. The underlying causal factors of these remarkable and technologically promising surface features are explored and discussed. [ABSTRACT FROM AUTHOR]

Through alteration of the polarity of DC plasma during the growth of carbon nanotubes in a PECVD reactor, significantly different morphologies of such species have been achieved. By using this approach, for the first time, both Half‐aligned and Entangled structures were synthesized, along with Full‐aligned carbon nanotubes, introducing three binder‐free electrodes with various levels of tortuosity. The crucial parameter and influential effect of tortuosity in these three‐dimensional nanostructure scaffolds for application in lithium‐ion batteries were investigated. Previous research findings suggested that increasing the tortuosity of the conductive scaffolds leads to preferential accumulation of lithium at the top surface and causes the loss of capacity in subsequent charge‐discharge cycles. Our finding reveals that there exists a trade‐off between lithium‐demand, capacity, and preferential accumulation of lithium at the top surface. Among the presented scaffolds, the Half‐aligned MWCNTs was able to maintain a high capacity of 876.9 mAh/g over more than 300 cycles, and demonstrate capacity improvement during this period and excellent rate capability, even at a rate of 5 C. This capacity is almost three times that can be achieved with graphite, showcasing promising and outstanding results for carbon nanotubes. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common primary malignant brain tumor diagnosed in adults, carrying with it an extremely poor prognosis and limited options for effective treatment. Various cell therapies have emerged as promising candidates for GBM treatment but fail in the clinic due to poor tumor trafficking, poor transplantation efficiency, and high systemic toxicity. In this study, we design, characterize, and test a 3D‐printed cell delivery platform that can enhance the survival of therapeutic cells implanted in the GBM resection cavity. Using continuous liquid interface production (CLIP) to generate a biocompatible 3D hydrogel, we demonstrate that we can effectively seed neural stem cells (NSCs) onto the surface of the hydrogel, and that the cells can proliferate to high densities when cultured for 14 days in vitro. We show that NSCs seeded on CLIP scaffolds persist longer than freely injected cells in vivo, proliferating to 20% higher than their original density in 6 days after implantation. Finally, we demonstrate that therapeutic fibroblasts seeded on CLIP more effectively suppress tumor growth and extend survival in a mouse model of LN229 GBM resection compared to the scaffold or therapeutic cells alone. These promising results demonstrate the potential to leverage CLIP to design hydrogels with various features to control the delivery of different types of cell therapies. Future work will include a more thorough evaluation of the immunological response to the material and improvement of the printing resolution for biocompatible aqueous resins. [ABSTRACT FROM AUTHOR]

This work presents the successful production of highly porous 3D nanofibrous hybrid scaffolds of polylactic acid (PLA)/polyethylene glycol (PEG) blends with the incorporation of calcium phosphate (CaP) bioceramics by a facile two-step process using the solution blow spinning (SBS) technique. CaP nanofibers were obtained at two calcium/phosphorus (Ca/P) ratios, 1.67 and 1.1, by SBS and calcination at 1000 °C. They were incorporated in PLA/PEG blends by SBS at 10 and 20 wt% to form 3D hybrid cotton-wool-like scaffolds. Morphological analysis showed that the fibrous scaffolds obtained had a randomly interconnected and highly porous structure. Also, the mean fiber diameter ranged from 408 ± 141 nm to 893 ± 496 nm. Apatite deposited considerably within 14 days in a simulated body fluid (SBF) test for hybrid scaffolds containing a mix of hydroxyapatite (HAp) and tri-calcium phosphate-β (β-TCP) phases. The scaffolds with 20 wt% CaP and a Ca/P ration of 1.1 showed better in vitro bioactivity to induce calcium mineralization for bone regeneration. Cellular tests evidenced that the developed scaffolds can support the osteogenic differentiation and proliferation of pre-osteoblastic MC3T3-E1 cells into mature osteoblasts. The results showed that the developed 3D scaffolds have potential applications for bone tissue engineering. [ABSTRACT FROM AUTHOR]

The advancing development in biomaterials and biology has enabled the extension of 3D printing technology to the bioadditive manufacturing of degradable hard tissue substitutes. One of the key advantages of bioadditive manufacturing is that it has much smaller design limitations than conventional manufacturing and is therefore capable of producing implants with complex geometries. In this study, three distinct blends of polylactic acid (PLA) and polyhydroxybutyrate (PHB) were produced using Fused Deposition Modeling (FDM) technology. Two of these blends were plasticized with oligomeric lactic acid (OLA) at concentrations of 5 wt% and 10 wt%, while the third blend remained unplasticized. Each blend was fabricated in two structural modifications: solid and porous. The biodegradation behavior of the produced specimens was examined through an in vitro experiment using three different immersion solutions: saline solution, Hank's balanced salt solution (HBSS), and phosphate-buffered saline (PBS). All examined samples were also subjected to chemical analysis: atomic absorption spectroscopy (AAS), scanning electron microscopy (SEM), and energy-dispersive spectrometry (EDS). The results of the degradation experiments indicated a predominantly better absorption capacity of the samples with a porous structure compared to the full structure. At the same time, the blend containing a higher concentration of OLA exhibited enhanced pH stability over the evaluation period, maintaining relatively constant pH values before experiencing a minor decline at the end of the study. This observation indicates that the increased presence of the plasticizer may provide a buffering effect, effectively mitigating the acidification associated with material degradation. [ABSTRACT FROM AUTHOR]

The emerging paradigm of personalised bone repair embodies a transformative triad comprising bio-inspired design, digital fabrication, and the exploration of innovative materials. The increasing average age of the population, alongside the rising incidence of fractures associated with age-related conditions such as osteoporosis, necessitates the development of customised, efficient, and minimally invasive treatment modalities as alternatives to conventional methods (e.g., autografts, allografts, Ilizarov distraction, and bone fixators) typically employed to promote bone regeneration. A promising innovative technique involves the use of cellularised scaffolds incorporating mesenchymal stem cells (MSCs). The selection of materials—ranging from metals and ceramics to synthetic or natural bio-derived polymers—combined with a design inspired by natural sources (including bone, corals, algae, shells, silk, and plants) facilitates the replication of geometries, architectures, porosities, biodegradation capabilities, and mechanical properties conducive to physiological bone regeneration. To mimic internal structures and geometries for construct customisation, scaffolds can be designed using Computer-aided Design (CAD) and fabricated via 3D-printing techniques. This approach not only enables precise control over external shapes and internal architectures but also accommodates the use of diverse materials that improve biological performance and provide economic advantages. Finally, advanced numerical models are employed to simulate, analyse, and optimise the complex processes involved in personalised bone regeneration, with computational predictions validated against experimental data and in vivo studies to ascertain the model's ability to predict the recovery of bone shape and function. [ABSTRACT FROM AUTHOR]

Although poly-ether-ether-ketone (PEEK) implants hold significant medical promise, their bioinert nature presents challenges in osseointegration and bone ingrowth within clinical contexts. To mitigate these challenges, the present study introduces Diamond PEEK/bioactive glass (BG) composite scaffolds, characterized by macro/micro dual-porous structures, precisely fabricated via laser powder bed fusion (LPBF) technology. The findings indicate that an increase in BG content within these scaffolds significantly augments their hydrophilicity and hydroxyapatite formation capacities. Stress-strain curve analysis demonstrates reliable load-bearing stability across all scaffold types. In vitro assessments confirmed the non-cytotoxicity of PEEK/BG samples and demonstrated improved osteogenic differentiation and mineralization with increased BG incorporation. Further, in vivo experiments illustrated that the Diamond porous structure of these scaffolds facilitated bone growth, an effect notably amplified with higher BG content. Particularly in groups with 15 wt.% and 25 wt.% BG scaffolds, new bone formation was observed not only within the macropores of the Diamond structure but also within the micropores inside the scaffold rod, suggesting an almost seamless fusion with the new bone. This demonstrates the scaffolds' effective osteointegration and bone ingrowth properties. This study conclusively established the effectiveness of Diamond-structured PEEK/BG composite scaffolds, fabricated via LPBF, in bone repair. It highlights the crucial role of BG in enhancing osteogenic potential through interaction with the macro/micro pores of the scaffold. This study addresses the bioinert nature of PEEK implants by developing Diamond-structured PEEK/bioactive glass (BG) composite scaffolds by laser powder bed fusion. The dual-porous macro/microstructure enhances hydrophilicity and hydroxyapatite formation, vital for bone regeneration. By adjusting the BG content, we controlled the melt viscosity and sintering rate, leading to the formation of beneficial microscale pores. These pores resolve the issue of ineffective bioactive fillers in previous LPBF-fabricated scaffolds, enhancing the osteogenic potential of BG and inducing superior bone ingrowth and osseointegration. In vitro and in vivo analyses show enhanced osteogenic differentiation, mineralization, and bone growth, underscoring the clinical potential of these scaffolds for bone repair. [Display omitted] [ABSTRACT FROM AUTHOR]

Gelatin methacrylate (GelMA) is a photo-cross-linkable biopolymer. A combination of GelMA with biodegradable polyesters such as PCL (poly‐ε‐caprolactone) and their triblock derivatives improve the mechanical properties of GelMA. PCL-PEG-PCL (PCEC) was synthesized using ring-opening polymerization of ε-caprolactone in the presence of polyethylene glycol (PEG). The GelMA- PCEC was fabricated using freeze-drying and 3D printing and their porosity, mechanical properties, and swelling behavior were investigated. Human dental pulp stem cells were cultured on the scaffolds for a period of 14 days and cell adhesion was evaluated by scanning electron microscopy. Cell viability was analyzed by MTT and osteogenic differentiation was evaluated by Alizarin red S. Results showed that the 3D-printed scaffold had higher water absorption rate, retaining its structure up to a strain of 0.2 %, and a higher Young's modulus compared to the freeze-dried scaffold. In terms of cell viability, the 3D-printed scaffold outperformed the freeze-dried scaffold with a percentage of 86 % and 63 % viability respectively. Moreover, the 3D-printed scaffold exhibited better osteodifferentiation with calcium deposition. Overall, these findings suggest that the 3D-printed scaffold may have advantages over the freeze-dried scaffold in tissue engineering applications that require high water absorption, elasticity, and cell viability. The fabricated scaffolds provided suitable cell proliferation. [ABSTRACT FROM AUTHOR]

Cell replacement therapy is under development for dry age‐related macular degeneration (AMD). A thin membrane resembling the Bruch's membrane is required to form a cell‐on‐membrane construct with retinal pigment epithelial (RPE) cells. These cells have been differentiated from human embryonic stem cells (hESCs) in vitro. A carrier membrane is required for cell implantation, which is biocompatible for cell growth and has dimensions and physical properties resembling the Bruch's membrane. Here a nanofiber electrospun poly‐L‐lactic acid (PLLA) membrane is tested for capacity to support cell growth and maturation. The requirements for laminin coating of the membrane are identified here. A porous electrospun nanofibrous PLLA membrane of ∼50 nm fiber diameter was developed as a prototype support for functional RPE cells grown as a monolayer. The need for laminin coating applied to the membrane following treatment with poly‐L‐ornithine (PLO), was identified in terms of cell growth and survival. Test membranes were compared in terms of hydrophilicity after laminin coating, mechanical properties of surface roughness and Young's modulus, porosity and ability to promote the attachment and proliferation of hESC‐RPE cells in culture for up to 8 weeks. Over this time, RPE cell proliferation, morphology, and marker and gene expression, were monitored. The functional capacity of cell monolayers was identified in terms of transepithelial electrical resistance (TEER), phagocytosis of cells, as well as expression of the cytokines, vascular endothelial growth factor (VEGF) and pigment epithelium‐derived factor (PEDF). PLLA polymer fibers are naturally hydrophobic, so their hydrophilicity was improved by pretreatment with PLO for subsequent coating with the bioactive protein laminin. They were then assessed for amount of laminin adsorbed, contact angle and uniformity of coating using scanning electron microscopy (SEM). Pretreatment with 100% PLO gave the best result over 10% PLO treatment or no treatment prior to laminin adsorption with significantly greater surface stiffness and modulus. By 6 weeks after cell plating, the coated membranes could support a mature RPE monolayer showing a dense apical microvillus structure and pigmented 3D polygonal cell morphology. After 8 weeks, PLO (100%)‐Lam coated membranes exhibited the highest cell number, cell proliferation, and RPE barrier function measured as TEER. RPE cells showed the higher levels of specific surface marker and gene expression. Microphthalmia‐associated transcription factor expression was highly upregulated indicating maturation of cells. Functionality of cells was indicated by expression of VEGF and PEDF genes as well as phagocytic capacity. In conclusion, electrospun PLLA membranes coated with PLO‐Lam have the physical and biological properties to support the distribution and migration of hESC‐RPE cells throughout the whole structure. They represent a good membrane candidate for preparation of hESC‐RPE cells as a monolayer for implantation into the subretinal space of AMD patients. [ABSTRACT FROM AUTHOR]

Infected mandibular defects pose a formidable challenge without an entirely satisfactory repair strategy. Here, a coaxial 3D printing scaffold comprising a shell loaded is dveloped with the antibiotic minocycline hydrochloride and a core wrapped with traditional Chinese medicine antler powers. This study is conducted to evaluate the efficacy of the scaffold in facilitating the repair of infected mandibular defects. In vitro investigations exhibit that this construct possesses a porous microstructure, exceptional mechanical properties, appropriate degradability, acceptable water absorption capacity, and satisfactory biocompatibility. Transcriptome analyses further reveal a notable upregulation of relevant genes and signaling pathways associated with cell activity, osteogenesis, and angiogenesis. In vivo rat (Φ = 5 mm) and rabbit (5 mm × 4 mm × 10 mm) mandibular defect models confirm the scaffold's ability to sequentially regulate bone healing by suppressing infection and inflammation, followed by promoting osteogenesis and angiogenesis. This advanced graft holds significant translational potential for infectious bone regeneration. [ABSTRACT FROM AUTHOR]

3D‐printed biomaterial implants are revolutionizing personalized medicine for tissue repair, especially in orthopedics. In this study, a radiopaque bismuth oxide (Bi2O3) doped polycaprolactone (PCL) composite is developed and implemented to enable the use of diagnostic X‐ray technologies, especially spectral photon counting X‐ray computed tomography (SPCCT), for comprehensive tissue engineering scaffold (TES) monitoring. PCL filament with homogeneous Bi2O3 nanoparticle (NP) dispersion (0.8 to 11.7 wt%) is first fabricated. TES are then 3D printed with the composite filament, optimizing printing parameters for small features and severely overhung geometries. These composite TES are characterized via micro‐computed tomography (µCT), tensile testing, and a cytocompatibility study, with 2 wt% Bi2O3 NPs providing improved tensile properties, equivalent cytocompatibility to neat PCL, and excellent radiographic distinguishability. Radiographic performance is validated in situ by imaging 4 and 7 wt% Bi2O3 doped PCL TES in a mouse model with µCT, showing excellent agreement with in vitro measurements. Subsequently, CT image‐derived swine menisci are 3D printed with composite filament and re‐implanted in corresponding swine legs ex vivo. Re‐imaging the swine legs via clinical CT allows facile identification of device location and alignment. Finally, the emergent technology of SPCCT unambiguously distinguishes the implanted meniscus in situ via color K‐edge imaging. [ABSTRACT FROM AUTHOR]

Background: In connection with the war in Ukraine and the use of modern high-energy weapons by the enemy, the nature of injuries have changed. These changes require improvement of approaches to the treatment of patients with gunshot and mine-explosive bone defects. Case presentation: We present the case of treatment of a 28-year-old Ukranian man with a gunshot multifragmentary fracture of the proximal humerus with a bone defect using three-dimensional printing of a polyetheretherketone frame (scaffold) for alloplastic material. The analysis of this case expands the possibilities of using three-dimensional printing technologies of polyetheretherketone scaffolds in the treatment of significant bone defects. Conclusion: Modern military trauma requires individualized treatment for each patient. The use of individual polyetheretherketone scaffolds in the treatment of a gunshot multifragmentary fracture with a bone defect has a positive clinical effect. [ABSTRACT FROM AUTHOR]

With the severity of chronic kidney disease worldwide, strategies to recover renal function via tissue regeneration provide alternatives to kidney replacement therapy. To exclude side effects from direct cell transplantation, extracellular vesicles (EVs) are great substitutes representing paracrine cell signaling. To build three-dimensional structures for implantation into the 5/6 nephrectomy model by incorporating bioactive materials, including multifunctional EVs (mEVs), porous PMEZE/mEV scaffolds were developed in combination with edaravone (EDV; E) and mEV based on PMEZ scaffolds with PLGA (P), MH-RA (M), ECM (E), ZnO-ALA (Z). The oxygen free radical scavenger EDV was incorporated to induce tubular regeneration. mEVs were engineered to serve regenerative activities with a combination of two EVs from SDF-1α overexpressed tonsil-derived mesenchymal stem cells (sEVs) and intermediate mesoderm (IM) cells during differentiation into kidney progenitor cells (dEVs). mEVs displayed beneficial effects on regeneration by facilitating migration and inducing differentiation of surrounding stem cells, and EDV improved kidney function by regulating the GDNF/RET pathway and their downstream genes. The promotion of MSC recruitment was confirmed with sEV particles number dependently, and the regulation of the GDNF/RET pathway by the effect of EDV and its enhanced effect by mEVs were elucidated using in vitro analysis. The regeneration of tubules was additionally demonstrated through the increased expression of aquaporin-1 (AQP-1) and cadherin-16 (CDH16) for proximal tubules, and calbindin and PAX2 for distal tubules in the renal defect model. With these, structural regeneration and functional recovery were achieved with kidney regeneration in the 5/6 nephrectomy mice model. [ABSTRACT FROM AUTHOR]

The most common technologies in tissue engineering include growth factor therapies; metal implants, such as titanium; 3D bioprinting; nanoimprinting for ceramic/polymer scaffolds; and cell therapies, such as mesenchymal stem cells (MSCs). Cell therapy is a promising alternative to organ grafts and transplants in the treatment of numerous musculoskeletal diseases. MSCs have increasingly been used in generative medicine due to their specialized self‐renewal, immunomodulation, multiplication, and differentiation properties. To further expand the potential of these cells in tissue repair, significant efforts are currently dedicated to the production of biomaterials with desirable short‐ and long‐term biophysical properties that can aid the differentiation and expansion of MSCs. Biomaterials support MSC differentiation by modulating their characteristics, such as composition, mechanical properties, porosity, and topography. This review aimed to describe recent MSC approaches, including those associated with biomaterials, from experimental, clinical, and preclinical studies with sheep models. [ABSTRACT FROM AUTHOR]

Biological and mechanical mismatches between engineered scaffolds and native tissues poses widespread challenges for tissue restoration. Native‐like anisotropy is a critical characteristic for functional tissue replacements, yet it is an often‐overlooked aspect when designing new scaffolds. In this study, fiber‐reinforced tubular scaffolds are developed, mimicking the anisotropic characteristics of natural tissues, using native‐like silk fibroin. To predict the mechanical behavior of these innovative scaffolds, a mathematical model is employed, utilizing the properties of the scaffolds’ constituent materials, and experimentally validated through tensile testing. This approach addresses significant challenges in the design of new scaffold implants by enabling to efficiently predict the performance of several configurations, narrowing down the experimental research space. The proposed platform constitutes an appealing tool for the development of clinically relevant tissue‐equivalents. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bioactive glass is a multifunctional synthetic composite material that releases active ions slowly and exhibits certain biological activities after affinity with tissues. Their versatility stems from the versatility of their preparation processes and components, allowing them to be applied in different clinical scenarios. OBJECTIVE: To review the main application forms, application fields of bioactive glass, as well as the influence of doping different elements on its function. METHODS: A literature search was conducted across WanFang Medical Database, CNKI Database, PubMed Database, and Web of Science Database, using the search terms “bioactive glass, slow-release ions, bone tissue engineering, composite scaffold, tissue regeneration and repair, biomedical engineering” in Chinese and English. The timeframe was limited from 2000 to 2023. Finally, 88 articles were included for review. RESULTS AND CONCLUSION: (1) In terms of application forms, bioactive glass can be fabricated as coatings, particles, bone cements, and scaffolds according to needs. Coatings have the potential to enhance the biological activity of implants, yet they are susceptible to instability as a result of degradation. Particles offer a viable solution for the repair of irregular bone defects; however, particles produced through traditional methods often possess limited functionality. Bone cement provides the benefits of minimal invasiveness and injectability, yet its application is restricted to smaller bone defects. Scaffolds exhibit excellent mechanical properties and are commonly used for larger-sized bone defects, yet they have limited toughness. (2) In terms of applications, bioactive glass can be used in a variety of tissue regeneration and repair and disease treatment fields, including dentistry, orthopedics, soft tissue engineering, and cancer. (3) In terms of element doping, the addition of specific elements to bioactive glass not only improves its mechanical properties but also endows it with special biological functions such as bioactivity, degradability, and antibacterial properties. (4) Biologically active glass is a versatile material that can be used in different forms and functions by adjusting the preparation process and element doping to meet various clinical needs in bone tissue engineering and is widely used in the field of biomedical engineering. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, the treatment of infected bone defects has the problems of long course of disease, poor treatment effect and high cost. The osteogenic effect of personalized bone replacement materials in clinical treatment is limited. Therefore, a 3D-printed bone graft material with both good osteogenic effect and antibacterial effect is urgently needed for clinical treatment. OBJECTIVE: To summarize the research status of 3D-printed scaffolds loaded with antimicrobial agents for the treatment of infected bone defects. METHODS: PubMed, Web of Science, Elsevier, and CNKI databases from January 2010 to June 2022 were searched for related articles. The Chinese search terms were “bone defect, 3D printing, scaffold material, antibacterial, animal experiments, in vitro experiments”. English search terms were “bone defect, 3D printing, scaffold, antibiosis, animal experiment, in vitro”. Finally, 60 articles were included for review and analysis. RESULTS AND CONCLUSION: The 3D scaffolds made of titanium, magnesium, tantalum and other metals and their alloys have certain osteogenic properties, but do not have antibacterial function. Hydroxyapatite and other bioceramic materials have good biocompatibility and are prone to be degraded, whereas due to the lack of strength, they are usually combined with artificial polymer materials to form composite materials, which respectively mimic the inorganic and organic components in natural bone, and play their respective excellent functions. Antibiotics, silver/copper nanoparticles, antimicrobial peptides, gallium and other antibacterial agents play an antibacterial role by destroying bacterial cell membrane, producing reactive oxygen species to interfere with bacterial DNA replication, inhibiting iron absorption and other mechanisms. As a result, the 3D-printed scaffold has both antibacterial and osteogenic effects. However, there are still some problems such as drug resistance and difficult to control effective concentrations. 3D-printed scaffolds are often loaded with antibacterial agents by loading drug-loaded microspheres on scaffolds, preparing antibacterial coating on the scaffold surface, and participating in joint 3D printing with drugs. The loading mode of antibacterial coating prepared on the scaffold surface is the most widely used, and its antibacterial effect is more stable. Nonetheless, the selection of the most suitable loading mode for antibacterial agents needs to be further discussed and summarized. It is a future research prospect to optimize the mechanical properties of composite scaffolds and prepare biomimetic bone scaffolds so that the degradation rate is consistent with the bone reconstruction rate in infected bone defects. The ideal antibacterial agents may play a role through a variety of antibacterial mechanisms, thus being expected to play a good antibacterial effect through low antibacterial concentration, which should be a hot spot of anti-bone infection research. After loading antibacterial agents on the surface of the scaffold, antibacterial agents can “intelligently” react to the local microenvironment, achieving controlled release, and regulating the osteogenesis, vascularization and immune response of the microenvironment, which is the focus of current research. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tissue engineering has brought new hope to the clinical challenge of liver failure, and the preparation of plant-derived decellularized fiber scaffolds holds significant importance in liver tissue engineering. OBJECTIVE: To prepare apple tissue decellularized scaffold material by using fresh apple slices and a solution of sodium dodecyl sulfate, and assess its biocompatibility. METHODS: Fresh apples were subjected to decellularization using phosphate buffer saline and sodium dodecyl sulfate solution, separately. Afterwards, the decellularized apple tissues and apple decellularized scaffold materials were decontaminated with phosphate buffer saline. Subsequently, scanning electron microscopy was used to assess the effectiveness of decellularization of the apple materials. Adipose-derived mesenchymal stem cells were extracted from the inguinal fat BALB/C of mice, and their expression of stem cell-related markers (CD45, CD34, CD73, CD90, and CD105) was identified through flow cytometry. The cells were then divided into a scaffold-free control group and a scaffold group. Equal amounts of adipose-derived mesenchymal stem cells were seeded onto both groups. The biocompatibility of the decellularized scaffold with adipose-derived mesenchymal stem cells was evaluated using CCK-8 assay, hematoxylineosin staining, and phalloidine staining. Cell adhesion and growth on the scaffold were observed under light microscopy and scanning electron microscopy. Furthermore, the scaffold was subdivided into the non-induced group and the hepatogenic-induced group. Adipose-derived mesenchymal stem cells were cultured on the decellularized apple scaffold, and they were cultured for 14 days in regular culture medium or hepatogenic induction medium for comparison. Immunofluorescent staining using liver cell markers, including albumin, cytokeratin 18, and CYP1A1, was performed. Enzyme-linked immunosorbent assay was used to detect the secretion of alpha fetoprotein and albumin. Additionally, scanning electron microscopy was employed to observe the morphology of the induced cells on the scaffold, verifying the expression of liver cell-related genes on the decellularized scaffold material. Finally, the cobalt-60 irradiated and sterilized decellularized apple scaffolds were transplanted onto the surface of mouse liver and the degradation of the scaffold was observed by gross observation and hematoxylin-eosin staining after 28 days. RESULTS AND CONCLUSION: (1) The scanning electron microscopy results revealed that the decellularized apple scaffold material retained a porous structure of approximately 100 μm in size, with no residual cells observed. (2) Through flow cytometry analysis, the cultured cells were identified as adipose-derived mesenchymal stem cells. (3) CCK-8 assay results demonstrated that the prepared decellularized apple tissue scaffold material exhibited no cytotoxicity. Hematoxylin-eosin staining and phalloidine staining showed that adipose-derived mesenchymal stem cells were capable of adhering and proliferating on the decellularized apple tissue scaffold. (4) The results obtained from immunofluorescence staining and enzyme-linked immunosorbent assay revealed that adipose-derived mesenchymal stem cells cultured on the decellularized apple scaffolds exhibited elevated expression of liver-specific proteins, including albumin, alpha-fetoprotein, cytokeratin 18, and CYP1A1. These results suggested that they were induced differentiation into hepatocyte-like cells possessing functional characteristics of liver cells. (5) The decellularized apple scaffold implanted at 7 days has integrated with the liver, with partial degradation of the scaffold observed. By 28 days, the decellularized apple scaffold has completely degraded and has been replaced by newly-formed tissue. (6) The results indicate that the decellularized scaffold material derived from apple tissue demonstrates favorable biocompatibility, promoting the proliferation, adhesion, and hepatic differentiation of adipose-derived mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

The in vitro macrophage response on Aloe vera-blended collagen-chitosan (COL-CS-AV) scaffold was studied using Murine Raw 264 macrophage cells. The cells were cultured on 1-cm2 scaffolds in a standard condition; at a predefined period, the cultured constructs were subjected to various experimental studies. The cytocompatibility of the constructs was assessed by dead/live examination by acridine orange/ethidium bromide (AO/EB) fluorescent dyes, and the live cells were quantified by MTT assay. The morphology of macrophages was determined using scanning electron microscopy (SEM). The cellular apoptosis and necrosis were examined by flow cytometer using annexin V FITC conjugate and propidium iodide (PI) fluorescent probes. The cellular total antioxidant level was estimated from the cell lysate of macrophages cultured on the scaffold construct. Matrix metalloproteinase-9 (MMP-9) activity was assessed by the gelatinolytic property of cell lysate by zymography technique. The expression of pro-inflammatory markers TNFα and IL-6 was studied by western blot analysis using its specific antibody. The COL-CS-AV scaffold showed promising results over the collagen-chitosan. Overall, the increased biological property with less activation of macrophage response by downregulating the TNFα and IL-6 was observed in the Aloe vera-blended scaffold construct. In support of this, the active form of MMP-9 disappeared in earlier days than without Aloe vera-blended scaffold. Through these encouraging results, we conclude that the COL-CS-AV scaffold may be used as a better solution for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Background/Objectives: Three-dimensional (3D) cell culture technologies allow us to overcome the constraints of two-dimensional methods in different fields like biochemistry and cell biology and in pharmaceutical in vitro tests. In this study, a novel 3D hydrogel sponge scaffold, composed of a crosslinked polyacrylic acid forming a porous matrix, has been developed and characterized. Methods: The scaffold was obtained via an innovative procedure involving thermal treatment followed by a salt-leaching step on a matrix-containing polymer along with a gas-forming agent. Based on experimental design for mixtures, a series of formulations were prepared to study the effect of the three components (polyacrylic acid, NaHCO3 and NaCl) on the scaffold mechanical properties, density, swelling behavior and morphological changes. Physical appearance, surface morphology, porosity, molecular diffusion, transparency, biocompatibility and cytocompatibility were also evaluated. Results: The hydrogel scaffolds obtained show high porosity and good optical transparency and mechanical resistance. The scaffolds were successfully employed to culture several cell lines for more than 20 days. Conclusions: The developed scaffolds could be an important tool, as such or with a specific coating, to obtain a more predictive cellular response to evaluate drugs in preclinical studies or for testing chemical compounds, biocides and cosmetics, thus reducing animal testing. [ABSTRACT FROM AUTHOR]

In the study, a new strategy is presented to make PLGA (poly lactic‐co‐glycolic acid) and POEGMEMA (poly(oligo(ethylene glycol) methyl ether methacrylate)) based biodegradable and biocompatible tissue scaffold via a new physical cross‐linking method. The advantage of brushed structure of POEGMEMA polymer and the hydrophobic character of PLGA polymer is taken to make physically entangled network in aqueous media. The hydrophobic nature of PLGA allows to get scaffolds even at low ratio of PLGA (25%, w/w) when using POEGMEMA (yield: 86%). This strategy gives robust polymeric networks in aqueous media without using chemical reactions through high hydrophilic polymer content. Scaffolds with high POEGMEMA ratio (75%, w/w) show two times higher water uptake ratio (≈300%) and two times lower compression strength (19 kPa) compared to the ones with lower POEGMEMA content (50%, w/w). They also show desired degradation profiles in various aqueous solutions. While the scaffolds prepared with 25% and 50% PLGA are almost stable in first 20 days, they completely degrade in 40–50 days. Both scaffold formulations (25% PLGA‐75% POEGMEMA and 50% PLGA‐50% POEGMEMA) have similar proliferative properties for fibroblast cells. The scaffolds also do not show toxicity compared to control group according to live‐dead assay. [ABSTRACT FROM AUTHOR]

Mycetoma is currently considered as a neglected tropical disease. The incidence of mycetoma is unknown but most of the worldwide cases are present in the "mycetoma belt" including countries like Mexico, India, Senegal, and others. The treatment of mycetoma depends on the etiological agent responsible for the case. Treatment success reaches 60 to 90%; however, common treatment has been reported to be ineffective in some cases, due in part to resistance to the prescribed antibiotics. Therefore, it is necessary to develop new therapeutic options. In the past two decades, quinoxaline derivatives have shown relevance as antibacterial agents. Therefore, in this work, esters of quinoxaline 1,4-di-N-oxide derivatives were evaluated in vitro against the reference strain CECT-3052 from N. brasiliensis, six clinical isolates, and macrophages J774A.1 to determine their cytotoxicity and security index. Additionally, nine reference drugs were evaluated as controls. The results show that nine esters of quinoxaline 1,4-di-N-oxide derivatives had a minimum inhibitory concentration (MIC) < 1 µg/mL against the reference strain and four of them (N-05, N-09, N-11, and N-13) had an MIC < 1 µg/mL against the clinical isolates. Therefore, the scaffold quinoxaline 1,4-di-N-oxide could be used to develop new and more potent antinocardial agents. [ABSTRACT FROM AUTHOR]

Background: The performance of an everolimus-eluting bioresorbable scaffold (BRS) was inferior to an everolimus-eluting metallic drug-eluting stent (DES) with permanent polymer, mainly due the mechanical features of BRS technology. The performance of BRS as compared to metallic DES with bioresorbable polymers remains unstudied. Methods: This prospective, randomized, multicenter, clinical trial enrolled patients who underwent coronary stenting for de novo coronary lesions. Patients were randomly assigned to bioresorbable polymer everolimus-eluting stents (BP-EES) or everolimus-eluting BRS. The primary endpoint was percentage diameter stenosis (in-device) at 6- to 8-month angiographic surveillance. The main secondary endpoint was the device-oriented composite endpoint (DOCE) of cardiac death/target vessel-myocardial infarction/target lesion revascularization assessed after 12 months and 5 years. Results: The trial was prematurely terminated after the enrollment of 117 of 230 patients (BP-EES, n = 60; BRS, n = 57) due to safety issues associated with BRS technology. The primary endpoint of in-device diameter stenosis at angiographic surveillance was 12.5 ± 7.7% with BP-EES versus 19.3 ± 16.5% with BRS (p = 0.01). The DOCE occurred in 5.0% in the BP-EES group versus 12.3% of patients in the BRS group (hazard ratio [HR] 2.48, 95% confidence interval [CI] 0.64–9.58, p = 0.19) after 12 months and in 11.7% in the BP-EES group versus 26.4% of patients in the BRS group (HR 2.38, 95% CI 0.97–5.84, p = 0.06) after 5 years. Conclusions: BP-EES showed superior mid-term angiographic performance compared with BRS. Clinical event rates did not differ significantly between the groups up to 5 years of follow-up. These results should be interpreted with caution in view of the premature discontinuation of the study. [ABSTRACT FROM AUTHOR]

Placental-derived products have been used since the early 1900s for wound applications and have shown clinical utility in supporting wound healing. A hypothermically stored amniotic membrane (HSAM) was developed using a proprietary process to allow for the retention of the extracellular matrix (ECM), viable cells, and key proteins. To evaluate its utility, we characterized the HSAM and compared it to a native unprocessed amniotic membrane (uAM) and a dehydrated amniotic membrane (dAM), as well as assessing the functionality of the HSAM as a scaffold to promote cell growth. The HSAM, uAM, and dAM were compared using scanning electron microscopy (SEM), histology, and thickness. Scaffold durability was assessed in vitro using mechanical testing and a simulated wound fluid (SWF) model. The ability of the HSAM to act as a scaffold was evaluated using an in vitro attachment model. The HSAM showed similar structural characteristics compared to the uAM; however, the dAM was significantly more compact. There were no significant differences between the HSAM and the uAM following degradation in an SWF model. ECM- and placental-related proteins were shared between the HSAM and uAM, and the HSAM enhanced the attachment and proliferation of fibroblasts in vitro. The HSAM is substantially similar to the uAM by retaining key regulatory proteins, resisting degradation in SWF, and acting as a scaffold for cellular growth and invasion. [ABSTRACT FROM AUTHOR]

In this study, specific additives were incorporated in polyhydroxyalcanoate (PHB) and polylactic acid (PLA) blend to improve its compatibility, and so enhance the cell metabolic activity of scaffolds for tissue engineering. The formulations were manufactured through material extrusion (MEX) additive manufacturing (AM) technology. As additives, petroleum-based poly(ethylene) with glicidyl metacrylate (EGM) and methyl acrylate-co-glycidyl methacrylate (EMAG); poly(styrene-co-maleic anhydride) copolymer (Xibond); and bio-based epoxidized linseed oil (ELO) were used. On one hand, standard geometries manufactured were assessed to evaluate the compatibilizing effect. The additives improved the compatibility of PHB/PLA blend, highlighting the effect of EMAG and ELO in ductile properties. The processability was also enhanced for the decrease in melt temperature as well as the improvement of thermal stability. On the other hand, manufactured scaffolds were evaluated for the purpose of bone regeneration. The mean pore size and porosity exhibited values between 675 and 718 μm and 50 and 53%, respectively. According to the results, the compression stress was higher (11–13 MPa) than the required for trabecular bones (5–10 MPa). The best results in cell metabolic activity were obtained by incorporating ELO and Xibond due to the decrease in water contact angle, showing a stable cell attachment after 7 days of culture as observed in SEM. [ABSTRACT FROM AUTHOR]

Tissue engineering is a multidisciplinary field that uses biomaterials to restore tissue function and assist with drug development. Over the last decade, the fabrication of three-dimensional (3D) multifunctional scaffolds has become commonplace in tissue engineering and regenerative medicine. Thanks to the development of 3D bioprinting technologies, these scaffolds more accurately recapitulate in vivo conditions and provide the support structure necessary for microenvironments conducive to cell growth and function. The purpose of this review is to provide a background on the leading 3D bioprinting methods and bioink selections for tissue engineering applications, with a specific focus on the growing field of developing multifunctional bioinks and possible future applications. [ABSTRACT FROM AUTHOR]

Tissue engineering presents a promising approach for the treatment of meniscal injuries, yet the development of meniscal scaffolds that exhibit both superior biomechanical properties and biocompatibility remains a considerable challenge. In this study, decellularized skin matrix (DSM) scaffolds were first prepared using porcine skin through decellularization and freeze-drying techniques. The DSM scaffold has favorable porosity, hydrophilicity, and biocompatibility. Importantly, the collagen content and tensile modulus of the scaffold are comparable to those of native meniscus (44.13 ± 2.396 mg/g vs. 42.41 ± 2.40 mg/g and 103.30 ± 2.98 MPa vs. 128.80 ± 9.115 MPa). Subsequently, the peptide PFSSTKT (PFS) with mesenchymal stem cells (MSCs) recruitment capability was used to modify DSM to construct DSM-PFS scaffolds. Compared to the DSM scaffold, the optimized DSM-PFS scaffold enhanced in vitro collagen and glycosaminoglycan (GAG) production and upregulated the expression of cartilage-specific genes. Furthermore, the DSM-PFS scaffold was more effective in recruiting MSCs in vitro. In vivo studies in rabbit models showed that the DSM-PFS scaffold successfully promoted meniscus tissue regeneration. Three months post-implantation, meniscus tissue formation can be observable, and after six months, the neo-meniscus exhibited tissue structure and tensile properties similar to the native meniscus. Notably, the DSM-PFS scaffold exhibited significant chondroprotective effects, slowing osteoarthritis (OA) progression. In conclusion, the DSM-PFS scaffold may represent a promising candidate for future applications in meniscus tissue engineering. We developed a decellularized skin matrix (DSM) meniscus scaffold using whole-layer porcine skin, demonstrating superior biomechanical strength and biocompatibility. Following modification with the stem cell-recruiting peptide PFS, the optimized DSM-PFS scaffold outperformed the DSM scaffold in cell attraction, collagen and glycosaminoglycan production, and cartilage-specific gene expression. Implanted into rabbit knee joints, the cell-free DSM-PFS scaffold induced meniscal tissue formation within three months, achieving the histological structure and tensile strength of the native meniscus by six months. Moreover, it significantly protected the cartilage. Our findings provide new insights into the fabrication of scaffolds for meniscal tissue engineering, with the DSM-PFS scaffold emerging as an ideal candidate for future applications. [Display omitted] [ABSTRACT FROM AUTHOR]

This paper aimed to evaluate the effects of different preparation parameters, including agitation speed, agitation time, and chilling temperature, on the structural and mechanical properties of a novel gelatin/elastin/sodium hyaluronate tissue engineering scaffold, recently developed by our research group. Fabricated using a combination of foaming and freeze-drying techniques, the scaffolds were assessed to understand how these parameters influence their morphology, internal microstructure, porosity, mechanical properties, and degradation behavior. The fabrication process used in this study involved preparing a homogeneous aqueous solution containing 8% gelatin, 2% elastin, and 0.5% sodium hyaluronate (w/v), which was then subjected to mechanical agitation at speeds of 500, 1000, and 1500 rpm for durations of 5, 15, and 25 min. This mixture was subsequently frozen at −20 °C and −80 °C, followed by freeze-drying and cross-linking. Morphological analyses using laser microscopy and scanning electron microscopy (SEM) demonstrated that the scaffolds had pore sizes ranging from 100 to 300 µm, which are conducive to effective cell interaction and tissue regeneration. This confirmed the efficacy of the combined foaming and freeze-drying method in creating highly interconnected porous structures. Our findings indicated that chilling temperature slightly influenced pore size. In contrast, higher agitation speeds and longer duration times led to increased porosity and degradation rate but decreased modulus. Mathematical estimators were developed for the porosity and compressive modulus of the scaffolds by statistical analysis of the preparation parameters. The estimators were validated experimentally, with the error between estimated and experimental values being less than 6% for porosity and less than 21% for compressive modulus. [ABSTRACT FROM AUTHOR]

The development of new biomaterials for musculoskeletal tissue repair is currently an important branch in biomedicine research. The approach presented here is centered around the development of a prototypic synthetic glycerogel scaffold for bone regeneration, which simultaneously features therapeutic activity. The main novelty of this work lies in the combination of an open meso and macroporous nanocrystalline cellulose (NCC)-based glycerogel with a fully biocompatible microporous bioMOF system (CaSyr-1) composed of calcium ions and syringic acid. The bioMOF framework is further impregnated with a third bioactive component, i.e., ibuprofen (ibu), to generate a multifold bioactive system. The integrated CaSyr-1(ibu) serves as a reservoir for bioactive compounds delivery, while the NCC scaffold is the proposed matrix for cell ingrowth, proliferation and differentiation. The measured drug delivery profiles, studied in a phosphate-buffered saline solution at 310 K, indicate that the bioactive components are released concurrently with bioMOF dissolution after ca. 30 min following a pseudo-first-order kinetic model. Furthermore, according to the semi-empirical Korsmeyer-Peppas kinetic model, this release is governed by a case-II mechanism, suggesting that the molecular transport is influenced by the relaxation of the NCC matrix. Preliminary in vitro results denote that the initial high concentration of glycerol in the NCC scaffold can be toxic in direct contact with human osteoblasts (HObs). However, when the excess of glycerol is diluted in the system (after the second day of the experiment), the direct and indirect assays confirm full biocompatibility and suitability for HOb proliferation. [ABSTRACT FROM AUTHOR]

As a novel class of smart biomaterials with promising potentials, metal-organic frameworks (MOFs) are widely utilized in the field of biomedicine. Current researches indicate that the therapeutic strategies for osteoarthritis (OA) are highly limited to achieving symptom improvement and reducing both pain and inflammation. Together, the introduction of MOFs into the treatment of OA holds the potential to offer significant benefits. This is because MOFs not only have intrinsic biological activities, but also act as carriers to facilitate controlled drug delivery and prolong the duration in the management of OA. This paper presents a review of the recent studies that have explored the potential usage of MOFs as drugs or carriers in the treatment of OA, which also examines the progress of MOFs in tissue engineering for the treatment of OA. These studies are anticipated to not only enhance the comprehension of MOFs but also provide strong evidence in favor of their utilization in the treatment of OA. [ABSTRACT FROM AUTHOR]

Creating acellular vascularized constructs from animal and plant tissue is one of the well‐known strategies for scaffold assembly. Decellularization takes an important position among these strategies. The most common method is chemical decellularization. This approach employs high concentrations of detergents, primarily Triton X‐100, sodium dodecyl sulfate (SDS), and sodium hypochlorite (SH). In this work, novel techniques for decellularizing spinach were developed using detergents frequently utilized in laboratories. Spinach leaves were decellularized using Tween‐20, SDS, and SH at low concentrations to generate an acellular plant matrix for tissue engineering. We measured the quantities of DNA and protein, as well as the decellularization using hematoxylin and eosin (H&E) staining. The biocompatibility and capacity of the biostructures to stimulate fibroblast wound healing were assessed using MTT and the Scratch assay. The antibacterial activity of the scaffolds was also tested against a gram‐positive bacterium, Staphilococcus aureus, which is a common pathogen associated with wound healing. The best shape, evident vascularization, and good biocompatibility were seen in the Tween‐20 decellularized samples at 1% concentration at 21°C and 37°C through the enhancement of cell proliferation and wound healing. In terms of antibacterial activity, all scaffold samples had a significant effect on Staphilococcus aureus, where the number of bacterial colonies in all six scaffold groups became zero after 4 h of treatment. The scaffolds also showed a 100% kill rate on Staphilococcus aureus, which could avoid wound infection during the repair process, and that can be suggested as a scaffold for tissue engineering applications and an important constituent for pharmacological activities. [ABSTRACT FROM AUTHOR]

To repair damaged mesothelium tissue, which lines internal organs and cavities, a tissue engineering approach with mesothelial cells seeded to a functional nanostructured scaffold is a promising approach. Therefore, this study explored the uses of electrospun nanofiber membrane scaffolds (NMSs) as scaffolds for mesothelial cell culture and transplantation. We fabricated a composite NMS through electrospinning by blending polycaprolactone (PCL) with gelatin. The addition of gelatin enhanced the membrane's hydrophilicity while maintaining its mechanical strength and promoted cell attachment. The in vitro study demonstrated enhanced adhesion of mesothelial cells to the scaffold with improved morphology and increased phenotypic expression of key marker proteins calretinin and E-cadherin in PCL/gelatin compared to pure PCL NMSs. In vivo studies in rats revealed that only cell-seeded PCL/gelatin NMS constructs fostered mesothelial healing. Implantation of these constructs leads to the regeneration of new mesothelium tissue. The neo-mesothelium is similar to native mesothelium from hematoxylin and eosin (H&E) and immunohistochemical staining. Taken together, the PCL/gelatin NMSs can be a promising scaffold for mesothelial cell attachment, proliferation, and differentiation, and the cell/scaffold construct can be used in therapeutic applications to reconstruct a mesothelium layer. [ABSTRACT FROM AUTHOR]

Recent interest in tissue engineering (TE) has focused on electrically conductive biomaterials. This has been inspired by the characteristics of the cells' microenvironment where signalling is supported by electrical stimulation. Numerous studies have demonstrated the positive influence of electrical stimulation on cell excitation to proliferate, differentiate, and deposit extracellular matrix. Even without external electrical stimulation, research shows that electrically active scaffolds can improve tissue regeneration capacity. Tissues like bone, muscle, and neural contain electrically excitable cells that respond to electrical cues provided by implanted biomaterials. To introduce an electrical pathway, TE scaffolds can incorporate conductive polymers, metallic nanoparticles, and ceramic nanostructures. However, these materials often do not meet implantation criteria, such as maintaining mechanical durability and degradation characteristics, making them unsuitable as scaffold matrices. Instead, depositing conductive layers on TE scaffolds has shown promise as an efficient alternative to creating electrically conductive structures. A stratified scaffold with an electroactive surface synergistically excites the cells through active top-pathway, with/without electrical stimulation, providing an ideal matrix for cell growth, proliferation, and tissue deposition. Additionally, these conductive coatings can be enriched with bioactive or pharmaceutical components to enhance the scaffold's biomedical performance. This review covers recent developments in electrically active biomedical coatings for TE. The physicochemical and biological properties of conductive coating materials, including polymers (polypyrrole, polyaniline and PEDOT:PSS), metallic nanoparticles (gold, silver) and inorganic (ceramic) particles (carbon nanotubes, graphene-based materials and Mxenes) are examined. Each section explores the conductive coatings' deposition techniques, deposition parameters, conductivity ranges, deposit morphology, cell responses, and toxicity levels in detail. Furthermore, the applications of these conductive layers, primarily in bone, muscle, and neural TE are considered, and findings from in vitro and in vivo investigations are presented. Tissue engineering (TE) scaffolds are crucial for human tissue replacement and acceleration of healing. Neural, muscle, bone, and skin tissues have electrically excitable cells, and their regeneration can be enhanced by electrically conductive scaffolds. However, standalone conductive materials often fall short for TE applications. An effective approach involves coating scaffolds with a conductive layer, finely tuning surface properties while leveraging the scaffold's innate biological and physical support. Further enhancement is achieved by modifying the conductive layer with pharmaceutical components. This review explores the under-reviewed topic of conductive coatings in tissue engineering, introducing conductive biomaterial coatings and analyzing their biological interactions. It provides insights into enhancing scaffold functionality for tissue regeneration, bridging a critical gap in current literature. [Display omitted] [ABSTRACT FROM AUTHOR]

The preparation of scaffolds that are both macroporous and mechanically strong is a significant challenge in the development of bioactive ceramic materials for bone substitution. Furthermore, the introduction of beneficial extra-functionalities such as bacterial inhibition is highly appealing but adds complexity to implant design and production. In this study, we aimed to fabricate highly porous, bioactive and antibacterial glass-ceramic scaffolds with interconnected macropores through the foam replica method. The scaffolds were sintered at two different temperatures (620 and 850 °C), yielding glassy or partially crystallized materials, respectively. The scaffold produced at higher temperature was found to be highly porous (>75 vol%), mechanically stronger and able to induce hydroxyapatite formation after three days of soaking in SBF (in vitro bioactivity). In order to confer antibacterial activity, silver (Ag) ions were introduced onto the scaffold surface through ion exchange in an aqueous solution. Compositional analysis confirmed the successful doping of the scaffold surface with silver, which was continuously released in SBF for at least 28 days, as revealed by ICP-MS. Finally, the antibacterial action of the Ag-doped scaffold was confirmed towards Staphylococcus epidermidis. Overall, the results reported in this work show the potential of foam-like Ag-doped bioactive glass-ceramic scaffolds to be used in applications requiring bone substitution and antibacterial properties. [ABSTRACT FROM AUTHOR]

Three-dimensional cancer cell cultures have been a valuable research model for developing new drug targets in the preclinical stage. However, there are still limitations to these in vitro models. Scaffold-based systems offer a promising approach to overcoming these challenges in cancer research. In this study, we show that two-photon polymerization (TPP)-assisted printing of scaffolds enhances 3D tumor cell culture formation without additional modifications. TPP is a perfect fit for this task, as it is an advanced 3D-printing technique combining a μm-level resolution with complete freedom in the design of the final structure. Additionally, it can use a wide array of materials, including biocompatible ones. We exploit these capabilities to fabricate scaffolds from two different biocompatible materials—PEGDA and OrmoClear. Cubic spheroid scaffolds with a more complex architecture were produced and tested. The biological evaluation showed that the human ovarian cancer cell lines SKOV3 and A2780 formed 3D cultures on printed scaffolds without a preference for the material. The gene expression evaluation showed that the A2780 cell line exhibited substantial changes in CDH1, CDH2, TWIST, COL1A1, and SMAD3 gene expression, while the SKOV3 cell line had slight changes in said gene expression. Our findings show how the scaffold architecture design impacts tumor cell culture 3D spheroid formation, especially for the A2780 cancer cell line. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tissue engineering seeks to improve, maintain, or replace the biological functions of damaged organs or tissues with biological substitutes such as the development of scaffolds. In the case of bone tissue, they must have excellent mechanical properties like native bone. OBJECTIVE: In this work, three geometric models were designed for scaffolds with different structure lattices and porosity that could be biomechanically suitable and support cell growth for trabecular bone replacement applications in tissue engineering and regenerative medicine to the proximal femur area. METHODS: Geometries were designed using computer-aided design (CAD) software and evaluated using finite element analysis in compression tests. Three loads were considered according to the daily activity: 1177 N for slow walking, 2060 N for fast walking, and 245.25 N for a person in a bipedal position. All these loads for an adult weight of 75 kg. For each of them, three biomaterials were assigned: two polymers (poly-glycolic acid (PGA) and poly-lactic acid (PLA)) and one mineral (hydroxyapatite (HA)). 54 tests were performed: 27 for each of the tests. RESULTS: The results showed Young's modulus (E) between 1 and 4 GPa. CONCLUSION: If the resultant E is in the range of 0.1 to 5 GPa, the biomaterial is considered an appropriate alternative for the trabecular bone which is the main component of the proximal bone. However, for the models applied in this study, the best option is the poly-lactic acid which will allow absorbing the acting loads. [ABSTRACT FROM AUTHOR]

Organoids are small, self-organizing three-dimensional cell cultures that are derived from stem cells or primary organs. These cultures replicate the complexity of an organ, which cannot be achieved by single-cell culture systems. Organoids can be used in testing of new drugs instead of animals. Development and validation of organoids is thus important to reduce the reliance on animals for drug testing. In this review, we have discussed the developmental and regulatory aspects of organoids and highlighted their importance in drug development. We have first summarized different types of culture-based organoid systems such as submerged Matrigel, micro-fluidic 3D cultures, inducible pluripotent stem cells, and air-liquid interface cultures. These systems help us understand the intricate interplay between cells and their surrounding milieu for identifying functions of target receptors, soluble factors, and spatial interactions. Further, we have discussed the advances in humanized severe-combined immunodeficiency mouse models and their applications in the pharmacology of immune-oncology. Since regulatory aspects are important in using organoids for drug development, we have summarized FDA and EMA regulations on organoid research to support pre-clinical studies. Finally, we have included some unique studies highlighting the use of organoids in studying infectious diseases, cancer, and fundamental biology. These studies also exemplify the latest technological advances in organoid development resulting in improved efficiency. Overall, this review comprehensively summarizes the applications of organoids in early drug development during discovery and pre-clinical studies. [ABSTRACT FROM AUTHOR]

Despite the great progress in developing wound dressings, delayed wound closure still remains a global challenge. Thus, developing novel wound dressings and employing advanced strategies, including tissue engineering, are urgently desired. The carboxylated cellulose was developed through the in situ synthesis method and further reinforced by incorporating pal-KTTKS to stimulate collagen synthesis and improve wound healing. The developed composites supported cell adhesion and proliferation and showed good biocompatibility. To boost wound-healing performance, adipose-derived mesenchymal stem cells (MSC) were seeded on the pal-KTTKS-enriched composites to be implanted in a rat model of burn wound healing. Healthy male rats were randomly divided into four groups and wound-healing performance of Vaseline gauze (control), carboxylated cellulose (CBC), pal-KTTKS-enriched CBC (KTTKS-CBC), and MSCs seeded on the KTTKS-CBC composites (MSC-KTTKS-CBC) were evaluated on days 3, 7, and 14 post-implantation. In each group, the designed therapeutic dressings were renewed every 5 days to increase wound-healing performance. We found that KTTKS-CBC and MSC-KTTKS-CBC composites exhibited significantly better wound healing capability, as evidenced by significantly alleviated inflammation, increased collagen deposition, improved angiogenesis, and considerably accelerated wound closure. Nevertheless, the best wound-healing performance was observed in the MSC-KTTKS-CBC groups among all four groups. This research suggests that the MSC-KTTKS-CBC composite offers a great deal of promise as a wound dressing to enhance wound regeneration and expedite wound closure in the clinic. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: There are different situations in which an extrahepatic bile duct replacement or substitute is needed, such as initial and localized stages of bile duct cancer, agenesis, stenosis, or bile duct disruption. Materials and Methods: A prosthesis obtained by electrospinning composed of Poly (D,L-lactide-co-glycolide) (PGLA) - Polycaprolactone (PCL) - Gelatin (Gel) was developed, mechanical and biological tests were carried out to evaluate resistance to tension, biocompatibility, biodegradability, cytotoxicity, morphological analysis and cell culture. The obtained prosthesis was placed in the extrahepatic bile duct of 15 pigs with a 2-year follow-up. Liver function tests and cholangioscopy were evaluated during follow-up. Results: Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable. The prosthesis implanted in the experimental model allowed cell adhesion, migration, and proliferation, maintaining bile duct permeability without altering liver function tests. Immunohistochemical analysis indicates the presence of biliary epithelium. Conclusions: A tubular scaffold composed of electrospun PGLA-PCL-Gel nanofibers was used for the first time to replace the extrahepatic bile duct in pigs. Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable, making it an excellent candidate for use in bile ducts and potentially in other tissue engineering applications. [ABSTRACT FROM AUTHOR]

Polylactic acid (PLA) is widely used in the treatment of bone defects due to its good properties, but the problem of its slow degradation rate needs to be solved urgently. In this study, different proportions of Mg were introduced into PLA to promote and regulate its degradation. A three-dimensional porous composite bone scaffold made of PLA and Mg was prepared using selective laser sintering (SLS). Degradation results showed that the weight loss rate of the Mg-containing scaffold within 4 weeks was nearly five times higher than that of the pure PLA scaffold. Moreover, the degradation mechanism was further explored, and it was believed that the addition of Mg could consume the acidic degradation products of PLA, thus destroying the integrity of the PLA molecular chain and accelerating the flow of the molecular chain, ultimately forming a cycle that promotes degradation. In addition, the magnesium-containing scaffold (PLA/3Mg) also showed good compressive strength (5.6 MPa), which was nearly twice as high as that of the pure PLA scaffold (2.67 MPa). Therefore, we believe that introducing an appropriate amount of Mg can better adjust the balance between the degradation and mechanical properties of PLA scaffolds. [ABSTRACT FROM AUTHOR]

Biphasic calcium phosphate (BCP), containing β-tricalcium phosphate and hydroxyapatite, was synthesized by co-precipitation method to obtain a biomimetic artificial bone-like composite using calcium nitrate tetrahydrate [Ca(NO3)∙4H2O] as calcium precursor and ammonium dihydrogen phosphate (NH4H2PO4) as phosphorous precursor, maintaining Ca/P ratio of 1.67. The synthesized biphasic calcium phosphate mixture was dispersed in a sodium alginate (Alg) matrix dissolved in distilled water and lyophilized. The chemical structure, possible interactions between components and morphology of the obtained powder and scaffolds were studied through Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) in order to observe the interactions between BCP and the polymer. The particle size of the powder was also analyzed using the dynamic light scattering (DLS) analysis. Calcined powder had a particle size of 1.8 μm. In addition to the low crystalline hydroxyapatite (HA), as the main phase in the dried samples, β-tricalcium phosphate (β-TCP) was formed after the thermal treatment of 1000˚C as shown by XRD and FT-IR. The obtained composite material presented a highly porous microstructure with interconnected layers where the BCP particles were well dispersed. The micro-structure of the scaffolds was influenced with the change in pore dimensions and rearrangement of the layers due to the incorporation of the BCP particles and by the treatment of the scaffolds with CaCl2. [ABSTRACT FROM AUTHOR]

Abstract Owing to their native extracellular matrix-like features, magnetic hydrogels have been proven to be promising biomaterials as tissue engineering templates In the present work, magnetic hydrogels scaffold based on chitosan, gelatin, hyaluronic acid, containing Fe3O4 as magnetic nanoparticles (IONPs) were prepared. The prepared hydrogels were loaded with ciprofloxacin hydrochloride as a model drug. The magnetic hydrogel was prepared using different volumes of chitosan, 1%, gelatin, 10%, and hyaluronic acid, 1% in glutaraldehyde as the crosslinking agent and Fe3O4 as magnetic nanoparticles. The hydrogel scaffold and magnetic scaffold hydrogel samples were characterized by scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), and Fourier-transform infrared spectroscopy (FTIR). The porosity, mechanical properties, swelling degree, and antibacterial activity of the hydrogel scaffold were also determined as well as the drug release profiles of the hydrogels. SEM imaging revealed that the magnetic hydrogel scaffold showed a relatively rough morphology with an irregular surface. The data obtained indicated that the hydrogel surface has three-dimensional porous microstructures and the porosity varied depending on the hydrogel formulation. The breaking load of the hydrogel scaffold increased from 1.361 Kgf to 4.98 Kgf by increasing the glutaraldehyde concentration from 0.2 mL to 0.8 mL. Swelling degree values in water were from 250 to 2000% after 24 h. The antibacterial activity of the hydrogel scaffold ranged from 54% to about 97% for Gram-positive bacteria (S. aureus) and from about 26–92% for Gram-negative bacteria (E. coli). The ciprofloxacin hydrochloride loaded hydrogel has a sustained release of ciprofloxacin hydrochloride over 10 h. The presence of IONPs gave a faster release of ciprofloxacin hydrochloride.

Abstract Since wound healing is one of the most important medical challenges and common dressings have not been able to manage this challenge well today, efforts have been increased to achieve an advanced dressing. Mesenchymal stem cells and exosomes derived from them have shown high potential in healing and regenerating wounds due to their immunomodulatory, anti-inflammatory, immunosuppressive, and high regenerative capacities. However, challenges such as the short life of these cells, the low durability of these cells in the wound area, and the low stability of exosomes derived from them have resulted in limitations in their use for wound healing. Nowadays, different scaffolds are considered suitable biomaterials for wound healing. These scaffolds are made of natural or synthetic polymers and have shown promising potential for an ideal dressing that does not have the disadvantages of common dressings. One of the strategies that has attracted much attention today is using these scaffolds for seeding and delivering MSCs and their exosomes. This combined strategy has shown a high potential in enhancing the shelf life of cells and increasing the stability of exosomes. In this review, the combination of different scaffolds with different MSCs or their exosomes for wound healing has been comprehensively discussed.

Abstract Initial studies on the immunogenicity of SARS-CoV-2 (CoV-2) S glycoprotein (“spike”) as a protein subunit vaccine suggested sub-optimal efficacy in mammals. Although protein engineering efforts have produced CoV-2 spike protein sequences with greatly improved immunogenicity, additional strategies for improving the immunogenicity of CoV-2 protein subunit vaccines are scaffolding and the use of adjuvants. Comparisons of the effectiveness of engineered protein-only and engineered protein-nanoparticles vaccines have been rare. To explore this knowledge gap, we inoculated mice with two doses of either sequence-optimized trimeric spike protein or one of several sequence-optimized spike nanoparticles. We measured their immune response up to two months after the first dose. We also measured the immune response and protection against live virus in hamsters inoculated with either sequence-optimized trimeric spike protein or a liposome-based sequence-optimized spike nanoparticle. We found that in the presence of adjuvant, the antibody and neutralization titers elicited by spike-nanoparticles were not significantly greater than those elicited by spike-only in mice, even at doses as low as 0.1 µg/animal. Hamsters vaccinated with spike-only or spike-nanoparticles were equally protected from live virus one month after their first inoculation. These results suggest that sequence-optimized protein subunit vaccines in the form of individual prefusion-stabilized trimers can be as effective in improving immunogenicity as scaffolded forms.