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Articular cartilage injury is a serious bone disease that can result in disabilities. With the rapid increase in the aging population, this disorder has become an increasingly important public health issue. Recently, stem cell-based cartilage tissue engineering has emerged as a promising therapeutic option for treating articular cartilage damage. Cellular scaffolds, which are among three key elements of tissue engineering, play significant roles in the repair of damaged articular cartilage by regulating cellular responses and promoting cartilage tissue regeneration. Biological macromolecules are commonly used as scaffold materials owing to their unique properties. For example, natural and synthetic polymer hydrogel scaffolds can effectively mimic the microenvironment of the natural extracellular matrix; exhibit high cytocompatibility, biocompatibility, and biodegradability; and have attracted increasing attention in bone and cartilage tissue engineering and regeneration medicine. Several types of hydrogel scaffolds have been fabricated to treat articular cartilage abnormalities. This article outlines the recent progress in the field of hydrogel scaffolds manufactured from various biomaterials for repairing damaged articular cartilage, discusses their advantages and disadvantages, and proposes directions for their future development. [ABSTRACT FROM AUTHOR]

Bone tissue engineering is a promising approach to overcome the limitations of traditional autograft bone transplantation. Graphene quantum dots (GQDs) have been suggested as an enhancement for osteogenic differentiation. This study aimed to investigate the ability of the fibrin hydrogel scaffold in the presence of graphene quantum dots to promote osteogenic differentiation of human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs). The hWJ-MSCs were isolated from the Wharton’s jelly of the human umbilical cord using a mechanical method. Fibrin hydrogel scaffolds were prepared by mixing 15 µl of thrombin solution with fibrinogen solution. GQDs were incorporated into the scaffolds at concentrations of 0, 5, and 10 µg/ml. Cell viability was determined through DAPI staining and the MTT assay. Osteogenic differentiation was assessed by measuring alkaline phosphatase (ALP) activity, quantifying calcium deposition using Alizarin Red S staining, and analyzing the gene expression of BGLAP, COL1A1, Runx-2 and ALP via qPCR. Scanning electron microscopy (SEM) was employed to analyze the scaffold architecture. SEM analysis revealed that the fibrin hydrogel exhibited a suitable architecture for tissue engineering, and DAPI staining confirmed cell viability. The MTT results indicated that the GQDs and fibrin hydrogel scaffold exhibited no cytotoxic effects. Furthermore, the incorporation of GQDs at a concentration of 10 µg/ml significantly enhanced ALP activity, calcium deposition, and the expression of osteogenesis-related genes compared to the control. The findings suggest that the combination of fibrin hydrogel and GQDs can effectively promote the osteogenic differentiation of hWJ-MSCs, contributing to the advancement of bone tissue engineering. [ABSTRACT FROM AUTHOR]

Mingkui Shen,1,* Lulu Wang,2,* Kuankuan Li,1 Jun Tan,1,3 Zhongxin Tang,1 Xiaohu Wang,4 Hejun Yang1 1Department of Mini-Invasive Spinal Surgery, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 2Department of Plastic Surgery, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 3Department of Clinical Medicine, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 4Department of Orthopedics, Zhengzhou Central Hospital, Zhengzhou, 450007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hejun Yang, Department of Mini-invasive Spinal Surgery, The Third People’s Hospital of Henan Province, Intersection of Zhengguang Road and Minsheng Road, Jinshui District, Zhengzhou, Henan, 450006, People’s Republic of China, Email hejunyang02@163.comBackground: The challenge in treating irreversible nerve tissue damage has resulted in suboptimal outcomes for spinal cord injuries (SCI), underscoring the critical need for innovative treatment strategies to offer hope to patients.Methods: In this study, gelatin methacrylic acid hydrogel scaffolds loaded with nerve growth factors (GMNF) were prepared and used to verify the performance of SCI. The physicochemical and biological properties of the GMNF were tested. The effect of GMNF on activity of neuronal progenitor cells (NPCs) was investigated in vitro. Histological staining and motor ability was carried out to assess the ability of SCI repair in SCI animal models.Results: Achieving nerve growth factors sustained release, GMNF had good biocompatibility and could effectively penetrate into the cells with good targeting permeability. GMNF could better enhance the activity of NPCs and promote their directional differentiation into mature neuronal cells in vitro, which could exert a good neural repair function. In vivo, SCI mice treated with GMNF recovered their motor abilities more effectively and showed better wound healing by macroscopic observation of the coronal surface of their SCI area. Meanwhile, the immunohistochemistry demonstrated that the GMNF scaffolds effectively promoted SCI repair by better promoting the colonization and proliferation of neural stem cells (NSCs) in the SCI region and targeted differentiation into mature neurons.Conclusion: The application of GMNF composite scaffolds shows great potential in SCI treatment, which are anticipated to be a potential therapeutic bioactive material for clinical application in repairing SCI in the future.Keywords: hydrogel scaffold, nerve growth factor, spinal cord injury, neuronal regeneration

Abstract Background Polyetheretherketone (PEEK) is well known for its excellent physical–chemical properties and biosafety. The study aimed to open up a new method for clinical application of PEEK to reconstruct large-scale bone defects. Methods A bilayer scaffold for bone regeneration was prepared by combining a sulfonated PEEK barrier framework (SPEEK) with a hydrogel layer loaded with aspirin (ASA) and nano-hydroxyapatite (nHAP) by the wet-bonding of Polydopamine (PDA). Results The hydrogel was successfully adhered to the surface of SPEEK, resulting in significant changes including the introduction of bioactive groups, improved hydrophilicity, and altered surface morphology. Subsequent tests confirmed that the bilayer scaffold exhibited enhanced compression resistance and mechanical compatibility with bone compared to a single hydrogel scaffold. Additionally, the bilayer scaffold showed stable and reliable bonding properties, as well as excellent biosafety verified by cell proliferation and viability experiments using mouse embryo osteoblast precursor (MC3T3-E1) cells. Conclusion The bilayer bone regeneration scaffold prepared in this study showed promising potential in clinical application for bone regeneration.

Diseases and traumatic injuries to the central nervous system (CNS) demand the development of new biomaterials to improve healing and treatment options. Matching material mechanical properties to specific tissues and optimizing material porous structures are central goals for improving biomaterials. However, biomaterials with both precision-controlled porous structures and brain-matched mechanical properties (low modulus) are still lacking. In this study, we developed soft hydrogel scaffolds with mechanical properties similar to that of CNS tissues, and a uniform 40 µm porous structure—40 µm pores have been shown to be optimal for healing in many tissues. The two characteristics were achieved by a new fabrication process combining phase separation and sphere templating. The resulting scaffolds are non-cytotoxic according to the ISO 10993-5 standard. In addition, the three-dimensional culture of microglial cells within the scaffolds demonstrates cell attachment and maintenance of a rounded, quiescent morphology, potentially due to spatial confinement. These results justify further in vivo studies and suggest broad potential in CNS applications, such as brain-computer interfaces, neural regeneration, and basic neurobiology. Subject classification codes: Neural Interfaces, soft hydrogel, synthetic biomaterials [ABSTRACT FROM AUTHOR]

Poly(2-hydroxyethyl methacrylate) (PHEMA) has been widely used in medical materials for several decades. However, the poor mechanical properties of this material have limited its application in the field of tissue engineering. The purpose of this study was to fabricate a scaffold with suitable mechanical properties and in vitro cell responses for soft tissue by using poly(HEMA-co-MMA) with various concentration ratios of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA). To customize the concentration ratio of HEMA and MMA, the characteristics of the fabricated scaffold with various concentration ratios were investigated through structural morphology, FT-IR, mechanical property, and contact angle analyses. Moreover, in vitro cell responses were observed according to the various concentration ratios of HEMA and MMA. Consequently, various morphologies and pore sizes were observed by changing the HEMA and MMA ratio. The mechanical properties and contact angle of the fabricated scaffolds were measured according to the HEMA and MMA concentration ratio. The results were as follows: compressive maximum stress: 254.24–932.42 KPa; tensile maximum stress: 4.37–30.64 KPa; compressive modulus: 16.14–38.80 KPa; tensile modulus: 0.5–2 KPa; and contact angle: 36.89–74.74°. In terms of the in vitro cell response, the suitable cell adhesion and proliferation of human dermal fibroblast (HDF) cells were observed in the whole scaffold. Therefore, a synthetic hydrogel scaffold with enhanced mechanical properties and suitable fibroblast cell responses could be easily fabricated for use with soft tissue using a specific HEMA and MMA concentration ratio. [ABSTRACT FROM AUTHOR]

Bone defects resulting from trauma, disease, or congenital abnormalities represent a significant clinical challenge, necessitating advanced regenerative therapies. This study presents the development and formulation of a drug-loaded hydrogel as a novel approach for bone regeneration. The hydrogel matrix is engineered to provide structural support and controlled release of therapeutic agents to enhance bone healing. Various biocompatible polymers and crosslinking strategies are investigated to optimize the hydrogel's mechanical properties, degradation kinetics, and drug release profiles. Furthermore, the study explores the efficacy of different drugs, growth factors, and osteoinductive molecules in promoting osteogenesis and bone tissue regeneration within the hydrogel scaffold. The developed drug-loaded hydrogel holds promise as a versatile platform for addressing diverse bone defects and advancing the field of regenerative orthopedics. [ABSTRACT FROM AUTHOR]

Background To address the limitations of Cultivated Limbal Epithelial Transplantation (CLET) and the use of amniotic membrane (AM) in treating Limbal Stem Cell Deficiency (LSCD), we aimed to develop a Collagen/Silk Fibroin (Co/SF) scaffold enriched with Platelet-Rich Growth Factor (PRGF) to support the proliferation, maintenance, and differentiation of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) into corneal epithelial cells (CECs). Method Scaffolds loaded with PRGF were evaluated through release studies, cytotoxicity assays, and cell differentiation. The proliferation and differentiation of WJMSCs and Limbal Epithelial Stem Cells (LESCs) were investigated using MTT assays, real-time PCR and immunostaining. Results The PRGF-loaded Co/SF scaffold significantly promoted the proliferation of both WJMSCs and LESCs in a concentration-dependent manner. Real-time PCR and immune staining revealed a significant increase in the expression of P63, ABCG2, and cytokeratin 3/12 markers in WJMSCs, a significant decrease in the expression of P63 and ABCG2, and a significant increase in the expression of cytokeratin 3/12 markers indicating successful differentiation into CECs. Conclusion The WJMSC cultured on PRGF-enriched Co/SF scaffold demonstrates potential as a viable alternative to conventional CLET, offering a promising strategy for corneal tissue regeneration. [ABSTRACT FROM AUTHOR]

Background: Polyetheretherketone (PEEK) is well known for its excellent physical–chemical properties and biosafety. The study aimed to open up a new method for clinical application of PEEK to reconstruct large-scale bone defects. Methods: A bilayer scaffold for bone regeneration was prepared by combining a sulfonated PEEK barrier framework (SPEEK) with a hydrogel layer loaded with aspirin (ASA) and nano-hydroxyapatite (nHAP) by the wet-bonding of Polydopamine (PDA). Results: The hydrogel was successfully adhered to the surface of SPEEK, resulting in significant changes including the introduction of bioactive groups, improved hydrophilicity, and altered surface morphology. Subsequent tests confirmed that the bilayer scaffold exhibited enhanced compression resistance and mechanical compatibility with bone compared to a single hydrogel scaffold. Additionally, the bilayer scaffold showed stable and reliable bonding properties, as well as excellent biosafety verified by cell proliferation and viability experiments using mouse embryo osteoblast precursor (MC3T3-E1) cells. Conclusion: The bilayer bone regeneration scaffold prepared in this study showed promising potential in clinical application for bone regeneration. [ABSTRACT FROM AUTHOR]

Background: Diabetic bone defects present significant challenges for individuals with diabetes. While metformin has been explored for bone regeneration via local delivery, its application in treating diabetic bone defects remains under-explored. In this study, we aim to leverage 3D printing technology to fabricate a GelMA-Nanoclay hydrogel scaffold loaded with metformin specifically for this purpose. The objective is to assess whether the in situ release of metformin can effectively enhance osteogenesis, angiogenesis, and immunomodulation in the context of diabetic bone defects. Materials and methods: Utilizing 3D printing technology, we constructed a GelMA-Nanoclay-Metformin hydrogel scaffold with optimal physical properties and biocompatibility. The osteogenic, angiogenic, and immunomodulatory characteristics of the hydrogel scaffold were thoroughly investigated through both in vitro and in vivo experiments. Results: GelMA10%-Nanoclay8%-Metformin5mg/mL was selected as the bioink for 3D printing due to its favorable swelling rate, degradation rate, mechanical strength, and drug release rate. Through in vitro investigations, the hydrogel scaffold extract, enriched with metformin, demonstrated a substantial enhancement in the proliferation and migration of BMSCs within a high-glucose microenvironment. It effectively enhances osteogenesis, angiogenesis, and immunomodulation. In vivo experimental outcomes further underscored the efficacy of the metformin-loaded GelMA-Nanoclay hydrogel scaffold in promoting superior bone regeneration within diabetic bone defects. Conclusions: In conclusion, while previous studies have explored local delivery of metformin for bone regeneration, our research is pioneering in its application to diabetic bone defects using a 3D printed GelMA-Nanoclay hydrogel scaffold. This localized delivery approach demonstrates significant potential for enhancing bone regeneration in diabetic patients, offering a novel approach for treating diabetic bone defects. The translational potential of this article: Our study demonstrates, for the first time, the successful loading of the systemic antidiabetic drug metformin onto a hydrogel scaffold for localized delivery. This approach exhibits significant efficacy in mending diabetic bone defects, presenting a promising new avenue for the treatment of such conditions.

In recent years, people have had more expectations from the developed technology in medicine, especially in the field of orthopedics and traumatology. Tissue engineers are interested in techniques that benefit from patients' cells and biomaterials, instead of prostheses and implants. On the other hand, researchers have begun to use various medicinal plants for regeneration and anti-cancer studies. In the present study, we aimed to produce cartilage and bone inductive scaffolds for osteochondral tissue engineering applications with the addition of hawthorn or elderberry extracts. Firstly, wet electro-spun poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid) fibers were integrated with a loofah mat. Then, they were impregnated into chitosan solution with/without hawthorn or elderberry extract. Composite hydrogel scaffolds were obtained by cross-linking with 0.3% (w/v) genipin. Fabricated scaffolds had more than 90% porosity and showed swelling capacity in the range of 1500–2200%. Based on the in vitro biocompatibility analyses using mesenchymal stem cells (MSCs), all the fabricated scaffolds were found to be biocompatible by WST-1, ALP activity, and GAG content analysis. Also, histological/immunohistochemical analyses showed that hawthorn and elderberry extract addition increased MSCs proliferation and collagen type I and II positivity. Consequently, all the scaffolds showed promising features for osteochondral tissue engineering applications. [ABSTRACT FROM AUTHOR]

Gelatin methacryloyl (GelMA) is an ideal bioink that is commonly used in bioprinting. GelMA is primarily acquired from mammalian sources; however, the required amount makes the market price extremely high. Since garbage overflow is currently a global issue, we hypothesized that fish scales left over from the seafood industry could be used to synthesize GelMA. Clinically, the utilization of fish products is more advantageous than those derived from mammals as they lower the possibility of disease transmission from mammals to humans and are permissible for practitioners of all major religions. In this study, we used gelatin extracted from fish scales and conventional GelMA synthesis methods to synthesize GelMA, then tested it at different concentrations in order to evaluated and compared the mechanical properties and cell responses. The fish scale GelMA had a printing accuracy of 97%, a swelling ratio of 482%, and a compressive strength of about 85 kPa at a 10% w/v GelMA concentration. Keratinocyte cells (HaCaT cells) were bioprinted with the GelMA bioink to assess cell viability and proliferation. After 72 h of culture, the number of cells increased by almost three-fold compared to 24 h, as indicated by many fluorescent cell nuclei. Based on this finding, it is possible to use fish scale GelMA bioink as a scaffold to support and enhance cell viability and proliferation. Therefore, we conclude that fish scale-based GelMA has the potential to be used as an alternative biomaterial for a wide range of biomedical applications. [ABSTRACT FROM AUTHOR]

Terminology is pivotal for facilitating clear communication and minimizing ambiguity, especially in specialized fields such as chemistry. In materials science, a subset of chemistry, the term "pore" is traditionally linked to the International Union of Pure and Applied Chemistry (IUPAC) nomenclature, which categorizes pores into "micro", "meso", and "macro" based on size. However, applying this terminology in closely-related areas, such as 3D bioprinting, often leads to confusion owing to the lack of consensus on specific definitions and classifications tailored to each field. This review article critically examines the current use of pore terminology in the context of 3D bioprinting, highlighting the need for reassessment to avoid potential misunderstandings. We propose an alternative classification that aligns more closely with the specific requirements of bioprinting, suggesting a tentative size-based division of interconnected pores into 'parvo'-(d < 25 µm), 'medio'-(25 < d < 100 µm), and 'magno'-(d > 100 µm) pores, relying on the current understanding of the pore size role in tissue formation. The introduction of field-specific terminology for pore sizes in 3D bioprinting is essential to enhance the clarity and precision of research communication. This represents a step toward a more cohesive and specialized lexicon that aligns with the unique aspects of bioprinting and tissue engineering. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aspirin is a classic non-steroidal anti-inflammatory drug. Appropriate doses of aspirin can regulate immunity and promote osteogenesis. The preparation of bone tissue engineering materials, which can release aspirin, regulate the immune microenvironment of the bone defect area and accelerate the repair of the bone defect, and is a current research focus. OBJECTIVE: To prepare a novel hydrogel scaffold that can modulate the immune microenvironment and quickly repair the bone defect area. METHODS: Hydrogel scaffolds containing 0%, 10% and 20% of nano-hydroxyapatite/aspirin/polyvinyl alcohol/gelatin/sodium alginate were prepared. The microstructure, porosity, chemical composition, crystal structure, drug release properties, mechanical properties, swelling properties and degradation properties of the hydrogel scaffolds were characterized. The biocompatibility of the hydrogel scaffolds was evaluated by cell proliferation and cytotoxicity experiments. RESULTS AND CONCLUSION: (1) Scanning electron microscope and porosity results showed that hydrogel scaffolds in the 0% nano-hydroxyapatite group and 10% nano-hydroxyapatite group had better biomimetic hierarchical porous structure, pore connectivity, and porosity. (2) The results of Fourier transform infrared spectroscopy and X-ray diffraction showed that the raw materials in the hydrogel scaffold were combined by physical and chemical double crosslinking, and the crystal phase structure of nano-hydroxyapatite was not be destroyed. (3) The results of mechanical properties showed that the 10% nanohydroxyapatite group had the best compressive modulus and compressive strength. (4) The results of drug release properties showed that the cumulative release rate of aspirin decreased with the increase of nano-hydroxyapatite, but the drug burst release rate decreased and the sustained release time prolonged. (5) The results of swelling properties and degradation properties showed that with the increase of nano-hydroxyapatite, the swelling rate and degradation rate of hydrogel scaffolds of each group decreased. (6) Using the hydrogel scaffold extract to culture mouse pre-osteoblasts, the results of cell proliferation and cytotoxicity experiments showed that the hydrogel scaffold extract could promote cell proliferation, without cytotoxicity. (7) It is concluded that 10% nanohydroxyapatite hydrogel scaffolds have better bionic characterization and biocompatibility, and are expected to be used as bone tissue engineering scaffolds for further studies of osteogenesis and immunomodulatory potential. [ABSTRACT FROM AUTHOR]

Background: Hydrogel scaffold is a biomaterial that can facilitate cells in forming a tissue structure. It can promote cell adhesion, migration, and proliferation. Further research to find a new scaffold from natural resources is challenging, so this study aimed to characterize a hydrogel composite scaffold, which has the potential to be used as a regenerative material. Methods: The formulation of HAp-Col-EGCG was mixed with different ratios of 1%, 2%, and 4% hydroxyapatite. We analyzed its injectability, pH, and gelation time. Scanning electron microscopy (SEM), energy X-ray Spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FTIR) were used to evaluate the surface morphologies, element composition, and chemical properties of HAp-Col-EGCG. Results: The results showed that the injectability test was almost 90 % in all groups. There was no significant difference in the median value of the pH at 0, 20, and 60 min in all groups, but there was a significant difference at 40 min. The average gelation times in all groups were not significant. SEM-EDX showed a microporous scaffold, with the HAp particles well distributed in the collagen pores at a ratio of 1.9, 2.29, and 1.89 Ca/P. The FTIR results showed intermolecular bonds in the HAp-Col-EGCG scaffold. The X-ray diffraction analysis showed that collagen and EGCG did not affect the crystal structure and size of HAp. Cytotoxicity test showed more dental pulp cell viability at the 4 % HAp concentration at 514.35 ± 15.45. Conclusion: This study indicates that hydrogel scaffold from eggshell hydroxyapatite, collagen, and EGCG has a high potential for pulp regenerative therapy.

Multicellular tumour cell spheroids embedded within three‐dimensional (3D) hydrogels or extracellular matrices (ECM) are widely used as models to study cancer growth and invasion. Standard methods to embed spheroids in 3D matrices result in random placement in space which limits the use of inverted fluorescence microscopy techniques, and thus the resolution that can be achieved to image molecular detail within the intact spheroid. Here, we leverage UV photolithography to microfabricate PDMS (polydimethylsiloxane) stamps that allow for generation of high‐content, reproducible well‐like structures in multiple different imaging chambers. Addition of multicellular tumour spheroids into stamped collagen structures allows for precise positioning of spheroids in 3D space for reproducible high‐/super‐resolution imaging. Embedded spheroids can be imaged live or fixed and are amenable to immunostaining, allowing for greater flexibility of experimental approaches. We describe the use of these spheroid imaging chambers to analyse cell invasion, cell–ECM interaction, ECM alignment, force‐dependent intracellular protein dynamics and extension of fine actin‐based protrusions with a variety of commonly used inverted microscope platforms. This method enables reproducible, high‐/super‐resolution live imaging of multiple tumour spheroids, that can be potentially extended to visualise organoids and other more complex 3D in vitro systems. LAY DESCRIPTION: Small groups of cancer cells can be embedded into a 3D scaffold to mimic cancer invasion seen in patients. Microscopy is a valuable tool for analysing cancer cell invasion in these models but is often limited by the level of detail achievable. Here, we present a method to achieve enhanced imaging of these processes by gaining control of the positioning of these cancer cell groups. This will improve understanding of the details of how cancer cells invade. [ABSTRACT FROM AUTHOR]

Cartilage tissue engineering has attracted great attention in defect repair and regeneration. The utilization of bioactive scaffolds to effectively regulate the phenotype and proliferation of chondrocytes has become an elemental means for cartilage tissue regeneration. On account of the simultaneous requirement of mechanical and biological performances for tissue-engineered scaffolds, in this work we prepared a naturally derived hydrogel composed of a bioactive kartogenin (KGN)-linked chitosan (CS-KGN) and an aldehyde-modified oxidized alginate (OSA) via the highly efficient Schiff base reaction and multifarious physical interactions in mild conditions. On the basis of the rigid backbones and excellent biocompatibility of these two natural polysaccharides, the composite hydrogel demonstrated favorable morphology, easy injectability, good mechanical strength and tissue adhesiveness, low swelling ratio, long-term sustainable KGN release, and facilitated bone marrow mesenchymal stem cell activity, which could simultaneously provide the mechanical and biological supports to promote chondrogenic differentiation and repair the articular cartilage defects. Therefore, we believe this work can offer a designable consideration and potential alternative candidate for cartilage and other soft tissue implants. [ABSTRACT FROM AUTHOR]

Hernia reconstruction is one of the most frequently practiced surgical procedures worldwide. Plastic surgery plays a pivotal role in reestablishing desired abdominal wall structure and function without the drawbacks traditionally associated with general surgery as excessive tension, postoperative pain, poor repair outcomes, and frequent recurrence. Surgical meshes have been the preferential choice for abdominal wall hernia repair to achieve the physical integrity and equivalent components of musculofascial layers. Despite the relevant progress in recent years, there are still unsolved challenges in surgical mesh design and complication settlement. This review provides a systemic summary of the hernia surgical mesh development deeply related to abdominal wall hernia pathology and classification. Commercial meshes, the first-generation prosthetic materials, and the most commonly used repair materials in the clinic are described in detail, addressing constrain side effects and rational strategies to establish characteristics of ideal hernia repair meshes. The engineered prosthetics are defined as a transit to the biomimetic smart hernia repair scaffolds with specific advantages and disadvantages, including hydrogel scaffolds, electrospinning membranes, and three-dimensional patches. Lastly, this review critically outlines the future research direction for successful hernia repair solutions by combing state-of-the-art techniques and materials.

Traditional cancer treatment is confronted with the problem of limited therapeutic effect, tissue defects, and lack of drug screening. Hydrogel scaffolds from biological macromolecules based on microfluidic technology are a promising candidate, which can mimic tumor microenvironments to screen personalized drugs, promote the regeneration of healthy tissues, and deliver drugs for enhanced localized antitumor treatment. This review summarizes the latest research on the composition of biomacromolecular hydrogel scaffolds, the architecture of hydrogel scaffolds from microfluidic technology, and their application in cancer therapy, including anti-tumor drug screening, anti-tumor treatment, and anti-tumor treatment and tissue repair. In addition, the potential breakthroughs of this innovative platform in the clinical transformation of cancer therapy are further discussed. The insights revealed in this review are intended to guide the utilization of microfluidic technology-based biomacromolecular hydrogel scaffolds in cancer therapy. [Display omitted] • We introduce composition and structure of biomacromolecular hydrogel scaffolds. • We present the applications of microfluidic hydrogel scaffolds in cancer therapy. • This review offers guidance in hydrogel scaffolds for enhanced cancer therapy. [ABSTRACT FROM AUTHOR]

Terminology is pivotal for facilitating clear communication and minimizing ambiguity, especially in specialized fields such as chemistry. In materials science, a subset of chemistry, the term “pore” is traditionally linked to the International Union of Pure and Applied Chemistry (IUPAC) nomenclature, which categorizes pores into “micro”, “meso”, and “macro” based on size. However, applying this terminology in closely-related areas, such as 3D bioprinting, often leads to confusion owing to the lack of consensus on specific definitions and classifications tailored to each field. This review article critically examines the current use of pore terminology in the context of 3D bioprinting, highlighting the need for reassessment to avoid potential misunderstandings. We propose an alternative classification that aligns more closely with the specific requirements of bioprinting, suggesting a tentative size-based division of interconnected pores into ‘parvo’-(d < 25 µm), ‘medio’-(25 < d < 100 µm), and ‘magno’-(d > 100 µm) pores, relying on the current understanding of the pore size role in tissue formation. The introduction of field-specific terminology for pore sizes in 3D bioprinting is essential to enhance the clarity and precision of research communication. This represents a step toward a more cohesive and specialized lexicon that aligns with the unique aspects of bioprinting and tissue engineering.

Neural stem cell (NSC) has gained considerable attention in traumatic brain injury (TBI) treatment because of their ability to replenish dysfunctional neurons and stimulate endogenous neurorestorative processes. However, their therapeutic effects are hindered by the low cell retention rate after transplantation into the dynamic brain. In this study, we found cerebrospinal fluid (CSF) flow after TBI is an important factor associated with cell loss following NSC transplantation. Recently, several studies have shown that hydrogels could serve as a beneficial carrier for stem cell transplantation, which provides a solution to prevent CSF flow-induced cell loss after TBI. For this purpose, we evaluated three different hydrogel scaffolds and found the gelatin methacrylate (GelMA)/sodium alginate (Alg) (GelMA/Alg) hydrogel scaffold showed the best capabilities for NSC adherence, growth, and differentiation. Additionally, we detected that pre-differentiated NSCs, which were loaded on the GelMA/Alg hydrogel and cultured for 7 days in neuronal differentiation medium (NSC [7d]), had the highest cell retention rate after CSF impact. Next, the neuroprotective effects of the NSC-loaded GelMA/Alg hydrogel scaffold were evaluated in a rat model of TBI. NSC [7d]-loaded GelMA/Alg markedly decreased microglial activation and neuronal death in the acute phase, reduced tissue loss, alleviated astrogliosis, promoted neurogenesis, and improved neurological recovery in the chronic phase. In summary, we demonstrated that the integration with the GelMA/Alg and modification of NSC differentiation could inhibit the influence of CSF flow on transplanted NSCs, leading to increased number of retained NSCs and improved neuroprotective effects, providing a promising alternative for TBI treatment.

Introduction: Current regenerative endodontic treatment approaches preserve pulp vitality and use tissue engineering concepts. One of the essential factors in pulp tissue engineering is a scaffold. In several reviews, direct bioactive material applied to the pulp without using scaffold will cause the temporary release, which was unstable. The scaffold can increase the success of pulp vital therapy treatment because the scaffold can facilitate stem cells to adhere, proliferate, differentiate and support regeneration. Hydrogel scaffold is considerable because it can mimicks extracellular matrix (ECM). It should have several essential characterizations, and one of them is biodegradable ability. New composite hydrogel scaffolds were developed as an organic and inorganic material hybrid. Objective: To compare the biodegradation value of Col-HA-EGCG hydrogel scaffold on days 3 and 7 after immersion. Materials and Methods: Samples were synthesized with the mixing of 1% hydroxyapatite solution and collagen solution until homogen, added 10 µmol/L EGCG into the solution. After that, 2% HPMC was used to stable the gelling process. Samples were freeze-dried for 24 hours and immersed in Phosphate Buffer Salin containing 1,6µg/ml of lysozyme enzyme. The degradation value percentages determined by measuring the difference weight of dry scaffold before and after immersion. Results: The data were analyzed by T-test, and it showed the Col-HA-EGCG hydrogel scaffold can be degraded, and there were no significant biodegradation values in 3 and 7 days. Conclusions: The Col-HAEGCG is biodegradable in lysozyme enzyme. The biodegradation rate on Col-HA-EGCG scaffold on 3 and 7 days were not significant. [ABSTRACT FROM AUTHOR]

Biomimetic brain structures and artificial neural networks have provided a simplified strategy for quantitatively investigating the complex structural and functional characteristics of highly interconnected neural networks. To achieve this, three-dimensional (3D) cell culture approaches have attracted much attention, which can mimic cell-cell interactions at the organism level and help better understand the function of specific neurons and neuronal networks than traditional two-dimensional cell culture methods. However, 3D scaffolds similar to the natural extracellular matrix to support the culturing, recording, and manipulation of neurons have long been an unresolved challenge. To resolve this, 3D hydrogel scaffolds can be fabricated via an innovative thermal treatment followed by an esterification process. A highly porous microstructure was formed within the bulk hydrogel scaffold, which showed a high porosity of 91% and a low Young's modulus of 6.11 kPa. Due to the merits of the fabricated hydrogel scaffolds, we constructed 3D neural networks and detected spontaneous action potentials in vitro. We successfully induced seizure-like waveforms in 3D cultured neurons and suppressed hyperactivated discharges by selectively activating γ-aminobutyric acid-ergic (GABAergic) interneurons. These results prove the advantages of our hydrogel scaffolds and demonstrate their application potential in the accurate dissection of neural circuits, which may help develop effective treatments for various neurological disorders. While 3D cell culture approaches have attracted much attention and offer more advantages than two-dimensional cell culture methods, 3D scaffolds similar to the natural extracellular matrix to support the culturing, recording, and manipulation of neurons have long been an unresolved challenge. Herein, we developed a simplified and low-cost strategy for fabricating highly porous and cytocompatible hydrogel scaffolds for the construction of three-dimensional (3D) neural networks in vitro. The cultured 3D neural networks can mimic the in vivo connection among different neuron subgroups and help accurately dissect and manipulate the structure and function of specific neural circuits. [Display omitted] [ABSTRACT FROM AUTHOR]

The number of cases of cartilage damage worldwide is increasing annually and this problem severely limits an individual's physical activities, subsequently contributing to additional medical problems. Hydrogels can repair cartilage defects and promote cartilage regeneration. In this study, a composite hydrogel scaffold was prepared with collagen (COL), carboxymethyl chitosan (CMC), and the Arg-Gly-Asp (RGD) peptide through one-step chemical crosslinking, in which the three compositions ratio was especially investigated. The hydrogel scaffold performed well in cell adhesion and biocompatibility experiments, mainly due to the favorable porosity (the aperture was concentrated at 100 μm and the porosity was >70 %) and RGD concentration (2 mM RGD was the optimal concentration, which could effectively improve the attachment of BMSCs to the stent). Moreover, bone marrow mesenchymal stem cells (BMSCs) filled in the hydrogel scaffold, together with transforming growth factor TGF-β3, which was applied to evaluate the feasibility on the repair of the injured cartilage of the rat. In vitro and in vivo study, according to the results of cell proliferation and cytotoxicity, the hydrogel material had no toxic effect on cells, and the COL2/CMC1 hydrogel scaffold had the most obvious role in promoting cell proliferation. The results of pathological section showed that the cell scaffold complex group provided good mechanical properties for the wound and supplemented the stem cells derived from chondrocytes and showed good cartilage defect repair effect; In the scaffold group, the surface fibrosis of the injured area was mainly filled with fibrocartilage and other collagen fibers The hydrogel/BMSCs complex based on COL and CMC can be beneficial for the regeneration of cartilage. [ABSTRACT FROM AUTHOR]

This study investigates the therapeutic potential of Msx1-overexpressing bone marrow mesenchymal stem cells (BMSCs) in enhancing tendon-bone healing in rotator cuff injuries. BMSCs were genetically modified to overexpress Msx1 and were evaluated in vitro for their proliferation, migration, and differentiation potential. Results demonstrated that Msx1 overexpression significantly increased BMSC proliferation and migration while inhibiting osteogenic and chondrogenic differentiation. In a rat model of acute rotator cuff injury, Msx1-BMSCs embedded in a hydrogel scaffold were implanted at the tendon-bone junction. Micro-CT analysis revealed substantial new bone formation in the Msx1-BMSC group, and histological evaluation showed organized collagen and cartilage structures at the repair site. Biomechanical testing further confirmed enhanced structural strength in the Msx1-BMSC-treated group. These findings suggest that Msx1 modification enhances BMSC-mediated repair by promoting cell proliferation and migration, facilitating tendon-bone integration. This Msx1-based approach presents a promising strategy for advancing regenerative therapies for rotator cuff injuries., (© 2024 Orthopaedic Research Society.)

Bioprinting has emerged as a powerful manufacturing platform for tissue engineering, enabling the fabrication of 3D living structures by assembling living cells, biological molecules, and biomaterials into these structures. Among various biomaterials, hydrogels have been increasingly used in developing bioinks suitable for 3D bioprinting for diverse human body tissues and organs. In particular, hydrogel blends combining gelatin and gelatin methacryloyl (GelMA; "GG hydrogels") receive significant attention for 3D bioprinting owing to their many advantages, such as excellent biocompatibility, biodegradability, intrinsic bioactive groups, and polymer networks that combine the thermoresponsive gelation feature of gelatin and chemically crosslinkable attribute of GelMA. However, GG hydrogels have poor electroactive properties, which hinder their applications in neural tissue engineering where electrical conductivity is required. To overcome this problem, in this study, a small amount of highly electroactive graphene oxide (GO) was added in GG hydrogels to generate electroactive hydrogels for 3D bioprinting in neural tissue engineering. The incorporation of GO nanoparticles slightly improved mechanical properties and significantly increased electrical conductivity of GG hydrogels. All GO/GG composite hydrogels exhibited shear thinning behavior and sufficient viscosity and hence could be 3D printed into 3D porous scaffolds with good shape fidelity. Furthermore, bioinks combining rat bone marrow-derived mesenchymal stem cells (rBMSCs) with GO/GG composite hydrogels could be 3D bioprinted into GO/GG constructs with high cell viability. GO nanoparticles in the constructs provided ultraviolet (UV) shading effect and facilitated cell survival during UV exposure after bioprinting. The GO/GG composite hydrogels appear promising for 3D bioprinting applications in repairing damaged neural tissues., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

In vitro three-dimensional (3D) skin tissue models are critical tools in advancing our understanding of basic skin physiology and function as well as in specific applications such as toxicity testing of dermatological compounds. However, the utilization of such skin models is often limited by the structural instability of the construct, lack of physiologically relevant features and weak barrier function. In this review, we highlight the current research efforts in hydrogel biomaterial selection and scaffold design that allow for maturation of engineered skin in vitro , with special emphasis on matured full-thickness (including epidermal and dermal compartments) skin. The different types of scaffold biomaterials, broadly categorized as natural, synthetic, or composite will also be discussed. At the same time, we will outline strategies for next-generation biomimetic skin templates incorporating skin appendages or perfusion systems that can more closely reflect the native skin environment. In vitro 3D human skin models are critical tools in advancing our understanding of skin physiology and function. Many of the existing reconstructed models are limited in terms of structure and complexity, thus failing to recapitulate native human skin. In order to address this, hydrogels have been identified as useful scaffold materials for fabricating the dermal equivalent of 3D skin models, allowing for greater flexibility and control in scaffold properties and cellular incorporation. This review aims to provide a critical discussion of the biomaterial selection and design strategies in the construction of hydrogel-based full-thickness skin equivalents. At the same time, we will offer insights into the future developments and technological advances which can accelerate the progress in this field. [Display omitted] [ABSTRACT FROM AUTHOR]

Complex shaped bone defects that need to be filled are very common in clinic. But after filling, gaps are inevitably left between substitutes and host bone due to the poor conformability of preformed implants, hence hindering bone regeneration. Therefore, based on our previous study, we here used the bioink (named PPG) composed of polyurethane, polyacrylamide, and gelatin with optimized composition ratio to three‐dimensionally (3D) print an inorganic/organic composite hydrogel scaffold with self‐expandability to fill irregular bone defects and bioactivity to accelerate bone healing through adjusting the content of bioactive ceramic (BC). The results indicated that, the 3D printed BC/PPG scaffold had a rough surface on each fiber; with the incorporation of BC powders, the composite hydrogel scaffolds in swelling experiments could perform a comparable self‐adaptability to PPG hydrogel scaffold; the bioactive ions including Ca, Mg, and Si could be released from the composite scaffold and induce the rapid deposition of bone‐like apatite. The mechanical tests proved that the BC(10%)/PPG scaffold was the top performer under compression. The in vitro cell assessment illustrated that compared with PPG hydrogel scaffold, the BC/PPG composite scaffolds were more favorable to the proliferation and spreading of bone mesenchymal stem cells (BMSCs). [ABSTRACT FROM AUTHOR]

The ability to noninvasively assess skeletal muscle microstructure, which predicts function and disease, would be of significant clinical value. One method that holds this promise is diffusion tensor magnetic resonance imaging (DT-MRI), which is sensitive to the microscopic diffusion of water within tissues and has become ubiquitous in neuroimaging as a way of assessing neuronal structure and damage. However, its application to the assessment of changes in muscle microstructure associated with injury, pathology, or age remains poorly defined, because it is difficult to precisely control muscle microstructural features in vivo. However, recent advances in additive manufacturing technologies allow precision-engineered diffusion phantoms with histology informed skeletal muscle geometry to be manufactured. Therefore, the goal of this study was to develop skeletal muscle phantoms at relevant size scales to relate microstructural features to MRI-based diffusion measurements. A digital light projection based rapid 3D printing method was used to fabricate polyethylene glycol diacrylate based diffusion phantoms with (1) idealized muscle geometry (no geometry; fiber sizes of 30, 50, or 70 μm or fiber size of 50 μm with 40% of walls randomly deleted) or (2) histology-based geometry (normal and after 30-days of denervation) containing 20% or 50% phosphate-buffered saline (PBS). Mean absolute percent error (8%) of the printed phantoms indicated high conformity to templates when "fibers" were >50 μm. A multiple spin-echo echo planar imaging diffusion sequence, capable of acquiring diffusion weighted data at several echo times, was used in an attempt to combine relaxometry and diffusion techniques with the goal of separating intracellular and extracellular diffusion signals. When fiber size increased (30-70 μm) in the 20% PBS phantom, fractional anisotropy (FA) decreased (0.32-0.26) and mean diffusivity (MD) increased (0.44 × 10-3 mm2/s-0.70 × 10-3 mm2/s). Similarly, when fiber size increased from 30 to 70 μm in the 50% PBS diffusion phantoms, a small change in FA was observed (0.18-0.22), but MD increased from 0.86 × 10-3 mm2/s to 1.79 × 10-3 mm2/s. This study demonstrates a novel application of tissue engineering to understand complex diffusion signals in skeletal muscle. Through this work, we have also demonstrated the feasibility of 3D printing for skeletal muscle with relevant matrix geometries and physiologically relevant tissue characteristics.

Skin wound healing is a principal clinical challenge, and it is necessary to develop effective alternative treatments. Excessive inflammatory response is linked to delayed healing. This study was the first to report a multi-functional chitosan/sodium alginate/velvet antler blood peptides (VBPs) hydrogel (CAVBPH) and explore its potential mechanism to promote wound healing. The results showed that CAVBPH possessed desirable characteristics including thermo-sensitivity, antioxidation, antibacterial activity, biosafety, VBPs release behavior, etc., and significantly accelerated skin wound healing in mice. Specifically, the CAVBPH treatment enhanced cell proliferation, angiogenesis, and extracellular matrix (ECM) secretion, and also relieved inflammation at the wound site compared to the PBS-treated group and blank hydrogel scaffold-treated group. Mechanistically, the efficacy of CAVBPH might be related to the activation of the PI3K/AKT/mTOR and SIRT1/NF-κB pathways. Overall, CAVBPH seems to be a promising therapy for skin repair, probably relying on the abundant short-chain peptides in VBPs. [ABSTRACT FROM AUTHOR]

In tissue engineering, hydrogel scaffolds allow various cells to be cultured and grown in vitro and then implanted to repair or replace the damaged areas. Here in this work, kartogenin (KGN), an effectively chondro-inductive non-protein bioactive drug molecule, was incorporated into a composite hydrogel comprising the positively charged chitosan (CS) and methacrylated gelatin (GelMA) polymers to fabricate appropriate microenvironments of bone marrow mesenchymal stem cells (BMSCs) for cartilage regeneration. Based on the combination of physical chain entanglements and chemical crosslinking effects, the resultant GelMA-CS@KGN composite hydrogels possessed favorable network pores and mechanical strength. In vitro cytotoxicity showed the excellent biocompatibility for facilitating the cell growth, adhesion, proliferation, and differentiation. The long-term sustainable KGN release from the hydrogel scaffolds in situ promoted the chondrogenic differentiation that can be employed as an alternative candidate for cartilage tissue regeneration. [ABSTRACT FROM AUTHOR]

Skin wound healing is a principal clinical challenge, and it is necessary to develop effective alternative treatments. Excessive inflammatory response is linked to delayed healing. This study was the first to report a multi-functional chitosan/sodium alginate/velvet antler blood peptides (VBPs) hydrogel (CAVBPH) and explore its potential mechanism to promote wound healing. The results showed that CAVBPH possessed desirable characteristics including thermo-sensitivity, antioxidation, antibacterial activity, biosafety, VBPs release behavior, etc., and significantly accelerated skin wound healing in mice. Specifically, the CAVBPH treatment enhanced cell proliferation, angiogenesis, and extracellular matrix (ECM) secretion, and also relieved inflammation at the wound site compared to the PBS-treated group and blank hydrogel scaffold-treated group. Mechanistically, the efficacy of CAVBPH might be related to the activation of the PI3K/AKT/mTOR and SIRT1/NF-κB pathways. Overall, CAVBPH seems to be a promising therapy for skin repair, probably relying on the abundant short-chain peptides in VBPs.

In tissue engineering, hydrogel scaffolds allow various cells to be cultured and grown in vitro and then implanted to repair or replace the damaged areas. Here in this work, kartogenin (KGN), an effectively chondro-inductive non-protein bioactive drug molecule, was incorporated into a composite hydrogel comprising the positively charged chitosan (CS) and methacrylated gelatin (GelMA) polymers to fabricate appropriate microenvironments of bone marrow mesenchymal stem cells (BMSCs) for cartilage regeneration. Based on the combination of physical chain entanglements and chemical crosslinking effects, the resultant GelMA-CS@KGN composite hydrogels possessed favorable network pores and mechanical strength. In vitro cytotoxicity showed the excellent biocompatibility for facilitating the cell growth, adhesion, proliferation, and differentiation. The long-term sustainable KGN release from the hydrogel scaffolds in situ promoted the chondrogenic differentiation that can be employed as an alternative candidate for cartilage tissue regeneration.

A new prototype of hybrid silk fibroin and sodium alginate (SF-SA) based osteogenic hydrogel scaffold with a concentration of 2.5% magnesium phosphate (MgP) based gel was prepared with the assistance of an extrusion-based three-dimensional (3D) printing machine in this study. To determine the optimum ratio of MgP-based gel in the hydrogel, a series of physical and biochemical experiments were performed to determine the proper concentration of MgP in two-dimensional hydrogel films, as well as the cell compatibility with these materials in sequence. The SF-SA hydrogel with 2.5wt% magnesium phosphate (SF-SA/MgP) stood out and then was used to fabricate 3D hydrogel scaffolds according to the consequences of the experiments, with SF-SA hydrogel as a control. Then the morphology and osteogenic activity of the scaffolds were further characterized by field emission scanning electron microscope (SEM), calcium mineralization staining, and reverse transcription-polymerase chain reaction (rt-PCR). The SF-SA/MgP hydrogel scaffold promoted the adhesion of rat mesenchymal stem cells with higher degrees of efficiency under dynamic culture conditions. After co-culturing in an osteogenic differentiation medium, cells seeded on SF-SA/MgP hydrogel scaffold were shown to have better performance on osteogenesis in the early stage than the control group. This work illustrates that the 3D structures of hybrid SF-SA/MgP hydrogel are promising headstones for osteogenic tissue engineering.

Pulp dentin complex regeneration can be initiated by hydrogel scaffold application in the pulp using tissue engineering concept and it gives many advantages. Excavation in deep dental caries, dental trauma, and iatrogenic reasons are several causes of dental pulp exposure that can affect the pulp vitality. It is crucial to maintain the pulp vitality because it can support the tooth survival by avoiding endodontic treatment which affect the resistance of tooth structure. Pulp vitality can be preserved by inducing pulp regeneration using appropriate material. New approach in endodontic regeneration is using tissue engineering concept with hydrogel scaffold, stem cells and growth factors mechanism. Hydrogel scaffold as three-dimensional media can provide cell homing process in pulp dentin complex and may support adhesion of stem cells to differentiate and initiate growth factors release. Based on several studies, hydrogel scaffold can be formulated to support dental pulp regeneration using tissue engineering concept. Many favorable conditions can be achieved such as acts as delivery drug factor with easy injectable application in tooth and it has a lot of potential in dental pulp tissue regeneration treatment. [ABSTRACT FROM AUTHOR]

The functional recovery of peripheral nerve injury (PNI) is unsatisfactory, whereas diabetes mellitus (DM) and its related complications further attenuate the restoration of diabetic PNI (DPNI). Adipose-derived stem cells (ADSCs) are promising candidates for treatment of DPNI due to their abundant source, excellent differentiation and paracrine ability. Our results showed that ADSCs remarkably enhanced the proliferation and migration of Schwann cells and endothelial cells, and tube formation. Mechanistically, ADSCs could regulate Nrf2/HO-1, NF-κB and PI3K/AKT/mTOR signaling pathways, showing multiple functions in reducing oxidative stress and inflammation, and regulating cell metabolism, growth, survival, proliferation, angiogenesis, differentiation of Schwann cell and myelin formation. In current study, novel graphene foam (GF)/hydrogel-based scaffold was developed to deliver ADSCs for treatment of DPNI. GF/hydrogel scaffold exhibited excellent mechanical strength, suitable porous network, superior electrical conductivity, and good biocompatibility. In vitro results revealed that GF/hydrogel scaffold could obviously accelerate proliferation of Schwann cells. Moreover, in vivo experiments demonstrated that ADSCs-loaded GF/hydrogel scaffold significantly promoted the recovery of DPNI and inhibited the atrophy of targeted muscles, thus providing a novel and attractive therapeutic approach for DPNI patients. [ABSTRACT FROM AUTHOR]

Bone defect repair and tissue engineering is specifically challenging process because of the distinctive morphological and structural behaviours of natural bone with complex healing and biochemical mechanisms. In the present investigation, we designed dopamine adhesive chemistry-based fabrication of silk fibroin hydrogel (SFD) with incorporation of nano-hydroxyapatite (nHA)-graphene oxide (GO) hybrid nanofillers with well-arranged porous morphology immobilized with bone morphogenic protein-2 (BMP-2) for the effective in vitro rabbit bone marrow derived mesenchymal stem cells loading compatibility and in vivo new bone regrowth and collagen deposition ability. We have achieved bone-specific hydrogel scaffolds with upgraded structural features, mechanical properties and particularly promoted in vitro osteogenic differentiation and compatibility of rabbit bone marrow mesenchymal stem cells (rBMSCs). Structural and microscopic analyses established greater distributions of components and well-ordered and aligned porous structure of the hydrogel network. In vivo result of new bone regrowth was promisingly higher in the Bm@nHG-SFD hydrogel (85%) group as compared to the other treatment groups of nHG-SFD (77%) and nH-SFD (64%) hydrogel. Overall, we summarized that morphologically improved hydrogel material with immobilization of BMP-2 could be have more attentions for new generation bone regeneration therapies. [Display omitted] • Newly designed dopamine adhesive chemistry-based SF hydrogel • Hydrogel functionalized with nHA-GO) hybrid nanofillers to enhance bioactivity. • BMP-2 immobilization on hydrogel structure improved rBMSCs osteogenic differentiation. • This material could be effective for new generation bone defect repair. [ABSTRACT FROM AUTHOR]

Abstract To produce polysaccharide-based hydrogels and cerium (Ce3+) doped hydroxyapatite plus chitosan and collagen to enable future applications in the treatment of joint degeneration. Hydrogel production and characterization were performed with Fourier transform infrared spectroscopy (FTIR), thermogravimetry analysis (TGA) and cytotoxicity testing with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. A final biomaterial composition was Kelcogel® Gelana (58%), chitosan (22.3%), Ce3+ doped hydroxyapatite (10.7%) and bovine collagen (9%), or selected aspect material gelatinous physical color with whitish color and can be injected. The biomaterial composition was proven in the FTIR and TGA, which also provided the maximum supported temperature. In the MTT assay, despite the reduction in viability of the experimental group compared to the control group, cell viability remained approximately 90%. In the FTIR and TGA tests, the material composition was proven. The material does not present cytotoxic behavior for the MTT test, being an alternative for the treatment of joint diseases.

Bipolar electrochemistry successfully realized the electrodeposition of calcium alginate hydrogels in specific target areas in tissue engineering. However, the shape and quantity of three-dimensional cannot be accurately controlled. We presented a novel growth model for fabricating hydrogels based on bipolar electrochemical by patterned bipolar electrodes using photolithography. This work highlights pattern customization and quantitative control of hydrogels in cell culture platforms. Furthermore, alginate hydrogels with different heights can be controlled by adjusting the key parameters of the growth model. This strategy exhibits promising potential for cell-oriented scaffolds in tissue engineering. [ABSTRACT FROM AUTHOR]

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[Display omitted] • Neurological injuries might be repaired by replacing cells and nerve tissue. • 3D scaffolds as in vitro platform hold great potential for bioapplication. • Human breast milk is a novel noninvasive source of stem cells for cell therapy. • Integrating advanced material with stem cells may improve cell functions. The extracellular matrix is recognized as an efficient and determining component in the growth, proliferation, and differentiation of cells due to its ability to perceive and respond to environmental signals. Applying three-dimensional scaffolds can create conditions similar to the extracellular matrix and provide an opportunity to investigate cell fate. In this study, we employed the PuraMatrix hydrogel scaffold as an advanced cell culture platform for the neural differentiation of stem cells derived from human breastmilk to design an opportune model for tissue engineering. Isolated stem cells from breastmilk were cultured and differentiated into neural-like cells on PuraMatrix peptide hydrogel and in the two-dimensional system. The compatibility of breastmilk-derived stem cells with PuraMatrix and cell viability was evaluated by scanning electron microscopy and MTT assay, respectively. Induction of differentiation was achieved by exposing cells to the neurogenic medium. After 21 days of the initial differentiation process, the expression levels of glial fibrillary acidic protein (GFAP), microtubule-associated protein (MAP2), β-tubulin III, and neuronal nuclear antigen (NeuN) were analyzed using the immunostaining technique. The results illustrated a notable expression of MAP2, β-tubulin-III, and NeuN in the three-dimensional cell culture in comparison to the two-dimensional system, indicating the beneficial effect of PuraMatrix scaffolds in the process of differentiating breastmilk-derived stem cells into neural-like cells. In view of the obtained results, the combination of breastmilk-derived stem cells and PuraMatrix hydrogel scaffold could be an advisable preference for neural tissue regeneration and cell therapy. [ABSTRACT FROM AUTHOR]

The optimal material for repairing skull defects should exhibit outstanding biocompatibility and mechanical properties. Specifically, hydrogel scaffolds that emulate the microenvironment of the native bone extracellular matrix play a vital role in promoting osteoblast adhesion, proliferation, and differentiation, thereby yielding superior outcomes in skull reconstruction. In this study, a composite network hydrogel comprising sodium alginate (SA), epigallocatechin gallate (EGCG), and zinc ions (Zn2+) was developed to establish an ideal osteogenic microenvironment for bone regeneration. Initially, physical entanglement and hydrogen bonding between SA and EGCG resulted in the formation of a primary network hydrogel known as SA-EGCG. Subsequently, the inclusion of Zn2+ facilitated the creation of a composite network hydrogels named SA-EGCG-Zn2+ via dynamic coordination bonds with SA and EGCG. The engineered SA-EGCG2 %-Zn2+ hydrogels offered an environment mimicking the native extracellular matrix (ECM). Moreover, the sustained release of Zn2+ from the hydrogel effectively enhanced cell adhesion, promoted proliferation, and stimulated osteoblast differentiation. In vitro experiments have shown that SA-EGCG2 %-Zn2+ hydrogels greatly enhance the attachment and growth of osteoblast precursor cells (MC3T3-E1), while also increasing the expression of genes related to osteogenesis in these cells. Additionally, in vivo studies have confirmed that SA-EGCG2 %-Zn2+ hydrogels promote new bone formation and accelerate the regeneration of bone in situ, indicating promising applications in the realm of bone tissue engineering. [Display omitted] • The physical/chemical cross-linking gives the hydrogel good mechanical properties. • Hydrogel has antioxidant, antibacterial and osteogenic differentiation properties. • The hydrogel provides a suitable biological microenvironment for cell growth. • Hydrogel releases zinc ions slowly to promote the repair of skull defects in rats. [ABSTRACT FROM AUTHOR]

The controlled delivery of the bone morphogenetic protein-2 (BMP-2) with tracking ability would overcome most of the side effects linked to the burst release and uncontrolled delivery of this growth factor for bone regeneration. Herein, BMP-2-conjugated carbon dots (CDs) was used as noninvasive detection platforms to deliver BMP-2 for therapeutic applications where osteogenesis and bioimaging are both required. With this in mind, the present work aimed to develop a controlled BMP-2-CDs release system using composite scaffolds containing BMP-2-CDs loaded pectin microparticles, which had been optimized for bone regeneration. By using microfluidic approach, we encapsulated BMP-2-CDs in pectin microparticles with narrow size distribution and then incorporated into composite scaffolds composed of gelatin, elastin, and hyaluronic acid. The BMP-2-CDs was released from the composite scaffolds in a sustained fashion for up to 21 days exhibited a high controlled delivery capacity. When tested in vitro with MG-63 cells, these extraction mediums showed the intercellular uptake of BMP-2-CDs and enhanced biological properties and pro-osteogenic effect. By utilizing the pectin microparticles carrying BMP-2-CDs as promising bioimaging agents for growth factor delivery and by tuning the composition of the scaffolds, this platform has immense potential in the field of bone tissue regeneration. [ABSTRACT FROM AUTHOR]

A thermosensitive quaternary ammonium chloride chitosan/β-glycerophosphate (HACC/β-GP) hydrogel scaffold combined with bone marrow mesenchymal stem cells (BMSCs) transfected with an adenovirus containing the glial cell-derived neurotrophic factor (GDNF) gene (Ad-rGDNF) was applied to spinal cord injury (SCI) repair. The BMSCs from rats were transfected with Ad-rGDNF, resulting in the expression of GDNF mRNA in the BMSCs increasing and their spontaneous differentiation into neural-like cells expressing neural markers such as NF-200 and GFAP. After incubation with HACC/β-GP hydrogel scaffolds for 2 weeks, neuronal differentiation of the BMSCs was confirmed using immunofluorescence (IF), and the expression of GDNF by the BMSCs was detected by Western blot at different time points. MTT assay and scanning electron microscopy confirmed that the HACC scaffold provides a non-cytotoxic microenvironment that supports cell adhesion and growth. Rats with SCI were treated with BMSCs, BMSCs carried by the HACC/β-GP hydrogel (HACC/BMSCs), Ad-rGDNF-BMSCs, or Ad-rGDNF-BMSCs carried by the hydrogel (HACC/GDNF-BMSCs). Animals were sacrificed at 2, 4, and 6 weeks of treatment. IF staining and Western blot were performed to detect the expression of NeuN, NF-200, GFAP, CS56, and Bax in the lesion sites of the injured spinal cord. Upon treatment with HACC/BMSCs, NF200 and GFAP were upregulated but CS56 and Bax were downregulated in the SCI lesion site. Furthermore, transplantation of HACC/GDNF-BMSCs into an SCI rat model significantly improved BBB scores and regeneration of the spinal cord. Thus, HACC/β-GP hydrogel scaffolds show promise for functional recovery in spinal cord injury patients. [ABSTRACT FROM AUTHOR]

Keywords: hydrogel scaffold; MDS-L; MDS-L-2007; MDS-LGF; myelodysplastic syndromes (MDS); NSG mice; NSGS mice; xenograft mouse model EN hydrogel scaffold MDS-L MDS-L-2007 MDS-LGF myelodysplastic syndromes (MDS) NSG mice NSGS mice xenograft mouse model 415 419 5 04/19/21 20210415 NES 210415 Myelodysplastic syndrome (MDS) represents a group of heterogeneous haematopoietic disorders characterised by diverse clinical symptoms varying from mild anaemia to multilineage cytopenia.1,2 Importantly, one-third of MDS patients will exhibit a transformation towards acute myeloid leukaemia,3,4 increasing the complexity of the disease aetiology. Our study provides an in-depth characterisation of both the MDS-L-2007 and MDS-LGF subclones and reports the development of a novel indolent high-risk MDS phenotype model using the MDS-LGF cells. Overall, our observations underline that the two MDS cell lines (MDS-LGF and MDS-L-2007) present with quite drastic differences in major key phenotypes characterising MDS (i.e. del5q and TET2 mutation). MDS-L, MDS-L-2007, MDS-LGF, myelodysplastic syndromes (MDS), hydrogel scaffold, NSGS mice, NSG mice, xenograft mouse model. [Extracted from the article]

Organoids have emerged as major technological breakthroughs and novel organ models that have revolutionized biomedical research by recapitulating the key structural and functional complexities of their in vivo counterparts. The combination of organoid systems and microfluidic technologies has opened new frontiers in organoid engineering and offers great opportunities to address the current challenges of existing organoid systems and broaden their biomedical applications. In this review, the key features of the existing organoids, including their origins, development, design principles, and limitations, are described. Then the recent progress in integrating organoids into microfluidic systems is highlighted, involving microarrays for high-throughput organoid manipulation, microreactors for organoid hydrogel scaffold fabrication, and microfluidic chips for functional organoid culture. The opportunities in the nascent combination of organoids and microfluidics that lie ahead to accelerate research in organ development, disease studies, drug screening, and regenerative medicine are also discussed. Finally, the challenges and future perspectives in the development of advanced microfluidic platforms and modified technologies for building organoids with higher fidelity and standardization are envisioned., (© 2023 Wiley‐VCH GmbH.)