Collagen membrane has attracted much attention from researchers due to its excellent properties such as wide source, degradable absorption, and low immunogenicity. However, they are limited by poor mechanical stability and rapid degradation. To enhance their physicochemical properties and biological functions, researchers have developed various strategies, including cross-linking, incorporation of growth factors or drugs, combination with other biomaterials, optimization of composition and structure, and substitution with marine-derived collagen. These advances aim to expand the clinical applications of collagen membranes in oral medicine. With the urgent demand for high-performance biomaterials in oral medicine, summarizing recent progress on collagen membranes provides valuable insights into their mechanisms, clinical efficacy, and limitations, offering reference for optimized design and broader clinical use. Furthermore, further trends may include integrating advanced manufacturing technologies to develop personalized collagen membranes, which could significantly improve therapeutic outcomes in oral diseases.
Collagen/therapeutic use* ; Humans ; Biocompatible Materials/chemistry* ; Membranes, Artificial ; Oral Medicine/methods* ; Tissue Engineering/methods*

Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry* ; Animals ; Bone Regeneration ; Rabbits ; Tissue Scaffolds ; Printing, Three-Dimensional ; Humans ; Human Umbilical Vein Endothelial Cells ; Neovascularization, Physiologic ; Osteogenesis ; Tissue Engineering/methods* ; Biomimetic Materials ; Cell Proliferation ; Angiogenesis

Collagen-based materials, renowned for their biocompatibility and minimal immunogenicity, serve as exemplary substrates in a myriad of biomedical applications. Collagen-based micro/nanogels, in particular, are valued for their increased surface area, tunable degradation rates, and ability to facilitate targeted drug delivery, making them instrumental in advanced therapeutics and tissue engineering endeavors. Although extensive reviews on micro/nanogels exist, they tend to cover a wide range of biomaterials and lack a specific focus on collagen-based materials. The current review offers an in-depth look into the manufacturing technologies, drug release mechanisms, and biomedical applications of collagen-based micro/nanogels to address this gap. First, we provide an overview of the synthetic strategies that allow the precise control of the size, shape, and mechanical strength of these collagen-based micro/nanogels by controlling the degree of cross-linking of the materials. These properties are crucial for their performance in biomedical applications. We then highlight the environmental responsiveness of these collagen-based micro/nanogels, particularly their sensitivity to enzymes and pH, which enables controlled drug release under various pathological conditions. The discussion then expands to include their applications in cancer therapy, antimicrobial treatments, bone tissue repair, and imaging diagnosis, emphasizing their versatility and potential in these critical areas. The challenges and future perspectives of collagen-based micro/nanogels in the field are discussed at the end of the review, with an emphasis on the translation to clinical practice. This comprehensive review serves as a valuable resource for researchers, clinicians, and scientists alike, providing insights into the current state and future directions of collagen-based micro/nanogel research and development.
Collagen/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Tissue Engineering/methods* ; Animals ; Biocompatible Materials/chemistry*

To assess the implantation effectiveness of porous scaffolds, it is essential to consider not only their mechanical properties but also their biological performance. Given the high cost, long duration and low reproducibility of biological experiments, simulation studies as a virtual alternative, have become a widely adopted and efficient evaluation method. In this study, based on the secondary development environment of finite element analysis software, the strain energy density growth criterion for bone tissue was introduced to simulate and analyze the cell proliferation-promoting effects of four different lattice porous scaffolds under cyclic compressive loading. The biological performance of these scaffolds was evaluated accordingly. The computational results indicated that in the early stages of bone growth, the differences in bone tissue formation among the scaffold groups were not significant. However, as bone growth progressed, the scaffold with a porosity of 70% and a pore size of 900 μm demonstrated markedly superior bone formation compared to other porosity groups and pore size groups. These results suggested that the scaffold with a porosity of 70% and a pore size of 900 μm was most conducive to bone tissue growth and could be regarded as the optimal structural parameter for bone repair scaffold. In conclusion, this study used a visualized simulation approach to pre-evaluate the osteogenic potential of porous scaffolds, aiming to provide reliable data support for the optimized design and clinical application of implantable scaffolds.
Tissue Scaffolds/chemistry* ; Porosity ; Finite Element Analysis ; Tissue Engineering/methods* ; Computer Simulation ; Bone Development ; Osteogenesis ; Humans ; Cell Proliferation

The three-dimensional (3D) printed bone tissue repair guide scaffold is considered a promising method for treating bone defect repair. In this experiment, chitosan (CS), sodium alginate (SA), and mineralized collagen (MC) were combined and 3D printed to form scaffolds. The experimental results showed that the printability of the scaffold was improved with the increase of chitosan concentration. Infrared spectroscopy analysis confirmed that the scaffold formed a cross-linked network through electrostatic interaction between chitosan and sodium alginate under acidic conditions, and X-ray diffraction results showed the presence of characteristic peaks of hydroxyapatite, indicating the incorporation of mineralized collagen into the scaffold system. In the in vitro collagen release experiments, a weakly alkaline environment was found to accelerate the release rate of collagen, and the release amount increased significantly with a lower concentration of chitosan. Cell experiments showed that scaffolds loaded with mineralized collagen could significantly promote cell proliferation activity and alkaline phosphatase expression. The subcutaneous implantation experiment further verified the biocompatibility of the material, and the implantation of printed scaffolds did not cause significant inflammatory reactions. Histological analysis showed no abnormal pathological changes in the surrounding tissues. Therefore, incorporating mineralized collagen into sodium alginate/chitosan scaffolds is believed to be a new tissue engineering and regeneration strategy for achieving enhanced osteogenic differentiation through the slow release of collagen.
Chitosan/chemistry* ; Alginates/chemistry* ; Tissue Scaffolds/chemistry* ; Printing, Three-Dimensional ; Osteogenesis ; Collagen/chemistry* ; Cell Differentiation ; Animals ; Tissue Engineering/methods* ; Cell Proliferation ; Biocompatible Materials ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry*

OBJECTIVE: To summarize the research progress of bioactive scaffolds in the repair and regeneration of osteoporotic bone defects. METHODS: Recent literature on bioactive scaffolds for the repair of osteoporotic bone defects was reviewed to summarize various types of bioactive scaffolds and their associated repair methods. RESULTS: The application of bioactive scaffolds provides a new idea for the repair and regeneration of osteoporotic bone defects. For example, calcium phosphate ceramics scaffolds, hydrogel scaffolds, three-dimensional (3D)-printed biological scaffolds, metal scaffolds, as well as polymer material scaffolds and bone organoids, have all demonstrated good bone repair-promoting effects. However, in the pathological bone microenvironment of osteoporosis, the function of single-material scaffolds to promote bone regeneration is insufficient. Therefore, the design of bioactive scaffolds must consider multiple factors, including material biocompatibility, mechanical properties, bioactivity, bone conductivity, and osteogenic induction. Furthermore, physical and chemical surface modifications, along with advanced biotechnological approaches, can help to improve the osteogenic microenvironment and promote the differentiation of bone cells. CONCLUSION With advancements in technology, the synergistic application of 3D bioprinting, bone organoids technologies, and advanced biotechnologies holds promise for providing more efficient bioactive scaffolds for the repair and regeneration of osteoporotic bone defects.
Humans ; Tissue Scaffolds/chemistry* ; Bone Regeneration ; Osteoporosis/therapy* ; Tissue Engineering/methods* ; Biocompatible Materials/chemistry* ; Printing, Three-Dimensional ; Calcium Phosphates/chemistry* ; Osteogenesis ; Ceramics ; Cell Differentiation ; Hydrogels ; Bioprinting ; Bone and Bones

OBJECTIVE: To summarize the latest research progress of graphene and its derivatives (GDs) in bone repair. METHODS: The relevant research literature at home and abroad in recent years was extensively accessed. The properties of GDs in bone repair materials, including mechanical properties, electrical conductivity, and antibacterial properties, were systematically summarized, and the unique advantages of GDs in material preparation, functionalization, and application, as well as the contributions and challenges to bone tissue engineering, were discussed. RESULTS: The application of GDs in bone repair materials has broad prospects, and the functionalization and modification technology effectively improve the osteogenic activity and material properties of GDs. GDs can induce osteogenic differentiation of stem cells through specific signaling pathways and promote osteogenic activity through immunomodulatory mechanisms. In addition, the parameters of GDs have significant effects on the cytotoxicity and degradation behavior. CONCLUSION GDs has great potential in the field of bone repair because of its excellent physical and chemical properties and biological properties. However, the cytotoxicity, biodegradability, and functionalization strategies of GDs still need to be further studied in order to achieve a wider application in the field of bone tissue engineering.
Graphite/pharmacology* ; Tissue Engineering/methods* ; Humans ; Osteogenesis/drug effects* ; Biocompatible Materials/pharmacology* ; Bone Regeneration ; Tissue Scaffolds/chemistry* ; Cell Differentiation ; Bone and Bones ; Bone Substitutes/chemistry* ; Animals

OBJECTIVE: To prepare decellularized nerve grafts from alpha-1, 3-galactosyltransferase (GGTA1) gene-edited pigs and explore their biocompatibility for xenotransplantation. METHODS: The sciatic nerves from wild-type pigs and GGTA1 gene-edited pigs were obtained and underwent decellularization. The alpha-galactosidase (α-gal) content in the sciatic nerves of GGTA1 gene-edited pigs was detected by using IB4 fluorescence staining and ELISA method to verify the knockout status of the GGTA1 gene, and using human sciatic nerve as a control. HE staining and scanning electron microscopy observation were used to observe the structure of the nerve samples. Immunofluorescence staining and DNA content determination were used to evaluate the degree of decellularization of the nerve samples. Fourteen nude mice were taken, and subcutaneous capsules were prepared on both sides of the spine. Decellularized nerve samples of wild-type pigs ( n=7) and GGTA1 gene-edited pigs ( n=7) were randomly implanted in the subcutaneous capsules. Blood was drawn at 1, 3, 5, and 7 days after implantation to detect neutrophil counting. RESULTS: IB4 fluorescence staining and ELISA detection showed that GGTA1 gene was successfully knocked out in the nerves of GGTA1 gene-edited pigs. HE staining showed that the structure of the decellularized nerve from GGTA1 gene-edited pigs was well preserved; the nerve basement membrane tube structure was visible under scanning electron microscopy; no cell nuclei was observed, and the extracellular matrix components was retained in the nerve grafts by immunofluorescence staining; and the DNA content was significantly reduced when compared with the normal nerves ( P<0.05). In vivo experiments showed that the number of neutrophils in the two groups were similar at 1, 3, and 7 days after implantation, with no significant difference ( P>0.05); only at 5 days, the number of neutrophils was significantly lower in the GGTA1 gene-edited pigs than in the wild-type pigs ( P<0.05). CONCLUSION The decellularized nerve grafts from GGTA1 gene-edited pigs have well-preserved nerve structure, complete decellularization, retain the natural nerve basement membrane tube structure and components, and low immune response after xenotransplantation through in vitro experiments.
Animals ; Transplantation, Heterologous ; Galactosyltransferases/genetics* ; Sciatic Nerve/immunology* ; Swine ; Tissue Engineering/methods* ; Humans ; Graft Rejection/prevention & control* ; Gene Editing ; Mice ; Mice, Nude ; Heterografts/immunology* ; Animals, Genetically Modified ; Tissue Scaffolds ; Decellularized Extracellular Matrix

OBJECTIVE: To review the latest research advancements in surgical techniques for the treatment of limb lymphedema. METHODS: The relevant literature at home and abroad in recent years was extensively reviewed, and the research on the treatment of limb lymphedema by surgical techniques were summarized and analyzed. RESULTS: Lymphovenous anastomosis has demonstrated good effectiveness for early to mid-stage limb lymphedema, however its long-term effectiveness and applicability for late-stage limb lymphedema still require further validation. Autologous lymphatic/venous grafting has shown clinical feasibility in the treatment of secondary limb lymphedema. Research on tissue-engineered lymphatic scaffolds remains insufficient, primarily due to the complexity of lymphatic anatomical structures and the technical challenges involved. Nevertheless, its potential application is promising. Vascularized lymph node flap transplantation has shown significant effectiveness in treating limb lymphedema, particularly yielding good outcomes in upper limb cases. However, it can not guarantee a complete cure for the condition. Charles' operation is the most effective treatment option for patients with late-stage limb lymphedema, but its extensive incision and severe postoperative complications limit its application. Liposuction has the advantages such as minimal invasiveness, high safety, and repeatability. It is suitable for patients with late-stage limb lymphedema who have failed conservative treatment or developed adiposity. However, its effectiveness is limited in patients with significant limb fibrosis. CONCLUSION Current treatments for limb lymphedema require further improvement, and there is considerable debate regarding treatment strategies for different stages of the condition. Future high-quality, multi-system combined treatment approaches are anticipated to guide clinical practice.
Humans ; Lymphedema/surgery* ; Surgical Flaps/blood supply* ; Lymphatic Vessels/surgery* ; Anastomosis, Surgical/methods* ; Lymph Nodes/transplantation* ; Lipectomy/methods* ; Extremities/surgery* ; Treatment Outcome ; Tissue Engineering ; Tissue Scaffolds ; Veins/transplantation*

OBJECTIVE: To review clinical application and research progress of different types of intelligent responsive hydrogels in repairing articular cartilage injury. METHODS: The animal experiments and clinical studies of different types of intelligent responsive hydrogels for repairing articular cartilage injury were summarized by reviewing relevant literature at home and abroad. RESULTS: The intrinsic regenerative capacity of articular cartilage following injury is limited. Intelligent responsive hydrogels, including those that are temperature-sensitive, light-sensitive, enzyme-responsive, pH-sensitive, and other stimuli-responsive hydrogels, can undergo phase transitions in response to specific stimuli, thereby achieving optimal functionality. These hydrogels can fill the injured cartilage area, promote the proliferation and differentiation of chondrocytes, and expedite the repair of the damaged site. With advancements in cartilage tissue engineering materials research, intelligent responsive hydrogels offer a novel approach and promising potential for the treatment of cartilage injuries. CONCLUSION Intelligent responsive hydrogel is a kind of flexible, controllable, efficient, and stable polymer, which has similar structure and functional properties to articular cartilage, and has become one of the important biomaterials for cartilage repair. However, there is still a lack of unified treatment standards and simple and efficient preparation technology.
Hydrogels/therapeutic use* ; Cartilage, Articular/injuries* ; Tissue Engineering/methods* ; Humans ; Animals ; Chondrocytes/cytology* ; Biocompatible Materials/chemistry* ; Tissue Scaffolds/chemistry*