Recent advances of acellular cartilage matrix in cartilage regeneration / 中华骨科杂志

Osteoarthritis is a common degenerative joint disease, and cartilage damage is often considered an early factor in irreversible joint degeneration. Repairing damaged cartilage remains a medical challenge due to its limited ability to self-repair and regenerate. In recent years, the application of tissue engineering strategies to treat cartilage defects has been recognized as an emerging therapeutic avenue. Acellular cartilage matrix (ACM) is an ideal material for cartilage repair and regeneration as it retains the extracellular matrix structure and bioactive components of natural cartilage, mimicking the extracellular environment of natural cartilage to the greatest extent. Type II collagen is the main type of hyaline cartilage and plays an important role in regulating the mechanical properties of cartilage tissue. It has been shown that type II collagen, growth factors and the hypoxic microenvironment play important roles in promoting cartilage regeneration. Type II collagen induces cell aggregation and chondrogenic differentiation in a specific way; Various growth factors contained in the ACM induce Sox9 expression and promote chondrogenic differentiation of stem cells; The hypoxic microenvironment upregulates the expression of type II collagen (COL2A1), Sox9 and maintains chondrocyte phenotype. In addition, ACM has been widely used in cartilage regeneration studies, either as a decellularized scaffold, hydrogel or 3D bioprinting technique for the repair of defective cartilage. Although the ACM-derived biomaterials discussed in this paper have many advantages, there are still some difficulties in their practical applications, such as loss of ACM components and reduced scaffold performance, which are still worth exploring in depth.

Scaffolds Vasculares Descelularizados Provenientes de Vasos Sanguíneos de Placenta Bovina / Decellularized Vascular Scaffolds Derived from Bovine Placenta Blood Vessels

Resumo Fundamento As doenças associadas ao aparelho circulatório são as principais causas de morbidade e mortalidade em todo o mundo, implicando a necessidade de implantes vasculares. Assim, a produção de biomateriais vasculares tem se mostrado uma alternativa promissora às terapias utilizadas em estudos e pesquisas relacionados à fisiologia vascular. Objetivos O presente projeto visa ao desenvolvimento artificial de vasos sanguíneos pela recelularização de scaffolds vasculares derivados de vasos placentários bovinos. Métodos A superfície corioalantoide da placenta bovina foi utilizada para produzir biomateriais descelularizados. Para a recelularização, 2,5 x 104 células endoteliais foram semeadas acima de cada fragmento de vaso descelularizado durante três ou sete dias, quando a cultura foi interrompida e os fragmentos foram fixados para análise de adesão celular. Biomateriais descelularizados e recelularizados foram avaliados por histologia básica, microscopia eletrônica de varredura e imuno-histoquímica. Resultados o processo de descelularização produziu vasos que mantiveram a estrutura natural e o conteúdo de elastina, e não foram observadas células e gDNA remanescentes. Além disso, células precursoras endoteliais se ligaram ao lúmen e à superfície externa do vaso descelularizado. Conclusão nossos resultados mostram a possibilidade de usos futuros desse biomaterial na medicina cardiovascular, como, por exemplo, no desenvolvimento de vasos artificiais.

Background Diseases associated with the circulatory system are the main causes of worldwide morbidity and mortality, implying the need for vascular implants. Thus, the production of vascular biomaterials has proven to be a promising alternative to therapies used in studies and research related to vascular physiology. Objectives The present project aims to achieve the artificial development of blood vessels through the recellularization of vascular scaffolds derived from bovine placental vessels. Methods The chorioallantoic surface of the bovine placenta was used to produce decellularized biomaterials. For recellularization, 2.5 x 104 endothelial cells were seeded above each decellularized vessel fragment during three or seven days, when culture were interrupted, and the fragments were fixed for cell attachment analysis. Decellularized and recellularized biomaterials were evaluated by basic histology, scanning electron microscopy, and immunohistochemistry. Results The decellularization process produced vessels that maintained natural structure and elastin content, and no cells or gDNA remains were observed. Endothelial precursor cells were also attached to lumen and external surface of the decellularized vessel.Conclusion: Our results show a possibility of future uses of this biomaterial in cardiovascular medicine, as in the development of engineered vessels.

Decellularized extracellular matrix mediates tissue construction and regeneration / 医学前沿

Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and cellular-function regulation. Containing the crucial traits of the cellular microenvironment, ECM substitutes mediate cell-matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo. However, these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well. Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select, produce, and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration. Overall, the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed. Moreover, current preclinical applications by which ECM components modulate the wound-healing process are reviewed.

Preparation and application of decellularized extracellular matrix bioink: a review / 生物工程学报

Decellularized extracellular matrix (dECM), which contains many proteins and growth factors, can provide three-dimensional scaffolds for cells and regulate cell regeneration. 3D bioprinting can print the combination of dECM and autologous cells layer by layer to construct the tissue structure of carrier cells. In this paper, the preparation methods of tissue and organ dECM bioink from different sources, including decellularization, crosslinking, and the application of dECM bioink in bioprinting are reviewed, with future applications prospected.

Properties of gelatin methacrylate/decellularized meniscus extracellular matrix composite hydrogel with different crosslinking densities / 中国组织工程研究

BACKGROUND: Crosslinked polymer chains have a remarkable effect on the fundamental properties and cytocompatiblllty of hydrogels, and crosslinking density can significantly change the formation of polymer chains. There are few studies on the effect of the properties of hydrogels caused by crosslinking density. OBJECTIVE: To prepare a composite hydrogel with a favorable cytocompatlbility and to explore the effect of crosslinking density on the properties of the hydrogel. METHODS: Gelatin methacrylate solution was prepared, and decellularized meniscus extracellular matrix and LAP solution were added to prepare the pre-gel solution, which was crosslinked by blue ray. The crosslinking time was 10, 30 and 60 seconds. The compression elastic modulus, swelling ratio and degradability of hydrogels were detected. Meniscus fibrochondrocytes were added Into the pre-gel solution, and crosslinked by blue ray. The cell viability, morphology and gathering were detected at 10, 30 and 60 seconds of crosslinking. RESULTS AND CONCLUSION: (1) The hydrogel with 60 seconds of cross-linking time had higher compression elastic modulus than that of the hydrogel with 10 and 30 seconds of cross-linking time (P 0.05). (3) With the crosslinking time Increasing, the degradation time of hydrogels Increased. The hydrogels with 60 seconds of cross-linking time degraded completely at 80 minutes, and hydrogels with 10 seconds of cross-linking time degraded completely at 50 minutes. (4) After 24 hours of culture, the cell viability In all groups was over 95% (P > 0.05). (5) At 1 day after culture, the cells were In sphere-shape and distributed evenly In all groups. On day 4, the cells In all groups began to extend, and there were small cell masses in the hydrogels with 10 seconds of cross-linking time. On day 7, the dendritic extension in all groups was obvious, and there were dominant cell masses In the hydrogels with 10 seconds of cross-linking time. (6) After 1, 7 and 14 days of culture, cell viability In all groups was over 85%. At 1 day after culture, the cells In the hydrogels with 10 seconds of cross-linking time were in sphere-shape and distributed evenly. On day 28, the cells extended In dendritic shape, and gathered in reticular formation. (7) In summary, the property of gelatin methacrylate/decellularized meniscus extracellular matrix composite hydrogel can be optimized by adjusting crosslinking density.

Research progress of decellularized extracellular matrix hydrogel in regenerative medicine / 生物医学工程学杂志

Decellularized extracellular matrix (dECM) has been widely used as a scaffold for regenerative medicine due to its high biomimetic and excellent biocompatibility. As a functional polymer material with high water content and controlled fluidity, hydrogel is very promising for some minimally invasive surgery in clinical practice. In recent years, with the rapid development of hydrogel theory and technology, dECM hydrogel has gradually become a research hotspot in the field of regenerative medicine. In this paper, the related researches in recent years are reviewed regarding the preparation of dECM hydrogel and its preclinical application. The future clinical use is also prospected.