MSC-Hydrogel for cartilage repair

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项目简介:Articular cartilage injury is still a signifcant challenge because of the poor intrinsic healingpotential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilagerepair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability thatcan fill any shape of cartilage defects and closely integrate with the host cartilage are desirable.Tissue engineering scaffolds provide cells with adhesion growth, whose material compositionand microstructure characteristics have an effect on cell growth. Therefore, good tissueengineering scaffolds need both biocompatibility and microstructure formation . Naturally sourcedinjectable thermosensitive hydrogels can simultaneously encapsulate and release growth factors.Meanwhile , they have the ability to recruit MSCs from surrounding tissues to migrate tomaterials.In this study, we constructed an injectable temperature-sensitive bioactiveagarose/gelatin/hyaluronic acid hydrogel scaffold modifed by Chondrocyte extracellular matrix(ECM) particles for cartilage engineering. As a natural plant polysaccharide material, agarose is alinear polymer, whose solution has good temperature sensitivity. It is generally soluble in water at90℃. When the temperature drops to 40℃, a stable hydrogel structure can be formed. As a naturalhydrogel, agarose hydrogel has the advantages of non-toxic cells, low material cost, and simplegelation method. In this study, the preparation of hydrogel with agarose not only made the wholehydrogel have temperature-sensitive properties, but also enhanced the biomechanical strength ofthe whole system to some extent. Gelatin is a product of alkaline or acidic hydrolysis of collage,which is non-toxic, low in immunogenicity, and has good cell adhesion, biodegradability andbiocompatibility. The hydrogel scaffold prepared by gelatin in this study has many excellentproperties, which not only improves the compressive strength and cell adhesion ability of thewhole system, but also promotes the proliferation and differentiation of cells. HA is an anioniclinear high molecular weight polysaccharide, which is an important component ofglycosaminoglycan (GAG) in the cartilage matrix and can be used to make injectable hydrogels.For that it can support cell proliferation and maintain cartilage phenotype formation, HA hasattracted wide attention of researchers, and has been widely used in artificial tissue, wound healingand chondrocyte culture and so on. Previous studies have reported that HA binds to the cellsurface receptor CD44 and promotes cell expression of more chondrocyte markers such as SOX-9,aggrecan and COL II. Obviously, HA plays an important role in the formation of cartilage matrix.Therefore, it is an important component of the entire hydrogel system.Cartilage ECM is a filling between cartilage cells and a scaffold for cartilage tissue. TheECM particles retain the basic skeleton of natural cartilage tissue,which is a loose porousstructure composed of abundant proteoglycans and collagen fibers.They play an important role inthe aspects of the increase in chondrocytes, migration, signal transmission between cells andmechanical response of tissue engineered cartilage. Specifically speaking, the role of ECM intissue engineered cartilage is mainly reflected in three aspects: First, ECM itself is a loose porousstructure similar to natural cartilage tissue, which can provide a microenvironment suitable fornormal stem cell survival, meanwhie, can promote Cell adhesion, proliferation and induction ofdifferentiation into the cartilage direction; Second, the addition of ECM particles can significantlyimprove the biomechanical strength of the hydrogel-cell composite scaffold; third, the additionof ECM particles makes the hydrogel-cell composite scaffold more in line with the 3D structure ofnatural cartilage tissue. This is mainly reflected in the presence of cell growth factors such astransforming progesterone β and insulin-like growth factor 1 in the cartilage matrix . Transforminggrowth factor beta is abundant in articular cartilage and is a known growth factor that plays animportant role in the primary stage of chondrogenesis. It not only promotes the secretion ofcartilage matrix including type II collagen, but also induces Mesenchymal stem cells differentiateinto chondrocytes, playing an important role in the survival of cells grown in serum-free medium.The hydrogel scaffold we prepared exhibited a good ultrastructure, which provided a 3Dmicroenvironment that supports cell adhesion and proliferation. Cell proliferation and DNAcontent analysis indicated that the agarose/gelatin/hyaluronic acid/DBA hydrogel scaffoldpromoted better rat bone mesenchymal MSCs (BMSCs) survival than the agarose/ gelatin/hyaluronic acid groups. Meanwhile, the agarose/ gelatin/ hyaluronic acid /ECM hydrogel scaffoldincreased matrix production and improved chondrogenic differentiation ability of CHs-BMSCs invitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups,the regenerated tissue in the agarose/ gelatin/ hyaluronic acid/ECM hydrogel group exhibitedtranslucent and superior cartilage-like structures, as indicated by gross observation, histologicalexamination, and assessment of matrix staining. Overall, the functional composite scaffold ofagarose/ gelatin/ hyaluronic acid/DBA hydrogel is a promising option for repairing irregularlyshaped cartilage defects.  



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