Preparation And Preliminary Properties Of Collagen Based Hydrogel Containing Chondroitin Sulfate Or Its Microsphere

Hydrogels,a kind of soft materials crosslinked by polymer,present three-dimensional network structure with strong water absorption and water retention capacity.Hydrogels have been developed into a variety of medical device products and used in clinical operations such as wound healing,cartilage repair,wound adhesion,playing important roles in the frontier research fields of tissue engineering,artificial organs and regenerative medicine.Although hydrogels can effectively promote the speed of wound healing,there are still considerable challenges in the clinical treatment of wound healing.The main problem is that hydrogels can not effectively regulate the excessive inflammatory reaction of the wound,resulting in the formation of wound scar,low degree of vascularization,poor healing quality and lack of physiological function.The purpose of this study is to develop a kind of hydrogels imitating the structure of extracellular matrix,which are provided with the ability of multiple regulation of wound inflammation for the repair and treatment of chronic wound.The main research contents and results are as follows:In this paper,extracellular matrix mimetic hydrogels were constructed based on the verification of the anti-inflammatory effect of chondroitin sulfate,and their abilities in wound hemostasis and regulating early wound inflammation were evaluated.The hydrogels were prepared by cross-linking collagen and compounded with chondroitin sulfate A(CSA)or chondroitin sulfate C(CSC)solution with aldehyded polyethylene glycol.The pores of the hydrogels were observed to be dense and uniform by scanning electron microscope.The comprehensive swelling test results showed good water absorption,which was conducive to the absorption of tissue exudate when applied to the wound in the later stage.The hemolysis rate of the hydrogel was lower than 1.5%,and the coagulation index(BCI)was significantly reduced,showing a certain hemostatic effect.In addition,the hydrogels had no cytotoxicity,showed good biocompatibility,and significantly inhibited the release of NO from LPS induced RAW264 7 cells,indicating favorable anti-inflammatory effect.The above hydrogels possessed the potential to regulate wound inflammation,but the loaded chondroitin sulfate trended to be lost in a short time,and the ability to inhibit the excessive proliferation of fibroblasts in the late stage of wound healing was insufficient.In order to improve these two defects,the microsphere hydrogels were prepared by crosslinking of microspheres with collagen under UV irradiation.The microsphere consisted of methyl methacrylate grafted chondroitin sulfate A or chondroitin sulfate C and methyl methacrylate conjugated gelatin followed by encapsulating the transforming growth factor inhibitor SB431542.It was confirmed that the microsphere hydrogels not only effectively stabilized the release of chondroitin sulfate,but also realized the sustained release of SB431542.This synergistic release behavior was conducive to the effect on the stable regulation of inflammation by chondroitin sulfate,and reducing the proliferation rate of fibroblasts(NIH 3T3)in the later stage of the culture cycle,exhibiting the ability to regulate wound inflammation and reduce the degree of wound fibrosis.In conclusion,the collagen hydrogels compounded with chondroitin sulfate or chondroitin sulfate microspheres studied in this paper presented the potential to regulate wound inflammation,inhibit wound fiber proliferation and improve the quality of wound repair,which would be considerable choice of wound dressings.