Abstract：Preventing cardiac fibrosis is the main strategy to improve cardiac function. In this study, the extracellular matrix of myocardium (ECM) and doxycycline composite hydrogels were designed and developed to solve the problems of tissue regeneration and rapid fibrin deposition in myocardial infarction sites. Porcine cardiacs were subjected to SDS, TritonX-100 treatment to remove intracellular material. Then dissolved with pepsin and added fibroin microcapsules containing 54.63~89.27 μg/mg doxycycline. The mixed solution wasspontaneouslyformed into hydrogel at 37℃. The structure of composite hydrogel microcapsules and fibroin microcapsules were observed by scanning electron microscopy, and the feasibility of composite hydrogel treatment was tested by in vitro degradation, sustained drug release and cardiac fibroblast culture experiments. Finally, myocardial infarction rats were treated in vivo (n=9) and infarct size and hemodynamic changes were analyzed to simulate the clinical therapeutic effect. The results showed that the composite hydrogel had a dense pore structure. Compared with the drug-loaded microcapsules, the porous fibroin microcapsules with a diameter of 1~3 μm were evenly distributed in the hydrogel, which not only achieved slow release of the drug, but also significantly prolonged the degradationtime of the hydrogel. In the compound hydrogel, 13% of the total drug load was slowly released for 9 days, and the amount of collagen deposition in fibroblasts was reduced. In vivo treatment studies, the composite water gel inhibited cardiac fibrosis and significantly reduced the myocardial infarction area. After 4 weeks of treatment, LVSP and (dp/dt)max of myocardial infarction rats increasedto (116.67±3.50) and (2359.24±133.06) mmHg/s compared with (73.52±4.24) and (1 020.96±100.68) mmHg/s in control group. There were significant differences in both of them (P<0.01), which indicated that the pumping ability of the heart was enhanced. In conclusion, the composite hydrogel has good biocompatibility, slow release function, the ability to inhibit fibrosis and enhance cardiac function, It's expected to play a role in clinical treatment.
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