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Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect
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作者 Qinfeng Yang Guihua Liu +15 位作者 Guanghao Chen Guo Chen Keyu Chen Lei Fan Yuesheng Tu Jialan Chen Zhanjun Shi Chuan Chen Shubo Liu Geyang Deng Xiaoqian Deng chunhan sun Xiaoyang Li Shuofei Yang Shaowei Zheng Bin Chen 《Bioactive Materials》 SCIE 2024年第12期85-111,共27页
Hemophilic articular cartilage damage presents a significant challenge for surgeons,characterized by recurrent intraarticular bleeding,a severe inflammatory microenvironment,and limited self-repair capability of carti... Hemophilic articular cartilage damage presents a significant challenge for surgeons,characterized by recurrent intraarticular bleeding,a severe inflammatory microenvironment,and limited self-repair capability of cartilage tissue.Currently,there is a lack of tissue engineering-based integrated therapies that address both early hemostasis,anti-inflammation,and long-lasting chondrogenesis for hemophilic articular cartilage defects.Herein,we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin,loaded with exosomes derived from bone marrow stem cells(BMSCs)(Hydrogel-Exos).This hydrogel demonstrated favorable injectability,self-healing,biocompatibility,biodegradability,swelling,frictional and mechanical properties,providing a comprehensive approach to treating hemophilic articular cartilage defects.The adhesive hydrogel,featuring dynamic Schiff base bonds and hydrogen bonds,exhibited excellent wet tissue adhesiveness and hemostatic properties.In a pig model,the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions.Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway.This immunoregulatory effect,coupled with the extracellular matrix components provided by the adhesive hydrogel,enhanced chondrogenesis,promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects.In conclusion,our results highlight the significant application potential of Hydrogel-Exos for early hemostasis,immunoregulation,and long-term chondrogenesis in hemophilic patients with cartilage injuries.This innovative approach is well-suited for application during arthroscopic procedures,offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage. 展开更多
关键词 Hemophilic articular cartilage defect Adhesive hydrogel Exosomes Anti-inflammation Chondrogenesis
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