摘要
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.
基金
supported by the National Natural Science Foundation of China Youth Fund(82202662)
the Guangzhou Science and Technology Program(2023A04J2314)
the National Natural Science Foundation of China(12,272,164)
the China Postdoctoral Science Foundation(2023M741563)
the Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education(LC2019ZD001)
the Clinical Research Program of Nanfang Hospital,Southern Medical University(2019CR016)
the Project of Drug Clinical Evaluate Research of Chinese Pharmaceutical Association(CPA-Z06-ZC-2021-004)
the National Natural Science Foundation of China(82370497)
the Medical Scientific Research Foundation of Guangdong(A2024366)
Huizhou Science Technology Project Foundation(2022CZ010423)
the Macao Science and Technology Development fund(FDCT(0012/2021/AMJ,003/2022/ALC,0092/2022/A2,0144/2022/A3))
the Shenzhen-Hong Kong-Macao Science and Technology Fund(Category C:SGDX20220530111203020)
the Foundation of Guangdong Basic and Applied Basic Research Foundation(2022A1515140151&2022A1515140189&2023A1515140045&2022A1515140071)
the National Orthopaedics Key Clinical Specialty Construction Research Foundation of Huizhou Central People’s Hospital.
作者简介
Corresponding authors:Bin Chen,E-mail addresses:smu.edu.cn;Corresponding authors:Shaowei Zheng,E-mail addresses:zswljq@126.com;Corresponding authors:Shuofei Yang,E-mail addresses:doctor_yangshuofei@163.com:Corresponding authors:,Xiayang Li,E-mail addresses:lixiaoyang1@wmu.edu.cn;Corresponding authors:Zhanjun Shi,E-mail addresses:18719096889@163.com;Qinfeng Yang,contributed equally to this work;Guihua Liu,contributed equally to this work;Guanghao Chen,contributed equally to this work;Guo Chen,contributed equally to this work.
