Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect  

作　　者：Qinfeng Yang Guihua Liu 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 

机构地区：[1]Division of Orthopaedics and Traumatology,Department of Orthopaedics,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong,510515,China [2]Division of Orthopaedic Surgery,Department of Orthopaedics,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong,510515,China [3]Institute of Orthopaedics,Huizhou Central People’s Hospital,Huizhou,Guangdong,516008,China [4]Department of Orthopaedics,The Second Hospital of Jiaxing,The Second Affiliated Hospital of Jiaxing University,Jiaxing,Zhejiang,314000,China [5]Department of Obstetrics and Gynecology,Core Facility Center,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,Anhui,230001,China [6]State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science,Guangzhou,Guangdong,510060,China [7]Department of Vascular Surgery,The Quzhou Affiliated Hospital of Wenzhou Medical University,Quzhou People’s Hospital,Quzhou,Zhejiang,324000,China [8]Department of Vascular Surgery,Renji Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai,200127,China [9]Department of Sports Medicine and Rehabilitation,Peking University Shenzhen Hospital,Shenzhen,China [10]State Key Laboratory of Quality Research in Chinese Medicines,Laboratory of Drug Discovery from Natural Resources and Industrialization,School of Pharmacy,Macao University of Science and Technology,Macao,999078,China

出　　处：《Bioactive Materials》2024年第12期85-111,共27页生物活性材料（英文）

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.

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.

关 键 词：Hemophilic articular cartilage defect Adhesive hydrogel EXOSOMES ANTI-INFLAMMATION CHONDROGENESIS 

分 类 号：TQ427.26[化学工程] R684.3[医药卫生—骨科学]