Extracellular Vesicle Clicking on Osteoimplants Through Biomimetic Molecular Adhesion Enables Immune‐Enhanced Osseointegration in Diabetics

Author:

Ge Gaoran1,Wang Wei1,Wang Qing12,Wang Miao3,Wang Tao4,Yu Lei1,Zhang Xianzuo2,Zhu Chen2,Xu Yaozeng1,Yang Huilin1,Bai Jiaxiang12ORCID,Pan Guoqing3ORCID,Geng Dechun1

Affiliation:

1. Department of Orthopedics The First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 P. R. China

2. Department of Orthopedics Centre for Leading Medicine and Advanced Technologies of IHM The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei 230022 P. R. China

3. Institute for Advanced Materials, School of Materials Science and Engineering Jiangsu University Zhenjiang Jiangsu 212013 P. R. China

4. Department of Orthopedics Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200080 P. R. China

Abstract

AbstractExtracellular vesicles (EVs) derived from differentiating induced stem cells maintain their original stemness and differentiating trends and possess strong immunoregulatory capability. Biomaterials equipped with EVs are very promising in regenerative medicine. However, surface EV‐decoration on osteoimplants remains a challenge, due to the complexity of traditional molecular conjugations and the fragility of EVs. Here, mussel‐like molecular adhesion is combined with bioorthogonal click conjugation to introduce EVs on titanium (Ti) implants. The biomimetic adhesion and clickable molecular linkage allow mild and stable tethering of pre‐osteogenic mesenchymal stem cell (MSC)‐derived EVs on Ti implants. EV‐decorated implants exhibit significantly enhanced osseointegration on the bone‐implant surface under diabetic conditions, promoting increased expression of osteogenic genes. Modified surfaces impelled phenotypic alterations in macrophage polarization via multi‐pathway regulation, decreasing proinflammatory M1 macrophage formation, which can lead to the promotion of surface osteogenesis. On Ti rods implanted in a diabetic rat model, EV coating inhibited M1macrophages around the prosthesis, resulting in satisfactory long‐term osseointegration. This study offers a new perspective to represent a simple and effective means for surface EV decoration, providing an osteoimmunomodulatory effect to enhance the diabetic osseointegration of implants.

Funder

National Postdoctoral Program for Innovative Talents

National Natural Science Foundation of China

Natural Science Foundation of Jiangsu Province

Priority Academic Program Development of Jiangsu Higher Education Institutions

Publisher

Wiley

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