journal article·2024-04

Injectable Microgels with Hybrid Exosomes of Chondrocyte‐Targeted FGF18 Gene‐Editing and Self‐Renewable Lubrication for Osteoarthritis Therapy

Manyu Chen, Yan Lu, Yuhan Liu, Quanying Liu, Siyan Deng, Yuan Liu, Xiaolin Cui, Jie Liang, Xingdong Zhang, Yujiang Fan, Qiguang Wang

Advanced Materials· Volume 36· Issue 16
Publisher page

Abstract

Abstract Abnormal silencing of fibroblast growth factor (FGF) signaling significantly contributes to joint dysplasia and osteoarthritis (OA); However, the clinical translation of FGF18‐based protein drugs is hindered by their short half‐life, low delivery efficiency and the need for repeated articular injections. This study proposes a CRISPR/Cas9‐based approach to effectively activate the FGF18 gene of OA chondrocytes at the genome level in vivo, using chondrocyte‐affinity peptide (CAP) incorporated hybrid exosomes (CAP/FGF18‐hyEXO) loaded with an FGF18‐targeted gene‐editing tool. Furthermore, CAP/FGF18‐hyEXO are encapsulated in methacrylic anhydride‐modified hyaluronic (HAMA) hydrogel microspheres via microfluidics and photopolymerization to create an injectable microgel system (CAP/FGF18‐hyEXO@HMs) with self‐renewable hydration layers to provide persistent lubrication in response to frictional wear. Together, the injectable CAP/FGF18‐hyEXO@HMs, combined with in vivo FGF18 gene editing and continuous lubrication, have demonstrated their capacity to synergistically promote cartilage regeneration, decrease inflammation, and prevent ECM degradation both in vitro and in vivo, holding great potential for clinical translation.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Extracellular vesicles in disease · Polymer Surface Interaction Studies · Electrospun Nanofibers in Biomedical Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

National Engineering Research Center for Biomaterials Sichuan University 29 Wangjiang Road Chengdu 610064 P. R. China

College of Biomedical Engineering Sichuan University 29 Wangjiang Road Chengdu 610064 P. R. China

The Third Affiliated Hospital of Jinzhou Medical University Jinzhou Liaoning 121000 P. R. China

Institute of Rocket Force Medicine State Key Laboratory of Trauma Burns and Combined Injury Third Military Medical University (Army Medical University) Chongqing 400038 P. R. China

Orthopedics Research Institute Department of Orthopedics West China Hospital Sichuan University Chengdu 610041 P. R. China

School of medicine the Chinese University of Hong Kong Shenzhen 518172 P. R. China

Department of Orthopedic Surgery & Musculoskeletal Medicine Centre for Bioengineering & Nanomedicine University of Otago Christchurch 8140 New Zealand

Sichuan Testing Center for Biomaterials and Medical Devices Sichuan University 29 Wangjiang Road Chengdu 610064 P. R. China

Funding

National Natural Science Foundation of China · Higher Education Discipline Innovation Project

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