journal article·2024-08Open access

Injectable Hydrogel Based on Enzymatic Initiation of Keratin Methacrylate for Controlled Exosome Release in Intervertebral Disc Degeneration Therapy

Linjie Chen, Ke Peng, He Huang, Zehua Gong, Jinyi Huang, Abdihafid Mohamud Mohamed, Qizhu Chen, Wan Ting Sow, Liting Guo, Kenny Yat Hong Kwan, Bin Li, Moonis Ali Khan, Pooyan Makvnadi, Morgan Jones, Shuying Shen, Xiangyang Wang, Chao Ma, Huaqiong Li, Aimin Wu

Advanced Functional Materials· Volume 34· Issue 32

Abstract

Abstract The treatment of intervertebral disc degeneration (IVDD) using bone marrow mesenchymal stem cell‐derived exosomes has shown success in alleviating inflammation and restoring the extracellular matrix (ECM), however, challenges persist due to the deficiency in mechanical support and controlled release. Herein, a carbon‐carbon double bond modified keratin (KeMA) is synthesized by 2‐isocyanatoethyl modification for exosomes wrapping. This injectable KeMA hydrogel, initiated by a biocompatible glucose/ glucose oxidase/ horse radish peroxidase enzymatic cascade reaction with acetylacetone and N‐vinylpyrrolidone, displayed rapid gelation, resembling nucleus pulposus (NP) elasticity, and excellent cytocompatibility. In vitro studies showcased that the exosomes‐loaded KeMA hydrogel (Exo@KeMA) enhanced exosome release kinetics, suppressed inflammation, fostered extracellular matrix (ECM) regeneration, and reinstated NP biomechanics. RNA‐seq analysis indicated Exo@KeMA's effects involved PI3K‐Akt signaling for matrix regeneration and NF‐κB signaling inhibition for anti‐inflammation. In vivo IVDD rat models demonstrated Exo@KeMA attenuated inflammation, maintained NP water content, preserved disc height, and promoted structural regeneration. This research introduces an injectable KeMA hydrogel as a promising therapy for IVDD, by facilitating biomechanics restoration, anti‐inflammatory response, and ECM regeneration.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Spine and Intervertebral Disc Pathology · Wound Healing and Treatments · Bee Products Chemical Analysis

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

Affiliations

Department of Orthopaedics Key Laboratory of Structural Malformations in Children of Zhejiang Province Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou Zhejiang 325035 P. R. China

School of Biomedical Engineering School of Ophthalmology and Optometry and Eye Hospital Wenzhou Medical University Wenzhou Zhejiang 325035 P. R. China

Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325011 P. R. China

College of Chemistry and Materials Engineering Wenzhou University Wenzhou Zhejiang 325000 P. R. China

Department of Orthopaedics and Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China

Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Biology & Basic Medical Sciences Suzhou Medical College Soochow University Suzhou Jiangsu 215007 P. R. China

Chemistry Department College of Science King Saud University Riyadh 11451 Saudi Arabia

The Quzhou Affiliated Hospital of Wenzhou Medical University Quzhou People's Hospital Quzhou Zhejiang 324000 P. R. China

Spine Unit The Royal Orthopaedic Hospital Bristol Road South Northfield Birmingham B31 2AP UK

Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310000 P. R. China

Department of Chemistry Tsinghua University Beijing 100080 P. R. China

Funding

University of Chinese Academy of Sciences · National Natural Science Foundation of China · Key Research and Development Program of Zhejiang Province · Natural Science Foundation of Zhejiang Province

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