Multi-responsive injectable dECM hydrogel for sustained doxycycline delivery in osteoarthritis therapy

IF 7.9 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Ximing Wang , Ting Zheng , Luyao Cai , Clara Chen , Junjie Xu , Jinzhong Zhao
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Abstract

Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Current therapeutic approaches are limited by rapid drug clearance from the joint cavity, necessitating frequent administrations and failing to provide sustained therapeutic effects. Injectable hydrogels that can persistently remain within the joint space represent a promising strategy for comprehensive OA treatment. Herein, an injectable hydrogel system based on dermal-derived decellularized extracellular matrix (dECM) engineered with N-isopropylacrylamide, tannic acid, and sodium tetraborate was developed to achieve superior lubrication and strong tissue adhesion. The hydrogel exhibits exceptional lubrication properties and robust tissue adhesion, enabling prolonged retention within the joint cavity while providing continuous cartilage protection. Its excellent shear-thinning behavior and rapid self-healing capability facilitate minimally invasive injection and ensure conformal coverage of defect sites. In vitro and in vivo evaluations demonstrated that the hydrogel promotes cell proliferation, modulates anti-inflammatory responses, and significantly preserves cartilage integrity with enhanced proteoglycan and type II collagen (COL-2) expression. The sustained therapeutic efficacy was attributed to the hydrogel’s ability to maintain prolonged residence time while continuously delivering bioactive components and providing mechanical lubrication. These findings demonstrate that this multifunctional dECM-based injectable hydrogel represents a promising therapeutic platform for OA treatment suitable for clinical translation.

Abstract Image

多反应性注射dECM水凝胶用于骨关节炎治疗中强力霉素的持续递送
骨关节炎(OA)是世界上最常见的退行性关节疾病。目前的治疗方法受到药物快速从关节腔清除的限制,需要频繁给药,不能提供持续的治疗效果。可注射的水凝胶可以持久地留在关节间隙内,这是一种很有前途的OA综合治疗策略。本研究以n -异丙基丙烯酰胺、单宁酸和四硼酸钠为基础,开发了一种基于真皮来源的脱细胞细胞外基质(dECM)的可注射水凝胶系统,以实现卓越的润滑和强组织粘附。水凝胶具有优异的润滑性能和强大的组织粘附性,能够在关节腔内长时间保留,同时提供连续的软骨保护。其优异的剪切减薄性能和快速自愈能力有助于微创注射,并确保缺陷部位的适形覆盖。体外和体内评价表明,水凝胶促进细胞增殖,调节抗炎反应,并通过增强蛋白聚糖和II型胶原(COL-2)表达显著保持软骨完整性。持续的治疗效果归功于水凝胶在持续输送生物活性成分和提供机械润滑的同时保持较长停留时间的能力。这些发现表明,这种多功能的基于decm的可注射水凝胶代表了一个有前途的治疗平台,适合于临床翻译OA治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Materials & Design
Materials & Design Engineering-Mechanical Engineering
CiteScore
14.30
自引率
7.10%
发文量
1028
审稿时长
85 days
期刊介绍: Materials and Design is a multi-disciplinary journal that publishes original research reports, review articles, and express communications. The journal focuses on studying the structure and properties of inorganic and organic materials, advancements in synthesis, processing, characterization, and testing, the design of materials and engineering systems, and their applications in technology. It aims to bring together various aspects of materials science, engineering, physics, and chemistry. The journal explores themes ranging from materials to design and aims to reveal the connections between natural and artificial materials, as well as experiment and modeling. Manuscripts submitted to Materials and Design should contain elements of discovery and surprise, as they often contribute new insights into the architecture and function of matter.
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