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一种可注射的软骨涂层复合材料,具有长期保护、有效润滑和滋养软骨细胞的功能,可用于治疗骨关节炎。

An injectable cartilage-coating composite with long-term protection, effective lubrication and chondrocyte nourishment for osteoarthritis treatment.

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China; College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.

School of Medicine, the Chinese University of Hong Kong, Shenzhen 518172, China; Department of Orthopedic Surgery & Musculoskeletal Medicine, Centre for Bioengineering & Nanomedicine, University of Otago, Christchurch 8011, New Zealand.

出版信息

Acta Biomater. 2024 Apr 15;179:95-105. doi: 10.1016/j.actbio.2024.03.015. Epub 2024 Mar 19.

DOI:10.1016/j.actbio.2024.03.015
PMID:38513723
Abstract

The osteoarthritic (OA) environment within articular cartilage poses significant challenges, resulting in chondrocyte dysfunction and cartilage matrix degradation. While intra-articular injections of anti-inflammatory drugs, biomaterials, or bioactive agents have demonstrated some effectiveness, they primarily provide temporary relief from OA pain without arresting OA progression. This study presents an injectable cartilage-coating composite, comprising hyaluronic acid and decellularized cartilage matrix integrated with specific linker polymers. It enhances the material retention, protection, and lubrication on the cartilage surface, thereby providing an effective physical barrier against inflammatory factors and reducing the friction and shear force associated with OA joint movement. Moreover, the composite gradually releases nutrients, nourishing OA chondrocytes, aiding in the recovery of cellular function, promoting cartilage-specific matrix production, and mitigating OA progression in a rat model. Overall, this injectable cartilage-coating composite offers promising potential as an effective cell-free treatment for OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) in the articular cartilage leads to chondrocyte dysfunction and cartilage matrix degradation. This study introduces an intra-articular injectable composite material (HDC), composed of decellularized cartilage matrix (dECMs), hyaluronan (HA), and specially designed linker polymers to provide an effective cell-free OA treatment. The linker polymers bind HA and dECMs to form an integrated HDC structure with an enhanced degradation rate, potentially reducing the need for frequent injections and associated trauma. They also enable HDC to specifically coat the cartilage surface, forming a protective and lubricating layer that enhances long-term retention, acts as a barrier against inflammatory factors, and reduces joint movement friction. Furthermore, HDC nourishes OA chondrocytes through gradual nutrient release, aiding cellular function recovery, promoting cartilage-specific matrix production, and mitigating OA progression.

摘要

骨关节炎(OA)在关节软骨中的环境带来了重大挑战,导致软骨细胞功能障碍和软骨基质降解。虽然关节内注射抗炎药物、生物材料或生物活性物质已显示出一定的效果,但它们主要提供 OA 疼痛的暂时缓解,而不能阻止 OA 的进展。本研究提出了一种可注射的软骨涂层复合材料,由透明质酸和脱细胞软骨基质与特定的连接聚合物集成。它增强了材料在软骨表面的保留、保护和润滑,从而提供了一种有效的物理屏障,防止炎症因子,并减少与 OA 关节运动相关的摩擦和剪切力。此外,该复合材料逐渐释放营养物质,滋养 OA 软骨细胞,有助于恢复细胞功能,促进软骨特异性基质的产生,并在大鼠模型中减轻 OA 的进展。总的来说,这种可注射的软骨涂层复合材料作为一种有效的无细胞 OA 治疗方法具有很大的潜力。

意义声明

关节软骨中的骨关节炎(OA)导致软骨细胞功能障碍和软骨基质降解。本研究介绍了一种关节内可注射的复合材料(HDC),由脱细胞软骨基质(dECMs)、透明质酸(HA)和专门设计的连接聚合物组成,为 OA 提供了一种有效的无细胞治疗方法。连接聚合物将 HA 和 dECMs 结合在一起,形成具有增强的降解速率的集成 HDC 结构,这可能减少频繁注射和相关创伤的需要。它们还使 HDC 能够特异性地涂覆软骨表面,形成一个保护和润滑层,增强长期保留,作为炎症因子的屏障,并减少关节运动的摩擦。此外,HDC 通过逐渐释放营养物质滋养 OA 软骨细胞,帮助恢复细胞功能,促进软骨特异性基质的产生,并减轻 OA 的进展。

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