Lv Xiao, Sun Caixia, Hu Binwu, Chen Songfeng, Wang Zhe, Wu Qiang, Fu Kun, Xia Zhidao, Shao Zengwu, Wang Baichuan
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Gynecology, General Hospital of the Yangtze River Shipping, Wuhan, China.
Front Cell Dev Biol. 2020 Aug 27;8:864. doi: 10.3389/fcell.2020.00864. eCollection 2020.
The goal of treating articular cartilage (AC) injury is to regenerate cartilage tissue and to integrate the neo-cartilage with surrounding host cartilage. However, most current studies tend to focus on engineering cartilage; interface integration has been somewhat neglected. An endogenous regenerative strategy that simultaneously increases the recruitment of bone marrow mesenchymal stem cells (BMSCs) and chondrocytes may improve interface integration and cartilage regeneration. In this study, a novel functionalized self-assembling peptide hydrogel (KLD-12/KLD-12-LPP, KLPP) containing link protein N-peptide (LPP) was designed to optimize cartilage repair. KLPP hydrogel was characterized using transmission electron microscopy (TEM) and rheometry. KLPP hydrogel shared a similar microstructure to KLD-12 hydrogel which possesses a nanostructure with a fiber diameter of 25-35 nm. experiments showed that KLPP hydrogel had little cytotoxicity, and significantly induced chondrocyte migration and increased BMSC migration compared to KLD-12 hydrogel. results showed that defects treated with KLPP hydrogel had higher overall International Cartilage Repair Society (ICRS) scores, Safranin-O staining scores and cumulative histology scores than untreated defects or defects treated with KLD-12 hydrogel, although defects treated with KLD-12 and KLPP hydrogels received similar type II collagen immunostaining scores. All these findings indicated that the simple injectable functionalized self-assembling peptide hydrogel KLPP facilitated simultaneous recruitment of endogenous chondrocytes and BMSCs to promote interface integration and improve cartilage regeneration, holding great potential as a one-step surgery strategy for endogenous cartilage repair.
治疗关节软骨(AC)损伤的目标是再生软骨组织,并使新软骨与周围的宿主软骨整合。然而,目前大多数研究倾向于关注软骨工程;界面整合在一定程度上被忽视了。一种同时增加骨髓间充质干细胞(BMSC)和软骨细胞募集的内源性再生策略可能会改善界面整合和软骨再生。在本研究中,设计了一种含有连接蛋白N肽(LPP)的新型功能化自组装肽水凝胶(KLD-12/KLD-12-LPP,KLPP)以优化软骨修复。使用透射电子显微镜(TEM)和流变学对KLPP水凝胶进行了表征。KLPP水凝胶与KLD-12水凝胶具有相似的微观结构,KLD-12水凝胶具有纤维直径为25-35nm的纳米结构。实验表明,KLPP水凝胶细胞毒性小,与KLD-12水凝胶相比,能显著诱导软骨细胞迁移并增加BMSC迁移。结果表明,与未处理的缺损或用KLD-12水凝胶处理的缺损相比,用KLPP水凝胶处理的缺损具有更高的国际软骨修复协会(ICRS)总体评分、番红O染色评分和累积组织学评分,尽管用KLD-12和KLPP水凝胶处理的缺损获得了相似的II型胶原免疫染色评分。所有这些发现表明,简单可注射的功能化自组装肽水凝胶KLPP促进了内源性软骨细胞和BMSC的同时募集,以促进界面整合并改善软骨再生,作为内源性软骨修复的一步手术策略具有巨大潜力。