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双特异性滑液-半月板适体通过募集内源性靶向细胞修复缺血性半月板损伤。

Repairing Avascular Meniscal Lesions by Recruiting Endogenous Targeted Cells Through Bispecific Synovial-Meniscal Aptamers.

机构信息

Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

School of Chemistry, Sun Yat-sen University, Guangzhou, China.

出版信息

Am J Sports Med. 2023 Apr;51(5):1177-1193. doi: 10.1177/03635465231159668. Epub 2023 Mar 14.

Abstract

BACKGROUND

Tissue engineering is a promising treatment option for meniscal lesions in the avascular area, but a favorable cell source and its utilization in tissue-engineered menisci remain uncertain. Therefore, a more controllable and convenient method for cell recruitment is required.

HYPOTHESIS

Circular bispecific synovial-meniscal (S-M) aptamers with a gelatin methacryloyl (GelMA) hydrogel can recruit endogenous synovial and meniscal cells to the site of the defect, thereby promoting in situ meniscal regeneration and chondroprotection.

STUDY DESIGN

Controlled laboratory study.

METHODS

Synovial and meniscal aptamers were filtered through systematic evolution of ligands by exponential enrichment (SELEX) and cross-linked to synthesize the S-M aptamer. A GelMA-aptamer system was constructed. An in vitro analysis of the bi-recruitment of synovial and meniscal cells was performed, and the migration and proliferation of the GelMA-aptamer hydrogel were also tested. For the in vivo assay, rabbits (n = 90) with meniscal defects in the avascular zone were divided into 3 groups: repair with the GelMA-aptamer hydrogel (GelMA-aptamer group), repair with the GelMA hydrogel (GelMA group), and no repair (blank group). Regeneration of the repaired meniscus and degeneration of the cartilage were assessed by gross and histological evaluations at 4, 8, and 12 weeks postoperatively. The mechanical properties of repaired menisci were also evaluated.

RESULTS

In vitro synovial and meniscal cells were recruited simultaneously by the S-M aptamer with high affiliation and specificity. The GelMA-aptamer hydrogel promoted the migration of targeted cells. Compared with the other groups, the GelMA-aptamer group showed enhanced fibrocartilaginous regeneration, lower cartilage degeneration, and better mechanical strength at 12 weeks after meniscal repair.

CONCLUSION/CLINICAL RELEVANCE: Bispecific S-M aptamers could be used for avascular meniscal repair by recruiting endogenous synovial and meniscal cells and promoting fibrocartilaginous regeneration.

摘要

背景

组织工程是治疗非血管区半月板损伤的一种有前途的治疗方法,但合适的细胞来源及其在组织工程半月板中的应用仍不确定。因此,需要一种更可控和方便的细胞募集方法。

假设

具有明胶甲基丙烯酰(GelMA)水凝胶的圆形双特异性滑膜-半月板(S-M)适体可以募集内源性滑膜和半月板细胞到缺陷部位,从而促进半月板原位再生和软骨保护。

研究设计

对照实验室研究。

方法

通过指数富集的配体系统进化(SELEX)筛选滑膜和半月板适体,并交联合成 S-M 适体。构建了 GelMA-适体系统。进行了滑膜和半月板细胞双募集的体外分析,并测试了 GelMA-适体水凝胶的迁移和增殖。在体内试验中,将 90 只兔(非血管区半月板损伤)分为 3 组:GelMA-适体水凝胶修复(GelMA-aptamer 组)、GelMA 水凝胶修复(GelMA 组)和不修复(空白组)。术后 4、8 和 12 周,通过大体和组织学评估评估修复半月板的再生和软骨退变情况。还评估了修复半月板的机械性能。

结果

S-M 适体以高亲和力和特异性同时募集滑膜和半月板细胞。GelMA-适体水凝胶促进了靶细胞的迁移。与其他组相比,在半月板修复后 12 周,GelMA-aptamer 组表现出增强的纤维软骨再生、较低的软骨退变和更好的机械强度。

结论/临床相关性:双特异性 S-M 适体可通过募集内源性滑膜和半月板细胞并促进纤维软骨再生,用于治疗非血管性半月板损伤。

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