Department of Sports Medicine, Institute of Sports Medicine, Peking University Third Hospital, Peking University, Beijing, China.
Beijing Key Laboratory of Sports Injuries, Beijing, China.
Am J Sports Med. 2023 Nov;51(13):3509-3522. doi: 10.1177/03635465231194028. Epub 2023 Sep 25.
Unlike the adult meniscus, the fetal meniscus possesses robust healing capacity. The dense and stiff matrix of the adult meniscus provides a biophysical barrier for cell migration, which is not present in the fetal meniscus. Inspired by developmental characteristics, modifying the matrix of the adult meniscus into a fetal-like, loose and soft microenvironment holds opportunity to facilitate repair, especially in the avascular zone.
Modifying the dense and stiff matrix of the adult meniscus into a fetal-like, loose and soft microenvironment could enhance cell migration to the tear interface and subsequent robust healing capacity.
Controlled laboratory study.
Fresh porcine menisci were treated with hyaluronidase or collagenase. The density and arrangement of collagen fibers were assessed. The degradation of proteoglycans and collagen was evaluated histologically. Cell migration within the meniscus or the infiltration of exogenous cells into the meniscus was examined. Dendritic silica nanoparticles with relatively large pores were used to encapsulate hyaluronidase for rapid release. Mesoporous silica nanoparticles with relatively small pores were used to encapsulate transforming growth factor-beta 3 (TGF-β3) for slow release. A total of 24 mature male rabbits were included. A longitudinal vertical tear (0.5 cm in length) was prepared in the avascular zone of the medial meniscus. The tear was repaired with suture, repaired with suture in addition to blank silica nanoparticles, or repaired with suture in addition to silica nanoparticles releasing hyaluronidase and TGF-β3. Animals were sacrificed at 12 months postoperatively. Meniscal repair was evaluated macroscopically and histologically.
The gaps between collagen bundles increased after hyaluronidase treatment, while collagenase treatment resulted in collagen disruption. Proteoglycans degraded after hyaluronidase treatment in a dose-dependent manner, but collagen integrity was maintained. Hyaluronidase treatment enhanced the migration and infiltration of cells within meniscal tissue. Last, the application of fibrin gel and the delivery system of silica nanoparticles encapsulating hyaluronidase and TGF-β3 enhanced meniscal repair responses in an orthotopic longitudinal vertical tear model.
The gradient release of hyaluronidase and TGF-β3 removed biophysical barriers for cell migration, creating a fetal-like, loose and soft microenvironment, and enhanced the fibrochondrogenic phenotype of reparative cells, facilitating the synthesis of matrix and tissue integration.
Modifying the adult matrix into a fetal-like, loose and soft microenvironment via the local gradient release of hyaluronidase and TGF-β3 enhanced the healing capacity of the meniscus.
与成人半月板不同，胎儿半月板具有强大的愈合能力。成人半月板致密而僵硬的基质为细胞迁移提供了生物物理屏障，而胎儿半月板则没有。受发育特征的启发，将成人半月板的基质修改为类似胎儿的、疏松柔软的微环境，有可能促进修复，尤其是在无血管区。
将成人半月板致密而僵硬的基质修改为类似胎儿的、疏松柔软的微环境，可以促进细胞迁移到撕裂界面，并随后具有强大的愈合能力。
对照实验室研究。
新鲜猪半月板用透明质酸酶或胶原酶处理。评估胶原纤维的密度和排列。组织学评估蛋白聚糖和胶原的降解情况。检查半月板内的细胞迁移或外源性细胞浸润半月板。相对较大孔径的树枝状二氧化硅纳米粒子用于封装透明质酸酶以实现快速释放。相对较小孔径的介孔二氧化硅纳米粒子用于封装转化生长因子-β3（TGF-β3）以实现缓慢释放。共纳入 24 只成熟雄性兔。在半月板无血管区制备 0.5cm 长的纵向垂直撕裂。用缝线修复撕裂，缝线修复加空白二氧化硅纳米粒子，或缝线修复加释放透明质酸酶和 TGF-β3 的二氧化硅纳米粒子。术后 12 个月处死动物。宏观和组织学评估半月板修复情况。
透明质酸酶处理后胶原束之间的间隙增加，而胶原酶处理导致胶原破坏。透明质酸酶处理呈剂量依赖性降解蛋白聚糖，但胶原完整性得以维持。透明质酸酶处理增强了细胞在半月板组织内的迁移和浸润。最后，纤维蛋白凝胶的应用和透明质酸酶和 TGF-β3 包封的二氧化硅纳米粒子的递药系统增强了原位纵向垂直撕裂模型中半月板的修复反应。
透明质酸酶和 TGF-β3 的梯度释放消除了细胞迁移的生物物理屏障，创造了类似胎儿的、疏松柔软的微环境，并增强了修复细胞的纤维软骨样表型，促进了基质的合成和组织整合。
通过局部梯度释放透明质酸酶和 TGF-β3 将成人基质修改为类似胎儿的、疏松柔软的微环境，增强了半月板的愈合能力。
