Abstract：
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.
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.
摘要：
■与成年半月板不同，胎儿半月板具有强大的愈合能力。成年半月板的致密而坚硬的基质为细胞迁移提供了生物物理屏障，胎儿半月板中不存在。受发育特征的启发，将成年半月板的基质改造成胎儿状，松散和柔软的微环境有机会促进修复，尤其是在无血管区。
■将成年半月板的致密而坚硬的基质修改为胎儿状，松散和柔软的微环境可以增强细胞迁移到泪液界面和随后强大的愈合能力。
■对照实验室研究。
■用透明质酸酶或胶原酶处理新鲜的猪半月板。评估胶原纤维的密度和排列。通过组织学评估蛋白聚糖和胶原蛋白的降解。检查半月板内的细胞迁移或外源细胞向半月板的浸润。具有相对大孔的树枝状二氧化硅纳米颗粒用于包封透明质酸酶以快速释放。具有相对小的孔的介孔二氧化硅纳米颗粒用于包封转化生长因子-β3(TGF-β3)以用于缓慢释放。总共包括24只成熟的雄性兔。在内侧半月板的无血管区中制备纵向垂直撕裂（长度为0.5cm）。用缝线修复了撕裂，除了空白二氧化硅纳米颗粒外，用缝合线修复，或除了释放透明质酸酶和TGF-β3的二氧化硅纳米颗粒外，用缝合线修复。在术后12个月处死动物。通过宏观和组织学评估半月板修复。
■透明质酸酶处理后胶原蛋白束之间的间隙增加，而胶原酶处理导致胶原破坏。透明质酸酶处理后蛋白聚糖以剂量依赖性方式降解，但胶原蛋白的完整性得以维持。透明质酸酶处理增强了半月板组织内细胞的迁移和浸润。最后,在原位纵向垂直撕裂模型中，纤维蛋白凝胶和包裹透明质酸酶和TGF-β3的二氧化硅纳米颗粒递送系统的应用增强了半月板修复反应。
■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障碍，创造一个像胎儿一样的，宽松和软的微环境，增强了修复细胞的纤维软骨表型，促进基质的合成和组织的整合。
■将成年基质修改为胎儿状，通过透明质酸酶和TGF-β3的局部梯度释放，松软的微环境增强了半月板的愈合能力。
■将成年半月板的致密而坚硬的基质修改为胎儿状，松散和柔软的微环境可以增强细胞迁移到泪液界面和随后强大的愈合能力。
■对照实验室研究。
■用透明质酸酶或胶原酶处理新鲜的猪半月板。评估胶原纤维的密度和排列。通过组织学评估蛋白聚糖和胶原蛋白的降解。检查半月板内的细胞迁移或外源细胞向半月板的浸润。具有相对大孔的树枝状二氧化硅纳米颗粒用于包封透明质酸酶以快速释放。具有相对小的孔的介孔二氧化硅纳米颗粒用于包封转化生长因子-β3(TGF-β3)以用于缓慢释放。总共包括24只成熟的雄性兔。在内侧半月板的无血管区中制备纵向垂直撕裂（长度为0.5cm）。用缝线修复了撕裂，除了空白二氧化硅纳米颗粒外，用缝合线修复，或除了释放透明质酸酶和TGF-β3的二氧化硅纳米颗粒外，用缝合线修复。在术后12个月处死动物。通过宏观和组织学评估半月板修复。
■透明质酸酶处理后胶原蛋白束之间的间隙增加，而胶原酶处理导致胶原破坏。透明质酸酶处理后蛋白聚糖以剂量依赖性方式降解，但胶原蛋白的完整性得以维持。透明质酸酶处理增强了半月板组织内细胞的迁移和浸润。最后,在原位纵向垂直撕裂模型中，纤维蛋白凝胶和包裹透明质酸酶和TGF-β3的二氧化硅纳米颗粒递送系统的应用增强了半月板修复反应。
■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障碍，创造一个像胎儿一样的，宽松和软的微环境，增强了修复细胞的纤维软骨表型，促进基质的合成和组织的整合。
■将成年基质修改为胎儿状，通过透明质酸酶和TGF-β3的局部梯度释放，松软的微环境增强了半月板的愈合能力。
