Biomaterial-based therapy that can restore annulus fibrosus (AF) function in early stage and promote endogenous repair of AF tissues is a promising approach for AF tissue repair. In this study, we established a genipin-crosslinked decellularized AF hydrogels (g-DAF-G) that are injectable and could manifest better in situ formability than noncrosslinked decellularized AF hydrogel, while preserving the capacity of directing differentiation of human bone mesenchymal stem cells (hBMSCs) towards AF cells. Hematoxylin and eosin staining, 4',6-diamidino-2-phenylindole staining, and so forth showed that the majority of cellular components were removed, whereas extracellular matrix and microstructure were largely preserved. The storage modulus increased from 465.5 ± 9.4 Pa to 3.29 ± 0.24 MPa after 0.02% genipin crosslinking of decellularized AF hydrogels (DAF-G) to form g-DAF-G. AF-specific genes (COL1A1, COL5A1, TNMD, IBSP, FBLN1) were significantly higher in DAF-G and g-DAF-G groups than that in control group after 21 days of culturing. g-DAF-G significantly restored nucleus pulposus water content and preserved intervertebral structure in vivo. Summarily, we produced a novel AF regeneration biomaterial, g-DAF-G, which exhibited well biocompatibility, great bioactivity, and much higher mechanical strength than DAF-G. This study will provide an easy and fast therapeutic alternative to repair AF injuries or tears.

中文翻译：

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Genipin交联的脱细胞纤维环水凝胶可诱导骨髓间充质干细胞的组织特异性分化和椎间盘再生。

可在早期恢复纤维环（AF）功能并促进AF组织的内源性修复的基于生物材料的疗法是一种有前途的AF组织修复方法。在这项研究中，我们建立了可注射的genipin交联的脱细胞AF水凝胶（g-DAF-G），与非交联的脱细胞AF水凝胶相比，它可以表现出更好的原位可成型性，同时保留了引导人骨间充质干细胞分化的能力（ hBMSC）转移至AF细胞。苏木精和曙红染色，4'，6-二mid基-2-苯基吲哚染色等表明，大部分细胞成分被去除，而细胞外基质和微结构被保留得最多。储能模量从0开始从465.5±9.4 Pa增加到3.29±0.24 MPa。去细胞的AF水凝胶（DAF-G）的02％Genipin交联形成g-DAF-G。培养21天后，DAF-G和g-DAF-G组的AF特异性基因（COL1A1，COL5A1，TNMD，IBSP，FBLN1）显着高于对照组。g-DAF-G可在体内显着恢复髓核水含量并保留椎间结构。综上所述，我们生产了一种新型的AF再生生物材料g-DAF-G，与DAF-G相比，它具有良好的生物相容性，出色的生物活性和更高的机械强度。这项研究将提供一种简便，快速的治疗方法来修复AF损伤或眼泪。g-DAF-G可在体内显着恢复髓核水含量并保留椎间结构。综上所述，我们生产了一种新型的AF再生生物材料g-DAF-G，与DAF-G相比，它具有良好的生物相容性，出色的生物活性和更高的机械强度。这项研究将提供一种简便，快速的治疗方法来修复AF损伤或眼泪。g-DAF-G可在体内显着恢复髓核水含量并保留椎间结构。综上所述，我们生产了一种新型的AF再生生物材料g-DAF-G，与DAF-G相比，它具有良好的生物相容性，出色的生物活性和更高的机械强度。这项研究将提供一种简便，快速的治疗方法来修复AF损伤或眼泪。