Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Department of Neurological Surgery, Weill Cornell Medical College, New York, NY, USA.
Acta Biomater. 2019 Oct 1;97:428-436. doi: 10.1016/j.actbio.2019.08.024. Epub 2019 Aug 16.
Intervertebral disc (IVD) herniations are currently treated with interventions that leave the IVD with persistent lesions prone to further herniations. Annulus fibrosus (AF) repair has become of interest as a method to seal defects in the IVD and prevent reherniation, but this requires strong adhesion of the implanted biomaterial to the native AF tissue. Our group has previously developed a high-density collagen (HDC) gel for AF repair and tested its efficacy in vivo, but its adhesion to the AF could be improved. Increased cell adhesion to cartilage has previously been reported through chondroitinase ABC (ChABC) digestion, which removes proteoglycans and increases access to cell binding motifs. Such approaches could also increase biomaterial adhesion to tissue, but the effects of ChABC digestion on AF have yet to be investigated. In this study, ovine AF tissue was digested with either 10 U/mL ChABC or saline for up to 10 min and the effect of this treatment on collagen adhesion between AF tissue samples was investigated by histology and mechanical testing in a lap-shear configuration. ChABC digestion removed proteoglycans within the AF in a time-dependent fashion and enhanced adhesion of the HDC gel to the AF. ChABC digestion increased the elastic toughness and total shear energy of the HDC gel-AF interface by 88% and 46% respectively. ChABC treatment enhanced the adhesion of the HDC gel to the AF without significantly decreasing native AF cell viability. Thus, ChABC digestion is a viable method to improve adhesion of biomaterials for AF repair. STATEMENT OF SIGNIFICANCE: Intervertebral disc herniations are currently treated with interventions that leave persistent lesions in the annulus fibrosus that are prone to further herniations. Annular repair is a promising method to seal lesions and prevent reherniation, but requires strong adhesion of the implanted biomaterial to native annulus fibrosus. Since large proteoglycans like aggrecan occupy regions of the extracellular matrix between collagen fibers in the annulus fibrosus, we hypothesized that removing proteoglycans via chondroitinase digestion would increase the adhesion of annular repair hydrogels. This investigation demonstrated that chondroitinase removed proteoglycans within annulus fibrosus tissue, enhanced the interaction of an injected collagen gel with the native tissue, and mechanically improved adhesion between the collagen gel and annulus fibrosus. This is the first study of its kind to evaluate the biochemical and mechanical effects of short-term chondroitinase digestion on annulus fibrosus tissue.
椎间盘（IVD）突出症目前采用的干预措施会在纤维环中留下持续存在的病变，容易进一步突出。纤维环修复已成为一种封闭 IVD 缺陷并防止再次突出的方法，但这需要植入生物材料与天然纤维环组织牢固结合。我们的团队之前开发了一种高密度胶原蛋白（HDC）凝胶用于纤维环修复，并在体内测试了其功效，但它与纤维环的结合力可以提高。先前有报道称，通过软骨素酶 ABC（ChABC）消化可以增加软骨细胞的粘附，软骨素酶 ABC 消化可以去除蛋白聚糖并增加细胞结合基序的可及性。这种方法也可以增加生物材料与组织的粘附，但 ChABC 消化对纤维环的影响尚未得到研究。在这项研究中，羊纤维环组织用 10 U/mL ChABC 或生理盐水消化，最长达 10 分钟，通过组织学和 lap-shear 配置下的力学测试研究了这种处理对纤维环组织样本之间胶原粘附的影响。ChABC 消化以时间依赖性方式去除纤维环中的蛋白聚糖，并增强 HDC 凝胶与纤维环的粘附。ChABC 消化分别将 HDC 凝胶-纤维环界面的弹性韧性和总剪切能提高了 88%和 46%。ChABC 处理增强了 HDC 凝胶与纤维环的粘附，而不会显著降低天然纤维环细胞的活力。因此，ChABC 消化是一种可行的方法，可以提高纤维环修复用生物材料的粘附力。
目前，椎间盘突出症采用的干预措施会在纤维环中留下持续存在的病变，这些病变容易进一步突出。环形修复是一种有前途的密封病变和防止再次突出的方法，但需要将植入的生物材料与天然纤维环牢固结合。由于像聚集蛋白聚糖这样的大蛋白聚糖占据纤维环中胶原纤维之间的细胞外基质区域，我们假设通过软骨素酶消化去除蛋白聚糖会增加环形修复水凝胶的粘附力。这项研究表明，软骨素酶去除了纤维环组织中的蛋白聚糖，增强了注射胶原凝胶与天然组织的相互作用，并在胶原凝胶和纤维环之间的机械性能上改善了粘附力。这是第一项评估短期软骨素酶消化对纤维环组织的生化和机械影响的研究。
