Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Department of General Surgery, Cleveland Clinic, Cleveland, Ohio.
J Biomed Mater Res B Appl Biomater. 2019 Nov;107(8):2664-2672. doi: 10.1002/jbm.b.34357. Epub 2019 Mar 12.
Biologic grafts used in hernia repair undergo rapid cellular infiltration and remodeling, but their premature degradation often results in hernia recurrence. We hypothesize that a temporary barrier that prevents infiltration of acute inflammatory cells into the graft during the initial 4 weeks of implantation could mitigate graft degradation. The purpose of this study is to design tyramine-substituted hyaluronan (THA) hydrogel coatings with tunable degradation properties, as a means to develop a resorbable barrier for human acellular dermis grafts (HADM). THA plugs prepared at different cross-linking densities, by varying cross-linking agent concentration (0.0001-0.0075% H O ), demonstrated varying rates of in vitro degradation (25 U/mL hyaluronidase, 48 h). Based on these results, HADM grafts were coated with THA at three cross-linking densities (0.0001%, 0.00075%, and 0.003% H O ) and THA coating degradation was evaluated in vitro (25 U/mL hyaluronidase, 48 h) and in vivo (rat intraperitoneal implantation, 1-4 weeks). THA coatings degraded in vitro and in vivo with the lowest cross-linking density (0.0001% H O ), generally showing greater degradation as evidenced by significant decrease in coating cross-sectional area. However, all three coatings remained partially degraded after 4 weeks of in vivo implantation. Alternate strategies to accelerate in vivo degradation of THA coatings are required to allow investigation of the study hypothesis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2664-2672, 2019.
生物移植物用于疝修补术时会迅速发生细胞浸润和重塑,但过早降解通常会导致疝复发。我们假设,在植入后的最初 4 周内,一种临时的屏障可以阻止急性炎症细胞浸润移植物,从而减轻移植物的降解。本研究旨在设计具有可调节降解特性的酪胺取代透明质酸(THA)水凝胶涂层,作为开发人脱细胞真皮移植物(HADM)可吸收屏障的一种手段。通过改变交联剂浓度(0.0001%-0.0075%HO),在不同交联密度下制备的 THA 塞子表现出不同的体外降解速率(25 U/mL 透明质酸酶,48 h)。基于这些结果,用三种交联密度(0.0001%、0.00075%和 0.003%HO)对 HADM 移植物进行 THA 涂层,并在体外(25 U/mL 透明质酸酶,48 h)和体内(大鼠腹腔内植入,1-4 周)评估 THA 涂层的降解情况。THA 涂层在体外和体内均发生降解,交联密度最低(0.0001%HO),一般表现出更大的降解,这表现为涂层横截面积显著减小。然而,所有三种涂层在体内植入 4 周后仍部分降解。需要寻找替代策略来加速 THA 涂层在体内的降解,以验证研究假设。 © 2019 威立出版公司