Research and Development, Healthpoint Biotherapeutics, Fort Worth, TX, USA.
Int Wound J. 2012 Feb;9(1):44-53. doi: 10.1111/j.1742-481X.2011.00843.x. Epub 2011 Aug 31.
Small intestine submucosa (SIS), a bioactive extracellular matrix (ECM) containing critical components of the ECM including collagens, proteoglycans, and glycosaminoglycans, has been widely used for wound healing. The purpose of this study was to investigate the interaction between SIS and matrix metalloproteinases (MMPs). MMP-1, MMP-2, and MMP-9 displayed different binding affinities, indicated by a loss in activity in solution upon incubation with SIS at 53·8%, 85·9%, and 36·9% over 24 hours, respectively. A cell migration study was conducted to evaluate the effects of MMPs and SIS on keratinocytes. The results indicated that MMPs inhibit keratinocyte migration in vitro, and that the inhibition can be significantly reduced by pre-incubating the MMP solution with SIS. To evaluate activity in vivo a diabetic mouse wound healing study was conducted. Biopsy samples were collected on different days for analysis of MMP levels by gelatin zymography. MMP activity was found to be attenuated by SIS treatment on day 3 after wounding. On day 7, the attenuation became less significant indicating that the MMP binding ability of SIS had become saturated. SIS was able to reduce MMP activity immediately, and may reduce the inhibitory effects of MMPs on keratinocyte migration.
小肠黏膜下层（SIS）是一种具有生物活性的细胞外基质（ECM），含有 ECM 的关键成分，包括胶原蛋白、蛋白聚糖和糖胺聚糖，已广泛用于伤口愈合。本研究旨在研究 SIS 与基质金属蛋白酶（MMPs）之间的相互作用。MMP-1、MMP-2 和 MMP-9 与 SIS 孵育 24 小时后在溶液中的活性分别损失 53.8%、85.9%和 36.9%，表明它们具有不同的结合亲和力。进行了一项细胞迁移研究，以评估 MMPs 和 SIS 对角质形成细胞的影响。结果表明，MMPs 抑制体外角质形成细胞迁移，并且 MMP 溶液与 SIS 预孵育可显著降低抑制作用。为了评估体内活性，进行了糖尿病小鼠伤口愈合研究。在不同天数采集活检样本，通过明胶酶谱法分析 MMP 水平。发现 MMP 活性在受伤后第 3 天通过 SIS 处理而减弱。在第 7 天，这种衰减变得不那么明显，表明 SIS 对 MMP 的结合能力已经饱和。SIS 能够立即降低 MMP 活性，并可能降低 MMPs 对角质形成细胞迁移的抑制作用。
