In vitro and in vivo studies on matrix metalloproteinases interacting with small intestine submucosa wound matrix

Abstract

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.

Outcome of conjunctival flap repair for corneal defects with and without an acellular submucosa implant in 73 canine eyes

“…A collagen bioscaffold is formed by decellularization of the submucosa through physical, chemical, and enzymatic processes . Acellular submucosa has a decreased susceptibility to bacterial colonization, the potential to inhibit matrix metalloproteinases, and a low antigenic potential . In addition, the extracellular matrix of the submucosa plays a role in angiogenesis, cell proliferation, and cell migration .…”

Ovine-Based Collagen Matrix Dressing: Next-Generation Collagen Dressing for Wound Care

“…1 Applying sufficient collagen to affect protease levels for the duration of treatment application would seem to be necessary to buffer MMP activity effectively and change the chronic proteolytic wound environment. Shi et al 29 demonstrated that the attenuation effect of MMPs by porcine small intestine submucosa (SIS) diminished over time. The buffering effect was maximal at day 3, but subsided by day 7.…”

“…Consumption of the collagen by MMPs occurred and the dressing was consumed. 29 Thus, for a given chronic wound, a certain dosing of collagen would be necessary.…”

Modified penetrating keratoplasty with Acell® bioscaffold implant in seven horses with deep full‐thickness corneal stromal abscess

“…[14][15][16][17][18][19][20][21][22] Extracellular matrix xenografts are composed of structural and functional proteins, glycoproteins and proteoglycans, forming a scaffold for tissue morphogenesis, maintenance, and wound remodeling and have been used in various tissue engineering and surgical applications. 23 Additional benefits of extracellular matrix include a low antigenic potential, support of angiogenesis, cell migration and proliferation, 24,25 inhibition of matrix metalloproteinases, 26 and resistance to bacterial infection. 27 Limited reports exist for the use of SIS in the equine patient.…”