Introduction: While acute wounds progress through the phases of wound healing, chronic wounds often stall at the inflammation phase, resulting in excess inflammation and elevated matrix metalloproteinase (MMP) levels. MMPs are critical for remodeling the wound environment, but excess expression can result in the breakdown of newly formed extracellular matrix (ECM) and granulation tissue. As such, wound products consisting of native ECM that can inhibit MMPs may help wounds progress through the natural healing process. In this study, we characterized native ECM matrix products and evaluated both durability in an in vitro chronic wound model and the ability to inhibit MMPs.
Methods: Initial characterization of purified native type 1 collagen ECM plus polyhexamethylene biguanide* (PCMP) and PCMP-Extra Thick† (PCMP-XT) was performed using histological and scanning electron microscopy (SEM) imaging. PCMP, PCMP-XT, and Ovine Forestomach Matrix⁰ (OFM), were assessed for product degradation using simulated wound fluid (SWF) with and without collagenase I and II as an in vitro chronic wound model. Finally, MMP inhibition utilizing a solid-state assay for each product was tested using Enzo MMP kits.
Results: PCMP and PCMP-XT endured 7 days of degradation in SWF/Collagenase I/Collagenase II, while OFM degraded in 24-48 hours. PCMP had masses of 10.36mg (day 0), 6.79mg (day 3), and 2.59mg (day 7), representing 75% degradation. PCMP-XT had masses of 19.43mg (day 0), 13.14mg (day 3), and 6.84mg (day 7), resulting in 65% degradation. PCMP-XT had 2x greater mass remaining after 7 days. OFM was unable to withstand degradation, with a drop in mass from 9.36mg to 0.74mg after 24 hours. PCMP/XT were statistically better than OFM at inhibiting collagenases, gelatinases, and stromelysins (p< 0.05), but all products inhibited some MMPs.
Discussion: Herein, we have characterized native collagen structure and thickness of PCMP and PCMP-XT, which are two- and five-layer products, respectively. Compared to OCM, the cross-linked structure of PCMP and PCMP-XT native collagen ECM products resulted in both improved durability in an in vitro chronic wound model and increased MMP inhibition.