(WHS-O.01) Impact of Extracellular Matrix Graft Composition on Degradation Dynamics and Scaffold Functionality
Thursday, May 16, 2024
6:00 PM – 6:30 PM East Coast USA Time
Extracellular matrix (ECM) grafts are emerging as a promising treatment option for chronic wounds due to their scaffold properties. Here, two porcine small intestinal submucosa-derived cross-linked collagen matrices with PHMB (PCMP*,2layers; PCMP-XT°,5layers) were compared to ovine forestomach matrix (OFM^,1layer) derived from propria submucosa and assessed for their durability in a simulated wound environment and functionality as a scaffold by their ability to inhibit proteases and support cell attachment and proliferation. Matrices were evaluated for structure using scanning electron microscopy (SEM) and histology, ability to modulate matrix metalloproteinases (MMPs) using fluorometric assays, and graft durability using an in vitro degradation model comprised of simulated wound fluid plus collagenases type I and II (SWF+). Throughout degradation, scaffold functionality was assessed using an in vitro primary human dermal fibroblast cell attachment model. Grafts differed in matrix structure, composition, and thickness. SEM demonstrated a more fibrous structure in OFM and PCMP-XT, which was confirmed following histological evaluation. When evaluating tissue thickness, PCMP-XT was significantly thicker than PCMP, while PCMP and OFM were comparable. All matrices resulted in inhibition of collagenases, gelatinases, and stromelysins, but PCMP and PCMP-XT were overall more inhibitory compared to OFM. In an in vitro SWF+ degradation model, OFM degraded rapidly ( <3 hours) and was therefore omitted from further analysis. Both PCMP and PCMP-XT significantly degraded in the SWF+ model within 7 days (p < 0.0001), with PCMP having a significantly higher degradation rate (p < 0.05). To assess scaffold functionality, intact (non-degraded) and degraded grafts were seeded with primary human fibroblasts and evaluated for attachment and proliferation over 7 days. Cells readily attached to both matrices. Cells seeded on PCMP resulted in significant proliferation on days 3 and 7 (p < 0.01), while cells seeded on PCMP-XT demonstrated significant proliferation at day 7 (p < 0.05). To assess the ability of matrices to support cell attachment through degradation, 3-and 5-day SWF+ degraded scaffolds were evaluated for cell proliferation for 7 days. PCMP and PCMP-XT exhibited robust cell attachment on 3- and 5-day degraded scaffolds, with significant proliferation on both by day 7. Interestingly, 5-day degraded PCMP resulted in overall more proliferation compared to 3-day degraded samples on day 7 (p < 0.01), while proliferation was comparable for both 3- and 5-day degraded PCMP-XT groups (p < 0.0001). Together, these findings demonstrate that differing compositions of ECM grafts result in varying MMP inhibition and durability. Throughout degradation, both PCMP and PCMP-XT demonstrated a maintenance of scaffold properties by supporting fibroblast attachment and proliferation. *Puraply® AM; Puraply® AM-XT, Organogenesis, Canton, MA Endoform, Aroa Biosurgery, San Diego, CA