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Small Intestinal Submucosa (SIS*) Provides a Natural Extracellular Matrix Microarchitecture for Difficult to Heal and Chronic Wounds

Edith S. Nihsen, M.S., Cook Biotech Incorporated, Research Scientist, 1425 Innovation Place, West Lafayette, IN 47906 and Chad E. Johnson, Ph.D., Cook Biotech Incorporated, Research Engineer, 1425 Innovation Place, West Lafayette, IN 47906.

The extracellular matrix (ECM) in difficult to heal and chronic wounds is deficient or damaged. Bioactive materials can be useful in treating these wounds by providing a substitute ECM. One such biomaterial is a naturally derived scaffold consisting of porcine small intestinal submucosa (SIS*). SIS* is prepared using a process that preserves the structural molecules, such as collagen and fibronectin, before and after lyophilization and ethylene oxide sterilization. Preclinical and clinical studies demonstrated that treatment with SIS* promoted tissue infiltration, remodeling, and regeneration of the host-specific tissue and increased healing of chronic ulcerative wounds.

Tissue regeneration occurs through interactions of complex processes, including angiogenesis, and the microarchitecture of ECM is likely important.

The present study examined the effect of biomaterial microarchitecture on angiogenesis in an in vivo murine implant model, by comparing SIS* to an oxidized regenerated cellulose/collagen composite material (ORC**).

Fluorescent microangiography illustrated reduced angiogenic response in the ORC** compared to SIS*. This was measured by vessel ingrowth distance (<1mm vessel ingrowth vs. ~3mm vessel ingrowth SIS*). This result was verified by fluorescence quantitation and histological examination by hematoxylin and eosin staining, which showed little to no cellular infiltration into the ORC**.

These results suggest that having a natural ECM microarchitecture improves the angiogenic response in a cross-species, in vivo angiogenesis assay. Therefore, the ECM microarchitecture plays a role in blood vessel ingrowth into biomaterials and is beneficial to wound healing.

*Oasis® Wound Matrix, manufactured by Cook Biotech Incorporated, West Lafayette IN, distributed exclusively by Healthpoint Ltd., Fort Worth TX.

**Promogran Matrix Wound Dressing, manufactured by Johnson & Johnson MEDICAL Limited, Gargrave, Skipton, UK


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