Early kinetics of integration of collagen-glycosaminoglycan regenerative scaffolds in a diabetic mouse model

BACKGROUND:: Collagen-glycosaminoglycan scaffolds, originally designed to treat severe burns, are now commonly used in patients with complex wounds associated with diabetes mellitus. In this study, the authors investigated how the thickness of the scaffold would affect cellular integration with the diabetic host and whether this can be accelerated using subatmospheric pressure wound therapy devices. METHODS:: Collagen-glycosaminoglycan scaffolds, 500 to 2000-μm thick, were applied to dorsal wounds in genetically diabetic mice. In addition, 1000-μm collagen-glycosaminoglycan scaffolds with and without silicone were treated with a subatmospheric pressure device (-125 mmHg). On days 5 and 10, cellular and vascular integration of tissues was studied by histology, immunohistochemistry, corrosion casting, and qRT-polymerase chain reaction. RESULTS:: Cells and vessels from the wound surface populated the scaffold to form layers with varying cellular density. Areas of high cell density and proliferation were noted at the bottom of the scaffold. Increasing the thickness of the scaffold did not affect the extent of cellular ingrowth, so that thicker scaffolds had a thicker residual acellular layer on the surface. The thickness of cellular ingrowth was stable between days 5 and 10, whereas vessels seen in the scaffolds on day 10 were not yet present on day 5. Subatmospheric pressure devices applied to silicone-covered collagen- glycosaminoglycan scaffolds minimized the granulation tissue formation beneath the scaffold, which enhanced vessel ingrowth. CONCLUSIONS:: The early kinetics of cellular integration into collagen-glycosaminoglycan scaffolds is independent of scaffold thickness in a diabetic wound model. Scaffold adherence to the wound and integration can be improved using a subatmospheric pressure device.