The Acellular Dermal Replacement Scaffolds Strattice® and Integra®: A Quantitative In-Vivo Model of Graft Incorporation

Introduction: Rapid and effective vascularization via host cell invasion is key to the integration of avascular dermal replacement scaffolds. Two widely-applied commercially-available products are Strattice^ñ (decellularized porcine dermis with a retained microvascular architecture) and Integra^ñ (a combination of bovine collagen and glycosaminoglycans containing a latticework of random pores).  While these products are commonly used in clinical practice, the effects of their respective architectures on the speed and extent of host cell invasion and vascularization have not yet been studied.  We therefore sought to determine which product facilitates more rapid cellular and vascular invasion in a quantitative in vivo model of graft incorporation.

Methods: Four 8mm discs of Integra^ñ or Strattice^ñ were implanted subcutaneously in the dorsum of 12 C57BL/6 mice and harvested after 3, 7,  or 14 days.  Hematoxylin & eosin and immunohistochemical (IHC) staining for CD31 were performed. Sections were counterstained with 4',6-diamidino-2-phenylindole (DAPI). Differential cell densities were calculated by quantifying DAPI-positive cells per cross-sectional area.  Lastly, 15 representative 200µm x 500µm images were combined to create cell frequency maps denoting extent of invasion by location within the scaffold.

Results: Qualitative analyses demonstrated diffuse and extensive cellular infiltration into Integra^ñ by day 3 and increasing over the 2-week period. Invasion of Strattice^ñ was patchy and sparse, even after 14 days. IHC staining for CD31 revealed blood vessel formation within Integra^ñ by day 14, but no analogous neovascularization in Strattice^ñ. Cell density measurements showed that at all time points, Integra^ñ manifested a greater density and depth of cellular invasion as compared with Strattice^ñ, a finding confirmed by cell frequency mapping (Figure).

Conclusions: These data confirm empiric clinical observations that Integra^ñ is more rapidly and extensively vascularized than Strattice^ñ when placed in a suitable host bed. Furthermore, we have demonstrated that the presence of a remnant microvasculature template as seen in Strattice^ñ is not sufficient for rapid cellular ingrowth into an artificial tissue construct. These findings provide the first quantitative comparison between these dermal replacements and reaffirm clinical insights regarding the appropriate use of these products. Finally, these data can be further extrapolated into a means of improving future tissue replacement products so as to elicit more rapid host cellular invasion and vascular incorporation.

FIGURE: Cell frequency maps. Blue dots represent nuclei in the (r.z)-plane.