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Mathematical Modeling and Frequency Gradient Analysis of Cellular and Vascular Invasion into Integra and Strattice: Toward Optimal Design of Tissue Regeneration Scaffolds

Reiffel, Alyssa J. M.D.; Henderson, Peter W. M.D., M.B.A.; Krijgh, David D. M.Sc.; Belkin, Daniel A. B.A.; Zheng, Ying Ph.D.; Bonassar, Lawrence J. Ph.D.; Stroock, Abraham D. Ph.D.; Spector, Jason A. M.D.

Plastic & Reconstructive Surgery: January 2012 - Volume 129 - Issue 1 - p 89–99
doi: 10.1097/PRS.0b013e318230c5f1
Experimental: Original Articles

Background: Rapid, effective host cell invasion and vascularization is essential for durable incorporation of avascular tissue-replacement scaffolds. In this study, the authors sought to qualitatively and quantitatively determine which of two commercially available products (i.e., Strattice and Integra) facilitates more rapid cellular and vascular invasion in a murine model of graft incorporation.

Methods: Integra and Strattice were implanted subcutaneously into the dorsa of C57BL/6 mice; harvested after 3, 7, or 14 days; and stained with hematoxylin and eosin, 4′,6-diamidino-2-phenylindole, and immunohistochemical stains for CD31 and α-smooth muscle actin. Exponential decay equations describing cellular invasion through each layer were fit to each material/time point. Mean cell density and cell frequency maps were created denoting extent of invasion by location within the scaffold.

Results: Qualitative analysis demonstrated extensive cellular infiltration into Integra by 3 days and increasing over the remaining 14 days. Invasion of Strattice was sparse, even after 14 days. α-Smooth muscle actin immunohistochemistry revealed blood vessel formation within Integra by 14 days but no analogous neovascularization in Strattice. Mean decay equations for Integra and Strattice were y = 76.3(0.59)x and y = 75.5(0.33)x, respectively. Both cell density measurements and frequency mapping demonstrated that, at all time points, Integra manifested a greater density/depth of cellular invasion when compared with Strattice.

Conclusions: These data confirm empiric clinical observations that Integra is more rapidly invaded than Strattice when placed in a suitable host bed. A remnant microvasculature template is not sufficient for effective cellular ingrowth into an artificial tissue construct. These findings provide insight into means for improving future dermal replacement products.

New York and Ithaca, N.Y.

From the Division of Plastic Surgery, Weill Cornell Medical College, and the School of Chemical and Biomolecular Engineering, the Department of Biomedical Engineering, and the Sibley School of Mechanical and Aerospace Engineering, Cornell University.

Received for publication February 22, 2011; accepted April 18, 2011.

Disclosure: The authors have no financial interests to disclose.

Jason A. Spector, M.D.; Division of Plastic Surgery, Weill Cornell Medical College, 525 East 68th Street, Payson 709A, New York, N.Y. 10065,

©2012American Society of Plastic Surgeons