Collagenase-resistant collagen is a deficient substratum for growth factor–stimulated angiogenesis.

WT or collagenase-resistant, r/r collagen at equal concentrations was copolymerized with buffer alone or bFGF/VEGF, prior to placement on the chick CAM. The embryos containing the collagen implants were incubated for 66 hours. Immunofluorescent detection of endothelial marker von Willebrand factor in cryosectioned implants prepared from (A) WT collagen treated with bFGF/VEGF or (B) r/r collagen treated with bFGF/VEGF revealed decreased endothelial staining (red) and fewer vessel-like structures within the upper portion of r/r implants. The arrowheads indicate only some of the endothelial cell–containing vascular structures. Bar indicates 200 μm. (C) Results from a large series of CAM assays supported the histologic observation in panels A and B that r/r implants display reduced angiogenesis. Data represent 4 pooled experiments: WT alone, n = 35 implants; WT + bFGF/VEGF, n = 40; r/r alone, n = 34; and r/r + bFGF/VEGF, n = 45. Results of statistical analysis performed using Wilcoxon-signed rank test on matched pairs are as follows: WT alone versus WT + bFGF/VEGF, P < .001; r/r alone versus r/r + bFGF/VEGF, P < .01; WT + bFGF/VEGF versus r/r + bFGF/VEGF, P < .01; and WT alone versus r/r alone,P > .05.