Cell‐demanded release of VEGF from synthetic, biointeractive cell‐ingrowth matrices for vascularized tissue growth

• DOI: 10.1096/fj.02-1041fje
• Publication Date: 2003-10-21T00:21:40Z
• Authors: Andreas H. Zisch; Matthias P. Lutolf; Martin Ehrbar; George P. Raeber; Simone C. Rizzi; Neil Davies; Hugo Schmökel; Deon Bezuidenhout; Valentin Djonov; Peter Zilla; Jeffrey A. Hubbell
• Keywords: Matrix (chemical analysis)

Local, controlled induction of angiogenesis remains a challenge that limits tissue engineering approaches to replace or restore diseased tissues. We present new class bioactive synthetic hydrogel matrices based on poly(ethylene glycol) (PEG) and peptides exploits the activity vascular endothelial growth factor (VEGF) alongside base matrix functionality for cellular ingrowth, is, cell adhesion by pendant RGD-containing provision cell-mediated remodeling cross-linking metalloproteinase substrate peptides. By using Michael-type addition reaction, we incorporated variants VEGF121 VEGF165 covalently within matrix, available cells as they invade locally remodel material. The matrix-conjugated VEGF was preserved critical in vitro survival migration environment. Consistent with scheme restricted availability VEGF, grafting these VEGF-modified atop chick chorioallontoic membrane evoked strong blood vessel formation precisely at area graft-membrane contact. When implanted subcutaneously rats, VEGF-containing were completely remodeled into native, vascularized tissue. This type synthetic, biointeractive integrated angiogenic activity, presented released only upon local demand, could become highly useful number clinical healing applications therapeutic angiogenesis.