Enhancement of cell interactions with collagen/glycosaminoglycan matrices by RGD derivatization.
The interaction of three cell types important to the wound repair process with collagen/glycosaminoglycan (GAG) dermal regeneration matrices covalently modified with an Arg-Gly-Asp (RGD)-containing peptide was characterized. Function-blocking monoclonal antibodies directed against various integrin subunits were used to demonstrate that human fibroblasts attached to the unmodified matrix through the integrin, alpha2beta1. Human endothelial cells and human keratinocytes, however, attached minimally to the unmodified matrix. After modification of the collagen/GAG matrix with RGD-containing peptide, endothelial cells and keratinocytes attached and spread well on the matrix. This attachment was RGD dependent as evidenced by essentially complete inhibition with competing soluble peptide. In terms of overall cell number, fibroblast cell attachment remained unchanged on the RGD peptide-modified matrix compared to the unmodified material. Antibody and peptide inhibition studies demonstrate, however, that attachment to the modified matrix was mediated by both alpha2beta1 and RGD-binding integrins. We have successfully introduced a specific RGD receptor-mediated attachment site on collagen/GAG dermal regeneration matrices, resulting in enhanced cell interaction of important wound healing cell types. This modification could have important implications for the performance of these matrices in promoting dermal regeneration.
Grzesiak
J J
JJ
Telios Pharmaceuticals, Inc., an Integra Life Sciences Company, San Diego, CA 92121-1299, USA.
Pierschbacher
M D
MD
Amodeo
M F
MF
Malaney
T I
TI
Glass
J R
JR
D000911:Antibodies, Monoclonal; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D006025:Glycosaminoglycans; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen