Synthetic MMP-13 degradable ECMs based on poly(N-isopropylacrylamide-co-acrylic acid) semi-interpenetrating polymer networks. I. Degradation and cell migration.
Thermoresponsive and injectable semi-interpenetrating polymer networks (sIPNs) containing a biospecific cell-adhesive signal and proteolytically degradable domains were developed as a synthetic equivalent of the extracellular matrix (ECM). The sIPNs synthesized define a modular hydrogel ECM where different properties of the matrix can be manipulated independently, thus creating a system where parametric analysis of the effect of hydrogel properties on cell proliferation and differentiation is possible. sIPNs composed of poly(N-isopropylacrylamide-co-acrylic acid) [p(NIPAAm-co-AAc)] and RGD-grafted poly(acrylic acid) linear chains [p(AAc)-g-RGD] were synthesized with peptide crosslinkers containing a matrix metalloproteinase-13 (MMP-13, collagenase-3) degradable domain. The lower critical solution temperature (LCST) of peptide-crosslinked p(NIPAAm-co-AAc) sIPNs was not influenced by the addition of either linear p(AAc) or peptide-modified p(AAc) chains ( approximately 34 degrees C) in PBS. Degradation of peptide-crosslinked hydrogels and sIPNs was enzyme specific and concentration dependent. Exposure of rat calvarial osteoblast (RCO) culture to the degradation products from the peptide-crosslinked hydrogels did not significantly affect cell viability. Migration of RCOs into the sIPNs was dependent upon the presence of both a cell-adhesive RGD peptide (Ac-CGGNGEPRGDTYRAY-NH2) and proteolytically-degradable crosslinks; however, there was greater dependence on the latter. The sIPNs synthesized are versatile materials for assessing cell fate in synthetic ECM constructs in vitro and tissue regeneration in vivo.
Kim
Soyeon
S
Departments of Bioengineering and Materials Science and Engineering, University of California at Berkeley, 370 HMMB #1760, Berkeley, CA 94720, USA.
Chung
Eugene H
EH
Gilbert
Michele
M
Healy
Kevin E
KE
D000178:Acrylamides / Q000737:chemistry*; D000179:Acrylates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017364:Collagenases / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D006358:Hot Temperature; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020100:Hydrogels / Q000737:chemistry; D013058:Mass Spectrometry; D053509:Matrix Metalloproteinase 13; D008858:Microscopy, Phase-Contrast; D008956:Models, Chemical; D009842:Oligopeptides / Q000737:chemistry; D010006:Osteoblasts / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D051381:Rats; D012038:Regeneration; D012685:Sepharose / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D023822:Tissue Engineering
D000178:Acrylamides; D000179:Acrylates; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; C090629:N-isopropylacrylamide-acrylic acid copolymer; D009842:Oligopeptides; D010455:Peptides; D011108:Polymers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C047981:arginyl-glycyl-aspartic acid; D012685:Sepharose; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat