Synthetic MMP‐13 degradable ECMs based on poly(N‐isopropylacrylamide‐<i>co</i>‐acrylic acid) semi‐interpenetrating polymer networks. I. Degradation and cell migration

Abstract

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.