Temperature induced mechanomodulation of interpenetrating networks of star poly(ethylene glycol)-heparin and poly(N-isopropylacrylamide).

Thermoresponsive interpenetrating networks (IPNs) were prepared by sequential synthesis of a biohybrid network of star shaped poly(ethylene glycol) [starPEG] and heparin and a poly(N-isopropylacrylamide)-polymer network. Amide bond formation was used for crosslinking of the starPEG-heparin network and photo crosslinking with N,N' Methylenebisacrylamide was applied for the formation of the second polymer network. Both networks were linked by chain entanglements and hydrogen bonds only. The obtained sequential IPNs (seqIPNs) showed temperature-dependent network properties as reflected by swelling and elasticity data as well as by the release of glycosaminoglycan-binding growth factors. The elastic modulus of the IPNs was found to be amplified up to 50 fold upon temperature change from 22° C to 37° compared to the intrinsic elastic moduli of the two combined networks. The heparin concentration (as well as the complexation of growth factors with the hydrogel-contained heparin) was demonstrated to be variable independent from the mechanical properties (elastic moduli) of the hydrogels. Illustrating the usability of the developed IPN platform for cell fate control, the thermo-modulation of the release of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) is shown as well as the osteogenic differentiation of human mesenchymal stem cells exposed to stiff and BMP-2 releasing IPNs.