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 cross-linking of the starPEG-heparin network and photo-cross-linking with N,N'-methylenebis(acrylamide) 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 (seq-IPNs) 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 seq-IPNs was found to be amplified up to 50-fold upon temperature change from 22 to 37 °C 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 variably independent from the mechanical properties (elastic moduli) of the hydrogels. Illustrating the usability of the developed seq-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 seq-IPNs.