Mechanical, chemical, and topological properties are three major factors that influence cell behavior on the substrates.1 In this study, we used two types of biodegradable and photo-crosslinkable polymers, poly(ε-caprolactone) triacrylate (PCLTA) and poly(ethylene glycol) diacrylate (PEGDA), with different molecular weights to demonstrate the roles of mechanical and chemical factors in regulating nerve cell behavior. Crosslinked PCLTAs were hydrophobic while crosslinked PEGDAs were hydrophilic and formed hydrogels. All the networks were amorphous at 37 °C to ensure good controllability of mechanical properties by well-defined crosslinking density. Rat Schwann cell precursor line (SpL201) cells were used to evaluate their performance in terms of proliferation and differentiation. We found that SpL201 cells could proliferate more and differentiate better on stiffer substrates of both networks but differences existed between these two networks because of surface chemistry. The mechanisms how cell functions were tuned by surface properties have been investigated by blocking of β1 integrin prior to cell attachment. We found that SpL201 cells no longer showed dependence on mechanical properties if β1 integrins were blocked. The present results provide guidance for designing optimal nerve conduits made by crosslinked PCLTA and filled with PEGDA hydrogels for peripheral nerve regeneration.

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