Shape memory RGD-containing networks: Synthesis, characterization, and application in cell culture

Hydrogels have found wide application in tissue engineering and cell mechanobiology research due to their tunable, and often biomimetic, biochemical and biomechanical properties. Although it has been known for more than a decade that hydrogels can be designed to exhibit shape memory functionality-the ability to change from one defined shape to another when triggered by a defined stimulus-shape memory hydrogels have not previously been exploited in tissue engineering or mechanobiology research. Here we report the development of a biodegradable and biocompatible hydrogel with tailored shape memory as well as desirable mechanical property for soft-tissue applications. A shape memory hydrogel was synthesized by photopolymerization of PCL3k diacry-lates together with acrylate-PEG2k-GRGDS in the presence of a crosslinker, tetrathiol, and photoinitiator, DMPA, through thiol-ene chemistry. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) were carried out to examine the thermal, mechanical and shape memory properties of the hydrogel in dry and wet states. Cell culture studies were performed to characterize material cytocompatibility. We found that the PCL phase was crystalline in the hydrogel, providing an excellent, reproducible shape memory effect. The transition temperature (shape memory "trigger") was tuned to fall between room and body temperature. Both cell attachment and proliferation studies revealed that the presentation of GRGDS molecules in the hydrogel facilitated fibroblasts adhesion and spreading on the hydrogel surface. This hydrogel, tailored to exhibit shape memory behavior in the cell culture compatible temperature range, should provide new opportunities for "smart" shape-changing scaffolds and substrates for application in tissue engineering and investigation of cell mechanobiology.