Poly(N-isopropylacrylamide) (PNIPAm) is a three-dimensional (3D) crosslinked polymer that can interact with human cells and play an important role in the development of tissue morphogenesis in both in vitro and in vivo conditions. PNIPAm-based scaffolds possess many desirable structural and physical properties required for tissue regeneration, but insufficient mechanical strength, biocompatibility, and biomimicry for tissue development remain obstacles for their application in tissue engineering. The structural integrity and physical properties of the hydrogels depend on the crosslinks formed between polymer chains during synthesis. A variety of design variables including crosslinker content, the combination of natural and synthetic polymers, and solvent type have been explored over the past decade to develop PNIPAm-based scaffolds with optimized properties suitable for tissue engineering applications. These design parameters have been implemented to provide hydrogel scaffolds with dynamic and spatially patterned cues that mimic the biological environment and guide the required cellular functions for cartilage tissue regeneration. The current advances on tuning the properties of PNIPAm-based scaffolds were searched for on Google Scholar, PubMed, and Web of Science. This review provides a comprehensive overview of the scaffolding properties of PNIPAm-based hydrogels and the effects of synthesis-solvent and crosslinking density on tuning these properties. Finally, the challenges and perspectives of considering these two design variables for developing PNIPAm-based scaffolds are outlined.
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