Rational hydrogel design to improve brain modulus matching for implantation

• Thermally responsive hydrogels are tuned for brain modulus matching. • Hydrogel hydrophilicity controls clinically relevant phase transition behavior. • Hydrogel hydrophilicity modulated viscosity for injection. Treating the brain is challenging due to the restrictive blood–brain barrier, and modulus-mismatched implants often cause problems. Herein, we have fabricated copolymer hydrogels from thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAAm), -r-hydrophilic polymer, poly(acrylic acid) (PAA), which are injectable and transform into soft implants above their lower critical solution temperature (LCST). PAA concentration can be leveraged to tune the LCST and viscosity of the PNIPAAm– r –PAA hydrogel in solution. Furthermore, the Young’s moduli of these materials, ranging from 1-4 kPa, are close to rat and human brain tissue, potentially leading to less inflammation and rejection due to significant modulus mismatch.