Injectable Hydrogels with Tissue-Adaptive Gelation and Mechanical Properties: Enhancing Softness and Stability.

Ultra-soft injectable hydrogels are paramount in biomedical applications such as tissue fillers, drug depots, and tissue regeneration scaffolds. Synthetic approaches relying on linear polymers are confronted by the necessity for significant dilution of polymer solutions to reduce chain entanglements. Bottlebrush polymers offer an alternative approach due to suppressed chain overlap and entanglements, which facilitates lower solution viscosities and increased gel softness. Leveraging the bottlebrush architecture in linear-bottlebrush-linear (LBL) block copolymer systems, where L is a thermosensitive linear poly(N-isopropylacrylamide) block, and B is a hydrophilic polyethylene glycol brush block, injectable hydrogels were designed to mimic tissues as soft as the extracellular matrix at high polymer concentrations. Compared to an analogous system with shorter brush side chains, increasing the side chain length enables a decrease in modulus by up to two orders of magnitude within 1-100 Pa at 20 wt% polymer concentrations, near to the physiological water content of ~70%. This system further exhibits thermal hysteresis, enabling stability with inherent body temperature fluctuations. The observed features are ascribed to kinetically hindered network formation by bulky macromolecules.