Construction of Nanohydroxyapatite/Poly(sodium lipoate)-Based Bioactive Hydrogels for Cranial Bone Regeneration

Persistent oxidative stress following bone defects significantly impedes the repair of bone tissue. Designing an antioxidative hydrogel with a suitable mechanical strength can help alter the local microenvironment and promote bone defect healing. In this work, α-lipoic acid (LA), a natural antioxidant small molecule, was chemically cross-linked with lipoic acid-functionalized poly(ethylene glycol) (PEG_<i>x</i>, <i>x</i> = 6k or 10k) in sodium bicarbonate solution, to prepare LA-PEG_<i>x</i> hydrogels (LP_<i>x</i>, <i>x</i> = 6k or 10k). Furthermore, nanohydroxyapatite (nHA)-LA-PEG_<i>x</i> (HLP_<i>x</i>, <i>x</i> = 6k) hydrogels were constructed through incorporating nHA. The hydrogels exhibited moderate mechanical strength, facile injectability, self-healability, adhesion, biodegradability, biocompatibility, and promising antioxidation efficiency. We verify the advantage of the HLP_6k-3 hydrogel in a rat cranial defect model. Through the regulation of reactive oxygen species (ROS), osteoconduction, and biomineralization capabilities, our system can promote new bone formation. Overall, bioactive hydrogels with multiple functions hold significant promise for repairing bone defects.