Injectable Hydrogel with NIR Light‐Responsive, Dual‐Mode PTH Release for Osteoregeneration in Osteoporosis

Abstract Effective treatments to overcome osteoblast/osteoclast imbalance are the key to achieving desirable bone regeneration for osteoporosis patients. When used for local bone repair, parathyroid hormone (PTH) often leads to either excessive osteoclasts under continuous exposure or insufficient osteoclasts with pulsatile release of PTH. Herein, an injectable multifunctional in situ‐generated calcium phosphate nanoparticle (ICPN)‐coordinated poly(dimethylaminoethyl methacrylate‐co‐2‐hydroxyethyl methacrylate) (DHCP) hydrogel loaded with PTH for near‐infrared (NIR)‐stimulated release is developed to achieve bone regeneration in an ovariectomized (OVX) model. Photothermal‐responsive poly(N‐acryloyl glycinamide‐co‐acrylamide) PNAm‐indocyanine green ICG‐PTH microspheres (PIP MSs) endow a dual‐mode release system with a sustained release at low concentrations, a pulse release of PTH, and in situ pore formation properties. The PIP MS‐encapsulated DHCP hydrogel (DHCP‐10PIP/d) is injected into the bone defects of OVX rats. Under NIR irradiation, the localized photothermal effects trigger on‐demand PTH release and in situ micropores formation through the gel–sol transition of PIP MSs, and the repeated treatment is harmless to the bioactivity of PTH. This platform can enhance osteoblast and osteoclast activity at the same time both in vitro and in vivo and repair the cranial defects of OVX rats successfully. Overall, this work provides a promising strategy for PTH delivery to repair osteoporotic bone defects.