Revitalizing osteoporotic bone repair via multilevel ROS scavenging and osteoimmune regulating hydrogel

Osteoporotic bone defects (OBDs) pose significant clinical challenges due to impaired tissue regeneration and osteogenic differentiation. Conventional combination therapies using systemic anti-osteoporosis drugs and graft fillings have yielded unsatisfactory results. Excessive reactive oxygen species (ROS) are a hallmark of OBDs, leading to abnormal inflammatory responses and a hostile osteoimmune microenvironment that impedes repair. In this study, we developed a multifunctional injectable hydrogel, termed PTSr@CP, composed of a strontium (Sr) and tannic acid (TA)-based metal–phenolic network core coated with polydopamine (PDA), integrated into a matrix of carboxymethyl chitosan and poly (γ-glutamic acid). The PTSr@CP hydrogel can be easily injected into bone defect sites, where it undergoes rapid in situ crosslinking and exhibits exceptional ROS-scavenging capabilities. Additionally, the hydrogel mediates mild photothermal therapy (MPTT), promoting local tissue repair. Both in vitro and in vivo studies demonstrated its excellent biosafety and confirmed synergistic bone regeneration through enhanced osteogenesis, angiogenesis, and osteoimmunomodulation. This work offers a compelling strategy for OBD treatment by combining mild hyperthermia-enhanced in situ bone repair with sustained delivery of bioactive agents to improve the osteoimmune microenvironment.