Antibacterial NIR responsive targeted nanocomposite hydrogels loaded with Taxifolin for bone repair

• The TZPG + NIR group can be released slowly for up to 30 days. • Preparation of hydrogels with superior photothermal conversion efficiency (η = 51.79 %). • TZPG + NIR synergistically builds a stable microenvironment at the bone defect. • TZPG + NIR homogenizes the defect site, thereby promoting bone reconstruction. Bone defects have long posed a challenge in trauma orthopedics. Despite advancements in bone tissue engineering, there remains a bottleneck in developing bone implants that are less toxic, more effective, and reduce the need for secondary surgeries. To address this, we devised a light-responsive bone-targeted smart nano-delivery system. This system integrates polydopamine (PDA)-coated TAX-loaded ZIF-8 nanoparticles into a hydrogel with strong bioadhesion and biocompatibility (TAX@ZIF-8@PDA/ODEX-HD, TZPG). When exposed to near-infrared light, TZPG + NIR demonstrated a high photothermal conversion efficiency of 51.79 %. It exhibited a 99 % inhibition rate against Staphylococcus aureus, while also enhancing the proliferation and differentiation of osteoblasts (MC3T3-E1), thereby accelerating bone defect repair in a rat cranial bone defect model. Additionally, TZPG + NIR accelerates bone tissue repair by upregulating osteogenic-related proteins (ALP, RUNX2, OSX, OCN) while enhancing the expression of COL-I and PDGFA proteins to promote angiogenesis. Overall, TZPG + NIR created an antimicrobial microenvironment in vitro , enabled intelligent controlled release, and programmed degradation during the bone repair cycle, achieving a one-time therapeutic effect. This study highlights the promising applications of near-infrared light-responsive material TZPG in regenerative medicine, offering a novel approach to developing multifunctional bone scaffolds for repairing bone defects as a viable alternative to autografts.