Injectable Zein-Based Photothermal Composite Hydrogel Enhances Osteoporotic Tendon-Bone Healing.

Osteoporotic rotator cuff tears represent a major clinical challenge owing to impaired tendon-bone interface (TBI) healing. To address this issue, we engineered an injectable Zein-based composite hydrogel (ZDC hydrogel) using electron-beam irradiation and, incorporated niacin-loaded mesoporous carbon nanospheres to achieve photothermal regulation and niacin release. The ZDC hydrogel exhibited favorable self-assembly, mechanical properties, photothermal performance, degradability, and biosafety. In vitro, ZDC hydrogel extracts enhanced the osteogenic differentiation of MC3T3-E1 cells and the tenogenic differentiation of tendon-derived stem cells (TDSCs). Mechanistically, ZDC hydrogel extracts increased intracellular nicotinamide adenine dinucleotide levels, suppressed p16 and p21 expression, and reduced cytosolic and mitochondrial reactive oxygen species (ROS) accumulation in MC3T3-E1 cells. In the osteoporotic rat rotator cuff repair model, ZDC hydrogels combined with near-infrared irradiation (NIR) enhanced new bone formation within the humeral head bone tunnel, improved fibrocartilaginous TBI reconstruction, and strengthened biomechanical properties of the repaired tendon-bone complex. Furthermore, in a rat skin wound model, ZDC hydrogels combined with NIR increased the expression of vascular endothelial growth factor (VEGF) and CD31 while reducing tumor necrosis factor-α levels, indicating enhanced angiogenesis and attenuated inflammatory responses. Collectively, these findings suggest that the injectable ZDC hydrogel is a promising strategy for osteoporotic rotator cuff tear repair.