Abstract

Osteoporotic fracture, which is a clinical complication of osteoporosis featured with the imbalance of bone homeostasis. Non-surgical intervention is frequently required post-operatively to ameliorate the fracture healing. Nevertheless, current non-surgical therapies are mostly performed in a non-targeted manner without giving enough consideration to the pathological characteristics of osteoporosis. Therefore, it is highly desirable to develop an optimal strategy for promoting fracture healing under osteoporotic conditions. In this study, a multifunctional therapeutic nanoplatform is designed to work in conjunction with near-infrared irradiation. Specifically, poly (lactic-co-glycolic acid) (PLGA) is functionalized with alendronate (ALE) and black phosphorus nanosheets (BPs) together with melatonin (MT) molecules are encapsulated by PLGA-ALE to produce the multifunctional BPs/MT@PLGA-ALE nanospheres. In this structure, BPs degrade gradually and deliver mild photothermal effects to facilitate bone regeneration, whereas MT has the dual-capability of suppressing osteoclastogenesis and promoting osteogenesis. Moreover, ALE endows the nanoplatform with the reliable bone-targeting capacity to improve the therapeutic effects. The combination of BPs/MT@PLGA-ALE nanospheres and photothermal therapy significantly improve post-surgical healing of osteoporotic fracture by modulating the tumor necrosis factor and cell death-related signaling pathways. This study reveals a promising strategy to treat osteoporotic fracture and broadens the application of nanomaterials in the biomedical field.