The combination of PLLA/PLGA/PCL composite scaffolds integrated with BMP-2-loaded microspheres and low-intensity pulsed ultrasound alleviates steroid-induced osteonecrosis of the femoral head

Low-intensity pulsed ultrasound (LIPUS), which has been previously reported to promote bone repair, is proposed to be a noninvasive form of therapy for the treatment of osteonecrosis. Bone fillers made from composite scaffolds have been demonstrated to be effective for preventing bone defects such as osteonecrosis. The present study aimed to investigate whether the application of LIPUS combined with bone morphogenetic protein-2 (BMP-2)-loaded poly-L-lactic acid/polylactic-co-glycolic acid/poly-ε-caprolactone (PLLA/PLGA/PCL) composite scaffolds can improve recovery in a rat model of steroid-induced osteonecrosis of the femoral head (ONFH). BMP-2-loaded PLGA microspheres incorporated into PLLA/PLGA/PCL composite scaffolds were constructed. Bilateral femoral head LIPUS intervention was conducted in rats with steroid-induced ONFH. LIPUS intervention alone contributed to the alleviation of osteonecrosis, in addition to improving load-carrying capacity and accelerated bone formation, angiogenesis and differentiation. Subsequently, femoral head parameters and assessment of load-carrying capacity, bone formation-related factors, and angiogenesis- and differentiation-related factors were measured in rats with or without implanted BMP-2-loaded PLLA/PLGA/PCL composite scaffolds. LIPUS combined with the implantation of PLLA/PLGA/PCL composite scaffolds loaded with BMP-2 microspheres protected rats against steroid-induced ONFH and improved load-carrying capacity, bone formation, angiogenesis and differentiation. Together, these data support the use of BMP-2-loaded PLLA/PLGA/PCL composite scaffolds combined with LIPUS for ONFH as a potential alternative curative solution for treating bone diseases.