Preventing septic implant failures in osteoporotic hip fractures using antibiotic-loaded functionalized nanocement

Osteoporosis is a prevalent skeletal disorder and the most common cause of debilitating hip fractures, primarily affecting post-menopausal women and elderly people. Implants used to stabilize osteoporotic fragility fractures are susceptible to bacterial infections, which further deteriorate the implantation site. In the current study, we developed a nanocement-based treatment for tackling hip implant infection in an osteoporotic rat model. The development of osteoporosis was confirmed by an 80% decrease in serum estradiol levels and a further reduced T-score value of −4.170 ± 0.411 for femur neck canal. Further, an infected K-wire was implanted in femoral neck canal to induce implant-associated osteomyelitis. In order to combat infection and promote bone healing, it was followed by debridement and implantation of rifampicin-loaded nanocement functionalized with various combinations of bone marrow MSCs (bMSC) exosomes, bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA). The findings of this study demonstrated the potential of exosomes as an alternative for reducing BMP-2 dosage, and the treatment promoted successful bone regeneration with enhanced mechanical strength, and a significant decrease in bacterial load. Improved bone remodeling and matrix deposition at the implantation site were confirmed by DXA, micro-CT, and histology. Further, immunohistochemical staining showed increased expression of collagen I and CD31, which indicated bone matrix deposition and vascularization, respectively, while reduced expression of α-SMA and NOS2 confirmed a reduction in fibrosis and inflammation, respectively. Overall, our one-step treatment strategy has the potential to prevent implant-associated bone infection in osteoporotic hip fractures, promote bone formation, and enhance the mechanical strength of osteoporotic bone, thereby preventing subsequent secondary fractures.