IMPROVED MINIMALLY INVASIVE RECONSTRUCTION OF FRACTURED OSTEOPOROTIC VERTEBRAE BASED ON NOVEL BIODEGRADABLE AND OSSEOINTEGRATIVE BONE CEMENT: SMALL AND LARGE ANIMAL STUDIES

Vertebroplasty, involving the injection of PMMA bone cement into fractured vertebral bodies, is endorsed for symptomatic osteoporotic fractures in spine. Regarding high leakage risk during injection and failure rate post-surgery of inert PMMA cement, it is essential to launch alternative candidate for vertebroplasty. In current work, a calcium phosphate-based nanocomposite (CPN) highlighted with excellent injectability, low leakage risk, biodegradability, and osteogenic potential found in vitro was tested in small and large osteoporotic animals with vertebral defect, as an effort to validate its efficacy and reliability before entering clinical trial phase. On one hand, the injection of CPN to cylindrical defect created on along the longitudinal axis of the vertebra of SD rats could maintain its vertebral mechanical strength and forming osseointegrative interface with surround bone in situ, accompanied with single-cell RNA sequencing identifying a critical osteoblast subpopulation expressing Spp1, Serpine2, Megf10, and Enpp1 genes. On the other hand, the 12 months osteoporotic goat models revealed CPN can greatly promote bone regeneration along with intrinsic progressive degradation. Additionally, a notable increase in trabecular thickness (Tb. Th) and mineralized tissue volume ratio (BV/TV) was witnessed in CPN group as compared to PMMA. Vertebral compressive strength was also tested, showing no statistically significant variances among the groups of CPN, PMMA and sham surgery group, affirming the reliability of CPN in maintaining mechanical stability of defected vertebral. These finding in preclinical stage thereby demonstrated the superiority of CPN over PMMA cement for vertebroplasty, forwarding its translation status to clinical trials.