DUAL ROLE OF BIORESORBABLE MAGNESIUM IMPLANTS ON BONE REMODELLING AND LIVER METABOLISM

Bioresorbable magnesium (Mg)-based implants are considered an attractive alternative to conventional metal implants (i.e. stainless steel, titanium alloys) particularly in pediatric cases where surgical interventions are intended to be minimized. Although general questions such as biocompatibility, degradation kinetics, and osseointegration of Mg-based implants have been mostly investigated, a few in vivo studies explored how Mg-based implants promote osteogenesis and modulate systemic tissue responses. The aim of this study was to evaluate the early and mid-term local and systemic tissue responses of degrading ultrahigh-purity ZX00 (Mg–Zn–Ca alloy) and ultrahigh-purity Mg (XHP-Mg) pins in a juvenile healthy rat model. Five SD rats per group underwent bilateral, transcortical implantation of cylindrical ZX00 and XHP-Mg pins (d=1.6 mm, l=8 mm) into the diaphysis of both femurs. The potential differences between degradable and permanent implant types and age-related changes were investigated using state-of-the-art control titanium (Ti), sham-operated, and control groups (non-intervention), respectively. Animals were euthanized after 3, 14, and 42 days post-surgery. The early and mid-term local responses to Mg-based implants were assessed via qRT-PCR, Magnetic Luminex® Assay, qualitative histological analysis, and SAXS analysis from isolated rat bone marrow stromal cells (rBMSCs) and extracted femur samples, respectively. Moreover, the potential systemic responses were investigated from extracted spleen, liver, and kidney tissues with immunohistochemistry, Magnetic Luminex® Assay, and NMR spectroscopy. Degradation products of ZX00 and XHP-Mg implants support the new bone tissue formation via promoting osteogenic lineage commitment of BMSC within the first 14 days, post-surgery. Histological examinations showed that both Mg-based implants support osseointegration better than Ti groups. Moreover, we found a more parallel hydroxyapatite/collagen orientation along Mg-based pins in the perimeter region compared to Ti pins. In the liver, glycogen levels decreased significantly in both ZX00 and XHP-Mg groups compared to the sham group on day 42, while only ZX00 group showed a higher serum glucagon level on day 14. In summary, results suggest i ) the degradation rate of the Mg-based implants has a crucial effect on osteogenesis via regulating Bmp2 and Opg expression in the medullary cavity and ii) both Mg pins promote glycogenolysis in the liver. Our findings highlight the dual role of Mg-based implants in bone remodeling and systemic metabolic modulation.