Region-dependent in vivo degradation and local repair responses of a magnesium artificial lamina in a rabbit lamina defect model.

Magnesium (Mg)-based implants are promising for lamina defect reconstruction because of their biodegradability, mechanical compatibility, and bioactivity. However, in vivo degradation is usually assessed at the whole-implant level, and it remains unclear whether distinct regions of the same implant experience different degradation-repair couplings. In this study, a ZE21C Mg alloy artificial lamina was implanted in a New Zealand rabbit lumbar lamina defect reconstruction model to evaluate region-dependent degradation and local repair responses. Finite element analysis showed higher equivalent stress and strain on the residual-bone side. SEM/EDS and micro-CT analyses demonstrated the asymmetric degradation of the same implant in vivo. The residual-bone side exhibited faster Mg degradation, more severe surface and interfacial degradation, and higher TRAP-related remodeling activity, whereas the opposite side degraded more slowly, maintained a denser interface, and exhibited better bone formation and tissue integration. At 12 weeks, the remaining implant volume was 20.2 ± 2.0% on the residual-bone side, compared with 41.9 ± 5.3% on the opposite side, demonstrating pronounced region-dependent degradation within the same implant. Transcriptomic analysis indicated that rapid degradation was accompanied by stronger bone resorption and inflammatory interface reactions. The slow degradation area is associated with a more vascularized repair microenvironment that supports the matrix. These findings indicate that accelerated regional degradation does not necessarily promote bone regeneration. Therefore, region-specific degradation control may be critical for designing biodegradable Mg implants in complex anatomical environments. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium implants are generally evaluated by their average degradation rate, despite regional differences in mechanical and biological environments. In a rabbit lamina reconstruction model, we directly compared two regions of the same ZE21C magnesium artificial lamina, limiting implant- and animal-level variability. The residual-bone side experienced higher stress, faster degradation, a less stable interface, stronger osteoclast-related activity, and poorer bone formation; the opposite side degraded more slowly and supported better tissue integration. Transcriptomic analysis linked these outcomes to distinct inflammatory, bone-resorptive, vascular, and matrix-remodeling responses. Thus, faster magnesium degradation does not necessarily improve repair. This work identifies region-specific degradation control as a key design principle for biodegradable orthopedic implants in complex anatomical environments.