Injectable Hydroxyapatite and Tetracalcium Phosphate Granules Combined with Autologous Bone Marrow Concentrate: Toward Shape-Adaptive, Single-Step Bone Regeneration

Background: Injectable bone graft substitutes offer a practical alternative to preformed ceramic scaffolds by adapting to irregular bone defects while preserving osteoconductive properties. This study investigated the in vivo performance of hydroxyapatite/tetracalcium phosphate (HA/TTCP) granules, uncoated or alginate-coated, with or without autologous ovine bone marrow concentrate (oBMC), in a standardized sheep bone defect model. Methods: oBMC was characterized for cellular composition, viability, and recovery. Implanted HA/TTCP formulations were evaluated after 6 and 12 weeks by micro-computed tomography and histomorphometry. Results: Uncoated HA/TTCP granules promoted bone formation, integrating with host bone. Alginate coating improved injectability and handling but influenced granule organization and degradation. Uncoated HA/TTCP + oBMC showed a more favorable response than the coated formulation, with higher bone-to-implant contact (p = 0.004) and bone volume (p = 0.031) at 12 weeks. A modest increase in peri-implant bone volume was observed from 6 to 12 weeks in the HA/TTCP + oBMC group, though this did not retain statistical significance once clustering was accounted for. No significant direct effect of oBMC was observed compared with the cell-free formulation. Conclusions: Injectable HA/TTCP granules + oBMC represent a promising single-step strategy for irregular bone defects, although further coating optimization is needed to preserve biological performance while maximizing handling advantages.