Pla/Amcp Nanocomposite Enhances Bone Regeneration Via Immunomodulation And Angiogenesis

To develop stable amorphous calcium magnesium phosphate (AMCP) and evaluate its immunomodulatory/angiogenic potential in a polylactic acid (PLA) nanocomposite for bone repair. Degradation of PLA, PLA/HA, PLA/AMCP-20, and PLA/AMCP-40 was assessed in simulated body fluid (37°C) over five weeks, with pH monitoring. Materials were co-cultured with rBMSCs to analyze osteogenic protein expression (7/14 days), and with HUVECs/Raw264.7 to evaluate angiogenesis and immunomodulation. Following approval by the Institutional Animal Ethics Committee, critical-sized jaw defects in 48 male Sprague-Dawley rats (7 weeks old) were systematically evaluated at 2, 4 and 12 weeks post-implantation using micro-CT, histological assessments (hematoxylin-eosin and Masson’s trichrome staining), and immunohistochemical analysis of collagen type I (COL-1), osteocalcin (OCN), osteopontin (OPN),inducible nitric oxide synthase (iNOS), CD31, and CD206. PLA/AMCP maintained physiological pH during degradation, similar to PLA/HA. It enhanced early bone regeneration by promoting M2 macrophage polarization and upregulating angiogenic genes. Micro-CT and histology confirmed superior bone formation in PLA/AMCP groups, with elevated COL-1, OCN, and CD31 levels indicating osteogenesis and angiogenesis. Immunohistochemistry revealed reduced pro-inflammatory markers (iNOS) and increased pro-healing responses (CD206). The PLA/AMCP nanocomposite demonstrates excellent biocompatibility and effectively accelerates jaw defect repair. It neutralizes PLA-induced acidity, reduces inflammation, and synergistically enhances osteogenesis and angiogenesis, positioning it as a promising bone regeneration material.