Dual Route Amine Functionalized Poly(l-lactic acid)/Mesoporous Bioactive Glass Based 3D Printed Composite Scaffolds: An Investigation on In Vitro and In Vivo Characteristics.

Surface modification of bioactive materials and implants can contribute more efficiently in the bone healing process. Amine modification of mesoporous bioactive glass (MBG) enhances its suitability by improving cell adhesion, pH stability, degradation control, and osteogenic potential in bone tissue engineering application. In this study, amine-grafted MBG was incorporated into PLA (30:70 organic:inorganic) to fabricate 3D printed (3DP) composite scaffolds, followed by surface decoration with branched PEI (MW ∼ 1200). Despite high N-MBG loading, the mechanical strength significantly improved by ∼144% due to amide bonding between grafted amines and PLA. SBF tests showed rapid hydroxyapatite formation within 1 day. In vitro assays (MTT, Live/Dead, ARS, ALP, and qRT-PCR) confirmed excellent biocompatibility and osteogenic activity of 3DP PLA/N-MBG and PLA/N-MBG/PEI composite scaffolds. PLA/N-MBG/PEI scaffolds exhibited significantly enhanced osteogenic activity, with the highest ALP activity (∼9 mU/mL) and upregulation of COL1A2 (∼1.8-fold), BMP2 (∼2.7-fold), and OCN (∼1.7-fold) by day 14. Further, in vivo studies in Wistar rats (subcutaneous and calvarial defect models) demonstrated a superior bone regeneration efficacy without chronic inflammation. This dual functionalization strategy markedly enhances scaffold bioactivity, mechanical integrity, and bone healing capacity, offering strong promise for bone tissue engineering.