<i>In situ</i> co-assembly of carboxylated PLGA and nano-hydroxyapatite to construct a BMP-2 sustained-released scaffold for accelerating bone regeneration

Abstract Incorporating inorganic nanoparticles into organic polymer matrices to form scaffolds enhances osteogenesis through structural and bioactive properties. However, 3D printing and electrospinning techniques impose strict requirements on the flowability and stability of bio-inks, limiting the permissible content of inorganic nanoparticles. Meanwhile, traditional physically mixed scaffolds often suffer from nanoparticle aggregation and uneven distribution because of the high surface energy and gravitational effects of the densely packed nanoparticles, ultimately compromising material performance. To address these challenges, this study utilized carboxylated PLGA (PLGA-COOH) as a matrix and employed an in situ co-assembly technique to uniformly disperse nano-hydroxyapatite (nHAP) throughout the PLGA-COOH. Using the phase separation/particle leaching method, PLGA-COOH/nHAP composite scaffolds with a hierarchical porous structure were developed. The scaffold features macropores, mesopores and micropores, with macropores averaging 309.15 ± 7.5 μm in diameter and a porosity of 90.2 ± 2.2%. It exhibits excellent biocompatibility, biodegradability and mechanical properties closely matching those of trabecular bone. Furthermore, bone morphogenetic protein-2 (BMP-2) was incorporated into the scaffold to construct the PLGA-COOH/nHAP/BMP-2 composite scaffold. In vitro experiments demonstrated that carboxylated PLGA facilitates the uniform distribution of nHAP within the scaffold and acts as a sustained-release carrier for BMP-2, thereby promoting osteogenic differentiation. The scaffold’s in vivo bone repair efficacy was evaluated using a rabbit critical-sized ulnar defect model. Experimental results confirmed that this strategy synergistically combines the uniform dispersion of nHAP with the sustained-release properties of BMP-2 to improve bone repair outcomes. In conclusion, this study significantly enhances the bone repair efficiency of composite scaffolds through carboxylation modification, in situ co-assembly and sustained-release carrier construction. It provides novel insights and strategies for the repair of critical-sized bone defects and exhibits promising applications in the field of bone tissue regeneration.