Work

Erythropoietin Functionalized Hierarchical Scaffolds Enable Immunomodulated and Vascularized Bone Repair in Periodontal Defect

Year: 2026

Type: article

Abstract: The regeneration of periodontal bone is hindered by unresolved inflammation, insufficient angiogenesis, and compromised osteogenesis, conditions that are rarely addressed simultaneously by existing scaffold designs. Conventional hydrogel-based constructs often lack the mechanical robustness required for maxillofacial defects, while many synthetic scaffolds fail to replicate the multiscale pore organization essential for functional regeneration. Here, we present a dual-fabrication strategy for constructing hierarchically porous scaffolds via digital light processing (DLP)-based 3D printing of a porogen-containing resin. This hybrid approach achieves well-defined macropores for load-bearing stability and vascular infiltration, together with interconnected hierarchical micro-nanoporous that promote nutrient transport and cell-matrix interactions. To endow the scaffold with biological functionality, it was modified with polydopamine (PDA) for efficient immobilization and sustained release of erythropoietin (EPO). The resulting scaffolds (DMPS-PDA-EPO) simultaneously regulated inflammation by promoting M2 macrophage polarization, enhanced angiogenesis through endothelial migration and tube formation, and stimulated osteogenic differentiation of human periodontal ligament stem cells under pro-inflammatory conditions. In vivo implantation in rat periodontal defect models resulted in markedly enhanced bone regeneration, with bone volume fraction and bone mineral density increasing by 161.9% and 167%, respectively, at 8 weeks compared with controls. By integrating structural precision, mechanical robustness, and immuno-angiogenic bioactivity, this EPO-functionalized hierarchical scaffold represents a clinically translatable strategy for the treatment of complex periodontal defects.

Source: ACS Applied Materials & Interfaces

DOI: 10.1021/acsami.5c24484