3D-Printed DOX-LF-Loaded PLGA Biphasic Composite Scaffold Modulates Macrophage Polarization and Enhances Osteogenic-Angiogenic Regenerative Potential for Periodontitis.

Authors

Chunfeng Wang, Caijuan Wu, Chan Xiao, Yepo Hou

Published in

Frontiers in bioscience (Landmark edition). Volume 31. Issue 9. Pages 54017. Sep 18, 2026.

Abstract

To develop an immunomodulatory scaffold integrating antibacterial activity with osteogenic-angiogenic coupling for inflammatory periodontal repair.
A biphasic poly(lactic-co-glycolic acid) (PLGA) scaffold incorporating doxycycline-lactoferrin (DOX-LF)-loaded calcium alginate microspheres and fibroblast growth factor 2/bone morphogenetic protein 9 (FGF2/BMP9)-loaded chitosan nanospheres was fabricated by low-temperature three-dimensional (3D) printing, porogen leaching, and freeze-drying. Material properties, antibacterial activity, macrophage polarization, periodontal ligament stem cell (PDLSC) osteogenesis, and human umbilical vein endothelial cell (HUVEC) angiogenesis were evaluated. Small interfering RNA (siRNA)-mediated milk fat globule-epidermal growth factor 8 (MFGE8) knockdown was used to investigate the underlying mechanism.
The scaffold formed an interconnected porous network and released approximately 88.4% of DOX and 60% of LF over 240 h. PLGA/DOX-LF reduced Porphyromonas gingivalis viability to approximately 20% (p < 0.001). In lipopolysaccharide (LPS)-stimulated macrophages, it produced the greatest suppression of M1-associated markers and induction of M2-associated markers, while MFGE8 knockdown significantly reduced MFGE8 expression (p < 0.001) and attenuated these effects. Conditioned medium restored PDLSC migration, ALP activity, and mineralization to approximately 70%, 70-75%, and 80% of control levels, respectively, and increased HUVEC tube length (p < 0.01) and angiogenic gene expression (all p < 0.001).
A 3D-printed biphasic PLGA scaffold incorporating DOX-LF-loaded calcium alginate microspheres and FGF2/BMP9-loaded chitosan nanospheres was successfully constructed. These in vitro findings support PLGA/DOX-LF as a proof-of-concept platform for antibacterial immunomodulation and osteogenic-angiogenic coupling, pending in vivo validation.

PMID:
42811969
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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