Functionalized 3D-Printed Scaffolds for Enhanced Osteogenesis and Guided Bone Regeneration Publisher Pubmed



M Hosseini Hooshiar MOHAMMAD ; N Ostadsharifmemar NEGIN ; T Javaheri TOHID ; N Salehinia NEGIN ; M Golozar MELIKA ; Es Sadeghi Ensieh SAGHEB ; A Zamani ATEFEH ; P Heydari PARISA ; A Zarrabi ALI ; M Mahdevar MOHAMMAD
Source: Journal of Materials Chemistry B Published:2025

Abstract

In this study, we introduced an innovative approach to guided bone regeneration (GBR) that effectively addresses the challenges of treating large bone defects. Our pioneering 3D-printed multifunctional scaffolds uniquely integrate polycaprolactone (PCL), chitosan (Cs), l-arginine (l-Arg), and β-tricalcium phosphate (β-TCP), leveraging the synergistic effects of these materials to enhance immunomodulation, bioactivity, and mechanical integrity. These PCL/Cs-l-Arg/βTCP scaffolds exhibit remarkable mechanical properties (Young's modulus ∼32.84 ± 4.11 MPa) and maintain structural integrity for 60 days under physiological conditions when fabricated through extrusion-based 3D printing. A key feature of this composite is the dual role of l-Arg, which not only supports osteogenesis but also acts as a potent immunomodulator. The scaffolds facilitate the sustained release of l-arginine over 21 days, fostering a pro-regenerative environment that promotes significant immunomodulatory effects, including a decrease in pro-inflammatory cytokines (IL-6, TNF-α) and an enhancement of anti-inflammatory and osteogenic growth factors (BMP-2, TGF-β) in macrophages. This cytokine profile shift suggests a transition from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. A progressive increase in alkaline phosphatase activity, nearly double that of PCL/Cs scaffolds by day 21, reflects enhanced osteogenic differentiation. Additionally, the scaffolds demonstrate exceptional bioactivity, with over 83% and 93% reductions in calcium and phosphorus ions, respectively, in simulated body fluid over 28 days, as evidenced by Alizarin red staining. This integrated approach signifies a major breakthrough in biomaterial design for GBR, presenting transformative potential for treating bone defects in dental and orthopedic applications, and marking a significant leap forward in the field of bone regeneration. © 2025 Elsevier B.V., All rights reserved.