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



Hooshiar MH^{1, 4} ; Ostadsharifmemar N⁴ ; Javaheri T^{2, 4} ; Salehinia N^{3, 4} ; Golozar M⁴ ; Sadeghi ES⁴ ; Zamani A^{4, 5} ; Heydari P⁶ ; Zarrabi A^{7, 8} ; Mahdevar M^{4, 9}
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 The Royal Society of Chemistry.