Development and biological validation of a dexamethasone-loaded, polylactic acid-based 3D-printable composite filament for bone tissue engineering
Critical-sized bone defects remain a major clinical challenge, motivating the development of biomaterial-based alternatives to autografting. Among additive manufacturing techniques, fused filament fabrication offers a scalable approach for producing patient-specific scaffolds with integrated bioactive functionality. This study aimed to fabricate and evaluate a dexamethasone (DEXA)-loaded polylactic acid (PLA) filament for controlled local drug delivery through fused filament fabrication. DEXA–PLA composite filaments containing 0.1% and 1% (w/w) DEXA were produced via melt extrusion and characterized in terms of their thermal, chemical, surface, and mechanical properties. Drug release was quantified over 28 days, and biological performance was evaluated using human mesenchymal stromal cells (MSCs) and THP-1-derived macrophages. DEXA incorporation preserved the physicochemical properties of PLA. The 0.1% formulation exhibited a transient release profile, whereas the 1% DEXA–PLA formulation provided sustained release over 28 days. MSC metabolic activity was unaffected by either formulation. However, the 1% DEXA–PLA formulation significantly enhanced osteogenic differentiation, as indicated by increased ALPL expression and extracellular matrix mineralization, with levels comparable to those observed in cells cultured in standard osteogenic medium. In M1 macrophages, the 1% formulation decreased metabolic activity and IL1B expression and reduced the secretion of IL-1β, IL-6, and TNF-α. It also increased the expression of the anti-inflammatory markers CD163 and PPARG. In conclusion, the 1% DEXA–PLA filament maintained material integrity and enabled sustained delivery of bioactive DEXA, promoting both osteogenic and immunomodulatory responses. These findings demonstrate the feasibility of incorporating DEXA into a controlled-release system for bone tissue engineering applications.

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