Abstract

Biodegradable nanocomposite scaffolds fabricated using advanced 3D-printing techniques hold transformative potential for localized bone cancer therapy combined with post-tumor reconstruction. This study presents the design, fabrication, and preclinical evaluation of 3D-printed, biodegradable nanocomposite scaffolds composed of Poly (Lactic-Co-Glycolic Acid) (PLGA) reinforced with Hydroxyapatite nanoparticles (nHA) and loaded with a chemotherapeutic agent-doxorubicin-targeted at osteosarcoma treatment. The scaffolds were fabricated via extrusion-based Fused Deposition Modelling (FDM), achieving controlled porosity (300-600μm) and mechanical properties approximating those of cancellers bone (compressive modulus ~200MPa). In vitro assessments demonstrated sustained drug release over 21 days, with an initial burst release followed by zero-order kinetics. Cytotoxicity assays against human osteosarcoma MG-63 cells revealed ~85% cell death within 7 days, while human osteoblasts (hFOB 1.19) maintained >90% viability, indicating effective cancer cell targeting with minimal impact on healthy bone cells. Degradation studies in Simulated Body Fluid (SBF) showed scaffold resorption over 12 weeks, coinciding with gradual loss of mechanical integrity-suggesting compatibility with bone healing timelines. Preliminary in vivo implantation in a rat critical-size femoral defect model confirmed biocompatibility, new bone formation at margins, and local tumor growth suppression. These findings underscore the feasibility of a multifunctional scaffold platform integrating mechanical support, biodegradability, and localized chemotherapy delivery. Future investigations will explore optimization of drug-loading ratios, in vivo pharmacokinetics, and long-term bone regeneration outcomes for translational advancement.

Keywords:3D printing; Biodegradable nanocomposites; Osteosarcoma; Bone tissue engineering; Localized drug delivery