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This study investigates a novel 3D-printed polycaprolactone-gelatin (PCL-gelatin) composite for musculoskeletal tissue engineering, assessing its biocompatibility, degradation, and osteogenic potential. The researchers fabricated PCL-gelatin composites with varying gelatin content and β-tricalcium phosphate, characterizing them through mechanical testing, degradation studies, and in vitro cell culture with human mesenchymal stem cells, followed by in vivo subcutaneous implantation and critical-size femoral defect studies in rats. The PG30 composite demonstrated enhanced mechanical properties, biocompatibility, and increased preosteoblast density at bone interfaces compared to PCL controls at 4 weeks.
3D-printed PCL-gelatin composites, particularly with 30% gelatin content, show promise for enhanced early bone regeneration in critical-size femoral defects compared to PCL alone in a rat model.
In musculoskeletal tissue engineering, there is a need for bone implants that are biocompatible, resorbable, promote tissue regeneration, and degrade at a rate matching healing. Polycaprolactone (PCL), an FDA-approved biodegradable and bioinert polymer, can be functionalized with natural components without harsh crosslinking. This study presents the first demonstration of a homogeneous bulk polycaprolactone-gelatin (PCL-gelatin, PG) composite containing self-assembled gelatin nanoparticles that retain bioactivity despite thermal processing for 3D printing applications. PG composites with varying gelatin content (10%, 20%, and 30%) and β-tricalcium phosphate incorporation were fabricated through casting and melt processing into printable filaments at 110°C. Comprehensive characterization using mechanical testing, contact angle measurements, FTIR, TGA, EDS, and SEM confirmed homogeneous gelatin distribution as nanoscale particles throughout the PCL matrix, with systematic increases in hydrophilicity and enhanced mechanical properties proportional to gelatin content. Accelerated degradation studies revealed tunable degradation rates correlated with gelatin concentration, while in vitro studies with human mesenchymal stem cells demonstrated enhanced proliferation and early osteogenic differentiation markers, particularly in PG30 compositions. Subcutaneous implantation in rats over 24 weeks showed biocompatibility comparable to PCL with minimal inflammatory response and biphasic degradation behavior characterized by initial swelling followed by controlled volume reduction. In critical-size femoral defects, PG30 exhibited superior early mechanical properties and increased preosteoblast density at bone interfaces compared to PCL and PCL-TCP controls at 4 weeks. This developed fabrication methodology enables precise spatial control through 3D printing while preserving gelatin bioactivity. This approach offers a promising advancement for tissue engineering applications requiring enhanced cellular interactions and controlled degradation.