Characterization of Hydrolytic and Thermomechanical Stability of 3D-Printed PLDLA-TMC 60/40 Scaffolds for Cartilage Tissue Applications

Biodegradable thermoplastic polymers are increasingly explored in regenerative medicine due to their potential to mimic native tissue environments. Among them, poly-(L-<i>co</i>-D,L-lactic acid-<i>co</i>-trimethylene carbonate) (PLDLA-TMC) offers tunable degradation and biocompatibility features. However, extrusion-based 3D printing may induce polymer chain scission, compromising scaffold integrity under physiological conditions. Although PLDLA-TMC has been explored in various biomedical applications, there is a lack of studies assessing its performance under mechanically stimulated environments that emulate <i>in vivo</i> conditions, which limits its translation to load-bearing tissues such as cartilage. To address this gap, this study investigates the hydrolytic and thermomechanical degradation of 3D-printed PLDLA-TMC 60/40 scaffolds and their biological behavior under dynamic perfusion culture. Temperature-dependent degradation was confirmed, as printing at 120 °C preserved polymer integrity more efficiently, while both <i>M</i> _n and <i>M</i> _w decreased by approximately 50% after 2 weeks of hydrolytic degradation and by 80% after 4 weeks (<i>p</i> < 0.01). Dynamic culture assays demonstrated enhanced chondrogenesis, with type II collagen and SOX9 showing approximately 2-fold higher fluorescence intensities. Although aggrecan displayed slightly higher total labeling under static culture, dynamic perfusion reduced the fluorescence peak width by 40%, supporting a more stratified hyaline-like matrix. Perfusion also promoted significantly greater cell infiltration (<i>p</i> < 0.05). Altogether, these results highlight the suitability of PLDLA-TMC scaffolds for mechanically stimulated tissue-engineering applications, particularly cartilage regeneration.