Influence of scaffold porosity on the degradation of 3D-printed biodegradable polymers: Coupled bioreactor, modeling, and in vivo validation

The clinical translation of biodegradable scaffolds for bone tissue engineering requires a comprehensive understanding of their degradation behavior under physiologically relevant conditions. This study investigates the in vitro and in vivo degradation of 3D-printed poly(L-lactide-co-trimethylene carbonate) (PLATMC) scaffolds, fabricated in two distinct architectures: one incorporating internal microporosity introduced by post-printing salt leaching within filaments, and the other with non-porous filaments. For in vitro degradation, scaffolds were incubated at 37 °C under both dynamic (with and without enzymatic supplementation) and static non-enzymatic conditions using a custom perfusion bioreactor that simulates physiological flow. The scaffolds were also implanted subcutaneously in rats, for in vivo degradation. In vitro , porous PLATMC (p-PLATMC) exhibited significantly greater mass loss (60 ± 5%) and increased porosity, particularly under dynamic enzymatic conditions, whereas non-porous scaffolds showed minimal degradation (∼3%). Micro-CT analysis revealed a progressive increase in pore size and porosity, accompanied by a reduction in wall thickness across all conditions. To further assess the impact of polymer chemistry, p-PLATMC scaffolds were compared with porous polycaprolactone (p-PCL) scaffolds under identical conditions. The p-PLATMC scaffolds degraded more rapidly than their p-PCL counterparts, particularly under dynamic enzymatic flow. Notably, the in vivo study showed a degradation pattern consistent with the in vitro results. p-PLATMC exhibited pronounced mass loss (24.7 ± 4.4%) and a marked increase in porosity (65.1 ± 3.2%) and pore size, whereas p-PCL remained structurally stable (2.3 ± 0.9% mass loss). Coupling in vitro bioreactor studies with computational analysis and in vivo study highlighted the critical influence of scaffold architecture, flow dynamics, and polymer chemistry on degradation kinetics. These findings emphasize the predictive value of the combined approach for scaffold design, providing critical insights into the development of next-generation biodegradable scaffolds in bone tissue engineering.