Dynamic degradation patterns of porous polycaprolactone/β-tricalcium phosphate composites orchestrate macrophage responses and immunoregulatory bone regeneration

Biodegradable polycaprolactone/β-tricalcium phosphate (PT) composites are desirable candidates for bone tissue engineering applications. A higher β-tricalcium phosphate (TCP) ceramic content improves the mechanical, hydrophilic and osteogenic properties of PT scaffolds in vitro. Using a dynamic degradation reactor, we established a steady in vitro degradation model to investigate the changes in the physio-chemical and biological properties of PT scaffolds during degradation.PT46 and PT37 scaffolds underwent degradation more rapidly than PT scaffolds with lower TCP contents. In vivo studies revealed the rapid degradation of PT (PT46 and PT37) scaffolds disturbed macrophage responses and lead to bone healing failure. Macrophage co-culture assays and a subcutaneous implantation model indicated that the scaffold degradation process dynamically affected macrophage responses, especially polarization. RNA-Seq analysis indicated phagocytosis of the degradation products of PT37 scaffolds induces oxidative stress and inflammatory M1 polarization in macrophages. Overall, this study reveals that the dynamic patterns of biodegradation of degradable bone scaffolds highly orchestrate immune responses and thus determine the success of bone regeneration. Therefore, through evaluation of the biological effects of biomaterials during the entire process of degradation on immune responses and bone regeneration are necessary in order to develop more promising biomaterials for bone regeneration.