Regulated macrophage immune microenvironment in 3D printed scaffolds for bone tumor postoperative treatment

Abstract

The 3D printing technique is suitable for patient-specific implant preparation for bone repair after bone tumor resection. However, improving the survival rate due to tumor recurrence remains a challenge for implants. The macrophage polarization induction to M2-type tumor-associated macrophages (TAMs) by the tumor microenvironment is a key factor of immunosuppression and tumor recurrence. In this study, a regenerative scaffold regulating the macrophage immune microenvironment and promoting bone regeneration in a dual-stage process for the postoperative treatment of bone tumors was constructed by binding a colony-stimulating factor 1 receptor (CSF-1R) inhibitor GW2580 onto in situ cosslinked hydroxybutylchitosan (HBC)/oxidized chondroitin sulfate (OCS) hydrogel layer covering a 3D printed calcium phosphate scaffold based on electrostatic interaction. The hydrogel layer on scaffold surface not only supplied abundant sulfonic acid groups for stable loading of the inhibitor, but also acted as the cover mask protecting the bone repair part from exposure to unhealthy growth factors in the microenvironment at the early treatment stage. With local prolonged release of inhibitor being realized via the functional material design, CSF-1R, the main pathway that induces polarization of TAMs, can be efficiently blocked, thus regulating the immunosuppressive microenvironment and inhibiting tumor development at a low therapeutic dose. At the later stage of treatment, calcium phosphate component of the scaffold can facilitate the repair of bone defects caused by tumor excision. In conclusion, the difunctional 3D printed bone repair scaffold regulating immune microenvironment in stages proposed a novel approach for bone tumor postoperative treatment.