A novel photothermally controlled multifunctional scaffold for clinical treatment of osteosarcoma and tissue regeneration

Abstract: After an osteosarcoma excision, recurrence, large bone defects, and soft tissue injury are significant challenges for clinicians. Conventional treatment by implanting bone replacement materials can induce bone regeneration after surgery, but this does not prevent bleeding, promote soft tissue repair, or help destroy the residual tumor cells. We attempted to develop a new multifunctional scaffold, with the clinical goals of facilitating tumor cell death through thermal ablation and promoting osteogenesis. Accordingly, we first investigated the effect of nano-hydroxyapatite/graphene oxide (nHA/GO) composite particles with different proportions on human osteosarcoma cells (HOS), pre-osteoblastic MC3T3-E1 cells, and human bone marrow mesenchymal stem cells (hBMSC) with or without 808-nm near-infrared (NIR) light irradiation. Next, we fabricated a novel temperature-controlled multifunctional nano-hydroxyapatite/graphene oxide/chitosan (nHA/GO/CS) scaffold, which can effectively kill human osteosarcoma cells under 808-nm NIR irradiation by reaching a temperature of 48?°C and further promote osteogenesis of hBMSC at 42?±?0.5?°C in coordination with nHA. This scaffold demonstrates the best post-operative bone volume/tissue volume (BV/TV) ratio performance (20.36%) 8?weeks after scaffold implantation in the cranial defects of rats. Further exploration has revealed that NIR irradiation may promote the osteogenesis of hBMSC with the addition of nHA by enhancing the BMP2/Smad signaling pathway. Further, this scaffold has a good hemostatic effect and facilitates soft tissue repair under irradiation. This novel photothermally controlled multifunctional scaffold, which not only kills human osteosarcoma cells but also facilitates tissue regeneration, is a promising clinical tool for treating tissue injuries from an osteosarcoma resection.