Self-Assembled Hydroxyapatite-Graphene Scaffold for Photothermal Cancer Therapy and Bone Regeneration.

Abstract

Repairing large tumor-related bone defects remains a difficult clinical problem because of the significant risk of locoregional relapse after surgical curettage. In this study, a composite scaffold of nano-hydroxyapatite (nHA) and reduced graphene oxide (rGO) sheets was fabricated by self-assembly, and a 20 wt% nHA-rGO sheet solution formed the most stable hydrogel. In vitro, nHA-rGO scaffolds killed all but 8% of osteosarcoma cells (MG-63) under 808 nm near-infrared laser irradiation for 20 min. SEM images and live/dead staining of MG-63 cells in nHA-rGO also confirmed the therapeutic efficacy of the scaffolds. Tumors implanted with nHA-rGO scaffolds reached 60 °C after 4 min. of irradiation; xenografted tumors stopped growth or even decreased in size after photothermal therapy. In vitro the scaffolds promoted adhesion, proliferation, and osteogenic mineralization of rat bone marrow stem cells (rBMSCs). Live cell staining and CCK-8 showed good proliferation for rBMSCs in nHA-rGO scaffolds. Alkaline phosphatase activity and qPCR demonstrated osteogenic mineralization of rBMSCs in nHA-rGO scaffolds. Micro-CT and histology verified that the scaffold promotes bone regeneration in rat cranial defects. At 8 weeks, 35% of the cranial defect area remained in the scaffold-implanted group, while 80% remained for the control. Bone mineral density of the scaffold-implanted group reached 284.58±20.78 mg/cm³, indicating new bone mineral deposition, versus only 96.04±2.67 mg/cm³ for the control. Histology showed scaffold stimulation of osteoblast mineralization and collagen deposition. Therefore, nHA-rGO scaffolds may be an effective treatment of large tumor-related bone defects due to their excellent photothermal and osteogenic effects.