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. <i>In vitro</i>, 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. <i>In vitro</i> 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.