Biomimetic Calcium Phosphate Bone Substitute and Related Additives for Bone Regeneration in Osteosarcoma Therapy

Bone defects can be classified into two categories based on their association with cancer cells: cancer-associated and non-cancer-associated bone defects. To repair these defects, various bone substitutes, including metals, polymers, hydrogels, and calcium phosphate (CaP) ceramics, have been developed, leveraging advancements in material sciences and engineering. Although these substitutes have demonstrated successful applications in bone reconstruction within laboratory settings and clinical practice, their predominant use has been limited to non-cancer-associated bone defects. This restriction stems from concerns about potential bone cancer relapse induced by the utilization of these substitutes. This issue makes bone regeneration in a cancer scenario remain at a standstill, leaving many cancer patients with bone defects to endure functional impairment and disfigurement over the years. On the other hand, a bone substitute that can be used for cancer-related bone defect repair will drastically help cancer patients improve their quality of life and self-esteem. The pressing need for a bone substitute suitable for cancer-related bone defect repair is pronounced among osteosarcoma (OS) patients. OS, a primary bone neoplasm, exists a higher incidence in the juvenile and geriatric populations. Currently, the prevalent treatment for OS is surgical resection, even amputation. Therefore, severe bone defects commonly occur in OS patients, while frustratingly, up to date, no bone substitutes have been clinically approved for bone reconstruction for these patients. An ideal bone substitute for cancer-associated bone defects should theoretically demonstrate dual capabilities: pro-osteogenic and anti-cancer properties. Nevertheless, most of current bone substitutes are inherently only pro-osteogenic. To address the imperative of cancer suppression in the context of bone defect repair, doping anti-cancer agents into bone substitutes is an effective strategy, enabling bone defect repair in a cancer environment. In this thesis, two pro-osteogenetic drugs: bone morphogenetic protein-2 (BMP-2) and curcumin encapsualted into CaP materials were investigated for their potential application in bone defect repair in osteosarcoma. The results suggested these two drugs did not provoke osteosarcoma cells in vitro. This means the strategy, using BMP-2 or curcumin dopped CaP materials, may be resonable.