Dual-functional scaffolds of poly(L-lactic acid)/nanohydroxyapatite encapsulated with metformin: Simultaneous enhancement of bone repair and bone tumor inhibition

Abstract

Bone defects caused by tumors are difficult to repair clinically because of their poor morphology and residual tumor cell-induced recurrence. Scaffolds with the dual function of bone repair and bone tumor treatment are urgently needed to resolve this problem. In this study, a poly(L-lactic acid) (PLLA)/nanoscale hydroxyapatite (nHA)/metformin (MET) nanocomposite scaffold was constructed via selective laser sintering. The scaffolds were expected to combine the excellent mechanical strength and biodegradability of PLLA, the good bioactivity of nHA, and the water solubility and antitumor properties of MET. The PLLA/nHA/MET scaffolds showed improved cell adhesion, appropriate porosity, good biocompatibility and osteogenic-induced ability in vitro because metformin improves water solubility and promotes the osteogenic differentiation of cells within the scaffold. The PLLA/nHA/MET scaffold had an extended drug release time because the MET particles were wrapped in the biodegradable polymer PLLA and the wrapped MET particles were slowly released into body fluids as the PLLA was degraded. Moreover, the scaffold induced osteosarcoma (OS) cell apoptosis by upregulating apoptosis-related gene expression and showed excellent tumor inhibition characteristics in vitro. In addition, the scaffold induced osteogenic differentiation of bone marrow mesenchymal cells (BMSCs) by promoting osteogenic gene expression. The results suggest that the PLLA/nHA/MET composite scaffold has the dual function of tumor inhibition and bone repair and therefore it provides a promising new approach for the treatment of tumor-induced bone defects.

Keywords: Bone defect; Bone scaffold; Bone tumor; Drug delivery; Tissue engineering.