Enhancing the bioactivity of Poly(lactic-co-glycolic acid) scaffold with a nano-hydroxyapatite coating for the treatment of segmental bone defect in a rabbit model

De-Xin Wang,^1,* Yao He,^2,* Long Bi^1,* Ze-Hua Qu,² Ji-Wei Zou,¹ Zhen Pan,² Jun-Jun Fan,¹ Liang Chen,² Xin Dong,¹ Xiang-Nan Liu,² Guo-Xian Pei,¹ Jian-Dong Ding,<sup>2

1</sup>Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China; ²State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, People's Republic of China

*These authors contributed equally to this work

Purpose: Poly(lactic-co-glycolic acid) (PLGA) is excellent as a scaffolding matrix due to feasibility of processing and tunable biodegradability, yet the virgin scaffolds lack osteoconduction and osteoinduction. In this study, nano-hydroxyapatite (nHA) was coated on the interior surfaces of PLGA scaffolds in order to facilitate in vivo bone defect restoration using biomimetic ceramics while keeping the polyester skeleton of the scaffolds.
Methods: PLGA porous scaffolds were prepared and surface modification was carried out by incubation in modified simulated body fluids. The nHA coated PLGA scaffolds were compared to the virgin PLGA scaffolds both in vitro and in vivo. Viability and proliferation rate of bone marrow stromal cells of rabbits were examined. The constructs of scaffolds and autogenous bone marrow stromal cells were implanted into the segmental bone defect in the rabbit model, and the bone regeneration effects were observed.
Results: In contrast to the relative smooth pore surface of the virgin PLGA scaffold, a biomimetic hierarchical nanostructure was found on the surface of the interior pores of the nHA coated PLGA scaffolds by scanning electron microscopy. Both the viability and proliferation rate of the cells seeded in nHA coated PLGA scaffolds were higher than those in PLGA scaffolds. For bone defect repairing, the radius defects had, after 12 weeks implantation of nHA coated PLGA scaffolds, completely recuperated with significantly better bone formation than in the group of virgin PLGA scaffolds, as shown by X-ray, Micro-computerized tomography and histological examinations.
Conclusion: nHA coating on the interior pore surfaces can significantly improve the bioactivity of PLGA porous scaffolds.

Keywords: PLGA, nano-hydroxyapatite, bone tissue engineering, BMSCs, bone defect