Reconstruction of Large-scale Defects with a Novel Hybrid Scaffold Made from Poly(L-lactic acid)/Nanohydroxyapatite/Alendronate-loaded Chitosan Microsphere: in vitro and in vivo Studies

Hongwei Wu,Hua Liu,Yu Shrike Zhang,Jingzhou Yang,Longbo Zhang,Gengyan Liu,Wanting Niu,Yihe Hu,Jie Xie,Pengfei Lei,Chaoyue Zhang,Jianming Ruan

doi:10.1038/s41598-017-00506-z

Abstract

A chitosan-based microsphere delivery system has been fabricated for controlled release of alendronate (AL). The present study aimed to incorporate the chitosan/hydroxyapatite microspheres-loaded with AL (CH/nHA-AL) into poly(L-lactic acid)/nanohydroxyapatite (PLLA/nHA) matrix to prepare a novel microspheres-scaffold hybrid system (CM-ALs) for drug delivery and bone tissue engineering application. The characteristics of CM-ALs scaffolds containing 10% and 20% CH/nHA-AL were evaluated in vitro, including surface morphology and porosity, mechanical properties, drug release, degradation, and osteogenic differentiation. The in vivo bone repair for large segmental radius defects (1.5 cm) in a rabbit model was evaluated by radiography and histology. In vitro study showed more sustained drug release of CM-AL-containing scaffolds than these of CM/nHA-AL and PLLA/nHA/AL scaffolds, and the mechanical and degradation properties of CM-ALs (10%) scaffolds were comparable to that of PLLA/nHA control. The osteogenic differentiation of adipose-derived stem cells (ASCs) was significantly enhanced as indicated by increased alkaline phosphates (ALP) activity and calcium deposition. In vivo study further showed better performance of CM-ALs (10%) scaffolds with complete repair of large-sized bone defects within 8 weeks. A microspheres-scaffold-based release system containing AL-encapsulated chitosan microspheres was successfully fabricated in this study. Our results suggested the promising application of CM-ALs (10%) scaffolds for drug delivery and bone tissue engineering.

Highlights

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The morphology of scaffolds was quite different between the two scaffolds (PLLA/nHA and CM-AL) with CH/nHA-AL partially embedded in the CM-AL scaffolds (Fig. 1A)
Our previous study has successfully constructed a class of nHA/chitosan-based microspheres for controlled release of AL, with improved loading efficiency and sustained drug release, as well as the enhanced osteogenic activity of rabbit ASCs33

Summary

Introduction

The Harvard community has made this article openly available. Please share how this access benefits you. The present study aimed to incorporate the chitosan/hydroxyapatite microspheres-loaded with AL (CH/nHA-AL) into poly(L-lactic acid)/nanohydroxyapatite (PLLA/nHA) matrix to prepare a novel microspheres-scaffold hybrid system (CM-ALs) for drug delivery and bone tissue engineering application. Poly(L-lactic acid) (PLLA)-based scaffold is a synthetic bone graft substitute that has been largely investigated for bone tissue engineering applications[10, 11]. Both the PLLA and PLGA have been approved by the FDA and have been successflly used as orthopaedic implants for tissue engineering[7, 9]. Osteoinductive materials are often required for bone regeneration of the scaffolds

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