A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering

Abstract

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37 °C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.

Keywords:

• Polymeric biomaterials
• controlled delivery
• poly (lactic-co-glycolic acid) (PLGA)
• microspheres
• protein delivery
• tissue engineering
• mechanical properties
• formulation

Abbreviations:

• BMPs: bone morphogenetic proteins
• BSA: bovine serum albumin
• DCM: dichloromethane
• DMSO: dimethyl sulphoxide
• ECM: extracellular matrix
• FTIR: Fourier transform infrared
• hMSC: primary human mesenchymal stem cells
• PBS: phosphate-buffered saline
• PLGA: poly (lactic-co-glycolic acid)
• PVA: poly (vinyl alcohol)
• SDS: sodium dodecyl sulphate
• SEM: scanning electron microscopy
• TPP: sodium tripolyphosphate
• ToF-SIMS: time of flight secondary ion mass spectroscopy

Acknowledgements

The authors would also like to thank Enas Alkhader, Hilda Amekyeh, Abdulrahman Baki and Noura Alom (The University of Nottingham) for their support and assistance.