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.

Highlights

  • There is an urgent need for alternative approaches for the regeneration of bone following fracture or orthopaedic damage in lieu of traditional methods, and these alternative approaches constitute an important tissue engineering application (Vo et al, 2012)

  • We reported the formulation of a novel PLGA scaffold delivery system based on porous and protein-loaded microspheres that sintered at 37°C (Boukari et al, 2015)

  • We report the development of a ‘dual-application’ PLGA/chitosan composite scaffold formulation which sinters at 37°C when injected through a hypodermic needle as well as when implanted as a paste

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Summary

Introduction

There is an urgent need for alternative approaches for the regeneration of bone following fracture or orthopaedic damage in lieu of traditional methods, and these alternative approaches constitute an important tissue engineering application (Vo et al, 2012). The current ‘gold standard’ therapy is the bone graft procedure, which involves taking autologous bone, usually harvested from the iliac crest of the patient, and implanting it into their defect site (Martino et al, 2012; Amini et al, 2013). Allograft bone from donors or cadavers can be extracted from the femoral heads or extremities of other long bones (Delloye et al, 2007). This implanted tissue acts as a scaffold for the existing bone tissue to infiltrate and deposit extracellular matrix (ECM), leading to the remodelling of the fractured bone (Bostrom and Mikos, 1997). The shortcomings in the current clinical options have led to concerted efforts in search of alternative strategies for the repair of bone

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