Abstract
Background/Study Aim
Injectable scaffolds which also deliver cells and bioactive molecules to augment bone healing overcome many of the limitations associated with current bone graft substitutes. The aim of this study was to develop and test a novel injectable scaffold that self-assembles isothermically in situ to form a biodegradable porous osteoconductive material, and to assess the viability of human mesenchymal stem cells (hMSC) seeded onto the scaffold.
Methods
Rheological assessment was performed on three different molecular weights (Mw) of poly(lactic-co-glycolic acid) (PLGA) (26kDa, 53kDa and 92kDa) combined with differing ratios of polyethylene glycol (PEG) to control the temperature required for scaffold self-assembly. The strength (MPa) and stiffness (Young's Modulus) patterns of the scaffolds were assessed in compression. The cell viability, proliferation and distribution patterns of hMSCs seeded within the scaffold were assessed through various assays (Alamar Blue), confocal microscopy and micro-CT. The hMSC differentiation in osteogenic media was characterised by the identification of specific bone formation markers (e.g. alkaline phosphatase).
Results
Rheological assessment identified a stepwise control of the trigger-temperature required for scaffold self-assembly (37°C) through adjustment of PLGA Mw and PLGA/PEG ratios. Mechanical analysis of the scaffolds revealed compressive (2-6MPa) and stiffness (Young's Modulus of 10MPa) strengths similar to that of cancellous bone. Confocal microscopy analysis demonstrated the scaffold's interconnecting pores and biocompatibility supporting proliferation of viable HMSCs, and complemented data from cell proliferation assays. Identification of bone formation markers reinforced the scaffolds potential to provide a supporting osteoconductive environment for bone formation and deposition.
Conclusions
This study has generated injectable scaffold formulations that self-assemble at physiologically relevant temperatures and possess compressive and stiffness strengths in the range of cancellous bone. It is possible to tailor the architecture/mechanical/biodegradable properties of the scaffold through manipulation of PLGA Mw, and PEG ratios. This injectable scaffold system provides a means of delivery for hMSCs (and growth factors or antibiotics) and is an architecturally suitable 3D scaffold that has the potential to be not only osteoconductive, but also osteoinductive and osteogenic.
