A review of hydrogel use in fracture healing and bone regeneration

This review explores the application of hydrogels in orthopaedic clinical situations which may benefit from enhanced growth factor delivery and improved osteogenesis of bone graft material. Hydrogels are defined, and in vivo evidence supporting their application in these clinical areas is explored. Our focus is on clinically pertinent properties, such as the chemistry of formation, biocompatibility, efficacy of cell and growth factor delivery, ability to withstand mechanical loading and potential to be delivered via an injection. Naturally derived hydrogels, such as gelatin, hyaluronic acid and fibroin, together with a number of synthetic polyethylene glycol-based gels combined with protease-sensitive domains, have shown excellent biocompatibility. There is significant literature evidence supporting the ability of hydrogels to facilitate growth factor and cell delivery. Burst release of the selected growth factor remains a consistent challenge, which has been overcome in some studies with chemical modifications of the hydrogel. Interestingly, a number of studies detail percutaneous delivery with hydrogels combined with calcium-based minerals to enhance osteogenicity, with mixed results. Few of the studies explored the biomechanical properties of the materials, and none of the studies reviewed demonstrated the ability of a hydrogel/graft material to withstand mechanical loading in a clinically relevant segmental bone defect model.