Biomimetic nano-biomaterials for bone repair and regeneration
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Currently, over 1.7 billion people suffer from a musculoskeletal disorder; over 200 million operations take place annually; and in excess of 1 million new clinical cases are reported per year. Further, the annual healthcare expenditure exceeds US$ 950 billion Orthopaedic pathologies, such as osteoarthritis, tendinopathies, fractures, osteoporosis, intervertebral disc degeneration, low back pain, tumours and congenital deformities are among the largest group of debilitating diseases today. Therefore, the need for innovative regenerative strategies that are free from dysfunctional tissue healing remains ever relevant. Despite significant advances in the field, current biomaterial-based products for musculoskeletal repair and regeneration do not mimic the complex hierarchical structure and osteoinductive signals of the host native bone microenvironment. Herein, it is hypothesised that nano-textured biomaterials functionalised with carbohydrates moieties, by mimicking the native bone hierarchy and composition, would control osteoblast response in vitro and promote functional bone regeneration in vivo. Starting with nano-imprinting, this work revealed that topographical features in the middle nano-range (~306 nm) and low micron-range (~2,046 nm) induce cellular and matrix alignment and upregulation of osteogenic markers in vitro. However, these topographical features did not induce directional cell growth and neotissue formation in vivo. These data suggest that topographical features in two-dimensional scaffold (surface) can be utilised to maintain cell phenotype during in vitro cell expansion, enhancing that way clinical translation and commercialisation of cell-based therapies. With respect to electro-spinning, as low as 0.01 % functionalisation of electro-spun scaffolds with non-sulphated polysaccharides not only did not compromise the mechanical properties of the produced scaffolds, but also didn’t supress osteoblast adhesion, growth, proliferation and early in vitro osteogenesis. These data suggest that functionalisation of three-dimensional implantable devices with carbohydrates moieties (in this case non-sulphated polysaccharides) could promote functional bone repair and regeneration.