Application of inorganic nanomaterials in bone tissue engineering and regenerative medicine

Recently, tissue engineering and regenerative medicine, especially bone tissue engineering and regenerative medicine have developed rapidly. Bone tissue engineering is a complicated and dynamic bone remodeling process that starts with recruitment and migration of osteoblasts and then regulates their proliferation, differentiation, and mineralization. Scaffold is typically biodegradable material that plays a crucial role as one of the three elements of bone tissue engineering and regenerative medicine. Bone scaffold provides the mechanical support during reformation and repair of damaged or diseased bone. For more than a decade, a large amount of research work has been carried out on the designing of scaffolds, processing techniques, performance assessment, and medical application. Significant progress has been made toward scaffold materials for structural support for desired osteogenesis and angiogenesis abilities. To date, depending on the advanced technologies, the bioresorbable scaffolds possess controlled porosity and high mechanical properties are possible used as bone scaffold. Natural bone has delicate architectural structure that spans nanoscale to macroscopic dimensions, which determine the unique mechanical properties of bone. The hierarchical structure of natural bone can be defined as a nanocomposite consisting of inorganic nanocrystalline hydroxyapatite (HA), organic components (mostly are collagens) and water. The outside proteins assemble together to form an extracellular matrix (ECM) with nanostructured which influences the adhesion, proliferation, differentiation, and mineralization of several cell types, such as bone lining cell, mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. To better mimic the nanostructure in natural ECM, many research groups over the past decade developed nano-based scaffolds (nanotubes, nanofibers, nanoparticles, and hydrogel) to resemble the ECM for promising candidates in replacing defective tissues. The high biomimetic properties and excellent mechanical features of nano-based scaffolds plays a vital role in stimulating cell adhesion and proliferation, as well as directing bone tissue formation through mimetic the nanometer dimension of natural bone tissue. Besides, mechanical properties are key factors for bone regeneration and bone local function. Nowadays, a large number of research groups have tried to manipulate the mechanical properties of scaffolds through designing the different nanosturctures, including nanofiber, nanoparticle, polymer matrices to mimic the nanocomposite structure of natural bone. These materials have highly stiffness, strength, and toughness properties that are promising in bone tissue engineering. Nanobiomaterials, especially inorganic nanobiomaterials, have excellent mechanical properties and biocompatibility, and are ideal for the preparation of scaffold materials for bone tissue engineering and regenerative medicine, showing a broad application prospect. In this article, we systematically review the application of inorganic nanomaterials, including hydroxyapatite, silicon-based nanomaterials, carbon-containing nanomaterials and several metal nanomaterials in bone tissue engineering and regenerative medicine. Although nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering, the application in the clinical regenerative engineering has limited. Currently, there are several limitations in regenerative strategies, including low efficient cellular proliferation, differentiation and mineralization, insufficient mechanical strength of scaffolds, and limited production of growth factors necessary for efficient osteogenesis. Therefore, there are still some issues on the nano-based scaffold should be cleared: (1) The interaction of nano-based scaffold and bioactive molecules, growth factors, and genetic material, (2) the biocomptibility, cytotoxicity, and biodegradation of nano-based scaffold, and (3) nano-based scaffold mechanical stability, cellular survival, and molecular mechanism of inducing bone formation. As the development of nanotechnology, ultimate translation to the clinical application may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases.