Evidence that nanoscale surface properties stimulate and guide various molecular and biological processes at the implant/tissue interface is fostering a new trend in designing implantable metals. Cutting-edge expertise and techniques drawn from widely separated fields, such as nanotechnology, materials engineering and biology, have been advantageously exploited to nanoengineer surfaces in ways that control and direct these processes in predictable manners. In this review, we present and discuss the state-of-the-art of nanotechnology-based approaches currently adopted to modify the surface of metals used for orthopedic and dental applications, and also briefly consider their use in the cardiovascular field. The effects of nanoengineered surfaces on various in vitro molecular and cellular events are firstly discussed. This review also provides an overview of in vivo and clinical studies with nanostructured metallic implants, and addresses the potential influence of nanotopography on biomechanical events at interfaces. Ultimately, the objective of this work is to give the readership a comprehensive picture of the current advances, future developments and challenges in the application of the infinitesimally small to biomedical surface science. We believe that an integrated understanding of the in vitro and particularly of the in vivo behavior is mandatory for the proper exploitation of nanostructured implantable metals and, indeed, of all biomaterials.

A nanocomposite based on bacterial cellulose (BC) and type I collagen (COL) was evaluated for in vitro bone regeneration. BC membranes were modified by glycine esterification followed by cross-linking of type I collagen employing 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. Collagen incorporation was studied by spectroscopy analysis. X-Ray diffraction showed changes in the BC crystallinity after collagen incorporation. The elastic modulus and tensile strength for BC-COL decreased, while the strain at failure showed a slight increase, even after sterilization, as compared to pristine BC. Swelling tests and contact angle measurements were also performed. Cell culture experiments performed with osteogenic cells were obtained by enzymatic digestion of newborn rat calvarium revealed similar features of cell morphology for cultures grown on both membranes. Cell viability/proliferation was not different between BC and BC-COL membranes at day 10 and 14. The high total protein content and ALP activity at day 17 in cells cultured on BC-COL indicate that this composite allowed the development of the osteoblastic phenotype in vitro. Thus, BC-COL should be considered as alternative biomaterial for bone tissue engineering.

In the course of attempting to define the bone “secretome” using a signal-trap screening approach, we identified a gene encoding a small membrane protein novel to osteoblasts. Although previously identified in silico as ifitm5, no localization or functional studies had been undertaken on this gene. We characterized the expression patterns and localization of this gene in vitro and in vivo and assessed its role in matrix mineralization in vitro. The bone specificity and shown role in mineralization led us to rename the gene bone restricted ifitm-like protein (Bril). Bril encodes a 14.8-kDa 134 amino acid protein with two transmembrane domains. Northern blot analysis showed bone-specific expression with no expression in other embryonic or adult tissues. In situ hybridization and immunohistochemistry in mouse embryos showed expression localized on the developing bone. Screening of cell lines showed Bril expression to be highest in osteoblasts, associated with the onset of matrix maturation/mineralization, suggesting a role in bone formation. Functional evidence of a role in mineralization was shown by adenovirus-mediated Bril overexpression and lentivirus-mediated Bril shRNA knockdown in vitro. Elevated Bril resulted in dose-dependent increases in mineralization in UMR106 and rat primary osteoblasts. Conversely, knockdown of Bril in MC3T3 osteoblasts resulted in reduced mineralization. Thus, we identified Bril as a novel osteoblast protein and showed a role in mineralization, possibly identifying a new regulatory pathway in bone formation.