Nature-Inspired Unconventional Approaches to Develop 3D Bioceramic Scaffolds with Enhanced Regenerative Ability.

Material science is a relevant discipline in support of regenerative medicine. Indeed, tissue regeneration requires the use of scaffolds able to guide and sustain the natural cell metabolism towards tissue regrowth. This need is particularly important in musculoskeletal regeneration, such as in the case of diseased bone or osteocartilaginous regions for which calcium phosphate-based scaffolds are considered as the golden solution. However, various technological barriers related to conventional ceramic processing have thus far hampered the achievement of biomimetic and bioactive scaffolds as effective solutions for still unmet clinical needs in orthopaedics. Driven by such highly impacting socioeconomic needs, new nature-inspired approaches promise to make a technological leap forward in the development of advanced biomaterials. The present review illustrates ion-doped apatites as biomimetic materials whose bioactivity resides in their unstable chemical composition and nanocrystallinity, both of which are, however, destroyed by the classical sintering treatment. In the following, recent nature-inspired methods preventing the use of high-temperature treatments, based on (i) chemically hardening bioceramics, (ii) biomineralisation process, and (iii) biomorphic transformations, are illustrated. These methods can generate products with advanced biofunctional properties, particularly biomorphic transformations represent an emerging approach that could pave the way to a technological leap forward in medicine and also in various other application fields.

Superparamagnetic hybrid microspheres affecting osteoblasts behaviour.

The present work describes biomimetic hybrid microspheres made of collagen type I-like peptide matrix (RCP) mineralised with Fe2+/Fe3+ doping hydroxyapatite (RCPFeHA) by a bio-inspired process. Superparamagnetic RCPFeHA microspheres are obtained by emulsification of the hybrid slurries in the presence of citrate ions, to achieve a biomimetic surface functionalisation improving the bioactivity and the dispersion ability in cell culture medium. A biological in vitro study correlates the osteoblast cells behaviour to calcium and iron ions released by the hybrid microspheres in culture media mimicking physiological or inflammatory environment, evidencing a clear triggering of cell activity and bio-resorption ability. In presence of the microspheres, the osteoblast cells maintain their typical morphology and no cell damage were detected, whereas also showing up-regulation of osteogenic markers. The ability of the hybrid microspheres to undergo bio-resorption and release bioactive ions in response to different environmental stimuli without harmful effects opens new perspectives in bone regeneration, as magnetically active bone substitute with potential ability of drug carrier and smart response in the presence of inflammatory states.

New bioactive bone-like microspheres with intrinsic magnetic properties obtained by bio-inspired mineralisation process.

A bio-inspired mineralisation process was investigated and applied to develop novel hybrid magnetic materials by heterogeneous nucleation of Fe2+/Fe3+-doped hydroxyapatite nanocrystals onto a biopolymeric matrix made of a Type I collagen-based recombinant peptide (RCP). The effect of the synthesis temperature on the phase composition, crystallinity and magnetic properties of the nucleated inorganic phase was studied. The as-obtained magnetic materials were then engineered, by using a water-in-oil emulsification process, into hybrid magnetic microspheres, which were stabilized by de-hydrothermal treatment yielding cross-linking of the macromolecular matrix. Thorough investigation of the physicochemical, morphological and biological properties of the new hybrid microspheres, as induced by the presence of the inorganic nanophase and controlled iron substitution into hydroxyapatite lattice, revealed bone-like composition, good cytocompatibility, designed shape and size, and tailored magnetization. Such features are interesting and promising for application as new biomaterials with ability of remote activation and control by using external magnetic fields, for smart and personalized applications in medicine, particularly in bone tissue regeneration.