Bone is a complex biologic tissue, which is extremely relevant for various physiological functions, in addition to movement, organ protection, and weight bearing. The repair of critical size bone defects is a still unmet clinical need, and over the past decades, material scientists have been expending efforts to find effective technological solutions, based on the use of scaffolds. In this context, biomimetics which is intended as the ability of a scaffold to reproduce compositional and structural features of the host tissues, is increasingly considered as a guide for this purpose. However, the achievement of implants that mimic the very complex bone composition, multi-scale structure, and mechanics is still an open challenge. Indeed, despite the fact that calcium phosphates are widely recognized as elective biomaterials to fabricate regenerative bone scaffolds, their processing into 3D devices with suitable cell-instructing features is still prevented by insurmountable drawbacks. With respect to biomaterials science, new approaches maybe conceived to gain ground and promise for a substantial leap forward in this field. The present review provides an overview of physicochemical and structural features of bone tissue that are responsible for its biologic behavior. Moreover, relevant and recent technological approaches, also inspired by natural processes and structures, are described, which can be considered as a leverage for future development of next generation bioactive medical devices.

The present work investigates heterogeneous gas–solid reactions involved in the biomorphic transformation of natural wood into large 3-D hydroxyapatite (HA) scaffolds recapitulating physico-chemical, morphological and mechanical features typical of natural bone. In particular, we found that the use of a reactive CO₂/H₂O gas mixture, under supercritical conditions at high pressure, permits to control heterogeneous CaO-CO₂ reactions throughout the whole bulk and to direct the nucleation-growth of CaCO₃ at a relatively low temperature, thus obtaining a highly reactive 3-D precursor enabling the formation of a large biomorphic HA scaffold preserving fine nanostructure by a hydrothermal process. To the best of our knowledge, the application of heterogeneous chemical reactions in the 3-D state is an original way to generate large HA scaffolds maintaining bio-relevant ionic substitutions, with specific regard to Mg²⁺, Sr²⁺ and CO₃ ²⁻ ions, conferring a superior ability to guide cell fate. We hypothesize that the original nanostructure of the final 3-D HA scaffold, not achievable by the classic sintering procedure, and the multi-scale hierarchical organization inherited by the original template, account for its high compression strength with damage-tolerant mechanical behaviour. The ability of the new scaffold to induce bone regeneration is attested by the overexpression of genes, early and late markers of the osteogenic differentiation pathway, and by the in vivo osteoinductivity. We hypothesize that the unique association of bioactive chemical composition, nanostructure and multi-scale hierarchy can synergistically act as instructing signals for cells to generate new bone tissue with organized 3-D architecture. These results point to its great applicative potential for the regeneration of large bone defects, which is a still unmet clinical need.

Chemotherapeutics such as platinum-based drugs are commonly used to treat several cancer types, but unfortunately, their use is limited by several side effects, such as high degradation of the drug before entering the cells, off-target organ toxicity and development of drug resistance. An interesting strategy to overcome such limitations is the development of nanocarriers that could enhance cellular accumulation in target cells in addition to decreasing associated drug toxicity in normal cells. Here, we aim to prepare and characterize a graphene-oxide-based 2D nanoplatform functionalised using highly branched, eight-arm polyethylene-glycol, which, owing to its high number of available functional groups, offers considerable loading capacity over its linear modalities and represents a highly potent nanodelivery platform as a versatile system in cancer therapy. The obtained results show that the GO@PEG carrier allows for the use of lower amounts of Pt drug compared to a Pt-free complex while achieving similar effects. The nanoplatform accomplishes very good cellular proliferation inhibition in osteosarcoma, which is strictly related to increased cellular uptake. This enhanced cellular internalization is also observed in glioblastoma, although it is less pronounced due to differences in metabolism compared to osteosarcoma. The proposed GO@PEG nanoplatform is also promising for the inhibition of migration, especially in highly invasive breast carcinoma (i.e., MDA-MB-231 cell line), neutralizing the metastatic process. The GO@PEG nanoplatform thus represents an interesting tool in cancer treatment that can be specifically tailored to target different cancers.

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.

In an attempt to mimic the outstanding mechanical properties of wood and bone, a 3D heterogeneous chemistry approach has been used in a biomorphic transformation process (in which sintering is avoided) to fabricate ceramics from rattan wood, preserving its hierarchical fibrous microstructure. The resulting material (called biomorphic apatite ​[BA] henceforth) possesses a highly bioactive composition and is characterised by a multiscale hierarchical pore structure, based on nanotwinned hydroxyapatite lamellae, which is shown to display a lacunar fractal nature. The mechanical properties of BA are found to be exceptional (when compared with usual porous hydroxyapatite and other ceramics obtained from wood through sintering) and unique ​as they occupy a zone in the Ashby map previously free from ceramics, but not far from wood and bone. Mechanical tests show the following: (i) the strength in tension may exceed that in compression, (ii) failure in compression involves complex exfoliation patterns, thus resulting in high toughness, (iii) unlike in sintered porous hydroxyapatite, fracture does not occur 'instantaneously,' ​but its growth may be observed, and it exhibits tortuous patterns that follow the original fibrillar structure of wood, thus yielding outstanding toughness, (iv) the anisotropy of the elastic stiffness and strength show unprecedented values when situations of stresses parallel and orthogonal to the main channels are compared. Despite being a ceramic material, BA displays a mechanical behavior similar on the one hand to the ligneous material from which it was produced (therefore behaving as a 'ceramic with the signature of wood') and on the other hand to the cortical/spongy osseous complex constituting the structure of compact bone.