Andrea Ruffini

Biomimesis and biomorphic transformations: new concepts applied to bone regeneration.

In the last decades the activity of material scientists was more and more directed to the development of biomimetic scaffolds, able to drive and address cell activity towards proper differentiation and the repair of diseased human tissues. In case of bone, this requires the synthesis of three-dimensional constructs able to exchange chemical signals promoting osteogenesis and to progressively be resorbed during the formation and remodelling of new bone. Besides, particularly for the regeneration of extensive portions of bone, a morphological and mechanical biomimesis is also required, to allow cell colonization and formation of a proper vascularization tree. The healing of load-bearing bones also requires scaffolds with a hierarchically organized morphology, to provide improved biomechanical behaviour and allow a proper mechano-transduction of the mechanical stimuli down to the cell level. The present paper is an overview of the current technologies and devices developed in the last decade for the regeneration of bone tissue. In particular, novel biomimetic and biomorphic scaffolds, obtained by the controlled transformation of native ligneous structures, promise to adequately face the problem of obtaining complex hierarchical structures, not achievable otherwise by any currently existing manufacturing techniques.

Biomimetic magnesium-carbonate-apatite nanocrystals endowed with strontium ions as anti-osteoporotic trigger.

The present work investigates the preparation of biomimetic nanocrystalline apatites co-substituted with Mg, CO3 and Sr to be used as starting materials for the development of nanostructured bio-devices for regeneration of osteoporotic bone. Biological-like amounts of Mg and CO3 ions were inserted in the apatite structure to mimic the composition of bone apatite, whereas the addition of increasing quantities of Sr ions, from 0 up to 12 wt.%, as anti-osteoporotic agent, was evaluated. The chemical-physical features, the morphology, the degradation rates, the ion release kinetics as well as the in vitro bioactivity of the as-prepared apatites were fully evaluated. The results indicated that the incorporation of 12 wt.% of Sr can be viewed as a threshold for the structural stability of Mg-CO3-apatite. Indeed, incorporation of lower quantity of Sr did not induce considerable variations in the chemical structure of Mg-CO3-apatite, while when the Sr doping extent reached 12 wt.%, a dramatically destabilizing effect was detected on the crystal structure thus yielding alteration of the symmetry and distortion of the PO4. As a consequence, this apatite exhibited the fastest degradation kinetic and the highest amount of Sr ions released when tested in physiological conditions. In this respect, the surface crystallization of new calcium phosphate phase when immersed in physiological-like solution occurred by different mechanisms and extents due to the different structural chemistry of the variously doped apatites. Nevertheless, all the apatites synthesized in this work exhibited in vitro bioactivity demonstrating their potential use to develop biomedical devices with anti-osteoporotic functionality.

Biomineralization of a titanium-modified hydroxyapatite semiconductor on conductive wool fibers

Metal ions are frequently incorporated into crystalline materials to improve their electrochemical properties and to confer new physicochemical properties. Naturally-occurring phosphate apatite, which is formed geologically and in biomineralization processes, has extensive potential applications and is therefore an attractive functional material. In this study, we generate a novel building block for flexible optoelectronics using bio-inspired methods to deposit a layer of photoactive titanium-modified hydroxyapatite (TiHA) nanoparticles (NPs) on conductive polypyrrole(PPy)-coated wool yarns. The titanium concentration in the reaction solution was varied between 8-50 mol% with respect to the phosphorous, which led to titanate ions replacing phosphate in the hydroxyapatite lattice at levels up to 17 mol%. PPy was separately deposited on wool yarns by oxidative polymerization, using two dopants: (i) anthraquinone-2,6-disulfonic acid to increase the conductivity of the PPy layer and (ii) pyroglutamic acid, to reduce the resistivity of the wool yarns and to promote the heterogeneous nucleation of the TiHA NPs. A specific titanium concentration (25 mol% wrt P) was used to endow the TiHA NPs on the PPy-coated fibers with a desirable band gap value of 3.68 eV, and a specific surface area of 146 m2 g-1. This is the first time that a thin film of a wide-band gap semiconductor has been deposited on natural fibers to create a fiber-based building block that can be used to manufacture flexible electronic devices.

Towards Hierarchically Organized Scaffolds for Bone Substitutes from Wood Structures

The development of innovative ceramic scaffolds for bone substitution with superior biomechanical features and smart anisotropic performances was performed through chemical and physical transformations of natural hierarchic structures, as trees, shrubs, palms, etc. These final structures will be highly organized from the molecular to nano, micro and macro-scales, with extremely functional architectures able to constantly adapt to ever changing mechanical and biofunctional needs. This study reports the preliminary results of the ceramisation process: starting from suitable vegetal raw materials pyrolysed to produce carbon templates characterized by complex pore structure, then infiltrated by vapour phase calcium to produce calcium carbide and finally transformed into porous ceramic of calcium carbonate by multi-step thermic and hydrothermal treatment in controlled environment.

Tissue engineering and biomimetics with bioceramics

Today the scientific community is intensively devoted to the development of biomaterials exhibiting high mimesis of bone tissues and cell instructive ability, with the purpose of enabling new therapies for tissue regeneration, which is today a clinical need of steadily increasing relevance. In this respect, calcium phosphates are elective materials, due to their composition close to that of mineral bone. In particular, apatites are biomimetic materials that can be synthesized in a wide variety of atomic compositions and under different forms, enabling various applications in bone surgery. Multiple ion doping confers high bioactivity to nanocrystalline apatite phases, and these phases can be obtained as nanopowders, injectable bioactive cements, or as biohybrid materials, by exploiting bioinspired synthesis approaches. As hydroxyapatite can be processed into porous sintered scaffolds for reconstruction of large cranial bones, it can also be processed into three-dimensional biomimetic scaffold exhibiting bone-like composition and nanostructure, and hierarchical organization, thanks to the application of nature-inspired biomorphic transformations. In the coming decades it is expected that novel synthesis approaches developed on a bioinspiration basis will gain ground, as elective methods to obtain tissue-mimicking materials with increased effectiveness in promoting tissue regeneration.

Nature-Inspired Nanotechnology and Smart Magnetic Activation: Two Groundbreaking Approaches Toward a New Generation of Biomaterials for Hard Tissue Regeneration

Today, as the need of new regenerative solutions is steadily increasing, the demand for new bio-devices with smart functionality is pushing material scientists to develop new synthesis concepts. Indeed, the conventional approaches for biomaterials fail when it comes to generate nano-biocomposites with designed biomimetic composi‐ tion and hierarchically organized architecture mimicking biologically relevant tissue features. In this respect, an emerging concept in material science is to draw inspira‐ tion from natural processes and products, which we may consider as the most advanced examples of smart nanotechnology. Natural processes of supramolecular assembly and mineralization of organic macromolecules, known as biomineraliza‐ tion, generate complex hybrid 3D constructs that are the basis of skeletons, exoskele‐ tons, nacre and shells. On the other hand, natural structures such as woods and plants exhibit multi-scale hierarchic organization that is the source of smart and anisotropic mechanical properties associated with high porosity and lightness. The association of nature-inspired nano-technological products with smart functionalization can provide new advanced solutions to critical and still unmet clinical needs. In this respect, magnetic activation of biomaterials by the use of a recently developed biocompati‐ ble, resorbable magnetic apatite promises to represent a new safe and effective switching tool, enabling personalized applications in regenerative medicine and theranostics that so far were not feasible, due to the cytotoxicity of the currently used magnetic materials.

Biomateriali per la rigenerazione e la funzione endocrina dell’osso

RiassuntoLo sviluppo di nuovi materiali come impianti per la rigenerazione ossea trova oggi una crescente applicazione anche nelle patologie a carico dell’apparato scheletrico indotte da malattie sistemiche quali l’osteoporosi, che sbilanciando il fisiologico turnover dell’osso, comportano un’elevata incidenza di fratture a carico della colonna vertebrale e del collo del femore. A questo scopo vengono proposti e descritti nuovi compositi bio-ibridi preparati con processi biologicamente ispirati.