Composite Calcium Phosphate/Titania Scaffolds in Bone Tissue Engineering

Titanium and its alloys have been extensively used as implantation materials due to their favorable properties such as lower modulus, good tensile strength, excellent biocompatibility, and enhanced corrosion resistance. However, their intrinsic bioinertness generally prevents a direct bond with the bone on the surface especially at an early stage of implantation. In recent years, bioactive scaffolds for bone regeneration are progressively replacing bioinert prostheses in orthopedic, maxillofacial, and neurosurgery fields. Given the need of enhanced mechanical strength, several combinations of bioactive and reinforcing phases have been studied, but still no convincing solutions have been found so far. In this context, titanium oxides are light and high-resistance bioactive materials widely employed in dental and bone application due to their capacity of forming strong bonds with bone tissue via the formation of a tightly bound apatite layer on their surface. The addition of titania particles to hydroxyapatite has attracted considerable attention based on the assumption that resulting materials can enhance osteoblast adhesion and promote cell growth while also providing high strength and fracture toughness in the final composite material, thus being adequate for load-bearing applications

Synthesis of Nanostructured Hydroxyapatite via Controlled Hydrothermal Route

Hydroxyapatite represents the natural inorganic component of the bone and may be considered an essential element required for the development of bone substitutes in the field of regenerative medicine. Hydroxyapatite bone substitutes own biomimetic, osteoconductive, and osteoinductive properties thanks to their chemical-physical properties and nanostructure that play a critical role for the reconstruction of calcified tissues. Controlling the structure of hydroxyapatite nanocrystals is vital for obtaining a sustained product, and it should be an advantage on the final materials suitable for bone replacement, in terms of adsorptive activity, drug delivery system, etc. Compared to other synthesis techniques, hydrothermal processing (refers to a synthesis in aqueous solution at elevated pressure and temperature, in a closed system) has the ability to precipitate the hydroxyapatite from overheated solution, regulating the rate and uniformity of nucleation, growth, and maturation, which affect size, morphology, and aggregation of the crystals. This chapter wants to provide an overview of realization of nanosized hydroxyapatite-based bioceramics (e.g., powder and 3D structures) with desired morphology of crystallites, by hydrothermal processing. In this way, some critical hydrothermal parameters fundamental on the control of the crystal shape and dimension (pH, temperature, starting precursors, etc.) are discussed

In situ mechanical and molecular investigations of collagen/apatite biomimetic composites combining Raman spectroscopy and stress-strain analysis

We report the design, fabrication and application of a novel micro-electromechanical device coupled to a confocal Raman microscope that enables in situ molecular investigations of micro-fibers under uniaxial tensile load. This device allows for the mechanical study of micro-fibers with diameters in the range between 10 and 100 lm and lengths of several hundred micrometers. By exerting forces in the mN range, the device enables an important force range to be accessed between that of atomic force microscopy and macroscopic stress-strain measurement devices. The load is varied using a stiffness-calibrated glass micro-needle driven by a piezo-translator during simultaneous Raman microscopy imaging. The method enables experiments probing the molecular response of micro-fibers to external stress. This set-up was applied to biomimetic non-mineralized and mineralized collagen micro-fibers revealing that above 30% mineralization the proline-related Raman band shows a pronounced response to stress, which is not observed in non-mineralized collagen. This molecular response coincides with a strong increase in the Young’s modulus from 0.5 to 6 GPa for 0% and 70% mineralized collagen, respectively. Our results are consistent with a progressive interlocking of the collagen triple-helices by apatite nanocrystals as the degree of mineralization increases

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.info:eu-repo/semantics/publishedVersio

Nature-Inspired Processes and Structures: New Paradigms to Develop Highly Bioactive Devices for Hard Tissue Regeneration

Material scientists are increasingly looking to natural structures as inspiration for new-generation functional devices. Particularly in the medical field, the need to regenerate tissue defects claims, since decades, biomaterials with the ability to instruct cells toward formation and organization of new tissue. It is today increasingly accepted that biomimetics is a leading concept for biomaterials development. In fact, there is increasing evidence that the use of biomedical devices showing substantial mimicry of the composition and multi-scale structure of target native tissues have enhanced regenerative ability. As a relevant example, biomimetic materials have high potential to solve degenerative diseases affecting the musculoskeletal system, namely, bone, cartilage and articular tissues, which is of pivotal importance for most of human abilities, such as walking, running, manipulating, and chewing. In this respect, the adoption of nature-inspired processes and structures is an emerging fabrication concept, uniquely able to provide biomaterials with superior biological performance. The chapter will give an overview of the most recent results obtained in the field of hard tissue regeneration by using 3D biomaterials obtained by nature-inspired approaches. The main focus is given to porous hydroxyapatite-based ceramic or hybrid scaffolds for regeneration of bone and osteochondral tissues in neurosurgery and orthopedics

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 composition and hierarchically organized architecture mimicking biologically relevant tissue features. In this respect, an emerging concept in material science is to draw inspiration 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 biomineralization, generate complex hybrid 3D constructs that are the basis of skeletons, exoskeletons, 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 biocompatible, 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

Bio-inspired polymeric iron-doped hydroxyapatite microspheres as a tunable carrier of rhBMP-2

Hybrid superparamagnetic microspheres with bone-like composition, previously developed by a bio-inspired assembling/mineralization process, are evaluated for their ability to uptake and deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in therapeutically-relevant doses along with prolonged release pro- files. The comparison with hybrid non-magnetic and with non-mineralized microspheres highlights the role of nanocrystalline, nanosize mineral phases when they exhibit surface charged groups enabling the chemical linking with the growth factor and thus moderating the release kinetics. All the microspheres show excellent osteogenic ability with human mesenchymal stem cells whereas the hybrid mineralized ones show a slow and sustained release of rhBMP-2 along 14 days of soaking into cell culture medium with substantially bioactive effect, as reported by assay with C2C12 BRE-Luc cell line. It is also shown that the release extent can be modulated by the application of pulsed electromagnetic field, thus showing the potential of remote controlling the bioactivity of the new micro-devices which is promising for future application of hybrid biomimetic mi- crospheres in precisely designed and personalized therapies.info:eu-repo/semantics/publishedVersio