Search

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. Keywords: Hydroxyapatite, Mechanical properties, Strength, Fracture, Mechanical tests, Fractal porosity

Synthetic osteoinductive materials that mimic the human osteogenic niche have emerged as ideal candidates to address this area of unmet clinical need. In this study, we evaluated the osteoinductive potential in a rabbit orthotopic model of a magnesium-doped hydroxyapatite/type I collagen ​(MHA/Coll) composite. The composite was fabricated to exhibit a highly fibrous structure of carbonated MHA with 70% (±2.1) porosity and a Ca/P ratio of 1.5 (±0.03) as well as a diverse range of elasticity separated to two distinct stiffness peaks of low (2.35 ​± ​1.16 ​MPa) and higher (9.52 ​± ​2.10 ​MPa) Young's Modulus. Data suggested that these specific compositional and nanomechanical material properties induced the deposition of de novo mineral phase, while modulating the expression of early and late osteogenic marker genes, in a 3D in vitro model using human bone marrow-derived mesenchymal stem cells (hBM-MSCs). When tested in the rabbit orthotopic model, MHA/Col1 scaffold induction of new trabecular bone mass was observed by DynaCT scan, only 2 weeks after implantation. Bone histomorphometry at 6 weeks revealed a significant amount of de novo bone matrix formation. qPCR demonstrated MHA/Coll scaffold full cellularization in vivo and the expression of both osteogenesis-associated genes (Spp1, Sparc, Col1a1, Runx2, Dlx5) as well as hematopoietic (Vcam1, Cd38, Sele, Kdr) and bone marrow stromal cell marker genes (Vim, Itgb1, Alcam). Altogether, these data provide ​evidence of the solid osteoinductive potential of MHA/Coll and its suitability for multiple approaches of bone regeneration., Highlights • We tested magnesium-doped hydroxyapatite/type I collagen (MHA/Coll) in a biologics-free orthotopic bone regeneration model. • MHA/Coll allowed bone formation within 6 weeks in a rabbit orthotopic model. • MHA/Coll supported the formation of both an osteogenic and hematopoietic-like niche.

The International Agency for Research on Cancer of the World Health Organization predicts that there will be ∼13–17 million cancer-related deaths each year worldwide by 2030. Cancer is still an unmanageable disease, even though numerous prevention, diagnosis, and therapeutic options exist. The main obstructions are late diagnosis, tumor metastasis, drug resistance, and recurrence. Nanoparticle technology as a new therapeutic intervention has shown to be promising in in vitro, in vivo, and clinical scenarios. Multifunctional magnetic nanoparticles can be implemented for early drug delivery, diagnosis, detection, and thermal therapy. Future theranostic applications in clinical trials comprise of combination drug delivery, magnetic resonance imaging, and hyperthermia. In Subchapter 6.1, we present the design of multifunctional magnetic nanoparticles, their physicochemical properties, and preclinical/clinical applications in cancer therapeutics. Several emerging biomedical technologies, such as cell delivery and tissue engineering, need a powerful methodology to manipulate with live biological cells. Rendering cells with magnetic functionality is one of the promising technologies to produce magnetically responsive cells that can be directed by an external magnetic field. Cell surface engineering offers a good opportunity to tailor magnetic nanosized particles onto the surfaces (cell walls and/or cellular membranes) of microbial and mammalian cells. In Subchapter 6.2, we overview the recent advances in fabrication of magnetically responsive “cyborg” cells. Synthetic calcium phosphates are the most widely accepted biomaterials for the repair and reconstruction of bone tissue defects thanks to their excellent features, including biocompatibility, bioactivity, osteocondutivity, nontoxicity, and nonimmunogenicity. The recent advancements in the nanotechnological approaches to prepare calcium phosphate–based materials with tailored surface characteristics, nanometric dimensions, and colloidal stability have opened new perspectives in their use in nanomedicine. Nanomedicine is defined as the application of nanomaterials to address healthcare problems. The recent trend in this field is the achievement of theranostic nanosystems that can fulfill a therapeutic action and at the same time deliver diagnostic information through an imaging probe. Subchapter 6.3 outlines the principal characteristics of calcium phosphates to be used as promising theranostic agents and on the basis of a large literature survey, the most recent reports on multifunctional theranostic calcium phosphate nanoparticles are discussed. Glioblastoma is the most common and most aggressive primary tumor of the brain with a high mortality rate in adults. Despite multimodality treatment regimens, including surgery, radiotherapy, and the alkylating drug temozolomide, average survival following diagnosis remains only over 1 year. Nanoparticle-based theranostic approaches aim to improve early diagnosis, as well as therapy of malignant brain tumors. This article will focus on recent research progress concerning the application of functionalized nanocarriers for detection, targeting, and therapy of brain tumors.

Thanks to the possibility to be manipulated by applying a remote magnetic field, magnetic nanoparticles (NPs) are among the most studied nanosystems for cutting-edge applications in medicine. Magnetic core-shell nanoparticles (MCNPs) are emerging as interesting materials in the biotechnology and material science fields, as they provide several advantages over conventional magnetic NPs, such as the possibility of coating highly magnetic but toxic cores into protective and/or biocompatible shells, and of engineering the shell surface to confer specific abilities. Cores and shells can be assembled to confer to MCNPs different shapes and designs for specific applications, as in the case of hollow core-shell and yolk-shell magnetic NPs, whose ability to encapsulate high loads of bioactive molecules can be maximally exploited for drug delivery purposes. After reviewing the composition of cores and shells, in this contribution we present an overview on MCNPs applications in hyperthermia, magnetic driving and controlled drug release, starting from well-established approaches to some of the latest and most innovative ones in the field of nanomedicine. In this respect, the use of materials such as mesoporous silica, graphite, and smart bioactive polymers enabled the production of highly engineered NPs with the ability to accomplish two or more biomedical functions. However, it is important to remark that the increase of functionality always entails the production of structurally complex MCNPs requiring long and difficult regulatory processes before entering clinical trials.

This chapter presents an exhaustive description of the various ceramic and glass materials used in biomedical applications. Active oxides like calcium phosphates, carbonates, and sulfates are largely described as monocomponents and in combination with other inorganic or organic materials for bone regeneration but also as drug delivery systems. For dental and orthopedic prosthesis devices, besides the presentation of the commercial products based on bioinert oxides and related composites, the tendencies nowadays to develop new oxide compositions, silicon nitride and carbide ceramics allowing both strengthening and toughening with better durability are well highlighted. The synthesis and the bioreactive properties of bioglasses and bioactive glass ceramics are also deeply developed. Special attention is given to glass-ionomer cements used as injectable materials. The chapter ends with the recent development of magnetic bioceramics and bioglasses allowing cancer curing by hyperthermia or favoring the osteoinduction phenomenon.

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.

The establishment of new and effective approaches to regenerative medicine requires a high interdisciplinary character between materials science, biology and surgery; this new paradigm is today fostering large advances in materials science and a more clear definition of the key aspects related to bone tissue regeneration. In this respect new bio-inspired approaches for the synthesis of biomaterials, such as in vitro biomineralization, enables the production of a new generation of smart, multifunctional and stimuli-responsive biomimetic materials for hard tissue regeneration. Among these advances, the implementation of new functionalities triggered by external magnetic signals may open the way to new therapeutic approaches to increase the regenerative potential of the scaffold, also reducing invasiveness during the implantation surgery.

Scientific research on tissue regeneration is increasingly becoming the most promising response to a number of disabling pathologies with huge impact on the progressively growing and ageing world population. The biomimicry of scaffolds with the target tissue is now universally considered to be a key requirement to properly instruct cells towards the restoration of physiological functioning. In this respect, the present chapter presents an overview of recent findings on biomimetic materials and devices addressed to bone and osteochondral tissues as well as soft organ regeneration. Particular focus is given to new apatite phases, including the newly discovered superparamagnetic apatite and processes to develop ceramic, polymeric and hybrid regenerative scaffolds. © 2013 Woodhead Publishing Limited. All rights reserved.

An efficient method for the direct and covalent decoration of granules of nanostructured apatite with a sample monosaccharide is presented: the hydroxyapatite material was directly functionalised with a short azido-containing spacer arm, to which alpha-propargyl glucopyranoside has been chemoselectively ligated by Huisgen-type cycloaddition. The 'glycosylated' hydroxypatite was characterised by its ability to interact with glucose recognising lectins. (C) 2011 Elsevier Ltd. All rights reserved.

The development is discussed of biocomposites as scaffolds for regenerative medicine, particularly in reconstructive procedures for bone and osteochondral defects. After a brief introduction on the solutions and technologies currently adopted in the repair and regeneration of bone and osteochondral tissue, the most recent innovative solutions are illustrated, following two different approaches. First, the exploitation of biologically inspired biomineralization processes yields materials for bone substitution in the form of graded multi-functional scaffolds mimicking the osteochondral regions. Second, natural composites, such as wood, silk and cuttlefish are used as templates to convey peculiar intrinsic properties to the final designed scaffold. Examples are pre-processed lignocellulose fibre products treated by vapour-phase infiltration and current deposition techniques, which offer an elegant way to manufacture lightweight scaffolds with hierarchically organized pores, channels and fibrillar struts. Preliminary in vitro and in vivo tests are reported, showing the great potential of these new classes of materials.