Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods.
TL;DR: A comprehensive inventory of the progresses achieved so far is gathered, to allow fellow researchers to compare with ease and filter the best solutions for the cation substitution of HA-based materials and enable the development of multi-functional biomedical designs.
Abstract: High-performance bioceramics are required for preventing failure and prolonging the life-time of bone grafting scaffolds and osseous implants. The proper identification and development of materials with extended functionalities addressing socio-economic needs and health problems constitute important and critical steps at the heart of clinical research. Recent findings in the realm of ion-substituted hydroxyapatite (HA) could pave the road towards significant developments in biomedicine, with an emphasis on a new generation of orthopaedic and dentistry applications, since such bioceramics are able to mimic the structural, compositional and mechanical properties of the bone mineral phase. In fact, the fascinating ability of the HA crystalline lattice to allow for the substitution of calcium ions with a plethora of cationic species has been widely explored in the recent period, with consequent modifications of its physical and chemical features, as well as its functional mechanical and in vitro and in vivo biological performance. A comprehensive inventory of the progresses achieved so far is both opportune and of paramount importance, in order to not only gather and summarize information, but to also allow fellow researchers to compare with ease and filter the best solutions for the cation substitution of HA-based materials and enable the development of multi-functional biomedical designs. The review surveys preparation and synthesis methods, pinpoints all the explored cation dopants, and discloses the full application range of substituted HA. Special attention is dedicated to the antimicrobial efficiency spectrum and cytotoxic trade-off concentration values for various cell lines, highlighting new prophylactic routes for the prevention of implant failure. Importantly, the current in vitro biological tests (widely employed to unveil the biological performance of HA-based materials), and their ability to mimic the in vivo biological interactions, are also critically assessed. Future perspectives are discussed, and a series of recommendations are underlined.
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TL;DR: A novel series of lanthanide-based SBL metal complexes was successfully synthesized, and their functional groups were elaborately demonstrated using UV–visible, Fourier transform infrared (FT-IR), and fluorescence spectroscopy analyses.
Abstract: A Schiff base ligand (SBL), N2, N3-bis (anthracen-9-ylmethylene) pyridine-2, 3-diamine, was synthesized through the condensation of 2,6-diaminopyridine and anthracene-9-carbaldehyde using a 1:2 ratio. 1H NMR spectra confirmed the observation of non-involvement aromatic carboxylic proton in SBL. A novel series of lanthanide (i.e., praseodymium (Pr), erbium (Er), and ytterbium (Yb))-based SBL metal complexes was successfully synthesized, and their functional groups were elaborately demonstrated using UV–visible, Fourier transform infrared (FT-IR), and fluorescence spectroscopy analyses. FT-IR spectral studies revealed that SBL behaved as a bidentate ligand and it was structured with metal ions by the two azomethine nitrogens. The synthesized SBL-based metal complexes were elaborately performed for cytotoxicity activity versus Vero, human breast cancer (MCF7), and cervical (HeLa) anticancer cell lines.
102 citations
TL;DR: This work reports the successful preparation and characterization of two material platforms containing therapeutic ions: a copper(ii)-chitosan derivative and a strontium-substituted hydroxyapatite, showing ideal ion release profiles, offering burst release of an antibacterial agent together with a more sustained release of Strontium to achieve long-term osteogenesis.
Abstract: Therapeutic metal ions are a family of metal ions characterized by specific biological properties that could be exploited in bone tissue engineering, avoiding the use of expensive and potentially problematic growth factors and other sensitive biomolecules. In this work, we report the successful preparation and characterization of two material platforms containing therapeutic ions: a copper(ii)-chitosan derivative and a strontium-substituted hydroxyapatite. These biomaterials showed ideal ion release profiles, offering burst release of an antibacterial agent together with a more sustained release of strontium in order to achieve long-term osteogenesis. We combined copper(ii)-chitosan and strontium-hydroxyapatite into freeze-dried composite scaffolds. These scaffolds were characterized in terms of morphology, mechanical properties and bioactivity, defined here as the ability to trigger the deposition of novel calcium phosphate in contact with biological fluids. In addition, a preliminary biological characterization using cell line osteoblasts was performed. Our results highlighted that the combination of chitosan and hydroxyapatite in conjunction with copper and strontium has great potential in the design of novel scaffolds. Chitosan/HA composites can be an ideal technology for the development of tissue engineering scaffolds that deliver a complex arrays of therapeutic ions in both components of the composite, leading to tailored biological effects, from antibacterial activity, to osteogenesis and angiogenesis.
91 citations
TL;DR: This paper summarizes the most recently developed fluorescent materials based on hydroxyapatite, which use rare earth elements (REEs) as dopants, such as terbium (Tb3+), erbium, europium, lanthanum, or dysprosium (Dy3+) that have been developed in the biomedical field.
Abstract: One new, promising approach in the medical field is represented by hydroxyapatite doped with luminescent materials for biomedical luminescence imaging. The use of hydroxyapatite-based luminescent materials is an interesting area of research because of the attractive characteristics of such materials, which include biodegradability, bioactivity, biocompatibility, osteoconductivity, non-toxicity, and their non-inflammatory nature, as well their accessibility for surface adaptation. It is well known that hydroxyapatite, the predominant inorganic component of bones, serves a substantial role in tissue engineering, drug and gene delivery, and many other biomedical areas. Hydroxyapatite, to the detriment of other host matrices, has attracted substantial attention for its ability to bind to luminescent materials with high efficiency. Its capacity to integrate a large assortment of substitutions for Ca2+, PO43−, and/or OH− ions is attributed to the versatility of its apatite structure. This paper summarizes the most recently developed fluorescent materials based on hydroxyapatite, which use rare earth elements (REEs) as dopants, such as terbium (Tb3+), erbium (Er3+), europium (Eu3+), lanthanum (La3+), or dysprosium (Dy3+), that have been developed in the biomedical field.
85 citations
Cites background from "Cationic Substitutions in Hydroxyap..."
...Yearly distribution of scientific articles published on the doped/substituted hydroxyapatite topic in 1975–2018 (as of 15 August 2018) [36]....
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...Half-maximal cytotoxic concentration (in mM) of various cationic species [36]....
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...topic in 1975–2018 (as of 15 August 2018) [36]....
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...Synopsis of the realm of bio-functionality of cation-substituted hydroxyapatites (Has) [36]....
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TL;DR: The challenges and achievements in the intracellular delivery of these agents to tumor cells are discussed and the most important issues in the design and potential applications of CaP-based biominerals are addressed with more focus on their biodegradability in tumor microenvironment.
80 citations
TL;DR: A meta-analysis of the dependence of selected materials properties on dopant concentrations reported across the literature, showing that doping is a convenient way of controlling some, but not all properties in HAp and should be implemented ideally in combination with other structural and compositional factors of influence as discussed by the authors.
70 citations
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TL;DR: These findings suggest that HeLa cells readily internalize nonspherical particles with dimensions as large as 3 μm by using several different mechanisms of endocytosis, and it was found that rod-like particles enjoy an appreciable advantage when it comes to internalization rates.
Abstract: The interaction of particles with cells is known to be strongly influenced by particle size, but little is known about the interdependent role that size, shape, and surface chemistry have on cellular internalization and intracellular trafficking. We report on the internalization of specially designed, monodisperse hydrogel particles into HeLa cells as a function of size, shape, and surface charge. We employ a top-down particle fabrication technique called PRINT that is able to generate uniform populations of organic micro- and nanoparticles with complete control of size, shape, and surface chemistry. Evidence of particle internalization was obtained by using conventional biological techniques and transmission electron microscopy. These findings suggest that HeLa cells readily internalize nonspherical particles with dimensions as large as 3 μm by using several different mechanisms of endocytosis. Moreover, it was found that rod-like particles enjoy an appreciable advantage when it comes to internalization rates, reminiscent of the advantage that many rod-like bacteria have for internalization in nonphagocytic cells.
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