Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods

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.

Pulsed Laser Deposited Biocompatible Lithium-Doped Hydroxyapatite Coatings with Antimicrobial Activity

“…Lithium is considered as a trace metal in organisms and is used for the treatment of bipolar affective disorder [42] and refractory depression [43]. The safe administration of lithium for osteoporosis was reported more than two decades ago [44,45].…”

Current Status on Pulsed Laser Deposition of Coatings from Animal-Origin Calcium Phosphate Sources

“…If these substitutions take place simultaneously, a type-AB substitution occurs, as in the case of the bone mineral [32,39,40]. One should note that the mineral bone substitutions with various trace elements are considered directly responsible for the modifications in crystallinity, solubility, and biological response [41] and, therefore, they play a key role in the performance of hard tissues and the overall osseointegration process. As a consequence, alternative methods used to modify the HA structure by incorporating different ions to improve the osteoconductive properties of synthetic HA is currently of interest to the scientific community [2].…”

“…BioHA, is usually extracted from bones and teeth of various animals. To obtain the raw materials, cortical bones originating from bovines or swine are the choices generally reported in various studies tackling the extraction of natural/biological HA [2,41]. Two possible explanations for this preference might be advanced: (i) the immediate availability of cow and sheep bones in commercial shops and abattoirs to the difference of more exotic sources such as marine animals, and (ii) the extracellular matrix of bovine bones is mainly composed of HA nanocrystals and collagen fibers.…”

Novel Synthesis of Core-Shell Biomaterials from Polymeric Filaments with a Bioceramic Coating for Biomedical Applications

“…In this light, the already reported reconstruction methods involving metallic structures, polymeric biomaterials [6,7] (such as polylactic acid (PLA), thermoplastic polyurethane (TPU), polyglycolic acid (PGA), poly (vinyl alcohol) (PVA) [1,8,9]), and ceramics (mostly hydroxyapatite) [1,[10][11][12][13] are of crucial…”