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.
Highlights
Over the last decades, the biomedical orthopaedic and dentistry sectors have witnessed an unprecedented demand for a large variety and number of scaffolds, grafts, implants, and endo-Materials 2018, 11, 2081; doi:10.3390/ma11112081 www.mdpi.com/journal/materialsMaterials 2018, 11, 2081 prostheses
The quality of life for millions of people has been drastically improved by using hydroxyapatite (HA) and bioactive glasses (BGs) for bone repair and tissue regeneration [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]
This review focused on the current status of the cationic-substituted HA materials, their derived and many times complementary biofunctional effects, as well as critically surveying the most used in vitro biological interrogation/ investigation assays and conceptual experimental designs, along with their ability to mimic the in vivo biological interactions
Summary
The biomedical orthopaedic and dentistry sectors have witnessed an unprecedented demand for a large variety and number of scaffolds, grafts, implants, and endo-. The actin cytoskeleton receives mechanical stress stimuli from the focal adhesion type of junction, which will activate the YAP (yes-associated protein 1) transcription co-activator and TEAD (transcriptional enhanced associate domain) transcription factor (through Hippo signalling pathway) This increases transduction of genes related to proliferation or differentiation (e.g., c-fos, egr-1, iex-1, c-myc) [43]. The data on the fracture toughness of doped HA are not abundant, and thereby further unambiguous explorations are needed to confirm or advance new doping possibilities able to improve the mechanical properties of HA, allowing for its safe use for load-bearing biomedical applications. The cation doping of HA started to be recognized for its ability to lead to improved biological properties such as bioactivity, surface reactivity, and adsorption of proteins/growth factors, while fostering biocompatibility, non-genotoxicity and ability to promote cell proliferation [1,2,5,32,69,73,74,81]. Conclusions will be drawn, future perspectives will be discussed, and a series of recommendations will be highlighted
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