Development of the third generation of bioceramics: Doping hydroxyapatite with s-, p-, d-, and f-blocks cations and their potential applications in bone regeneration and void filling

Abstract

The bioceramic market is expected to grow at a compound annual growth rate (CAGR) of about 7% within 2022–2027. In this regard, hydroxyapatite (HA) is highly recommended as a leading material for the development of the third generation of bioceramics due to its intrinsic osteoconduction, osteoinduction, and osteogenesis properties. However, the use of synthetic HA is currently limited due to the unfavourable mechanical and morphological issues on cell infiltration and interaction. To overcome these obstacles, various strategies have been proposed, especially through a wide range of cationic and anionic doping. Among them, cationic doping seems to have a set of significant benefits over pure HA due to the significant microstructural modifications, and thus this strategy represents a major step forward in improving the inherent drawback of bioceramic implants, i.e., their poor mechanical properties. Accordingly, this review aims to highlight candidates with potential for further clinical development of the third-generation bioceramics through doping HA with s-, p-, d-, and f-blocks cations and to explore their potential applications in bone regeneration and void filling. We first introduce the concept of bone grafting and its classifications, and then we discuss bioceramic-based bone grafting materials. Subsequently, mono-, dual-, and multi-cationic substitutions in HA and their performances, especially in biomedical applications, are comprehensively reviewed. Finally, the challenges and prospects of ionic substitution in HA, particularly in lanthanoids- and actinoids-containing HA-based ceramics are proposed.