(Fe/Sr) Codoped Biphasic Calcium Phosphate with Tailored Osteoblast Cell Functionality

Abstract

Although doped bioceramics have been widely investigated for biomedical applications, the codoped bioceramics remain mostly unexplored for bone regeneration applications. For example, the impact of codoping of Sr2+ and Fe3+ ions on the phase stability and cytocompatibility is not explored so far. In this perspective, the objective of the present study is to quantitatively understand this aspect in case of Fe/Sr codoped biphasic calcium phosphate (BCP). Following sol–gel synthesis, codoped BCP samples with Sr/Fe dopant concentrations of 2, 10, 20, 30, and 40 mol % as well as doped BCPs with single dopant (Sr or Fe) with similar compositions were calcined at 800 °C in air. Using extensive Rietveld analysis, the dopant content dependent crystallographic properties (e.g lattice parameters) and phase stability of HA/TCP are quantitatively assessed. In vitro cytocompatibility of codoped samples has been assessed using mouse osteoblast cells. An important observation is that, while singular dopant of Sr/Fe at 20 mol % or higher amount reduces cell viability significantly, osteoblast viability is not compromised to any significant extent on Sr/Fe codoped BCP, compared to undoped BCP. Our results indicate that one can tailor osteoblast functionality by controlling the codopant content. More importantly, all the codoped BCPs support cell proliferation, when single doped BCP exhibits significant reductionin cell viability, at dopant content of 10 mol % or higher. Cell morphological analysis supports extensive cell spreading on codoped BCPs. An attempt has been made to correlate the variation in cellular response with HA/TCP ratio and ion dissolution behavior. Taken together, the present work establishes unique advantage of Sr/Fe codoping approach toward realizing their bone replacement application.

Effect of Strontium Substitution on the Physicochemical Properties and Bone Regeneration Potential of 3D Printed Calcium Silicate Scaffolds

“…There were no significant differences ( p > 0.05) between the water contact angle of CS scaffolds (70.17 ± 1.63°) and SrCS scaffold (67.32 ± 2.16°). Our results were consistent with studies made by others which further confirmed that addition of Sr made biomaterials hydrophilic [29]. Similarly, it had been stated that hydrophilicity led to enhanced osteoconductivity and improve subsequent bone tissue regeneration [30].…”

Epithelial cell functionality on electroconductive Fe/Sr co-doped biphasic calcium phosphate

“…46 The details of synthesis and characterization (phase assemblage and in vitro ion dissolution) have been discussed in our previous study. 32 In summary, a 2.5 M solution of diammonium hydrogen phosphate ((NH 4 ) 2 HPO 4 ) was added in dropwise manner to 3.0 M calcium nitrate tetrahydrate (Ca(NO 3 ) 2. 4H 2 O) solution maintaining the ratio of Ca/P at 1.67.…”

“…As different ions are present in the inorganic part of tooth and bone, it is assumed that co-doped BCP can mimic the functionality and properties of natural hard tissue more efficiently than undoped HA/TCP. 32 In particular. Sr is chosen as one of the dopants because of its well-known beneficiary effect on dental remineralization and osteoblast activity.…”

“…In our previous study, the cytocompatibility of the proposed material has already been assessed with osteoblast cells. 32 In the present study, we investigate the interaction of Fe/Sr co-doped BCPs with vero cells. Cellular functionality and cell-material interactions are dependent on micro-environmental cues.…”

Doped biphasic calcium phosphate: synthesis and structure

“…In addition, several reports can be found on the synthesis of carbonate, fluoride, and silicate-doped HA [91] [92,93]. Recently, our group has synthesized Sr/Fe co-doped BCP via sol-gel synthesis technique with a large particle size distribution (20 nm to >100 nm) [94,95].…”