Understanding the influence of electric field and dual doping on cytocompatibility of calcium phosphate bioceramics: Experimental and computational study

Abstract

Although doped bioceramics have been widely investigated for biomedical applications, the co-doped bioceramics remain mostly unexplored for bone regeneration and dental applications. Given this background, we have successfully developed Fe/Sr co-doped biphasic calcium phosphate (BCP) with varying dopant content and assessed its cytocompatibility with respect to different cell lines together with functional characterization. The Co-doped BCPs were found to be dielectric in nature and an increase in conductivity with dopant amount was recorded. The changes in lattice parameters were also probed using XRD based Rietveld refinement technique. An important observation is that, while the 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 co-doped BCP, compared to undoped BCP. Our results indicate that one can tailor osteoblast functionality by controlling the co-dopant content. From the clinical perspective of a dental implant, we have examined the cytocompatibility of the dual doped BCPs with epithelial cells. The cellular study showed a significant increase in both cellular viability and functionality with an increase in conductivity. Besides this, PCR study confirmed an absence of tumorigenic potential. Taken together, our study establishes unique advantage of Sr/Fe co-doping approach towards realizing their hard tissue replacement application. Another fundamental goal of biomaterials science is to develop an understanding of the interaction between a living organism and inorganic material surface at the molecular level. Given these facts, we examined the influence of external electric field stimulation (up to 1.00 V/nm) on fibronectin adsorption on hydroxyapatite (HA) (001) surface at 300K using all-atom classical MD simulation method. The molecular level interaction was found to be regulated by the attractive electrostatic interaction, which changed with the external field strength. Non-monotonous changes in the structural integrity of fibronectin were recorded with the change in field strength /direction due to the spatial rearrangement of local charges and global structural changes of the protein. The dipole moment vectors of fibronectin, water and HA quantitatively exhibited a similar pattern of orienting themselves parallel to the field direction. One of the striking observations in the context of the cell-material interaction is that the RGD sequence of FN was exposed to solvent side, when the field was applied along +z-direction. Summarizing, this dissertation reports the development of dual doped biphasic calcium phosphates and demonstrated their cytocompatibility. On fundamental aspects, this thesis also provided quantitative insights into the influence of electric field stimulation on molecular interactions involved in fibronectin adsorption on hydroxyapatite surface.