Development of an injectable bioactive bone filler cement with hydrogen orthophosphate incorporated calcium sulfate

Abstract

Calcium sulfate cement (CSC) has emerged as a potential bone filler material mainly because of the possibility of incorporating therapeutic agents. Delivery of the cement through a needle or cannula will make it more useful in clinical applications. However, it was not possible to make CSC injectable because of the inherent lack of viscosity. The present work demonstrates the design development of a viscous and fully-injectable CSC by incorporating hydrogen orthophosphate ions, which does not hamper the biocompatibility of the material. The effect of addition of hydrogen orthophosphate on the rheological properties of the CSC paste was studied using a custom made capillary rheometer. The physicochemical changes associated with cement setting process were examined using X-ray diffraction and Fourier transform infrared spectroscopy and the thermal changes were measured through isothermal differential scanning calorimetry. Micromorphological features of different compositions were observed in environmental scanning electron microscopy and the presence of phosphate ions was identified with energy dispersive X-ray spectroscopic analysis and inductively coupled plasma-optical emission spectroscopy. The results indicated that HPO4 (2-) ions have profound effects on the rheological properties and setting of the CSC paste. Significant finding is that the HPO4 (2-) ions are getting substituted in the calcium sulfate dihydrate crystals during setting. The variations of setting time and compressive strength of the cement with the additive concentration were investigated. An optimum concentration of 2.5 % w/w gave a fully-injectable cement with clinically relevant setting time (below 20 min) and compressive strength (12 MPa). It was possible to inject the optimised cement paste from a syringe through an 18-gauge needle with thumb pressure. This cement will be useful both as bone filler and as a local drug delivery medium and it allows minimally invasive bone defect management.

Preparation, characterization and in vitro assessment of ibuprofen loaded calcium phosphate/gypsum bone cements

“…Similar results were found by other researchers taking into account the dependence of the cement maturing i.e. setting time . Compressive strength for pure gypsum cements, is within the range determined by other researchers too .…”

Transformation from calcium sulfate to calcium phosphate in biological environment

“…Calcium sulfate has been generally regarded as bio-compatible [10,28,31,32]. However, many previous studies have also indicated that calcium sulfate lacks osteoinductivity [10,[32][33][34][35][36]. The present study demonstrates two important characteristics that support the bioactivity of a (Ca,Sr)SO 4 specimen.…”

Novel Osteogenic Behaviors around Hydrophilic and Radical-Free 4-META/MMA-TBB: Implications of an Osseointegrating Bone Cement

“…One approach has been to add a bioactive agent. Peri-cement bone formation and/or in vitro osteoblastic responses have been improved with bioactive glass [51][52][53][54][55][56], hydroxyapatite [57], or other calcium-containing molecules [58][59][60][61][62][63][64]. These studies adopted the strategy of literally adding bioactivity to bone cement materials via additives, but this approach does not fundamentally improve material biocompatibility.…”