Influences of combined supplementation of calcium citrate and calcium carbonate on injectable and anti-washout hydroxyapatite/collagen bone paste utilizing sodium alginate

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Influences of combined supplementation of calcium citrate (Ca–Cit) and calcium carbonate (CaCO₃) on the hydroxyapatite/collagen (HAp/Col)–sodium alginate (Na–Alg) paste (HAp/Col paste) were investigated. Supplementation amounts of Ca–Cit and CaCO₃ were denoted as Nx, where N is a multiplication number to Ca²⁺ ion amounts for the equivalent reaction with Na–Alg obtained previously. Combined supplementation of 10x Ca–Cit and 2x CaCO₃ improved the anti-washout property at a washout ratio of 2.42 ± 0.72% and pH maintenance at 7.34 ± 0.08, these values were better than the best HAp/Col paste using Ca–Cit (5.91 ± 2.73% washout ratio and 6.72 ± 0.06 of pH). This is due to coordinate effects of initial washout inhibition by weak but rapid formation of long-range network by citric acid followed by long term anti-washout inhibition by strong but slow network formation by Ca²⁺ ions. The paste also showed good cytocompatibilty that MG63 cells proliferated with the culture time without any significant difference with the HAp/Col dense bodies. The HAp/Col paste is expected to be utilized in minimally invasive surgery of bone defect.