Abstract
Strontium (Sr) and Magnesium (Mg) are bioactive ions that have been proven to exert a beneficial effect on bone; therefore, their incorporation into bone substitutes has long been viewed as a possible approach to improve tissue integration. However, the thermal instability of Mg-substituted hydroxyapatites has hitherto limited development. We previously described the creation of thermally consolidated porous constructs of Mg,Sr co-substituted apatites with adequate mechanical properties for their clinical use. The present paper describes the biocompatibility of Mg,Sr co-substituted granules using an alveolar-bone-derived primary model of human osteoblasts. Cells were cultured in the presence of different amounts of hydroxyapatite (HA), Sr-substituted HA, or MgSrHA porous macrogranules (with a size of 400–600 microns, obtained by grinding and sieving the sintered scaffolds) for three and seven days, and their viability was measured by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Protein content was measured using the Lowry assay at the same time points. Cell viability was not impaired by any of the tested compounds. Indirect and direct biocompatibility of these macrogranules was assessed by culturing cells in a previously conditioned medium with HA, SrHA, or MgSrHA, or in the presence of material granules. Osteoblasts formed larger and more numerous nodules around SrHA or MgSrHA granules. Furthermore, cell differentiation was evaluated by alkaline phosphatase staining of primary cells cultured in the presence of HA, SrHA, or MgSrHA granules, confirming the increased osteoconductivity of the doped materials.
Highlights
An effective approach for tissue regeneration is the use of scaffold materials designed to be implanted into the recipient site and support cell ingrowth from neighboring tissues and the deposition of a new extracellular matrix [1]
Strontium (Sr) and Magnesium (Mg) are bioactive ions that have been proven to exert a beneficial effect on bone; their incorporation into bone substitutes has long been viewed as a possible approach to improve tissue integration
We previously described the creation of thermally consolidated porous constructs of Mg,Sr co-substituted apatites with adequate mechanical properties for their clinical use
Summary
An effective approach for tissue regeneration is the use of scaffold materials designed to be implanted into the recipient site and support cell ingrowth from neighboring tissues and the deposition of a new extracellular matrix [1]. Occurring apatite presents numerous substitutions and contains traces of several elements, e.g., Mg and Sr, besides the more abundant Ca and P species [4]. These elements, albeit in small amounts, are important because they affect material properties and perform specific biological activities. Pre-clinical and clinical studies have reported that Sr enhances bone formation and attenuates bone resorption, increasing bone mass and bone mechanical properties [6,7] Incorporating these elements into hydroxyapatite (HA) has long appeared as an appealing strategy to increase HA resorbability and improve tissue responses to implantable materials, following a biomimetic approach [8,9]. We investigated whether these materials promote the expression of an osteoblastic phenotype as assessed by the expression of the differentiation marker alkaline phosphatase
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