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Mechanical and Biological Properties of Magnesium- and Silicon-Substituted Hydroxyapatite Scaffolds.

ABSTRACT: Magnesium (Mg)- and silicon (Si)-substituted hydroxyapatite (HA) scaffolds were synthesized using the sponge replica method. The influence of Mg²⁺ and SiO₄^4- ion substitution on the microstructural, mechanical and biological properties of HA scaffolds was evaluated. All synthesized scaffolds exhibited porosity >92%, with interconnected pores and pore sizes ranging between 200 and 800 μm. X-ray diffraction analysis showed that β-TCP was formed in the case of Mg substitution. X-ray fluorescence mapping showed a homogeneous distribution of Mg and Si ions in the respective scaffolds. Compared to the pure HA scaffold, a reduced grain size was observed in the Mg- and Si-substituted scaffolds, which greatly influenced the mechanical properties of the scaffolds. Mechanical tests revealed better performance in HA-Mg (0.44 ± 0.05 MPa), HA-Si (0.64 ± 0.02 MPa) and HA-MgSi (0.53 ± 0.01 MPa) samples compared to pure HA (0.2 ± 0.01 MPa). During biodegradability tests in Tris-HCl, slight weight loss and a substantial reduction in mechanical performances of the scaffolds were observed. Cell proliferation determined by the MTT assay using hBMSC showed that all scaffolds were biocompatible, and the HA-MgSi scaffold seemed the most effective for cell adhesion and proliferation. Furthermore, ALP activity and osteogenic marker expression analysis revealed the ability of HA-Si and HA-MgSi scaffolds to promote osteoblast differentiation.

SUBMITTER: Kunjalukkal Padmanabhan S

PROVIDER: S-EPMC8619624 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Magnesium (Mg) and its alloys have shown attractive biocompatibility and mechanical strength for medical applications, but low corrosion resistance of Mg in physiological environment limits its broad clinical translation. Hydroxyapatite (HA) nanoparticles (nHA) are promising coating materials for decreasing degradation rates and prolonging mechanical strength of Mg-based implants while enhancing bone healing due to their osteoconductivity and osteoinductivity. Conformal HA coatings with nano-to-submicron structures, namely nHA and mHA coatings, were deposited successfully on Mg plates and rods using a transonic particle acceleration (TPA) process under two different conditions, characterized, and investigated for their effects on Mg degradation in vitro. The nHA and mHA coatings enhanced corrosion resistance of Mg and retained 86-90% of ultimate compressive strength after in vitro immersion in rSBF for 6 weeks, much greater than non-coated Mg that only retained 66% of strength. Mg-based rods with or without coatings showed slower degradation than the respective Mg-based plates in rSBF after 6 weeks, likely because of the greater surface-to-volume ratio of Mg plates than Mg rods. This indicates that Mg-based plate and screw devices may undergo different degradation even when they have the same coatings and are implanted at the same or similar anatomical locations. Therefore, in addition to locations of implantation, the geometry, dimension, surface area, volume, and mass of Mg-based implants and devices should be carefully considered in their design and processing to ensure that they not only provide adequate structural and mechanical stability for bone fixation, but also support the functions of bone cells, as clinically required for craniomaxillofacial (CMF) and orthopedic implants. When the nHA and mHA coated Mg and non-coated Mg plates were cultured with bone marrow derived mesenchymal stem cells (BMSCs) using the in vitro direct culture method, greater cell adhesion densities were observed under indirect contact conditions than that under direct contact conditions for the nHA and mHA coated Mg. In comparison with non-coated Mg, the nHA and mHA coated Mg reduced BMSC adhesion densities directly on the surface, but increased the average BMSC adhesion densities under indirect contact. Further long-term studies in vitro and in vivo are necessary to elucidate the effects of nHA and mHA coatings on cell functions and tissue healing.

Project description:Our long-term goal is to develop smart biomaterials that can facilitate regeneration of critical-size craniofacial lesions. In this study, we tested the hypothesis that biomimetic scaffolds electrospun from chitosan (CTS) will promote tissue repair and regeneration in a critical size calvarial defect. To test this hypothesis, we first compared in vitro ability of electrospun CTS scaffolds crosslinked with genipin (CTS-GP) to those of mineralized CTS-GP scaffolds containing hydroxyapatite (CTS-HA-GP), by assessing proliferation/metabolic activity and alkaline phosphatase (ALP) levels of murine mesenchymal stem cells (mMSCs). The cells' metabolic activity exhibited a biphasic behavior, indicative of initial proliferation followed by subsequent differentiation for all scaffolds. ALP activity of mMSCs, a surrogate measure of osteogenic differentiation, increased over time in culture. After 3 weeks in maintenance medium, ALP activity of mMSCs seeded onto CTS-HA-GP scaffolds was approximately two times higher than that of cells cultured on CTS-GP scaffolds. The mineralized CTS-HA-GP scaffolds were also osseointegrative in vivo, as inferred from the enhanced bone regeneration in a murine model of critical size calvarial defects. Tissue regeneration was evaluated over a 3 month period by microCT and histology (Hematoxylin and Eosin and Masson's Trichrome). Treatment of the lesions with CTS-HA-GP scaffolds induced a 38% increase in the area of de novo generated mineralized tissue area after 3 months, whereas CTS-GP scaffolds only led to a 10% increase. Preseeding with mMSCs significantly enhanced the regenerative capacity of CTS-GP scaffolds (by ?3-fold), to 35% increase in mineralized tissue area after 3 months. CTS-HA-GP scaffolds preseeded with mMSCs yielded 45% new mineralized tissue formation in the defects. We conclude that the presence of HA in the CTS-GP scaffolds significantly enhances their osseointegrative capacity and that mineralized chitosan-based scaffolds crosslinked with genipin may represent a unique biomaterial with possible clinical relevance for the repair of critical calvarial bone defects.

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Mechanical and Biological Properties of Magnesium- and Silicon-Substituted Hydroxyapatite Scaffolds.

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