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Nanoscale Strontium-Substituted Hydroxyapatite Pastes and Gels for Bone Tissue Regeneration.

ABSTRACT: Injectable nanoscale hydroxyapatite (nHA) systems are highly promising biomaterials to address clinical needs in bone tissue regeneration, due to their excellent biocompatibility, bioinspired nature, and ability to be delivered in a minimally invasive manner. Bulk strontium-substituted hydroxyapatite (SrHA) is reported to encourage bone tissue growth by stimulating bone deposition and reducing bone resorption, but there are no detailed reports describing the preparation of a systematic substitution up to 100% at the nanoscale. The aim of this work was therefore to fabricate systematic series (0-100 atomic% Sr) of SrHA pastes and gels using two different rapid-mixing methodological approaches, wet precipitation and sol-gel. The full range of nanoscale SrHA materials were successfully prepared using both methods, with a measured substitution very close to the calculated amounts. As anticipated, the SrHA samples showed increased radiopacity, a beneficial property to aid in vivo or clinical monitoring of the material in situ over time. For indirect methods, the greatest cell viabilities were observed for the 100% substituted SrHA paste and gel, while direct viability results were most likely influenced by material disaggregation in the tissue culture media. It was concluded that nanoscale SrHAs were superior biomaterials for applications in bone surgery, due to increased radiopacity and improved biocompatibility.

SUBMITTER: Harrison CJ

PROVIDER: S-EPMC8235522 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Additive manufactured, porous bone implants have the potential to improve osseointegration and reduce failure rates of orthopaedic devices. Substantially porous implants are increasingly used in a number of orthopaedic applications. HA plasma spraying-a line of sight process-cannot coat the inner surfaces of substantially porous structures, whereas electrochemical deposition of calcium phosphate can fully coat the inner surfaces of porous implants for improved bioactivity, but the osseous response of different types of hydroxyapatite (HA) coatings with ionic substitutions has not been evaluated for implants in the same in vivo model. In this study, laser sintered Ti6Al4V implants with pore sizes of Ø 700 μm and Ø 1500 μm were electrochemically coated with HA, silicon-substituted HA (SiHA), and strontium-substituted HA (SrHA), and implanted in ovine femoral condylar defects. Implants were retrieved after 6 weeks and histological and histomorphometric evaluation were compared to electrochemically coated implants with uncoated and HA plasma sprayed controls. The HA, SiHA and SrHA coatings had Ca:P, Ca:(P+Si) and (Ca+Sr):P ratios of 1.53, 1.14 and 1.32 respectively. Electrochemically coated implants significantly promoted bone attachment to the implant surfaces of the inner pores and displayed improved osseointegration compared to uncoated scaffolds for both pore sizes (p<0.001), whereas bone ingrowth was restricted to the surface for HA plasma coated or uncoated implants. Electrochemically coated HA implants achieved the highest osseointegration, followed by SrHA coated implants, and both coatings exhibited significantly more bone growth than plasma sprayed groups (p≤0.01 for all 4 cases). SiHA had significantly more osseointegration when compared against the uncoated control, but no significant difference compared with other coatings. There was no significant difference in ingrowth or osseointegration between pore sizes, and the bone-implant-contact was significantly higher in the electrochemical HA than in SiHA or SrHA. These results suggest that osseointegration is insensitive to pore size, whereas surface modification through the presence of an osteoconductive coating plays an important role in improving osseointegration, which may be critically important for extensively porous implants.

Project description:Bone grafting is one of the commonest surgical procedures, yet all bone substitutes developed so far suffer from specific weaknesses and the search for a bone graft material with ideal physical and biological properties is still ongoing. Calcium phosphate pastes are the most frequently used synthetic bone grafts, yet they (a) often take an impractically long time to set, (b) release the drug content too fast, and (c) do not form pores large enough to accommodate host cells and foster osseointegration. To make up for these deficiencies, we introduced gelatin and silica to pastes composed of 5-15 nm sized hydroxyapatite nanoparticles and yielded a bioresorbable composite that is compact, yet flowing upon injection; that prevents setting at room temperature, but sets promptly, in minutes, at 37 °C; that displays an increase in surface porosity following immersion in physiological fluids; that allows for sustained release of antibiotics; and that sets in a tunable manner and in clinically relevant time windows: 1-3 minutes at its fastest. Timelapse, in situ X-ray diffraction analysis demonstrated that the setting process is accompanied by an increase in crystallinity of the initially amorphous hydroxyapatite, involving no polymorphic phase transitions in its course. Setting time can be tuned by controlling the weight content of gelatin or powder-to-liquid ratio. The release of vancomycin was slow, ~ 8 % after 2 weeks, and unaffected by the gelatin content. While vancomycin-loaded pastes were effective in reducing the concentration of all bacterial species analyzed, the bacteriostatic effects of the antibiotic-free pastes were pronounced against S. liquefaciens and E. coli. S. liquefaciens bacilli underwent beading and filamentation during the treatment, suggesting that the antimicrobial effects are attributable to cell wall disruption by hydroxyapatite nanoparticles. Vancomycin-loaded pastes augmented the activity of the antibiotic against P. aeruginosa and S. liquefaciens, while exhibiting no negative effects against human mesenchymal stem cells. They were also uptaken three times more abundantly than pure hydroxyapatite, indicating the theoretical favorability of their use for intracellular delivery of therapeutics. This selectivity, toxic for bacteria and harmless for primary stem cells, is promising for application as bone grafts for osteomyelitis.

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Nanoscale Strontium-Substituted Hydroxyapatite Pastes and Gels for Bone Tissue Regeneration.

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