Nanoscale Strontium-Substituted Hydroxyapatite Pastes and Gels for Bone Tissue Regeneration.
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ABSTRACT:
SUBMITTER: Harrison CJ
PROVIDER: S-EPMC8235522 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Synthetic bone graft substitutes have attracted increasing attention in tissue engineering. This study aimed to fabricate a novel, bioactive, porous scaffold that can be used as a bone substitute. Strontium and zinc doped nano-hydroxyapatite (Sr/Zn n-HAp) were synthesized by a water-based sol-gel technique. Sr/Zn n-HAp and poly (lactide-co-glycolide) (PLGA) were used to fabricate composite scaffolds by supercritical carbon dioxide technique. FTIR, XRD, TEM, SEM, and TGA were used to characterize Sr/Zn n-HAp and the composite scaffolds. The synthesized scaffolds were adequately porous with an average pore size range between 189 to 406 µm. The scaffolds demonstrated bioactive behavior by forming crystals when immersed in the simulated body fluid. The scaffolds after immersing in Tris/HCl buffer increased the pH value of the medium, establishing their favorable biodegradable behavior. ICP-MS study for the scaffolds detected the presence of Sr, Ca, and Zn ions in the SBF within the first week, which would augment osseointegration if implanted in the body. nHAp and their composites (PLGA-nHAp) showed ultimate compressive strength ranging between 0.4-19.8 MPa. A 2.5% Sr/Zn substituted nHAp-PLGA composite showed a compressive behavior resembling that of cancellous bone indicating it as a good candidate for cancellous bone substitute.
| S-EPMC8883951 | biostudies-literature
Project description:Surface modification of orthopedic and dental implants has been demonstrated to be an effective strategy to accelerate bone healing at early implantation times. Among the different alternatives, coating implants with a layer of hydroxyapatite (HAp) is one of the most used techniques, due to its excellent biocompatibility and osteoconductive behavior. The composition and crystalline structure of HAp allow for numerous ionic substitutions that provide added value, such as antibiotic properties or osteoinduction. In this article, we will review and critically analyze the most important advances in the field of substituted hydroxyapatite coatings. In recent years substituted HAp coatings have been deposited not only on orthopedic prostheses and dental implants, but also on macroporous scaffolds, thus expanding their applications towards bone regeneration therapies. Besides, the capability of substituted HAps to immobilize proteins and growth factors by non-covalent interactions has opened new possibilities for preparing hybrid coatings that foster bone healing processes. Finally, the most important in vivo outcomes will be discussed to understand the prospects of substituted HAp coatings from a clinical point of view.
| S-EPMC7116284 | biostudies-literature
Project description:Reconstruction of osteoporotic bone defects is a clinical problem that continues to inspire the design of new materials. Methods: In this work, bioceramics composed of strontium (Sr)-doped hydroxyapatite (HA) whiskers or pure HA whiskers were successfully fabricated by hydrothermal treatment and respectively named SrWCP and WCP. Both bioceramics had similar three-dimensional (3D) porous structures and mechanical strengths, but the SrWCP bioceramic was capable of releasing Sr under physiological conditions. In an osteoporotic rat metaphyseal femoral bone defect model, both bioceramic scaffolds were implanted, and another group that received WCP plus strontium ranelate drug administration (Sr-Ran+WCP) was studied for comparison. Results: At week 1 post-implantation, osteogenesis coupled blood vessels were found to be more common in the SrWCP and Sr-Ran+WCP groups, with substantial vascular-like structures. After 12 weeks of implantation, comparable to the Sr-Ran+WCP group, the SrWCP group showed induction of more new bone formation within the defect as well as at the implant-bone gap region than that of the WCP group. Both the SrWCP and Sr-Ran+WCP groups yielded a beneficial effect on the surrounding trabecular bone microstructure to resist osteoporosis-induced progressive bone loss. While an abnormally high blood Sr ion concentration was found in the Sr-Ran+WCP group, SrWCP showed little adverse effect. Conclusion: Our results collectively suggest that the SrWCP bioceramic can be a safe bone substitute for the treatment of osteoporotic bone defects, as it promotes local bone regeneration and implant osseointegration to a level that strontium ranelate can achieve.
| S-EPMC6993240 | biostudies-literature
Project description:BackgroundManaging massive bone defects, a great challenge to orthopaedics reconstructive surgery. The problem arise is the supply of suitable bone is limited with many complications. Tissue-engineered hydroxyapatite bone (TEHB) scaffold impregnated with osteoprogenitor cells developed as an alternative to promote bone regeneration.MethodsThis animal protocol has been approved by Universiti Kebangsaan Malaysia Animal Ethical Committee. The TEHB scaffold prepared from hydroxyapatite using gel casting method. A total of six adolescent female sheep were chosen for this study. Later, all the sheep were euthanized in a proper manner and the bone harvested for biomechanical study. Bone marrow was collected from iliac crest of the sheep and bone marrow stem cells (BMSCs) isolated and cultured. BMSCs then cultured in osteogenic medium for osteoprogenitor cells development and the plasma collected was seeded with osteoprogenitor cells mixed with calcium chloride. Bone defect of 3 cm length of tibia bone created from each sheep leg and implanted with autologous and TEHB scaffold in 2 different groups of sheep. Wound site was monitored weekly until the wound completely healed and conventional X-ray performed at week 1 and 24. Shear test was conducted to determine the shear force on the autologous bone and TEHB scaffold after implantation for 24 weeks.ResultsAll of the sheep survived without any complications during the study period and radiograph showed new bone formation. Later, the bone harvested was for biomechanical study. The highest shear force for the autologous group was 13 MPa and the lowest was 5 MPa while for the scaffold group, the highest was 10 MPa and the lowest was 3 MPa. Although, proximal and distal interface of autologous bone graft shows higher shear strength compared to the TEHB scaffold but there is no significant difference in both groups, p value > 0.05. Histologically in both proximal and distal interface in both arms shows bone healing and woven bone formation.ConclusionTEHB scaffold impregnated with osteoprogenitor cells has the potential to be developed as a bone substitute in view of its strength and capability to promote bone regeneration.
| S-EPMC8169720 | biostudies-literature
Project description:Malleable biomaterials such as Herschel-Bulkley (H-B) fluids possess shear responsive rheological properties and are capable of self-assembly and viscoelastic recovery following mechanical disruption (e.g., surgical placement via injection or spreading). This study demonstrated that the addition of moderate molecular weight glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) (Mw = 15-30 kDa) and hyaluronic acid (HA) (Mw = 20-41 kDa) can be used to modify several rheological properties including consistency index (K), flow-behavior index (n), and yield stress (?y) of submicrometer hydroxyapatite (HAP) (Davg ? 200 nm) colloidal gels. GAG-HAP colloidal mixtures exhibited substantial polymer-particle synergism, likely due to "bridging" flocculation, which led to a synergistic increase in consistency index (KGAG-HAP ? KGAG + KHAP) without compromising shear-thinning behavior (n < 1) of the gel. In addition, GAG-HAP colloids containing high concentrations of HAP (60-80% w/v) exhibited substantial yield stress (?y ? 100 Pa) and viscoelastic recovery properties (G'recovery ? 64%). While rheological differences were observed between CS-HAP and HA-HAP colloidal gels, both CS and HA represent feasible options for future studies involving bone defect filling. Overall, this study identified mixture regions where rheological properties in CS-HAP and HA-HAP colloidal gels aligned with desired properties to facilitate surgical placement in non-load-bearing tissue-filling applications such as calvarial defects.
| S-EPMC3974614 | biostudies-literature
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.
| S-EPMC6953817 | biostudies-literature
Project description:In this study, as a measure to enhance the antimicrobial activity of biomaterials, the selenium ions have been substituted into hydroxyapatite (HA) at different concentration levels. To balance the potential cytotoxic effects of selenite ions (SeO32-) in HA, strontium (Sr2+) was co-substituted at the same concentration. Selenium and strontium-substituted hydroxyapatites (Se-Sr-HA) at equal molar ratios of x Se/(Se + P) and x Sr/(Sr + Ca) at (x = 0, 0.01, 0.03, 0.05, 0.1, and 0.2) were synthesized via the wet precipitation route and sintered at 900 °C. The effect of the two-ion concentration on morphology, surface charge, composition, antibacterial ability, and cell viability were studied. X-ray diffraction verified the phase purity and confirmed the substitution of selenium and strontium ions. Acellular in vitro bioactivity tests revealed that Se-Sr-HA was highly bioactive compared to pure HA. Se-Sr-HA samples showed excellent antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus carnosus) bacterial strains. In vitro cell-material interaction, using human osteosarcoma cells MG-63 studied by WST-8 assay, showed that Se-HA has a cytotoxic effect; however, the co-substitution of strontium in Se-HA offsets the negative impact of selenium and enhanced the biological properties of HA. Hence, the prepared samples are a suitable choice for antibacterial coatings and bone filler applications.
| S-EPMC8072711 | biostudies-literature
Project description:The restoration of bone defects caused by osteoporosis remains a challenge for surgeons. Strontium ranelate has been applied in preventative treatment approaches due to the biological functions of the trace element strontium (Sr). In this study, we aimed to fabricate bioactive scaffolds through Sr incorporation based on our previously developed modified amino-functional mesoporous bioactive glass (MBG) and to systematically investigate the bioactivity of the resulting scaffold in vitro and in vivo in an osteoporotic rat model. The results suggested that Sr-incorporated amino-functional MBG scaffolds possessed favorable biocompatibility. Moreover, with the incorporation of Sr, osteogenic and angiogenic capacities were upregulated in vitro. The in vivo results showed that the Sr-incorporated amino-functional MBG scaffolds achieved better bone regeneration and vessel formation. Furthermore, bioinformatics analysis indicated that the Sr-incorporated amino-functional MBG scaffolds could reduce reactive oxygen species levels in bone marrow mesenchymal stem cells in the osteoporotic model by activating the cAMP/PKA signaling pathway, thus playing an anti-osteoporosis role while promoting osteogenesis. This study demonstrated the feasibility of incorporating trace elements into scaffolds and provided new insights into biomaterial design for facilitating bone regeneration in the treatment of osteoporosis.
| S-EPMC9399250 | biostudies-literature
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.
| S-EPMC5667689 | biostudies-literature
Project description:Achieving rapid osteogenesis and angiogenesis was the key factor for bone regeneration. In the present study, the strontium-substituted calcium silicate (SrCS)/silk fibroin (SF) composite materials have been constructed by combining the different functional component ratios of SrCS (12.5 wt%, 25 wt%) and SF. Then, the effects of SrCS/SF materials on proliferation, osteogenic differentiation, and angiogenic factor secretion of rat bone marrow-derived mesenchymal stromal cells (rBMSCs) were first evaluated in vitro. Moreover, the in vivo effect of osteogenesis was evaluated in a critical-sized rat calvarial defect model. In vitro studies showed that SrCS/SF significantly enhanced the cell proliferation, alkaline phosphatase (ALP) activity, and the expression of osteogenic and angiogenic factors of rBMSCs as compared with the SF and CS/SF, and the optimum proportion ratio was 25 wt%. Besides, the results also showed that CS/SF achieved enhanced effects on rBMSCs as compared with SF. The in vivo results showed that 25 wt% SrCS/SF could obviously promote new bone formation more than SF and CS/SF. The present study revealed that SrCS could significantly promote the osteogenic and angiogenic activities of SF, and SrCS/SF might be a good scaffold material for bone regeneration.
| S-EPMC9136068 | biostudies-literature