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Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has focused on the cellular and molecular pathophysiology associated with calcification, yet the detailed composition, structure, distribution and etiological history of mineral deposition remains unknown. Here transdisciplinary geology, biology and medicine (GeoBioMed) approaches prove that leaflet calcification is driven by amorphous calcium phosphate (ACP), ACP at the threshold of transformation toward hydroxyapatite (HAP) and cholesterol biomineralization. A paragenetic sequence of events is observed that includes: (1) original formation of unaltered leaflet tissues: (2) individual and coalescing 100s nm- to 1 μm-scale ACP spherules and cholesterol crystals biomineralizing collagen fibers and smooth muscle cell myofilaments; (3) osteopontin coatings that stabilize ACP and collagen containment of nodules preventing exposure to the solution chemistry and water content of pumping blood, which combine to slow transformation to HAP; (4) mm-scale nodule growth via ACP spherule coalescence, diagenetic incorporation of altered collagen and aggregation with other ACP nodules; and (5) leaflet diastole and systole flexure causing nodules to twist, fold their encasing collagen fibers and increase stiffness. These in vivo mechanisms combine to slow leaflet calcification and establish previously unexplored hypotheses for testing novel drug therapies and clinical interventions as viable alternatives to current reliance on surgical/percutaneous valve implants.

Based on hydrodynamic theory, blocking the dentinal tubules can reduce discomfort caused by dentin hypersensitivity. This study identified the crystals formed in dentinal tubules from tricalcium silicate (TCS) in phosphate-buffered saline (PBS) and evaluated the effect of PBS concentration on crystal formation. Sixty-nine specimens were made by isolating the cervical part of extracted premolars. TCS was applied by brushing for 10,000 strokes on dentin surface simulating sensitive dentin. Specimens were stored in PBS or solutions with concentrations 1/100, 1/10, 10, and 100 times that of PBS for 1, 30, 60, or 90 days (n = 3). Another nine specimens applied TCS, were immersed in PBS for 3 months, and divided into three subgroups: no treatment, sonication for 10 min, and 1M acetic acid treatment for 3 min. Crystal formation was examined using a scanning electron microscope, assigned five grade scores (0–4) according to maturation, and analyzed by a nonparametric two-way ANOVA (α = 0.05). Crystal components were analyzed using X-ray diffraction (XRD) and energy dispersion X-ray spectroscopy (EDS). The maturation of intratubular crystals was dependent on time and PBS concentration (P < 0.05). In all periods, the high-concentration group showed a higher maturation grade than the low-concentration group. Intratubular crystals were similar to hydroxyapatite according to XRD and EDS, and they withstood sonication and acid application. TCS with nanosized particles formed hydroxyapatite-like crystals in the dentinal tubules, which were dependent on time and concentration of PBS and withstood sonication and acid application. [ABSTRACT FROM AUTHOR]

Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.

Background/purpose: Based on hydrodynamic theory, blocking the dentinal tubules can reduce discomfort caused by dentin hypersensitivity. This study identified the crystals formed in dentinal tubules from tricalcium silicate (TCS) in phosphate-buffered saline (PBS) and evaluated the effect of PBS concentration on crystal formation. Materials and methods: Sixty-nine specimens were made by isolating the cervical part of extracted premolars. TCS was applied by brushing for 10,000 strokes on dentin surface simulating sensitive dentin. Specimens were stored in PBS or solutions with concentrations 1/100, 1/10, 10, and 100 times that of PBS for 1, 30, 60, or 90 days (n = 3). Another nine specimens applied TCS, were immersed in PBS for 3 months, and divided into three subgroups: no treatment, sonication for 10 min, and 1M acetic acid treatment for 3 min. Crystal formation was examined using a scanning electron microscope, assigned five grade scores (0–4) according to maturation, and analyzed by a nonparametric two-way ANOVA (α = 0.05). Crystal components were analyzed using X-ray diffraction (XRD) and energy dispersion X-ray spectroscopy (EDS). Results: The maturation of intratubular crystals was dependent on time and PBS concentration (P

In clinical practice, not all patients seem to benefit from treatment with calcium hydroxyapatite, often due to the improper indication of this procedure for patients who may require an associated surgical approach. In this context, our objective was to describe a practical method for evaluating and selecting the ideal patient for a non-surgical approach to abdominal skin laxity, along with presenting clinical cases treated with the combined use of calcium hydroxylapatite (CaHA) and microneedling with radiofrequency.

ABSTRACT Purpose: to evaluate biocompatibility and osteogenic potential of hydroxyapatite/alginate composite after its implantation on rat calvarian critical bone defect. Methods: thirty adults male Wistar rats were randomly distributed into two groups: GHA – critical bone defect filled with hydroxyapatite/alginate composite granules (HA/Alg) and CG – critical bone defect without biomaterial; evaluated at biological points of 15, 45 and 120 days. Results: the histomorphometrically analyses for GHA showed osteoid matrix deposition (OM) among the granules and towards the center of the defect in centripetal direction throughout the study, with evident new bone formation at 120 days, resulting in filling 4/5 of the initial bone defect. For CG, this finding was restricted to the edges of the bone margins and formation of connective tissue on the residual area was found in all biological points. Inflammatory response on GHA was chronic granulomatous type, discrete and regressive for all biological points. Throughout the study, the CG presented mononuclear inflammatory infiltrate diffuse and regressive. Histomorphometry analyses showed that OM percentage was evident for GHA group when compared to CG group in all analyzed periods (p > 0.05). Conclusions: the biomaterial evaluated at this study showed to be biocompatible, bioactive, osteoconductive and biodegradable synchronously with bone formation.

To supply adequate food, the ongoing and unrestrained administration of nitrogen fertilizer to agricultural fields is polluting the climate and living organisms. On the other hand, the agriculture sector urgently needs a technological upgrade to effectively confront hunger and poverty. Here, we report a rapid synthesis of zinc and magnesium-doped hydroxyapatite-urea nanohybrids for slow release and delivery of nitrogen to wheat and rice crops. Nanohybrids slowly release nitrogen for up to six weeks compared to the burst release of nitrogen from urea, and their use substantially reduces, by at least 3.8 times, ammonia emissions into the environment compared with that of urea fertilizer. A half‑nitrogen dose applied as multi-nutrient complexed nanohybrids maintained crop growth, yield, and nutritional compositions in wheat and subsequent rice crops. Nanohybrids enhanced the wheat crop yield and nitrogen uptake by 22.13% and 58.30%, respectively. The synthesized nitrogen nanohybrids remained in the soil for two continuous crop cycles, reduced ammonia volatilization, and achieved nitrogen delivery to the crops. Additionally, soil dehydrogenase activity (534.55% above control) and urease activities (81.82% above control) suggest that nanohybrids exhibited no adverse impact on soil microorganisms. Our comprehensive study demonstrates the advantages of 'doping' as a method for tailoring hydroxyapatite nanoparticles properties for extended agricultural and environmental applications. The use of nanohybrids substantially reduced greenhouse gas emissions and enabled the reduction, by half, of nitrogen inputs into the agricultural fields. This study, therefore, reports a novel nano-enabled platform of engineered hydroxyapatite-urea nanohybrids as a nitrogen fertilizer for efficient nitrogen delivery that results in improved crop growth while minimizing environmental pollution.

Human enamel is an incredibly resilient biological material, withstanding repeated daily stresses for decades. The mechanisms behind this resilience remain an open question, with recent studies demonstrating a crack-deflection mechanism contributing to enamel toughness and other studies detailing the roles of the organic matrix and remineralization. Here, we focus on the mineral and hypothesize that self-healing of cracks in enamel nanocrystals may be an additional mechanism acting to prevent catastrophic failure. To test this hypothesis, we used a molecular dynamics (MD) approach to compare the fracture behavior of hydroxyapatite (HAP) and calcite, the main minerals in human enamel and sea urchin teeth, respectively. We find that cracks heal under pressures typical of mastication by fusion of crystals in HAP but not in calcite, which is consistent with the resilience of HAP enamel that calcite teeth lack. Scanning transmission electron microscopy (STEM) images of structurally intact ("sound") human enamel show dashed-line nanocracks that resemble and therefore might be the cracks healed by fusion of crystals produced in silico. The fast, self-healing mechanism shown here is common in soft materials and ceramics but has not been observed in single crystalline materials at room temperature. The crack self-healing in sound enamel nanocrystals, therefore, is unique in the human body and unique in materials science, with potential applications in designing bioinspired materials.

Abstract Objective This study evaluated and compared the tibial component migration in cemented and uncemented total knee arthroplasty (TKA) with no hydroxyapatite coating 2, 5, and 10 years after surgery. Methods This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) based on PubMed and MeSH database queries from June to July 2022. Results The meta-analysis included eight randomized clinical studies evaluating 668 knees undergoing TKA. The maximum total point motion (MTPM) in cemented TKAs was higher in 5 years, with a mean value of 0.67 mm (95% confidence interval [CI], 0.52 to 0.87). Uncemented TKAs also presented higher mean MTPM in 5 years (1 mm; 95% CI, 0.82 to 1.22). Uncemented coated ATKs had a higher mean MTPM in 10 years (1.30 mm; 95% CI, 0.70 to 2.39). MTPM was statistically similar in the short- and long-term for cemented and uncemented techniques, with a standardized mean difference of -0.65 (95% CI, -1.65 to 0.35). Conclusion Tibial component migration in TKA was statistically similar at 2, 5, and 10 years in cemented and uncemented techniques, either with or without coating. However, due to the scarce literature, further studies are required with a longer follow-up time.

The ongoing and unrestrained application of nitrogen fertilizer to agricultural lands has been directly linked to climate change and reductions in biodiversity. The agricultural sector needs a technological upgrade to adopt sustainable methods for maintaining high yield. We report synthesis of zinc and magnesium doped and undoped hydroxyapatite nanoparticles, and their urea nanohybrids, to sustainably deliver nitrogen to wheat. The urea nanohybrids loaded with up to 42% nitrogen were used as a new source of nitrogen and compared with a conventional urea-based fertilizer for efficient and sufficient nitrogen delivery to pot-grown wheat. Doping with zinc and magnesium manipulated the hydroxyapatite crystallinity for smaller size and higher nitrogen loading capacity. Interestingly, 50% and 25% doses of urea nanohybrids significantly boosted the wheat growth and yield compared with 100% doses of urea fertilizer. In addition, the nutritional elements uptake and grain protein and phospholipid levels were significantly enhanced in wheat treated with nanohybrids. These results demonstrate the potential of the multi-nutrient complexes, the zinc and magnesium doped and undoped hydroxyapatite-urea nanoparticles, as nitrogen delivery agents that reduce nitrogen inputs by at least 50% while maintaining wheat plant growth and nitrogen uptake to the same level as full-dose urea treatments.

To explore the possible emergence and lived consequences of social inequality in the Atacama, we analyzed a large set (n = 288) of incredibly well preserved and contextualized human skeletons from the broad Middle Period (AD 500-1000) of the San Pedro de Atacama (Chile) oases. In this work, we explore model-based paleodietary reconstruction of the results of stable isotope analysis of human bone collagen and hydroxyapatite. The results of this modeling are used to explore local phenomena, the nature of the Middle Period, and the interaction between local situations and the larger world in which the oases were enmeshed by identifying the temporal, spatial, and biocultural correlates and dimensions of dietary difference. Our analyses revealed that: 1) over the 600-year period represented by our sample, there were significant changes in consumption patterns that may evince broad diachronic changes in the structure of Atacameño society, and 2) at/near 600 calAD, there was a possible episode of social discontinuity that manifested in significant changes in consumption practices. Additionally, while there were some differences in the level of internal dietary variability among the ayllus, once time was fully considered, none of the ayllus stood out for having a more (or less) clearly internally differentiated cuisine. Finally, sex does not appear to have been a particularly salient driver of observed dietary differences here. While we do not see any de facto evidence for complete dietary differentiation (as there is always overlap in consumption among individuals, ayllus, and time periods, and as isotopic analysis is not capable of pinpointing different foods items or preparations), there are broad aspects of dietary composition changing over time that are potentially linked to status, and foreignness. Ultimately, these stand as the clearest example of what has been termed "gastro-politics," potentially tied to the emergence of social inequality in the San Pedro oases.

ObjectivesTo characterize the paleodiet of individuals from Formative Period (1500 B.C.-A.D. 400) Atacama Desert sites of Ancachi and Quillagua as a means of understanding the dietary and cultural impacts of regional systems of exchange.Materials and methodsThirty-one bone samples recovered from the cemetery of Ancachi (02QU175) and in/around the nearby town of Quillagua were the subject of carbon and nitrogen stable isotope analysis of bone collagen and hydroxyapatite and multisource mixture modeling (FRUITS, food reconstruction using isotopic transferred signals) of paleodiet. These individuals were compared with nearly 200 other Formative Period individuals from throughout the region to identify differences in dietary behaviors.Results80.6% (25/31) of the samples yielded sufficient well-preserved collagen and were included in the multisource mixture model. The FRUITS model, which compared individuals with a robust database of available foods from the region, identified a wide diversity of diets in the Ancachi/Quillagua area (including both coastal and interior individuals), and, most notably, thirteen individuals who consumed an average of 11.2 ± 1.9% terrestrial animals, 19.8 ± 1.9% legumes, and 22.5 ± 3.1% marine fauna, a balanced pattern of protein consumption distinct from both the coastal and inland individuals in our larger regional sample.ConclusionsThe combination of stable isotope analysis and multisource mixture modeling permitted the characterization of dietary behavior of 25 individuals from nodal sites in the Atacama Desert, thus enhancing our understanding of the economic and social relationships that bound together Formative Period sites, populations, and individuals in this hyperarid region.

ABSTRACT The “RichBlend” protocol was designed for facial filling and collagen biostimulation, by means of a mixture of calcium hydroxyapatite (CaHA), hyaluronic acid (AH) and autologous platelet concentrates. This work reports the case of a 53-year-old patient with cutaneous photoaging, loss of facial volume, multiple rhythms in the frontal and periorbital regions, also marked skin flaccidity, especially the eyelid. The treatment was done with botulinum toxin (65 U) and the “RichBlend” protocol. Venipuncture was performed and the blood was centrifuged to obtain i-PRF (injectable platelet-rich fibrin) and plasma gel. After venipuncture and blood centrifugation, i-PRF and plasma gel were obtained. CaHA (Radiesse®) was diluted: a) in saline solution + i-PRF (hyperdilution) for biostimulationof the lower third of the face; and b) in AH (Juvederm Ultraplus XC®) + plasma gel, for hydrolifting on the forehead and dark circles, malar and temples. Plasma gel was applied to the nasogenian grooves and then the entire face was properly massaged. The “RichBlend” protocol rejuvenated the patient, as it promoted filling, volumizing, collagen formation (biostimulation), reduction of flaccidity, in addition to skin whitening. Since HA and CaHA are high-cost products, their mixture with autologous platelet concentrates, in liquid or gel form, allows the use of a greater amount of filled and biostimulator material on the face, at a more affordable cost.

Nonautologous bone grafts have limited osteoinductive potential and thus there is substantial interest in reconstituting these graft materials with osteogenic factors such as bone morphogenic protein 2 (BMP2). However, one limitation of this approach is that BMP2 is typically weakly bound to the graft, which can lead to side effects associated with BMP2 dissemination. In the current study we added a hydroxyapatite (HA)-binding domain onto BMP2 to increase coupling to the graft surface. A sequence consisting of eight glutamate residues (E8) was inserted into the C-terminus of BMP2, and the recombinant protein (rBMP2-E8) was expressed in E. coli. Compared with rBMP2, rBMP2-E8 displayed markedly enhanced binding to HA disks and was better retained on the disks following exposure to vigorous wash steps. Furthermore, rBMP2-E8 was purified using a heparin column, and evaluated for its capacity to stimulate osteoblastic cell signaling. Treatment of SAOS2 cells with rBMP2-E8 induced SMAD 1/5 activation, confirming that the protein retains activity. Collectively these results suggest that the E8 domain serves as an effective tool for improving rBMP2 coupling to graft materials. The increased retention of rBMP2-E8 on the graft surface is expected to prolong BMP2s osteoinductive activity within the graft site, while simultaneously reducing off-target effects.

Vascularization of bone grafts is vital for graft integration and bone repair, however non-autologous graft sources have limited potential to induce angiogenesis. Accordingly, intensive research has focused on functionalizing non-autologous materials with angiogenic factors. In the current study we evaluated a method for coupling an angiogenic peptide to the surface of two clinically-relevant graft materials, anorganic bovine bone (ABB) and synthetic hydroxyapatite (HA). Specifically, the VEGF-derived QK peptide was synthesized with a heptaglutamate (E7) domain, a motif that has strong affinity for calcium phosphate graft materials. Compared with unmodified QK, a 4-6 fold enrichment was observed in the binding of E7-modified QK (E7-QK) to ABB and HA. The E7-QK peptide was then assessed for its capacity to stimulate angiogenic cell behaviors. Human umbilical vein endothelial cells (HUVECs) were treated with solutions of either QK or E7-QK, and it was found that QK and E7-QK elicited equivalent levels of cell migration, tubule formation and activation of the Akt and ERK signaling pathways. These data confirmed that the inherent bioactivity of the QK sequence was not diminished by the addition of the E7 domain. We further verified that the activity of E7-QK was retained following peptide binding to the graft surface. HA disks were coated with QK or E7-QK, and then HUVECs were seeded onto the disks. Consistent with the increased amount of E7-QK bound to HA, relative to QK, markedly greater activation of Akt and ERK 1/2 was observed in cells exposed to the E7-QK-coated disks. Taken together, these results suggest that the E7 domain can be leveraged to concentrate angiogenic peptides on graft materials, facilitating delivery of higher peptide concentrations within the graft site. The ability to endow diverse graft materials with angiogenic potential holds promise for augmenting the regenerative capacity of non-autologous bone grafts.

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.

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ObjectiveCalcium hydroxyapatite (CaHA) is a common material for vocal fold injection augmentation. Durability is variable, and factors involved in implant longevity are not understood. Animal models of osteoporosis show decreased bone density and increased mineral liberation, suggesting CaHA retention may be altered in these conditions.Study designProspective murine investigation.MethodsFourteen skeletally mature, 10-month-old female Sprague-Dewley rats were treated by one of three interventions: oophorectomy, laparotomy without oophorectomy (sham), or monthly risedronate injection (90 μg/kg, subcutaneous). CaHA was implanted into the right lateral thigh muscle in all animals at the time of procedure or first risedronate injection. After 17 weeks, all rats were sacrificed, and the residual CaHA isolated from excised lateral thigh muscle through incubation in a 900 °C calcinator for 9 hours.ResultsMean CaHA mass remaining in the oophorectomy group was 65.9 (standard deviation ± 16.1) mg, compared to 44.4 ± 10.0 mg CaHA in the risedronate group and 48.6 ± 7.5 mg in the sham group. One-way analysis of variance found a statistically significant difference between the oophorectomy and risedronate groups but not between the sham and other groups, F(2,11) = 4.404, P = 0.039.ConclusionPersistent estrogen deficiency in a murine model of osteoporosis demonstrated decreased rate of CaHA resorption. This suggests that hormone alterations associated with osteoporosis may alter the longevity of CaHA implant resorption through an uncertain mechanism.Level of evidenceNA. Laryngoscope, 2576-2580, 2018.

Bone-to-bone integration can be obtained by osteoconductive ceramics such as hydroxyapatite (HAp) and beta-tricalcium phosphate (β-TCP), but cartilage-to-cartilage integration is notoriously difficult. Many cartilage repair therapies, including microfracture and mosaicplasty, capitalize on the reparative aspects of subchondral bone due to its resident population of stem cells and vascularity. A strategy of incorporating tissue engineered neocartilage into a ceramic to form an osteochondral construct may serve as a suitable alternative to achieve cartilage graft fixation. The use of a tissue engineered osteochondral construct to repair cartilage defects may also benefit from the ceramic's proximity to underlying bone and abundant supply of progenitor cells and nutrients. The objective of the first study was to compare HAp and β-TCP ceramics, two widely used ceramics in bone regeneration, in terms of their ability to influence neocartilage interdigitation at an engineered osteochondral interface. Additional assays quantified ceramic pore size, porosity, and compressive strength. The compressive strength of HAp was six times higher than that of β-TCP due to differences in porosity and pore size, and HAp was thus carried forward in the second study as the composition with which to engineer an osteochondral construct. Importantly, it was shown that incorporation of the HAp ceramic in conjunction with the self-assembling process resulted in functionally viable neocartilage. For example, only collagen/dry weight and ultimate tensile strength of the chondral control constructs remained significantly greater than the neocartilage cut off the osteochondral constructs. By demonstrating that the functional properties of engineered neocartilage are not negatively affected by the inclusion of an HAp ceramic in culture, neocartilage engineering strategies may be directly applied to the formation of an osteochondral construct.

Background: A growing population of patients is seeking treatments that not only affect their overlying features but also restore a more biologically youthful structure and function to the underlying tissue. These strategies are part of what is known as regenerative aesthetics (RA). As an emergent field, clarity regarding the precise definitions and aims of RA and methods to measure the regenerative capacity of RA treatments are lacking., Methods: A panel of 6 multidisciplinary experts discussed the foundational aspects of RA. Consensus statements covered aspects of RA including terminology, goals of treatment, treatment strategies, and biological benchmarks indicating regeneration. Consensus on a statement was defined as ≥75% agreement., Results: Panelists emphasized the importance of natural, youthful tissue architecture and function including cellular and extracellular components. Replacement of a single biological component was not considered sufficient for an aesthetic treatment to be described as regenerative. Rather, the relative amounts, ratios, types, and organization are important to determine regenerative potential. Calcium hydroxylapatite is an example of an aesthetic injectable with evidence of regenerative capacity, as demonstrated by its ability to improve collagen type I/III ratios as well as induce the production of elastin and proteoglycans, which ultimately improve measures of skin quality., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Periacetabular bone loss poses a considerable challenge in the longevity and stability of acetabular implants used in total hip arthroplasty (THA). Innovations in implant design, specifically the introduction of three-dimensional (3D) porous titanium constructs, might reduce bone resorption. The purpose of this study was to build upon our previous randomized controlled trial, which found no change in periacetabular bone loss between a 3D porous none-hydroxyapatite coated titanium cup and a standard porous hydroxyapatite coated cup over a two year follow-up period by extending the follow-up duration to ten years post-surgery., Methods: This was a single-centre, long-term follow-up study conducted over a ten year period in patients who had previously participated in a randomized controlled trial comparing a 3D porous titanium construct shell (PTC group) with a standard porous hydroxyapatite coated titanium shell (PC-group). The primary outcome measured was the change in bone mineral density (BMD) within four specific periacetabular zones, alongside overall bone loss, which was assessed through BMD in the lumbar spine at two, six and ten years postoperatively. Secondary outcomes included clinical outcome measures., Results: In total, 18 in the PTC and 20 in the PC group were analysed for the primary endpoint up to ten years. The mean bone mineral density in zones 1-4 was 3.7% higher in the PTC group than in the PC group at six years postoperatively and 12.0% higher at ten years. Clinical outcomes, and the frequency of adverse events did not differ between the groups., Conclusions: The PTC group displayed superior long-term bone preservation compared to the PC group while maintaining similar clinical outcomes up to ten years postoperatively. Although with a small sample size, our findings suggest that porous titanium cups have the potential to minimize BMD loss around the cup which could contribute to improving THA outcomes and implant durability., (© 2024. The Author(s).)

Phosphorus is a critical nutrient that significantly enhances tomato production, so maintaining an adequate level of phosphorus plays an essential role in enhancing the growth of tomato by being present in the soil. This study assessed the impact of soil texture and phosphorus content on tomato plant properties using a factorial, complete, randomized design with four replications. Treatments included clayey and sandy soils with varying phosphorus sources: non-phosphorus (P0), calcium phosphate (CaP1 and CaP2), and nano-hydroxyapatite (PN1 and PN2), where 1 indicates a concentration of 0.12 g and 2 indicates a concentration of 0.23 g per 5-kilogram pot of fertilizer. Results indicated that treatments significantly influenced yield parameters such as average fruit weight, juice content, antioxidant activity, and fruit volume. In the clayey soil, CaP2 treatment had a superior effect on yield, average fruit weight, and shoot fresh weight. In comparison with sandy conditions, CaP2 produced a 50% increase in fruit number, 29% increase in average fruit weight, and 91% increase in fruit yield. The treatments then impacted the shoot fresh weight and root length, while the phosphorus concentration appeared to be more dependent on soil type than on phosphorus sources. Similar to the CaP1 and CaP2 treatments, the PN1 treatment in clay soil also resulted in the highest fresh and dry weights of tomato shoots when compared with the control group. Generally, the findings from this study suggest that the use of CaP2 can serve as a reliable method to improve the growth, yield, and fruit quality of tomatoes, especially in clayey soil environments. However, nano-based phosphorous sources need to be tested more to see if they can improve tomato performance in a range of soil conditions. Also, further research should look into the long-term effects of phosphorous interventions on soil health and sustainability., (© 2024. The Author(s).)

Introduction: The most commonly accepted method of long bone deformity correction in children with osteogenesis imperfecta is surgical realignment with transphyseal telescopic intramedullary rodding. This approach ensures reinforcement of the bone throughout the growth period. Although longitudinal growth does occur with these implants there has been very little work carried out to calculate the effect of such factors as rod position or implant material on growth. We carried out a prospective comparative study on 12 puppies using titanium alloy telescopic tibial rods with and without hydroxyl-apatite coating. The aim of this non-randomized controlled experimental study was to assess the impact of telescopic intramedullary rodding on spontaneous growth of the tibia., Material and Methods: Twelve mongrel puppies aged of 5 months underwent intramedullary transphyseal rodding of the right tibia. In group I (6 dogs) a titanium telescopic rod was used, in group II (6 dogs) a titanium rod with hydroxyapatite (HA)-coated threaded end was used. The following radiological criteria were assessed before surgery and every month until age of 12 months (natural fusion of physes in dogs): length of tibia, amount of superposition of inner (male) rod into external (female) rod; alteration of anatomy in terms of joint angles (mMPTA, mLDTA, mPPTA, mADTA); positioning of threaded ends in proximal and distal epiphyses and evidence of premature growth arrest. Parameters were compared with left tibia serving as control segment. The null hypothesis was that neither rod position nor implant material altered growth., Results: The transphyseal rods did not lead to irreversible epiphysiodesis in either group. In group II (HA-coated) some loss of residual length was found in all six dogs, over 7mm (5.9%) in comparison to left intact tibia. In contrast to that, in group I (titanium nail) only one animal (16.7%) demonstrated a tibia length discrepancy of 8mm (4.8%). Eccentric ( posterior) positioning of the rod in the distal epiphysis resulted in a procurvatum deformity (increased anterior distal tibial angle) in both groups. We found no failure of telescoping and no loss of fixation of threaded parts in either epiphyses., Discussion: The presence of telescopic rods with HA-coated threads parts clearly contributes to inhibition of spontaneous longitudinal growth. We hypothesize that HA stimulates maturation of chondrocytes of growth plate. Our findings regarding the potential adverse effect of thread position in the distal physis demonstrate the importance of attempting to place the rod as central as possible., Conclusion: Titanium alloy telescopic rods did not reveal significant effect on physeal growth in puppies in comparison to HA-coated implants. Transphyseal HA-coated implants did however inhibit growth plate function with mean loss of length of 5.2% compared to the other side. Eccentric positioning of rods relative to center of physis resulted in angular deformity due to irregular growth. There were no cases of mechanical failure or loss of telescopic function with either group of titanium implant., Level of Evidence: II; prospective comparative experimental study., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

This study analyzed a recently developed bone substitute biomaterial made of chitosan-xanthanhydroxyapatite-graphene oxide (CXHAG). The CXHAG particles underwent in vitro structural and morphological characterization, and in vivo testing with or without osteogenic conditioned medium from mesenchymal stem cells. Aim: The aim of this study was to determine whether the CXHAG novel biomaterial, supplemented with conditioned medium from mesenchymal stem cells, could be useful for bone regeneration. Materials and Method: For the in vitro study, cells were incubated with 20mg of CXHAG granules for 24 hours and a MTT assay was performed to tests for cytotoxicity. For the in vivo study, critical size calvarial bone defects were created in twenty-five rats. One animal had the defect unfilled (Control Group-CG) and was euthanized after 42 days. Twelve rats received the CXHAG particles (Group 1-G1) and the other twelve received the CXHAG particles supplemented with the conditioned medium (Group 2-G2). All G1/G2 grafts were covered with a CXHAG membrane. G1/G2 animals were euthanized after 14 days (T1) or 42 days (T2). The specimens were processed and histologically evaluated. Results: SEM analysis of the CXHAG particles showed granules of 300-400μm, with a rough irregular surface. They were not cytotoxic to dental pulp stem cells in vitro. The CG specimen showed loose immature connective tissue and no bone formation at the center of the defect. G1 and G2 presented remnant biomaterial particles at both time points, but only G2 had bone formation at the enter of the defect. Conclusions: The conditioned medium had a positive effect on bone regeneration in rat calvarial critical size defects when associated with the novel bone substitute biomaterial., Competing Interests: The authors declare no conflicts of interest concerning the publication of this article, (SAIO.)

Background: Periodontal diseases are associated with dysbiosis in the oral microbial communities. Managing oral biofilms is therefore key for preventing these diseases. Management protocols often include over-the-counter antimicrobial mouth rinses, which lack data on their effects on the oral microbiome's ecology, bacterial composition, metabolic activity, and dysbiosis resilience. This study examined the efficacy of antimicrobial mouth rinses to halt dysbiosis in in vitro oral biofilms under periodontitis-simulating conditions., Methods: Multispecies oral biofilms were grown on hydroxyapatite discs (HADs) and rinsed daily with one of six mouth rinses. Positive and negative controls were included. After three rinses, biofilms were analyzed with viability quantitative polymerase chain reaction and visualized using scanning electron microscopy. Supernatants of rinsed biofilms were used for metabolic activity analysis. In addition, human oral keratinocytes were exposed to rinsed biofilms to assess their inflammatory response. All outputs were analyzed for correlation using Spearman coefficient., Results: Product-related changes were observed in the rinsed biofilms. Three of the six tested mouth rinses could significantly prevent dysbiosis with ≥30% reduction in pathobiont abundance relative to the control. These biofilms had lower metabolic activity, and the exposed human oral keratinocyte produced less interleukin-8. Interleukin-8 production correlated to both pathobiont quantity and the metabolic activity of the biofilms., Conclusion: Some mouth rinses could support biofilm resilience and stop dysbiosis evolution in the biofilm model, with a clear product-related effect. Such mouth rinses can be considered for patients under maintenance/supportive periodontal therapy to prevent/delay disease recurrence. Others are more useful for different periodontal therapy stages., (© 2024 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Aim: The present study examined the leaching and cytotoxicity of bismuth from ProRoot MTA and aimed to identify whether bismuth leaching was affected by the cement base and the immersion regime used., Methodology: The leaching profile of bismuth was examined from ProRoot MTA and compared with hydroxyapatite containing 20% bismuth oxide as well as hydroxyapatite and tricalcium silicate to investigate whether bismuth release changed depending on the cement base. Bismuth leaching was determined after 30 and 180 days of ageing immersed in Dulbecco's modified Eagle's medium (DMEM) using mass spectroscopy (ICP-MS). The media were either unchanged or regularly replenished. The pH, surface microstructure and phase changes of aged materials were assessed. Wistar rat femoral bone marrow stromal cells (BMSCs) and cutaneous fibroblasts were isolated, cultured and seeded for cell counting (trypan blue live/dead) after exposure to non-aged, 30- and 180-days-aged samples in regularly replenished DMEM. Aged DMEM in contact with materials was also used to culture BMSCs to investigate the effect of material leachates on the cells. Gene expression analysis was also carried out after direct exposure of cells to non-aged materials. Differences between groups were statistically tested at a significance level of 5%., Results: All materials exhibited alterations after immersion in DMEM and this increased with longer exposure times. The bismuth leached from ProRoot MTA as detected by ICP-MS. Aged ProRoot MTA samples exhibited a black discolouration and surface calcium carbonate deposition. ProRoot MTA influenced cell counts after direct exposure and its 180-days leachates reduced BMSC viability. After direct BMSC contact with non-aged ProRoot MTA an upregulation of metallothionein (MT1 and MT2A) expression and down-regulation of collagen-1a (Col-1a) and bone sialoprotein (BSP) expression was identified., Conclusions: Bismuth leaching was observed throughout 180-days observation period from all materials containing bismuth oxide. This negatively influenced cell viability and gene expression associated with bismuth exposure. This is the first study to report that metallothionein gene expression was influenced by exposure to ProRoot MTA., (© 2024 The Author(s). International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.)

Purpose: To evaluate the survival rates of dental implants with a hybrid macrostructure and the surface biomimetically coated with nanohydroxyapatite, placed in horizontally atrophic maxillae previously submitted to the guided bone regeneration (GBR) procedure, associated with the use of a deproteinized bovine bone graft (DBB)., Methods: Twenty-five patients who received 196 implants were involved in this study. First, these patients were submitted to GBR procedures and maxillary sinus lift, where DBB was used as the grafting material. The dental implants were placed after a minimum period of 6 months of the grafting procedures. The patients were followed up every six months and clinical/radiographic examinations were performed to assess the implants, using the following indicators as a reference: (1) Absence of mobility; (2) Absence of pain. Data about the age, surgery time, smoking status, implant size, and time between the grafting procedure and implant placement were correlated with implant failures., Results: Twelve implants failed, generating a survival rate of 94.23%. None of the variables analysed correlated with the implant failures., Conclusion: Implants with a hybrid macrostructure and surface biomimetically coated with nanohydroxyapatite present good survival rates in horizontally atrophic maxillae grafted with DBB., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Delayed vascularization and resultant resorption limits the clinical use of tissue engineered bony constructs. The objective of this study is to develop a strategy to accelerate the neovascularization of tissue-engineered bony constructs using endothelial differentiated adipose-derived stem cells (ASC). The authors harvested ASC from inguinal fat pads of male Lewis rats (n = 5) and induced toward endothelial and osteoblastic lineages. The authors created critical size calvarial defects on male Lewis rats (n = 30) and randomized the animals into 4 groups. For the repair of the defects the authors used hydroxyapatite/poly(lactide-co-glycolide) [HA-PLG] scaffolds in group I, HA-PLG scaffolds seeded with ASC in group II, HA-PLG scaffolds seeded with ASC-derived endothelial cells in group III, and HA-PLG scaffolds seeded with ASC-derived osteoblasts in group IV. The authors evaluated the bone healing histologically and with micro-computed tomography (CT) scans 8 weeks later. Adipose-derived stem cells exhibited the characteristics of endothelial and osteogenic lineages, and attached on HA-PLG scaffolds after differentiation. Micro-CT analysis revealed that highest bone mineral density was in group IV (1.46 ± 0.01 g/cm) followed by groups III (1.43 ± 0.05 g/cm), I (1.42 ± 0.05 g/cm), and II (1.3 ± 0.1 g/cm). Hematoxylin-Eosin and Masson Trichrome staining revealed similar results with the highest bone regeneration in group IV followed by groups II, III, and I. Regenerated bone in group IV also had the highest vascular density, but none of these differences achieved statistical significance (P > 0.05). The ASC-derived endothelial cells and osteoblasts provide a limited increase in calvarial bone healing when combined with HA-PLG scaffolds.

The formation of mineralized tissues is governed by extracellular matrix proteins that assemble into a 3D organic matrix directing the deposition of hydroxyapatite. Although the formation of bones and dentin depends on the self-assembly of type I collagen via the Gly-X-Y motif, the molecular mechanism by which enamel matrix proteins (EMPs) assemble into the organic matrix remains poorly understood. Here we identified a Y/F-x-x-Y/L/F-x-Y/F motif, evolutionarily conserved from the first tetrapods to man, that is crucial for higher order structure self-assembly of the key intrinsically disordered EMPs, ameloblastin and amelogenin. Using targeted mutations in mice and high-resolution imaging, we show that impairment of ameloblastin self-assembly causes disorganization of the enamel organic matrix and yields enamel with disordered hydroxyapatite crystallites. These findings define a paradigm for the molecular mechanism by which the EMPs self-assemble into supramolecular structures and demonstrate that this process is crucial for organization of the organic matrix and formation of properly structured enamel.

INTRODUCTION: Dentin hypersensitivity is a common pathology, produced by exposed dental tubules. OBJECTIVES: The aim of this study was the evaluation of the effectiveness of experimental toothpaste based on nano-hydroxyapatite (nHAP) obtained from chicken eggshell in the obliteration of dentinal tubules (DTs). MATERIAL AND METHODS: Toothpastes with different percentages of nHAP were formulated, including 3%, 7%, and 15% of nHAP, a commercial paste, and a toothpaste without nHAP. Assays were made using healthy premolar samples (n = 50). The pastes were applied and brushed for 7 days after a first erosive cycle, then a second erosive cycle was made at 15 days. Samples were analyzed using scanning electron microscopy and confocal Raman microscopy at three times: after the first erosive cycle (T0), after applications of the pastes (T7), and after the second erosive cycle (T15). RESULTS: The quantitative analysis of the micrographs showed a significant difference between the experimental toothpastes with respect to the controls. Moreover, there was no statistically significant difference between the experimental toothpastes at time T7. By mineral concentration analysis, the 3%-nHAP toothpaste presented a significant difference against conventional toothpaste, when evaluating mineral concentration at 7 days. CONCLUSIONS: The experimental paste is effective in obliterating DTs at concentrations of 7 and 15%, in addition to being stable over time. [ABSTRACT FROM AUTHOR]

NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research.

ObjectiveThe intent of the study is to describe an unusual pattern of intramuscular migration of calcific deposits related to hydroxyapatite deposition disease (HADD) involving the rotator cuff, to illustrate the characteristic imaging features of this phenomenon, and to discuss the clinical significance of such migration.Materials and methodsA series of cases of intramuscular accumulation of calcium hydroxyapatite crystals collected over a 7-year period at multiple hospitals within the same academic institution were retrospectively reviewed.ResultsThe patient group was composed of seven men and four women, ranging in age from 51 to 79 years, with a mean age of 63 years. All subjects presented with acute shoulder pain. The majority of subjects reported the spontaneous onset of the symptoms (64%), while others reported weight lifting (27%) and a fall on the arm (9%) as the mechanisms of injury. The right shoulder was affected in 73% of the subjects. The supraspinatus was the most commonly affected muscle (82%), followed by the infraspinatus muscle (36%).ConclusionsKnowledge of the imaging features of intramuscular migration of hydroxyapatite deposits is important in order to avoid the erroneous diagnosis of other causes of muscle edema and inflammation such as myotendinous injury, myositis, subacute denervation, and neoplasm.

Pluripotent stem cell aggregates offer an attractive approach to emulate embryonic morphogenesis and skeletal development. Calcium phosphate (CaP) based biomaterials have been shown to promote bone healing due to their osteoconductive and potential osteoinductive properties. In this study, we hypothesized that incorporation of CaP-coated hydroxyapatite mineral particles (MPs) within murine embryonic stem cell (ESC) aggregates could promote osteo-chondrogenic differentiation. Our results demonstrated that MP alone dose-dependently promoted the gene expression of chondrogenic and early osteogenic markers. In combination with soluble osteoinductive cues, MPs enhanced the hypertrophic and osteogenic phenotype, and mineralization of ESC aggregates. Additionally, MPs dose-dependently reduced ESC pluripotency and thereby decreased the size of teratomas derived from MP-incorporated ESC aggregates in vivo. Our data suggested a novel yet simple means of using mineral particles to control stem cell fate and create an osteochondral niche for skeletal tissue engineering applications.Statement of significanceDirecting stem cell differentiation and morphogenesis via biomaterials represents a novel strategy to promote cell fates and tissue formation. Our study demonstrates the ability of calcium phosphate-based mineral particles to promote osteochondrogenic differentiation of embryonic stem cell aggregates as well as modulate teratoma formation in vivo. This hybrid biomaterial-ESC aggregate approach serves as an enabling platform to evaluate the ability of biomaterials to regulate stem cell fate and regenerate functional skeletal tissues for clinical applications.

Urinary stone disease, particularly calcium oxalate, is common in both humans and cats. Calcifying nanoparticles (CNP) are spherical nanocrystallite material, and are composed of proteins (fetuin, albumin) and inorganic minerals. CNP are suggested to play a role in a wide array of pathologic mineralization syndromes including urolithiasis. We documented the development of a clinically relevant protocol to assess urinary CNP in 9 healthy cats consuming the same diet in a controlled environment using Nanoparticle Tracking Analysis (NTA®). NTA® is a novel method that allows for characterization of the CNP in an efficient, accurate method that can differentiate these particles from other urinary submicron particulates. The predominant nanoscale particles in feline urine are characteristic of CNP in terms of their size, their ability to spontaneously form under suitable conditions, and the presence of an outer layer that is rich in calcium and capable of binding to hydroxyapatite binders such as alendronate and osteopontin. The expansion of this particle population can be suppressed by the addition of citrate to urine samples. Further, compounds targeting exosomal surfaces do not label these particulates. As CNP have been associated with a number of significant urologic maladies, the method described herein may prove to be a useful adjunct in evaluating lithogenesis risk in mammals.

HER2-positive cancer is a prevalent subtype of malignancy with poor prognosis, yet current targeted therapies, like Trastuzumab and pyrotinib, have resulted in remission in patients with HER2-positive cancer. This study provides a novel approach for immunotherapy based on a hydroxyapatite (HA) gene delivery system producing a bispecific antibody for HER2-positive cancer treatment. An HA nanocarrier has been synthesized by the classical hydrothermal method. Particularly, the HA-nanoneedle system was able to mediate stable gene expression of minicircle DNA (MC) encoding a humanized anti-CD3/anti-HER2 bispecific antibody (BsAbHER2) in vivo. The produced BsAbs exhibited a potent killing effect not only in HER2-positive cancer cells but also in patient-derived organoids in vitro. This HA-nanoneedle gene delivery system features simple large-scale preparation and clinical applicability. Hence, the HA-nanoneedle gene delivery system combined with minicircle DNA vector encoding BsAbHER2 reported here provides a potential immunotherapy strategy for HER2-positive tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: We aimed to compare periprosthetic femoral bone remodeling after cementless total hip arthroplasty (THA) using a short-tapered wedge stem and a fully hydroxyapatite (HA)-coated stem., Materials and Methods: In this retrospective study, 24 primary cementless THA procedures with short-tapered wedge stem and 24 using a fully HA-coated stem were performed. The follow-up duration was 2 years for both groups. Clinical evaluation was performed using the Merle d'Aubigné and Postel scoring systems. Standardized anteroposterior radiographs of the pelvis and femur were obtained. Dual-energy X-ray absorptiometry was performed, and the bone mineral density (BMD) around the stem was assessed in each Gruen zone at the first postoperative week as a baseline value and at 6 weeks, 3 and 6 months, and 1 and 2 years postoperatively., Results: The mean Merle d'Aubigné and Postel scores improved significantly postoperatively in both groups. None of the hips showed loosening in either group. Spot welds occurred in zones 1, 2, 6, and 7 in the short-tapered wedge group, and in all zones in the fully HA-coated group. Significant BMD loss occurred only in zone 4 in the short-tapered wedge group, and no significant bone loss occurred in any zone in the fully HA-coated stem group; a significant difference between the two groups was observed only in zone 4 at 2 years after THA., Conclusions: Clinical and radiographical outcomes in both groups were good, and both stems suppressed postoperative BMD loss at 2 years., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Climate change and human activity have led to an increase in salinity levels and the toxicity of chromium (Cr). One promising approach to modifying these stressors in plants is to use effective nanoparticles (NPs). While titanium dioxide nanoparticles (TiO 2 NPs) and hydroxyapatite (HAP NPs) have been demonstrated to increase plant tolerance to abiotic stress by enhancing antioxidant capacity, lipid peroxidation, and secondary metabolites, it is unknown how these two compounds can work together in situations when salt and Cr toxicity are present. The objective of the current study was to determine the effects of foliar-applied TiO 2 NPs (15 mg L -1 ) and HAP NPs (250 mg L -1 ) separately and in combination on growth, chlorophyll (Chl), water content, lipid peroxidation, antioxidant capacity, phenolic content, and essential oils (EOs) of Solidago canadensis L. under salinity (100 mM NaCl) and Cr toxicity (100 mg kg -1 soil). Salinity was more deleterious than Cr by decreasing plant weight, Chl a + b, relative water content (RWC), EO yield, and increasing malondialdehyde (MDA), electrolyte leakage (EL), superoxide dismutase (SOD) activity, and catalase (CAT) activity. The co-application of TiO 2 and HAP NPs proved to be more successful. This was evidenced by the increased shoot weight (36%), root weight (29%), Chl a + b (23%), RWC (15%), total phenolic content (TPC, 34%), total flavonoid content (TFC, 28%), and EO yield (56%), but decreased MDA (21%), EL (11%), SOD (22%) and CAT activity (38%) in salt-exposed plants. The study demonstrated the effective strategy of co-applying these NPs to modify abiotic stress by enhancing phenolic compounds and EO yield as key results., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: This study aimed to compare the impact of different broach surface designs on post-operative clinical outcomes, bone reactions and changes in bone mineral density (BMD) in patients who underwent total hip arthroplasty (THA) using a fully hydroxyapatite coated and double tapered stem with either compaction shape (COM) or hybrid shape (HYB) broaches., Materials and Methods: A retrospective analysis was conducted on 76 patients (100 hips) who underwent primary THA using the Avenir complete stem®. Patients were divided into two groups: the COM broach group (50 hips) and HYB broach group (50 hips). We evaluated clinical outcomes using the Japanese Orthopaedic Association hip scores one month before the surgery, and 12 and 24 months after the surgery. Radiographic findings, including stem alignment angles, radiolucent lines, spot welds, and cortical hypertrophy, were assessed. BMD around the stem in Gruen zones 1-7 was evaluated using dual-energy X-ray absorptiometry (DEXA) at 7 days, 12, and 24 months post-operatively. The Dorr classification was used to assess femoral morphology., Results: There were no significant differences in clinical outcomes, radiographic findings, or BMD changes between the COM and HYB broach groups in the overall patient cohort. However, in Dorr type A femurs, the COM broach group demonstrated superior BMD superior preservation in zones 1 and 7 after 12 months and in zones 1, 6 and 7 after 24 months. Additionally, in Dorr type B femurs, significant BMD preservation was observed in zone 3 at 24 months in the COM broach group., Conclusions: This study suggests that the broach surface design of fully hydroxyapatite coated stems may influence periprosthetic BMD changes, especially in Dorr type A and B femurs. Surgeons should consider broach selection based on patient-specific femoral morphology to optimize BMD preservation in THA procedures using fully hydroxyapatite coated stems., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Periosteal expansion (PEO) results in the formation of new bone in the space created between existing bone by expanding the periosteum. PEO has already been performed on rabbit parietal bone and effective new bone formation has been demonstrated. In this study, the utility of a polyethylene terephthalate (PET) membrane as an activator was evaluated in the more complex morphology of the mandible., Methods: A PET membrane coated with hydroxyapatite (HA)/gelatine was placed in the rabbit mandibular bone at lower margin of mandibular molar region underneath periosteum, and screw-fixed. In the experimental group, the membrane was bent and screw-fixed along the lateral surface of the bone, with removal of the outer screw after 7 days followed by activation of the membrane. The experimental group was divided into two subgroups: with and without a waiting period for activation. Three animals were euthanized at 3 weeks and another three at 5 weeks postoperatively. Bone formation was assessed using micro-CT as well as histomorphometric and histological methods., Results: No PET membrane-related complications were observed. The area of newly formed bone and the percentage of new bone in the space created by the stretched periosteum did not significantly differ between the control and experimental groups. However, in the experimental group a greater volume was present after 5 weeks than after 3 weeks. Histologically, bone formation occurred close to the site of cortical bone perforation, with many sinusoidal vessels extending through the perforations in the new bone into the overlying fibrous tissue. Inflammatory cells were not seen in the bone., (© 2024 The Authors. Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)

Background: Clavicular midshaft fractures treated with titanium plates may encounter complications like implant failure. We assess if alternative biocompatible materials suchs as PLA, PLA/HA, PEEK offer comparable stability. Our study evaluates the biomechanical performance of these materials in surgical management of midshaft clavicle fractures., Methods: We simulated a personalized fixation implant with four different materials and conducted finite element analysis in ANSYS to assess maximum von Mises stress (MvMs)., Results: The MvMs occurring on the plates, screws, clavicle, and fracture site were recorded. MvMs on titanium material at the 6th hole level (764.79 MPa) and the 6th screw level (503.38 MPa), with the highest stresses observed at 48.52 MPa on the lateral clavicle at the 1st hole level and 182.27 MPa on the medial clavicle at the 6th hole level. In PLA material analyses, the highest MvMs were observed at the 3rd hole level (340.6 MPa) and the 3rd screw level (157.83 MPa), with peak stresses at 379.63 MPa on the lateral clavicle fracture line and 505.44 MPa on the medial clavicle fracture line. In PLA/HA material analyses, the highest MvMs were at the 3rd hole (295.99 MPa) and 3rd screw (128.27 MPa), with peak stresses at 220.33 MPa on the lateral clavicle and 229.63 MPa on the medial clavicle fracture line. In PEEK material analyses, the highest MvMs were at the 3rd hole (234.74 MPa) and 6th screw (114.48 MPa), with peak stresses at 184.36 MPa on the lateral clavicle and 180.1 MPa on the medial clavicle., Conclusion: Our findings indicate that titanium material shows significantly higher stresses on plates and screws compared to those on the clavicle, suggesting a risk of implant failure. PLA and PLA/HA were inadequate for fixation. Although stress on the plate with PEEK material is higher than on the clavicle, it remains lower than titanium, indicating potential stability at fracture site. Further research is needed to confirm these findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: In this study, dentine surface was analysed through Environmental-scanning-electron-microscopy (ESEM) with energy-dispersive-X-ray-spectrometry (EDX) and Fourier-transform-infrared-spectroscopy (FTIR) with attenuated total-reflectance (ATR) to assess the morpho-chemical changes and variations in mineralization degree after demineralizing treatment, after five toothpastes application (HA & Citrate toothpaste, Zinc-HA toothpaste, Calcium Sodium Phosphosilicate toothpaste, Arginine & Calcium carbonate toothpaste, Colgate-Triple-Action, and Control toothpaste), after soaking in artificial saliva and after citric acid attack., Methods: Ca/P, Ca/N and P/N ratios were calculated from EDX atomic data to evaluate the mineralization degree of dentine surface. The IR calcium phosphate (CaP)/collagen and carbonate/collagen ratios has been evaluated to assess the remineralization changes in dentine; the carbonate/collagen IR ratio was calculated to identify the nucleation of B-type-carbonated apatite and calcium carbonate., Results: ESEM-EDX and ATR-FTIR showed residuals of toothpastes after the treatments in all cases, with a general increase in the mineralization degree after soaking in artificial saliva and a decrease after acid attack. Treatment with Arginine & Calcium carbonate toothpaste showed the highest Ca/P value after treatment (Ca/P 1.62) and acid attack (Ca/P 1.5) in confirmation, IR showed the highest amount of carbonate after treatment and soaking in artificial saliva. Arginine and calcium carbonate toothpaste and HA and citrate toothpaste remained to a higher extent on the dentine surface and revealed a higher remineralization activity. These formulations showed higher resistance to demineralization attack, as demonstrated by a higher I CaP /I Amide II intensity ratio than those obtained after EDTA treatment., Conclusions: Toothpastes that remained to a higher extent on dentine surface (arginine and calcium carbonate toothpaste in particular) were more able to promote remineralization. The formed calcium phosphate (CaPs) phase was intimately bound to dentine rather than a simple deposit., (© 2023 The Authors. International Journal of Dental Hygiene published by John Wiley & Sons Ltd.)

Background: Hydroxyapatite-coated, triple-tapered, shorter-length stems with a medial collar have been reported with good results for a few years. We investigated whether contact between the medial collar and femoral neck affects clinical outcomes and changes in bone mineral density (BMD) in patients who have this type of stem in their total hip arthroplasty construct., Methods: This was a retrospective, single-center study involving 62 patients scheduled for unilateral total hip arthroplasty using a hydroxyapatite-coated, triple-tapered, shorter-length stem who were followed for at least 1 year postoperatively. All patients had a Dorr type B femoral canal shape. Contact between the medial collar and the femoral neck was evaluated by computed tomography at the third postoperative month, and patients were classified into 2 groups. Postoperative clinical outcomes were investigated by the Western Ontario and McMaster Universities Arthritis Index and the Japanese Orthopaedic Association scores; radiological evaluation included stem fixation, spot welds and cortical hypertrophy, postoperative 3-dimensional stem alignment, and periprosthetic BMD changes., Results: There were 51 patients in the Contact + group (collar and neck contact) and 11 in the Contact-group (no contact). There were no differences between the 2 groups in the improvement of Western Ontario and McMaster Universities Arthritis Index and Japanese Orthopaedic Association scores, stem fixation, occurrence of cortical hypertrophy, or 3-dimensional stem alignment. Radiolucent lines were present in zones 3, 4, and 5 in 6 patients (12%) in the Contact + group only, who had no statistical difference between the 2 groups. Bone mineral density (BMD) decreased most in zone 7 in both groups, with no difference between the 2 groups., Conclusions: The presence or absence of contact between the medial collar and femoral neck did not affect postoperative BMD changes or radiological or clinical results., Level of Evidence: Therapeutic Level III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: In-vitro studies were performed on dentin of extracted human molars to investigate the effectiveness of 9.3 μm CO 2 laser irradiation to occlude dentinal tubules. The observed occlusion of dentinal tubules with the irradiation was compared with application of three reagents: 2% Sodium Fluoride gel, an aqueous solution of hydroxyapatite nanoparticles and an equal mix of the two. We show that 9.3 μm CO 2 laser irradiation occludes dentinal tubules, and the use of laser irradiation produces better occlusion of the opened tubules compared to the use of topical reagents., Methods: Nine extracted and cleaned human molars were cut to obtain dentin disks of thickness of 3-5 mm. Each disc was divided into four quarters, and each quarter served as two samples corresponding to irradiated and non-irradiated group counterparts. Five disks were used to study the effect of various laser irradiation energies on the dentinal tubules to find a good pulse fluence for occlusion of the dentinal tubules, and four disks were used for studying the effects of reagents and irradiation at the pulse fluences found in the first part of the study. The samples were irradiated with a beam diameter of 1 mm (1/e 2 ) at 15 Hz pulse repetition rate, scanned automatically using a set of scanning mirrors. Samples were imaged using Scanning Electron Microscope (SEM) which were processed to determine tubule diameter. Safety of the irradiation treatment was investigated on 6 samples by measuring pulpal temperature rise. The effect of three topical reagents corresponding to 2% Sodium Fluoride gel (F), Hydroxyapatite nanoparticles (HA) and an equal mix of F and HA (HAF) on dentinal tubule occlusion was evaluated and compared with the laser irradiation., Results: In all examined cases, laser irradiation at a fluence of 0.81 J/cm 2 resulted in a temperature increase less than 3 °C which is safe, and no surface cracking was observed. There is a threshold pulse fluence of 0.27 J/cm 2 above which, laser produced surface melting. At a pulse fluence of 0.81 J/cm 2 a layer of recast of melted dentin was formed. Under this layer, peritubular dentin melting and occluding of the dentinal tubules was observed. Application of either F or HA or HAF did not produce visible occlusion effect on open tubules after washing and microbrushing with excess distilled water., Conclusions: 9.3 μm CO2 laser irradiation on extracted human molar dentin at pulse fluence of 0.81 J./cm 2 resulted in tubule area reduction by 97% without rising pulpal temperatures to unsafe levels., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: The aim of this study is to introduce a novel nanohydroxyapatite/polyamide 66(n-HA/PA66)n strut to improve biomechanical performance and reduce subsidence., Methods: One validated intact and 2 ACCF-simulated C3-C7 cervical spine models were developed (old strut: Group A, new strut: Group B). In the ACCF models, C5 underwent corpectomy and was fixed by an anterior cervical plate. Screw angles were categorized as 1 (0 ) and 2 (45 ) and divided into 4 groups, A1, A2, B1 and B2, for each model. An axial force of 74 N and a moment couple of 1.0 Nm were imposed on the C3 vertebra. The range of motion (ROM) of each segment and the stress distribution on the screw-vertebra interface, strut, and strut-endplate interface were recorded and analysed., Results: There was no significant difference in ROM between Group A and Group B during bending, extension and rotation under 74 N axial pressure. The stress concentration on the strut body in Group A was higher than that in Group B. The peak stress values at the screw-vertebral interface in Groups A1 and A2 were higher than those in Groups B1 and B2, except for during extension and lateral bending. Under axial pressure, the peak stress values at the strut body-endplate interface during bending, extension and rotation were lower in the A1 and A2 groups than in the B1 and B2 groups. The Group B model showed much higher graft stress than the Group A model., Conclusions: Based on finite-element analysis, compared with the old strut, the novel strut showed better biomechanical performance at the screw-vertebra interface., (© 2024. The Author(s).)

Background: As a two-stage surgical procedure, Masquelet's technique has been used to care for critical-size bone defects (CSD). We aimed to determine the effects of modified and altered bone cement with biological or chemical enriching agents on the progression of Masquelet's induced membrane (IM) applied to a rat femur CSD model, and to compare the histopathological, biochemical, and immunohistochemical findings of these cements to enhance IM capacity., Methods: Thirty-five male rats were included in five groups: plain polymethyl methacrylate (PMMA), estrogen-impregnated PMMA (E+PMMA), bone chip added PMMA (BC+PMMA), hydroxyapatite-coated PMMA (HA) and calcium phosphate cement (CPC). The levels of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) were analyzed in intracardiac blood samples collected at the end of 4 weeks of the right femur CSD intervention. All IMs collected were fixed and prepared for histopathological scoring. The tissue levels of rat-specific Transforming Growth Factor-Beta (TGF-β), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) were analyzed immunohistochemically., Results: Serum levels of BALP and OC were significantly higher in E+PMMA and BC+PMMA groups than those of other groups (P = 0.0061 and 0.0019, respectively). In contrast, TNF-α levels of all groups with alternative bone cement significantly decreased compared to bare PMMA (P = 0.0116). Histopathological scores of E+PMMA, BC+PMMA, and CPC groups were 6.86 ± 1.57, 4.71 ± 0.76, and 6.57 ± 1.51, respectively, which were considerably higher than those of PMMA and HA groups (3.14 ± 0.70 and 1.86 ± 0.69, respectively) (P < 0.0001). Significant increases in TGF-β and VEGF expressions were observed in E+PMMA and CPC groups (P = 0.0001 and <0.0001, respectively) whereas Runx2 expression significantly increased only in the HA group compared to other groups (P < 0.0001)., Conclusions: The modified PMMA with E and BC, and CPC as an alternative spacer resulted in a well-differentiated IM and increased IM progression by elevating BALP and OC levels in serum and by mediating expressions of TGF-β and VEGF at the tissue level. Estrogen-supplemented cement spacer has yielded promising findings between modified and alternative bone cement., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: This study aimed to assess the efficacy of adipose-derived mesenchymal stem cell exosomes (ASCs exosome) and platelet-rich fibrin (PRF) in treating critical long bone defects in Sprague-Dawley rats. Critical long bone defects, defined as exceeding 2 cm or 50% of the bone diameter, often pose a healing challenge. While autologous bone grafts have been considered, they have shown unreliable results and donor-site complications, necessitating alternative treatments., Methods: The research followed a quasi-experimental post-test only control group design involving 30 male Sprague-Dawley rats. The rats were divided into five groups and subjected to femur bone defect creation, internally fixed with a 1.4 mm K-wire, and treated with various combinations of hydroxyapatite (HA), bone graft (BG), ASCs exosome, and PRF. Histomorphometry and BMP-2 gene expression analysis were performed to evaluate bone healing., Results and Discussion: The results indicated that the group treated with HA + BG + ASCs exosome (group IV) exhibited the highest BMP-2 gene expression, while group III (HA + BG + ASCs exosome + PRF) had the highest chordin level. Overall, groups receiving ASCs exosome or PRF intervention showed elevated BMP-2 expression compared to the control group. The use of ASCs exosome and PRF showed comparable outcomes compared to bone graft administration in terms of histomorphometry analysis., Conclusion: The administration of adipose tissue derived mesenchymal stem cells and PRF has a comparable outcome with the use of bone graft in terms of osseus area and expression of BMP-2 in critical bone defect., (© 2024. The Author(s).)

Background: This study evaluated the clinical benefits of adding NanoBone ® with split-crest technique and simultaneous implant placement covered with platelet-rich fibrin membrane in horizontally deficient maxillary ridges in terms of crestal and horizontal bone changes and patient morbidity., Methods: Forty patients indicated for maxillary ridge splitting and simultaneous implant placement were assigned randomly to the study groups: control group (Platelet Rich Fibrin membrane) and test group (Platelet Rich Fibrin membrane + Nanobone ® ). The Cone Beam Computed Tomography Fusion technique was utilized to assess crestal and horizontal bone changes after five months of the surgical procedure. Patient morbidity was recorded for one week post-surgical., Results: Five months post-surgical, buccal crestal bone resorption was 1.26 ± 0.58 mm for the control group and 1.14 ± 0.63 mm for the test group. Lingual crestal bone resorption was 1.40 ± 0.66 mm for the control group and 1.47 ± 0.68 mm for the test group. Horizontal bone width gain was 1.46 ± 0.44 mm for the control group and 1.29 ± 0.73 mm for the test group. There was no significant statistical difference between study groups regarding crestal and horizontal bone changes and patient morbidity., Conclusions: The tomographic assessment of NanoBone ® addition in this study resulted in no statistically significant difference between study groups regarding crestal and horizontal bone changes and patient morbidity. More randomized controlled clinical trials on gap fill comparing different bone grafting materials versus no grafting should be conducted., Gov Registration Number: NCT02836678, 13 th January 2017., (© 2024. The Author(s).)

Purpose: This study evaluated the implant stability, volumetric changes, and patient-reported outcome measures (PROMs) of hydroxyapatite (HA) nano-coated sandblasted/acid-etched (SLA) implants compared to uncoated SLA implants., Methods: Forty patients were recruited and randomly allocated to HA nano-coated SLA group (test, n = 20) and uncoated SLA group (control, n = 20) using single-blinded/block randomization. Implants were immediately placed in maxillary posterior region using a digital surgical guide. Insertion torque and implant stability quotient (ISQ) were measured at implant surgery and 1, 2, 3, and 4 months postoperatively. Intraoral scans, PROMs and soft tissue inflammation data were collected, and multivariable linear regression analysis of ISQ was performed., Results: In total, 48 implants (test; n = 24, control; n = 24) in 37 patients (test; n = 19, control; n = 18) were analyzed. Despite no significant between-group difference at surgery, the test group showed higher ISQ values than the control group at 2 (76.53 ± 4.17 vs. 71.32 ± 4.79, p < 0.01), 3 (77.45 ± 4.41 vs. 73.85 ± 4.69, p < 0.05), and 4 months (79.08 ± 2.96 vs. 73.43 ± 3.52, p < 0.0001) postoperatively. There were no significant differences in linear and volumetric changes, PROMs, and soft tissue inflammation analysis between two groups. The ISQ at implant surgery was influenced by age and diabetes mellitus (DM) at the implant level and DM and predicted total bone-to-implant contact area at the patient level., Conclusion: HA nano-coated SLA implants promoted favorable immediate implants stability during early osseointegration phase compared to uncoated SLA implants, but displayed similar dimensional changes, PROMs, and soft tissue inflammation outcomes., Trial Registration: Clinical Research Information Service (CRIS), KCT0006364. Registered 21 July 2021, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24221&search&#95;page=L ., (© 2024. The Author(s).)