Hypophosphatemic Rickets and Short Stature.

An 18-month old male presented with gross motor delay and poor growth (weight z-score -2.21, length z-score -4.26). Radiographs showed metaphyseal irregularities suggesting metaphyseal dysplasia and sagittal craniosynostosis. Biochemical evaluation revealed evidence of hypophosphatemic rickets [serum phosphorus 2.3 mg/dL (reference range (RR) 4.3-6.8), alkaline phosphatase 754 unit/L (RR 156-369)] due to renal phosphate wasting (TmP/GFR 4.3 mg/dL, normal for age 4.3-6.8), with C-terminal FGF23 125 RU/mL (>90 during hypophosphatemia suggests FGF23-mediated hypophosphatemia). Treatment was initiated with calcitriol and phosphate. Genetic analysis showed a pathogenic variant of FGF23: c.527G > A (p.Arg176Gln) indicative of autosomal dominant hypophosphatemic rickets (ADHR). Consistent with reports linking iron deficiency with the ADHR phenotype, low ferritin was detected, 18 ng/mL (RR 24-336). Oral ferrous sulfate replacement was initiated. Following normalization of ferritin level (41 ng/mL) biochemical improvement was demonstrated (FGF23 69 RU/mL, phosphorus 5.0 mg/dL and alkaline phosphatase 228 unit/L). Calcitriol and phosphate were discontinued. Three years later, the patient demonstrated improved developmental milestones, linear growth (length Z-score -2.01), radiographic normalization of metaphyses, and stabilization of craniosynostosis. While the most common cause of hypophosphatemic rickets is X-linked hypophosphatemia, other etiologies should be considered as treatment differs. In ADHR, normalization of iron leads to biochemical and clinical improvement.

Branched polymer grafted graphene oxide (GO) as a 2D template for calcium phosphate growth.

HYPOTHESIS: Graphene Oxide (GO)-templated deposition of inorganic materials through synthesis on dispersed single sheets of GO is often complicated by the loss of the desired 2D morphology owing to the coagulation of GO sheets at high salt concentrations and non-templated homogenous nucleation. Modifying GO with anionic polymer is expected to solve both problems by i) enhancing electrostatic(steric) stabilization upon exposure to high concentrations of the ionic precursors, and ii) offering additional nucleation sites at the grafted anionic moieties to avoid homogeneous secondary nucleation. EXPERIMENTS: GO was grafted with branched copolymers of poly(ethylene glycol) methacrylate (PEGMA 500) and diethylene glycol dimethacrylate (DEGDMA) and ω-vinyl terminated methacrylic acid macromonomer (P(MAA)), the latter serving as an addition-fragmentation chain transfer agent. The colloidal stability of GO dispersions in water toward salt was evaluated before and after modification. Precipitation of calcium phosphate (CaP) was performed by incubating modified GO in the precursor solutions. The conditions were optimized to maximize the nucleation selectively onto GO without homogeneous CaP nucleation and coagulation of the GO-sheets. FINDINGS: The copolymer grafted GO-sheets shows superior colloidal stability when dispersed in water. No aggregation occurs in the incubating ionic CaP precursor solutions. The optimum templated deposition of CaP onto the GO sheets by precipitation is to add a second shot of precursors after the nucleation stage to obtain GO sheets fully decorated with calcium phosphate nanorods without self-nucleation. Via the careful design on the GO modification and incubation process, the growth of calcium phosphate nanorods were confined in the desired 2D order exclusively, hereby achieving the goal of an efficient GO-templated synthesis.

Injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel for local treatment of osteomyelitis: Fabrication, characterization, and in vitro performance evaluation.

The conventional treatment of osteomyelitis with antibiotic-loaded nondegradable polymethylmethacrylate (ATB-PMMA) beads has certain limitations, including impeded bone reconstruction and the need for secondary surgery. To overcome this challenge, this study aimed to develop and characterize an injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel (VC-SF/MC-CAPs). The VC-SF/MC-CAPs solution can be easily administered at room temperature with a low injectability force of ≤30 N and a high vancomycin (VC) content of ~96%. Additionally, at physiological temperature (37 °C), the solution could transform into a rigid hydrogel within 7 minutes. In vitro drug release performed under both physiological (pH 7.4) and infection conditions (pH 4.5) revealed a prolonged release pattern of VC-SF/MC-CAPs following the Peppas-Sahlin kinetic model. In addition, the released VC from VC-SF/MC-CAPs hydrogels exhibited antibacterial activity against Staphylococcus aureus for a period exceeding 35 days, as characterized by the disk diffusion assay. Furthermore, at pH 7.4, the VC-SF/MC-CAPs demonstrated >60% degradation within 35 days. Importantly, when exposed to physiological pH conditions, CAPs are transformed into bioactive hydroxyapatite, which benefits bone formation. Therefore, VC-SF/MC-CAPs showed significant potential as a local drug delivery system for treating osteomyelitis.

Non-industrial production of therapeutic lentiviral vectors: How to provide vectors to academic CAR-T.

Bringing effective cancer therapy in the form of chimeric antigen receptor technology to untapped markets faces numerous challenges, including a global shortage of therapeutic lentiviral or retroviral vectors on which all current clinical therapies using genetically modified T cells are based. Production of these lentiviral vectors in academic settings in principle opens the way to local production of therapeutic cells, which is the only economically viable approach to make this therapy available to patients in developing countries. The conditions for obtaining and concentrating lentiviral vectors have been optimized and described. The calcium phosphate precipitation method was found to be suitable for transfecting high cell-density cultures, a prerequisite for high titers. We describe protocols for gradually increasing production from 6-well plates to P100 plates, T-175 flasks, and 5-layer stacks while maintaining high titers, >108 transducing units. Concentration experiments using ultracentrifugation revealed the advantage of lower centrifugation speeds compared to competing protocols. The resulting batches of lentiviral vectors had a titer of 1010 infectious particles and were used to transduce primary human T lymphocytes generating chimeric antigen receptor T cells, the quality of which was checked and found potential applicability for treatment.

SGLT2 Inhibitor Use for Treatment of Hypocitraturia in a Distal Renal Tubular Acidosis.

5-Amino salicylic acid (5-ASA) is a known culprit for the development of tubulointerstitial nephritis. Together with impaired kidney function, tubulointerstitial nephritis can lead to specific tubular malfunctions including distal renal tubular acidosis. Distal renal tubular acidosis is an acid-base disorder in which acid secretion in the distal part of the renal tubular system is decreased. Patients with distal renal tubular acidosis are predisposed to recurrently form calcium phosphate kidney stones. This results from the inability to acidify the urine properly as well as from a decreased citrate concentration in the urine, which is another pathognomonic feature of distal renal tubular acidosis. We present the case of a man in his late 40s with Crohn's disease who developed tubulointerstitial nephritis associated with 5-ASA leading to the development of distal renal tubular acidosis and recurrent calcium phosphate nephrolithiasis. After steroid therapy and partial recovery of kidney function, we observed an increase of citraturia in response to treatment with dapagliflozin, potentially indicating beneficial effects of sodium/glucose cotransporter 2 inhibition on the recurrence of calcium phosphate stone disease in interstitial nephritis-induced distal tubular acidosis.

Drug delivery strategies through 3D-printed calcium phosphate.

3D printing has revolutionized bone tissue engineering (BTE) by enabling the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration. The superior biocompatibility, customizable bioactivity, and biodegradability have enabled calcium phosphate (CaP) to gain significance as a bone graft material. 3D-printed (3DP) CaP scaffolds allow precise drug delivery due to their porous structure, adaptable structure-property relationship, dynamic chemistry, and controlled dissolution. The effectiveness of conventional scaffold-based drug delivery is hampered by initial burst release and drug loss. This review summarizes different multifunctional drug delivery approaches explored in controlling drug release, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion printing for BTE applications. The review also outlines perspectives and future challenges in drug delivery research, paving the way for next-generation bone repair methodologies.

3D Printed Calcium Phosphate Physiochemically Dual-Regulating Pro-Osteogenesis and Antiosteolysis for Enhancing Bone Tissue Regeneration.

Osteoblasts and osteoclasts are two of the most important types of cells in bone repair, and their bone-forming and bone-resorbing activities influence the process of bone repair. In this study, we proposed a physicochemical bidirectional regulation strategy via ration by physically utilizing hydroxyapatite nanopatterning to recruit and induce MSCs osteogenic differentiation and by chemically inhibiting osteolysis activity through the loaded zoledronate. The nanorod-like hydroxyapatite coating was fabricated via a modified hydrothermal process while the zoledronic acid was loaded through the chelation within the calcium ions. The fabrication of a hydroxyapatite/zoledronic acid composite biomaterial. This biomaterial promotes bone tissue regeneration by physically utilizing hydroxyapatite nanopatterning to recruit and induce MSCs osteogenic differentiation and by chemically inhibiting osteolysis activity through the loaded zoledronate. The nanorod-like hydroxyapatite coating was fabricated via a modified hydrothermal process while the zoledronic acid was loaded through the chelation within the calcium ions. The in vitro results tested on MSCs and RAW 246.7 indicated that the hydroxyapatite enhanced cells' physical sensing system, therefore enhancing the osteogenesis. At the same time the zoledronic acid inhibited osteolysis by downregulating the RANK-related genes. This research provides a promising strategy for enhancing bone regeneration and contributes to the field of orthopedic implants.

Effect of a synthetic hydroxyapatite-based bone grafting material compared to established bone substitute materials on regeneration of critical-size bone defects in the ovine scapula.

Lately, the potential risk of disease transmission due to the use of bovine-derived bone substitutes has become obvious, demonstrating the urgent need for a synthetic grafting material with comparable bioactive behaviour and properties. Therefore, the effect of a synthetic hydroxyapatite (HA) (Osbone®) bone grafting material on bone regeneration was evaluated 2 weeks, 1 month, and 3, 6, 12 and 18 months after implantation in critical-size bone defects in the ovine scapula and compared to that of a bovine-derived HA (Bio-Oss®) and ß-tricalcium phosphate (TCP) (Cerasorb® M). New bone formation and the biodegradability of the bone substitutes were assessed histomorphometrically. Hard tissue histology and immunohistochemical analysis were employed to characterize collagen type I, alkaline phosphatase, osteocalcin, as well as bone sialoprotein expression in the various cell and matrix components of the bone tissue to evaluate the bioactive properties of the bone grafting materials. No inflammatory tissue response was detected with any of the bone substitute materials studied. After 3 and 6 months, ß-TCP (Cerasorb® M) showed superior bone formation when compared to both HA-based materials (3 months: ß-TCP 55.65 ± 2.03% vs. SHA 49.05 ± 3.84% and BHA 47.59 ± 1.97%; p ≤ 0.03; 6 months: ß-TCP 62.03 ± 1.58%; SHA: 55.83 ± 2.59%; BHA: 53.44 ± 0.78%; p ≤ 0.04). Further, after 12 and 18 months, a similar degree of bone formation and bone-particle contact was noted for all three bone substitute materials without any significant differences. The synthetic HA supported new bone formation, osteogenic marker expression, matrix mineralization and good bone-bonding behaviour to an equal and even slightly superior degree compared to the bovine-derived HA. As a result, synthetic HA can be regarded as a valuable alternative to the bovine-derived HA without the potential risk of disease transmission.

Alendronate as Bioactive Coating on Titanium Surfaces: An Investigation of CaP-Alendronate Interactions.

The surface modification of dental implants plays an important role in establishing a successful interaction of the implant with the surrounding tissue, as the bioactivity and osseointegration properties are strongly dependent on the physicochemical properties of the implant surface. A surface coating with bioactive molecules that stimulate the formation of a mineral calcium phosphate (CaP) layer has a positive effect on the bone bonding process, as biomineralization is crucial for improving the osseointegration process and rapid bone ingrowth. In this work, the spontaneous deposition of calcium phosphate on the titanium surface covered with chemically stable and covalently bound alendronate molecules was investigated using an integrated experimental and theoretical approach. The initial nucleation of CaP was investigated using quantum chemical calculations at the density functional theory (DFT) level. Negative Gibbs free energies show a spontaneous nucleation of CaP on the biomolecule-covered titanium oxide surface. The deposition of calcium and phosphate ions on the alendronate-modified titanium oxide surface is governed by Ca2+-phosphonate (-PO3H) interactions and supported by hydrogen bonding between the phosphate group of CaP and the amino group of the alendronate molecule. The morphological and structural properties of CaP deposit were investigated using scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy. This integrated experimental-theoretical study highlights the spontaneous formation of CaP on the alendronate-coated titanium surface, confirming the bioactivity ability of the alendronate coating. The results provide valuable guidance for the promising forthcoming advancements in the development of biomaterials and surface modification of dental implants.

Influence of Heating Temperature and pH on Acid Gelation of Micellar Calcium Phosphate-Adjusted Skim Milk.

Micellar calcium phosphate (MCP) plays an important role in maintaining the structure and stability of the casein micelle and its properties during processing. The objective of this study was to investigate how heating (10 min at 80 or 90 °C) at different pH levels (6.3, 6.6, 6.9, or 7.2) impacted the acid-induced gelation of MCP-adjusted milk, containing 67 (MCP67), 100 (MCP100), or 113 (MCP113) % of the original MCP content. The unheated sample MCP100 at pH 6.6 was considered the control. pH acidification to pH 4.5 at 30 °C was achieved with glucono delta-lactone while monitoring viscoelastic behaviour by small-amplitude oscillatory rheology. The partitioning of calcium and proteins between colloidal and soluble phases was also examined. In MCP-depleted skim milk samples, the concentrations of non-sedimentable caseins and whey proteins were higher compared to the control and MCP-enriched skim milk samples. The influence of MCP adjustment on gelation was dependent on pH. Acid gels from sample MCP67 exhibited the highest storage modulus (G'). At other pH levels, MCP100 resulted in the greatest G'. The pH of MCP-adjusted skim milk also impacted the gel properties after heating. Overall, this study highlights the substantial impact of MCP content on the acid gelation of milk, with a pronounced dependency of the MCP adjustment effect on pH variations.

Potential of Titanium Pins Coated with Fibroblast Growth Factor-2-Calcium Phosphate Composite Layers to Reduce the Risk of Impaired Bone-Pin Interface Strength in the External Fixation of Distal Radius Fractures.

Background: The risk of impaired bone-pin interface strength in titanium (Ti) pins coated with fibroblast growth factor (FGF)-calcium phosphate (CP) composite layers is yet to be evaluated in a clinical study. This retrospective study used Weibull plot analysis to evaluate bone-pin interface strength in Ti pins coated with FGF-CP layers for external distal radius fracture fixation. Methods: The distal radial fractures were treated with external fixation. The FGF-CP group comprised five patients (all women, aged 70.4 ± 5.9 (range: 62-77) years), and the uncoated pin group comprised ten patients (eight women and two men, aged 64.4 ± 11.7 (range: 43-83) years). The pins were removed after six weeks. The insertion and extraction peak torques were measured. The extraction peak torque was evaluated using Weibull plot analysis. Results: We compared the extraction torque of the two groups at or below 506 Nmm for a fair comparison using Weibull plot analysis. The Weibull plots were linear for both the FGF-CP and uncoated pin groups. The slope of the regression line was significantly higher in the FGF-CP group (1.7343) than in the uncoated pin group (1.5670) (p = 0.011). The intercept of the regression line was significantly lower in the FGF-CP group (-9.847) than in the uncoated pin group (-8.708) (p = 0.002). Thus, the two regression lines significantly differed. Conclusions: Ti pins coated with FGF-CP layers exhibit the potential to reduce the risk of impaired bone-pin interface strength in the external fixation of distal radius fractures.

High Strength and Shape Memory Spinal Fusion Device for Minimally Invasive Interbody Fusions.

Introduction: Lumbar interbody fusion is widely employed for both acute and chronic spinal diseases interventions. However, large incision created during interbody cage implantation may adversely impair spinal tissue and influence postoperative recovery. The aim of this study was to design a shape memory interbody fusion device suitable for small incision implantation. Methods: In this study, we designed and fabricated an intervertebral fusion cage that utilizes near-infrared (NIR) light-responsive shape memory characteristics. This cage was composed of bisphenol A diglycidyl ether, polyether amine D-230, decylamine and iron oxide nanoparticles. A self-hardening calcium phosphate-starch cement (CSC) was injected internally through the injection channel of the cage for healing outcome improvement. Results: The size of the interbody cage is reduced from 22 mm to 8.8 mm to minimize the incision size. Subsequent NIR light irradiation prompted a swift recovery of the cage shape within 5 min at the lesion site. The biocompatibility of the shape memory composite was validated through in vitro MC3T3-E1 cell (osteoblast-like cells) adhesion and proliferation assays and subcutaneous implantation experiments in rats. CSC was injected into the cage, and the relevant results revealed that CSC is uniformly dispersed within the internal space, along with the cage compressive strength increasing from 12 to 20 MPa. Conclusion: The results from this study thus demonstrated that this integrated approach of using a minimally invasive NIR shape memory spinal fusion cage with CSC has potential for lumbar interbody fusion.

The Synergistic Effect of High Intensity Focused Ultrasound on In-vitro Remineralization of Tooth Enamel by Calcium Phosphate Ion Clusters.

Background: Remineralization of dental enamel is an important intervention strategy for the treatment of demineralized lesions. Existing approaches have limitations such as failure to adequately reproduce both the ideal structural and mechanical properties of the native tooth. The ability of ultrasound to control and accelerate the crystallization processes has been widely reported. Therefore, a new approach was explored for in-vitro enamel remineralization involving the synergistic effect of high-intensity focused ultrasound (HIFU) coupled with calcium phosphate ion clusters (CPICs). Methods: The demineralized enamel was treated with CPICs, with or without subsequent HIFU exposure for different periods (2.5, 5, and 10 min). The specimens were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman spectroscopy. The surface hardness and crystallographic properties of the treated specimens were evaluated using Vickers microhardness testing and X-ray diffraction (XRD), respectively. Results: SEM revealed distinct, organized, and well-defined prismatic structures, showing clear evidence of remineralization in the combined CPIC/HIFU treatment groups. AFM further revealed a decrease in the surface roughness values with increasing HIFU exposure time up to 5 min, reflecting the obliteration of interprismatic spaces created during demineralization. The characteristic Raman band at 960 cm-1 associated with the inorganic phase of enamel dominated well in the HIFU-treated specimens. Importantly, microhardness testing further demonstrated that new mineral growth also recovered the mechanical properties of the enamel in the HIFU-exposed groups. Critical to our aspirations for developing this into a clinical process, these results were achieved in only 5 min. Conclusion: HIFU exposure can synergise and significantly accelerate in-vitro enamel remineralization process via calcium phosphate ion clusters. Therefore, this synergistic approach has the potential for use in future clinical interventions.

Injectable and high-strength PLGA/CPC loaded ALN/MgO bone cement for bone regeneration by facilitating osteogenesis and inhibiting osteoclastogenesis in osteoporotic bone defects.

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to the imbalance between osteogenesis and osteoclastogenesis, making osteoporotic bone defects healing a significant clinical challenge. Calcium phosphate cement (CPC) is a promising bone substitute material due to its good osteoinductive activity, however, the drawbacks such as fragility, slow degradation rate and incapability to control bone loss restrict its application in osteoporotic bone defects treatment. Currently, we developed the PLGA electrospun nanofiber sheets to carry alendronate (ALN) and magnesium oxide nanoparticle (nMgO) into CPC, therefore, to obtain a high-strength bone cement (C/AM-PL/C). The C/AM-PL/C bone cement had high mechanical strength, anti-washout ability, good injection performance and drug sustained release capacity. More importantly, the C/AM-PL/C cement promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and neovascularization via the release of Mg2+ (from nMgO) and Ca2+ (during the degradation of CPC), and inhibited osteoclastogenesis via the release of ALN in vitro. Moreover, the injection of C/AM-PL/C cement significantly improved bone healing in an OP model with femur condyle defects in vivo. Altogether, the injectable C/AM-PL/C cement could facilitate osteoporotic bone regeneration, demonstrating its capacity as a promising candidate for treatment of osteoporotic bone defects.

Modified and alternative bone cements can improve the induced membrane: Critical size bone defect model in rat femur.

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-ß), 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-ß 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-ß and VEGF at the tissue level. Estrogen-supplemented cement spacer has yielded promising findings between modified and alternative bone cement.

Development of Rapid Bioactivity-Expressed Zr-50Ti Alloys by Surface Treatment with Modified Simulated Body Fluid.

Zr-50Ti alloys are promising biomaterials due to their excellent mechanical properties and low magnetic susceptibility. However, Zr-50Ti alloys do not inherently bond well with bone. This study aims to enhance the bioactivity and bonding strength of Zr-50Ti alloys for orthopedic implant materials. Initially, the surface of Zr-50Ti alloys was treated with a sulfuric acid solution to create a microporous structure, increasing surface roughness and area. Subsequently, low crystalline calcium phosphate (L-CaP) precipitation was controlled by adding Mg2+ and/or CO32- ions in modified simulated body fluid (m-SBF). The treated Zr-50Ti alloys were then subjected to cold isostatic pressing to force m-SBF into the micropores, followed by incubation to allow L-CaP formation. The apatite-forming process was tested in simulated body fluid (SBF). The results demonstrated that the incorporation of Mg2+ and/or CO32- ions enabled the L-CaP to cover the entire surface of Zr-50Ti alloys within only one day. After short-term soaking in SBF, the L-CaP layer, modulated by Mg2+ and/or CO32- ions, formed a uniform hydroxyapatite (HA) coating on the surface of the Zr-50Ti alloys, showing potential for optimized bone integration. After soaking in SBF for 14 days, the bonding strength between the apatite layer and alloy has the potential to meet the orthopedic application requirement of 22 MPa. This study demonstrates an effective method to enhance the bioactivity and bonding strength of Zr-50Ti alloys for orthopedic applications.

New Avenues for Capturing Mineralization Events at Biomaterial Interfaces with Liquid-Transmission Electron Microscopy.

Liquid-transmission electron microscopy (liquid-TEM) provides exciting potential for capturing mineralization events at biomaterial interfaces, though it is largely unexplored. To address this, we established a unique approach to visualize calcium phosphate (CaP)-titanium (Ti) interfacial mineralization events by combining the nanofabrication of Ti lamellae by focused ion beam with in situ liquid-TEM. Multiphasic CaP particles were observed to nucleate, adhere, and form different assemblies onto and adjacent to Ti lamellae. Here, we discuss new approaches for exploring the interaction between biomaterials and liquids at the nanoscale. Driving this technology is crucial for understanding and controlling biomineralization to improve implant osseointegration and direct new pathways for mineralized tissue disease treatment in the future.

An Injectable Hydrogel Composing Anti-Inflammatory and Osteogenic Therapy toward Bone Erosions Microenvironment Remodeling in Rheumatoid Arthritis.

Healing bone erosions in rheumatoid arthritis (RA) remains greatly challenging via biomaterial strategies. Given the unsuccessful innate bone erosion healing due to an inflammatory disorder, over-activated osteoclasts, and impaired osteoblasts differentiation, RA pathogenesis-guided engineering of an innovative hydrogel platform is needed for remodeling osteoimmune and osteogenic microenvironment of bone erosion healing. Herein, in situ adaptable and injectable interpenetrating polymer network (IPN) hydrogel is developed through an ingenious combination of a bio-orthogonal reaction between hyaluronic acid (HA) and collagen, along with effective electrostatic interactions leveraging bisphosphonate (BP)-functionalized HA macromers (HABP) and nanorod shaped zinc (Zn)-doped biphasic calcium phosphate (ZnBCP). IPN hydrogel exhibits exceptional adaptability to the local shape complexity at bone erosions, and by integrating ZnBCP and HABP, a multi-stage releasing platform is engineered, facilitating controlled cargo delivery for remodeling more anti-inflammatory M2 cells and reducing over-activated osteoclastic activities, thereby reconstructing the bone regeneration microenvironment. Sustainedly co-delivering multiple ions (calcium and phosphate) can display excellent osteogenic properties and be conducive to the bone formation process, by effects of osteogenesis-associated cell differentiation. Overall, the introduced bioactive IPN hydrogel therapy remodels the osteoimmune environment by synergistic pro-inflammation-resolving, osteogenesis, and anti-osteoclastic activities, displaying excellent bone reconstruction in the collagen-induced arthritis rabbit model.

Rapid Corneal Calcification Following Endothelial Keratoplasty: A Case Report.

Corneal calcification typically progresses slowly but can occasionally advance rapidly. This report details severe stromal calcification following repeat Descemet's stripping automated endothelial keratoplasty (DSAEK) in a 75-year-old patient with diabetes, hypertension, and prior ocular surgeries, including cataract surgery, intraocular lens extraction with suturing, and trabeculectomy. Persistent epithelial defects after the surgery led to rapid central stromal calcification within four weeks, significantly reducing visual acuity. Management included switching from betamethasone sodium phosphate to fluorometholone, facilitating complete epithelial recovery within two months. However, persistent stromal opacity necessitated a subsequent penetrating keratoplasty. Infrared absorption spectrophotometry identified calcium phosphate as the primary component of the calcification. This case highlights the importance of vigilant monitoring and proactive management of epithelial defects to prevent rapid calcification following endothelial keratoplasty.

Comparative evaluation of remineralization potential of novel bioactive agents on eroded enamel lesions: A single-blinded in vitro study.

Objective: The escalating prevalence of noncarious tooth wear stands as a critical concern in the backdrop of evolving lifestyles and dietary patterns. Dental erosion, a progressive condition induced by both endogenous and exogenous acidic influences, directly impacts enamel integrity, resulting in surface loss. The contemporary surge in carbonated beverage consumption further exacerbates this erosive milieu, underscoring the urgency for dental practitioners to adopt meticulous treatment strategies. Existing literature underscores a noteworthy 94% reduction in tooth erosion risk for individuals abstaining from sweetened soft beverages, emphasizing the imperative for a well-devised remineralization protocol to counter demineralized surfaces. Methodology: Seventy-three enamel specimens were taken. Forty samples were subjected to pre-operative hardness testing, and five samples were subjected to baseline EDX evaluation followed by grouping of samples (Group 1 = control Group; Group 2 = casein phosphopeptide-amorphous calcium phosphate fluoride [CPP-ACPF] Group; Group 3 = Biomin F Group; and Group 4 = self-assembling peptide [SAP] P-114 Group). A demineralization-remineralization cycle was carried out for 5 days followed by testing through Vickers Microhardness Tester, EDX Evaluation, and Scanning Electron Microscopy (SEM) Imaging. Statistical analysis was performed using one-way analysis of variance followed by intergroup analysis using Tukey's post hoc test with SPSS software 25.0 version. Results: The mean percentage change in microhardness values was 30.05% in Group 1, 24.21% in Group 2, 18.85% in Group 3, and 12.08% in Group 4. The mean Ca/P ratio of samples tested through EDAX was 2.20 at baseline, 1.40 in Group 1 (Control Group), 1.62 in Group 2 (CPP-ACPF), 1.82 in Group 3 (Biomin F), and 2.01 in Group 4 (SAP-P114). Postintervention values were statistically significant from baseline values in both parameters. Conclusion: Curodont Protect exhibits superior efficacy, offering valuable insights for future in vivo studies and clinical applications. The multifaceted evaluation, encompassing microhardness testing, SEM analysis, and EDXS assessment, contributes to a nuanced interpretation of the agents' impact, paving the way for informed decisions in clinical practice and future research endeavors.