Mesenchymal Stem Cell Exosomes Enhance Posterolateral Spinal Fusion in a Rat Model.

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.

Time to full weight-bearing with the use of a calcium sulfate-calcium phosphate bone substitute as a bone void filler following extended curettage in the treatment of primary benign bone tumours.

PURPOSE: The primary objective of this study was to determine time to full weight-bearing after the use of a calcium-sulfate-calcium phosphate bone substitute (CaSO4/CaPO4) as a bone void filler in the treatment of primary benign bone tumours following intralesional curettage. The secondary objectives were to determine surgical complications and recurrence rates. METHODS: Retrospective review of patients identified from a surgeon-specific orthopaedic oncology database, who underwent curettage of benign bone tumours and subsequent bone void filling with CaSO4/CaPO4. RESULTS: A total of 39 patients (20 males, 19 females) met inclusion criteria with an average age of 31 years (range: 13 to 62 years), a median follow-up of 3.7 years, and a maximum follow-up of 11 years. The most common tumour diagnosis was giant cell tumour of bone (GCT) (n = 19), and the most common location was the proximal tibia (n = 9). The mean volume of tumour excised was 74.1 cm3 including extraosseous bone expansion due to tumour growth, with a mean of volume of 21.4 mL of CaSO4/CaPO4 used to fill the intraosseous cavitary defects to restore normal bone anatomy. None of the lesions required additional internal fixation. The primary outcome measure, average time to full weight-bearing/full range of motion, was 11 weeks and 6 weeks for upper and lower extremity lesions, respectively. Secondary outcomes included tumour recurrence requiring reoperation in five patients and infection requiring reoperation in two patients. CONCLUSION: This study demonstrates that CaSO4/CaPO4 is a viable option as a bone void filler in the reconstruction of cavitary defects following removal of primary benign bone tumours. CaSO4/CaPO4 provides sufficient bone regeneration early in the post-operative period to allow progression to full weight-bearing within weeks without the need for internal fixation. There were no graft-specific complications noted.

Patient-specific beta-tricalcium phosphate scaffold for customized alveolar ridge augmentation: a case report : Case Report: patient-specific ß-TCP scaffold for alveolar ridge CBR.

BACKGROUND: Beta-tricalcium phosphate (ß-TCP) is a biocompatible ceramic material widely used in the field of oral regeneration. Due to its excellent biological and mechanical properties, it is increasingly utilized for alveolar ridge augmentation or guided bone regeneration (GBR). With recent advances in computer-aided design and manufacturing (CAD/CAM), ß-TCP can now be used in the form of digitally designed patient-specific scaffolds for customized bone regeneration (CBR) of advanced defects in a two-stage implant therapy concept. In this case report following the CARE case report guidelines, we present a novel application of a patient-specific ß-TCP scaffold in pre-implant mandibular alveolar ridge augmentation. CASE PRESENTATION: A 63-year-old female patient with significant horizontal bone loss in the posterior mandible was treated with a custom ß-TCP scaffold in the context of a two-stage backward-planned implant therapy. Cone-beam computed tomography nine months after augmentation showed successful integration of the scaffold into the surrounding bone, allowing implant placement. Follow-up until two years after initial surgery showed excellent oral and peri-implant health. CONCLUSIONS: This case highlights the potential of patient-specific ß-TCP scaffolds for alveolar ridge augmentation and their advantage over traditional techniques, including avoidance of xeno-, allo-, and autografts. The results provide encouraging evidence for their use in clinical practice. Patient-specific ß-TCP scaffolds may be a promising alternative for clinicians seeking to provide their patients with safe, predictable, and effective alveolar ridge augmentation results in customized bone regeneration procedures.

A 3D In-vitro model of the human dentine interface shows long-range osteoinduction from the dentine surface.

Emerging regenerative cell therapies for alveolar bone loss have begun to explore the use of cell laden hydrogels for minimally invasive surgery to treat small and spatially complex maxilla-oral defects. However, the oral cavity presents a unique and challenging environment for in vivo bone tissue engineering, exhibiting both hard and soft periodontal tissue as well as acting as key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems, which will impact on cell fate and subsequent treatment efficacy. Herein, we design and bioprint a facile 3D in vitro model of a human dentine interface to probe the effect of the dentine surface on human mesenchymal stem cells (hMSCs) encapsulated in a microporous hydrogel bioink. We demonstrate that the dentine substrate induces osteogenic differentiation of encapsulated hMSCs, and that both dentine and ß-tricalcium phosphate substrates stimulate extracellular matrix production and maturation at the gel-media interface, which is distal to the gel-substrate interface. Our findings demonstrate the potential for long-range effects on stem cells by mineralized surfaces during bone tissue engineering and provide a framework for the rapid development of 3D dentine-bone interface models.

Kidney stone growth through the lens of Raman mapping.

Bulk composition of kidney stones, often analyzed with infrared spectroscopy, plays an essential role in determining the course of treatment for kidney stone disease. Though bulk analysis of kidney stones can hint at the general causes of stone formation, it is necessary to understand kidney stone microstructure to further advance potential treatments that rely on in vivo dissolution of stones rather than surgery. The utility of Raman microscopy is demonstrated for the purpose of studying kidney stone microstructure with chemical maps at ≤ 1 µm scales collected for calcium oxalate, calcium phosphate, uric acid, and struvite stones. Observed microstructures are discussed with respect to kidney stone growth and dissolution with emphasis placed on < 5 µm features that would be difficult to identify using alternative techniques including micro computed tomography. These features include thin concentric rings of calcium oxalate monohydrate within uric acid stones and increased frequency of calcium oxalate crystals within regions of elongated crystal growth in a brushite stone. We relate these observations to potential concerns of clinical significance including dissolution of uric acid by raising urine pH and the higher rates of brushite stone recurrence compared to other non-infectious kidney stones.

Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel-Ceramic Scaffold Application.

In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (ß-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/ß-TCP scaffold, a stem cell-loaded 3D-printed nHA/ß-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/ß-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/ß-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/ß-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.

Osteosarcoma cell death induced by innovative scaffolds doped with chemotherapeutics.

Osteosarcoma (OS) cancer treatments include systemic chemotherapy and surgical resection. In the last years, novel treatment approaches have been proposed, which employ a drug-delivery system to prevent offside effects and improves treatment efficacy. Locally delivering anticancer compounds improves on high local concentrations with more efficient tumour-killing effect, reduced drugs resistance and confined systemic effects. Here, the synthesis of injectable strontium-doped calcium phosphate (SrCPC) scaffold was proposed as drug delivery system to combine bone tissue regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC-MTX and SrCPC-DOX, respectively. The drug-loaded cements were tested in an in vitro model of human OS cell line SAOS-2, engineered OS cell line (SAOS-2-eGFP) and U2-OS. The ability of doped scaffolds to induce OS cell death and apoptosis was assessed analysing cell proliferation and Caspase-3/7 activities, respectively. To determine if OS cells grown on doped-scaffolds change their migratory ability and invasiveness, a wound-healing assay was performed. In addition, the osteogenic potential of SrCPC material was evaluated using human adipose derived-mesenchymal stem cells. Osteogenic markers such as (i) the mineral matrix deposition was analysed by alizarin red staining; (ii) the osteocalcin (OCN) protein expression was investigated by enzyme-linked immunosorbent assay test, and (iii) the osteogenic process was studied by real-time polymerase chain reaction array. The delivery system induced cell-killing cytotoxic effects and apoptosis in OS cell lines up to Day 7. SrCPC demonstrates a good cytocompatibility and it induced upregulation of osteogenic genes involved in the skeletal development pathway, together with OCN protein expression and mineral matrix deposition. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug-loaded cements is promising for future therapies aiming to combine bone regeneration and anticancer local therapy.

Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. METHODS: We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. RESULTS: 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22-1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29-1.56; p<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01-1.24; p=0.027), for each increment in sputum purulence. CONCLUSION: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

Inhibiting Pathological Calcium Phosphate Mineralization: Implications for Disease Progression.

Pathological calcifications, especially calcium phosphate microcalcifications (MCs), appear in most early breast cancer lesions, and their formation correlates with more aggressive tumors and a poorer prognosis. Hydroxyapatite (HA) is a key MC component that crystallizes in the tumor microenvironment. It is often associated with malignant breast cancer lesions and can trigger tumorigenesis in vitro. Here, we investigate the impact of additives on HA crystallization and inhibition, and how precancerous breast cells respond to minerals that are deposited in the presence of these additives. We show that nonstoichiometric HA spontaneously crystallizes in a solution simulating the tumor microenvironmental fluids and exhibits lump-like morphology similar to breast cancer MCs. In this system, the effectiveness of poly(aspartic acid) and poly(acrylic acid) (PAA) to inhibit HA is examined as a potential route to improve cancer prognosis. In the presence of additives, the formation of HA lumps is associated with the promotion or only minimal inhibition of mineralization, whereas the formation of amorphous calcium phosphate (ACP) lumps is followed by inhibition of mineralization. PAA emerges as a robust HA inhibitor by forming spherical ACP particles. When precancerous breast cells are exposed to various HA and ACP minerals, the most influential factors on cell proliferation are the mineral phase and whether the mineral is in the form of discrete particles or particle aggregates. The tumorigenic effects on cells, ranging from cytotoxicity and suppression of proliferation to triggering of proliferation, can be summarized as HA particles < HA aggregates < ACP particles < ACP aggregates. The cellular response to minerals can be attributed to a combination of factors, including mineral phase, crystallinity, morphology, surface texture, aggregation state, and surface potential. These findings have implications for understanding mineral-cell interactions within the tumor microenvironment and suggest that, in some cases, the byproducts of HA inhibition can contribute to disease progression more than HA itself.

Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect.

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and ß-Tricalcium Phosphate (ß-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. STATEMENT OF SIGNIFICANCE: Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into ß-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.

Challenging applicability of ISO 10993-5 for calcium phosphate biomaterials evaluation: Towards more accurate in vitro cytotoxicity assessment.

Research on biomaterials typically starts with cytocompatibility evaluation, using the ISO 10993-5 standard as a reference that relies on extract tests to determine whether the material is safe (cell metabolic activity should exceed 70 %). However, the generalized approach within the standard may not accurately reflect the material's behavior in direct contact with cells, raising concerns about its effectiveness. Calcium phosphates (CaPs) are a group of materials that, despite being highly biocompatible and promoting bone formation, still exhibit inconsistencies in basic cytotoxicity evaluations. Hence, in order to test the cytocompatibility dependence on different experimental setups and material-cell interactions, we used amorphous calcium phosphate, α-tricalcium phosphate, hydroxyapatite, and octacalcium phosphate (0.1 mg/mL to 5 mg/mL) with core cell lines of bone microenvironment: mesenchymal stem cells, osteoblast-like and endothelial cells. All materials have been characterized for their physicochemical properties before and after cellular contact and once in vitro assays were finalized, groups identified as 'cytotoxic' were further analyzed using a modified Annexin V apoptosis assay to accurately determine cell death. The obtained results showed that indirect contact following ISO standards had no sensitivity of tested cells to the materials, but direct contact tests at physiological concentrations revealed decreased metabolic activity and viability. In summary, our findings offer valuable guidelines for handling biomaterials, especially in powder form, to better evaluate their biological properties and avoid false negatives commonly associated with the traditional standard approach.

Surface functionalization of calcium magnesium phosphate cements with alginate sodium for enhanced bone regeneration via TRPM7/PI3K/Akt signaling pathway.

Although calcium­magnesium phosphate cements (CMPCs) have been widely applied to treating critical-size bone defects, their repair efficiency is unsatisfactory owing to their weak surface bioactivity and uncontrolled ion release. In this study, we lyophilized alginate sodium (AS) as a coating onto HAp/K-struvite (H@KSv) to develop AS/HAp/K-struvite (AH@KSv), which promotes bone regeneration. The compressive strength and hydrophilicity of AH@KSv significantly improved, leading to enhanced cell adhesion in vitro. Importantly, the SA coating enables continuous ions release of Mg2+ and Ca2+, finally leading to enhanced osteogenesis in vitro/vivo and different patterns of new bone ingrowth in vivo. Furthermore, these composites increased the expression levels of biomarkers of the TRPM7/PI3K/Akt signaling pathway via an equilibrium effect of Mg2+ to Ca2+. In conclusion, our study provides novel insights into the mechanisms of Mg-based biomaterials for bone regeneration.

Electrospun L-Lysine/Amorphous Calcium Phosphate Loaded Core-Sheath Nanofibers for Managing Oral Biofilm Infections and Promoting Periodontal Tissue Repairment.

Introduction: Periodontitis, a chronic inflammatory disease prevalent worldwide, is primarily treated through GTR for tissue regeneration. The efficacy of GTR, however, remains uncertain due to potential infections and the intricate microenvironment of periodontal tissue. Herein, We developed a novel core-shell structure multifunctional membrane using a dual-drug-loaded coaxial electrospinning technique (Lys/ACP-CNF), contains L-lysine in the outer layer to aid in controlling biofilms after GTR regenerative surgery, and ACP in the inner layer to enhance osteogenic performance for accelerating alveolar bone repair. Methods: The biocompatibility and cell adhesion were evaluated through CCK-8 and fluorescence imaging, respectively. The antibacterial activity was assessed using a plate counting assay. ALP, ARS, and RT-qPCR were used to examine osteogenic differentiation. Additionally, an in vivo experiment was conducted on a rat model with acute periodontal defect and infection. Micro-CT and histological analysis were utilized to analyze the in vivo alveolar bone regeneration. Results: Structural and physicochemical characterization confirmed the successful construction of the core-shell fibrous structure. Additionally, the Lys/ACP-CNF showed strong antibacterial coaggregation effects and induced osteogenic differentiation of PDLSCs in vitro. The in vivo experiment confirmed that Lys/ACP-CNF promotes new bone formation. Conclusion: Lys/ACP-CNF rapidly exhibited excellent antibacterial activity, protected PDLSCs from infection, and was conducive to osteogenesis, demonstrating its potential application for clinical periodontal GTR surgery.

The Dual Angiogenesis Effects via Nrf2/HO-1 Signaling Pathway of Melatonin Nanocomposite Scaffold on Promoting Diabetic Bone Defect Repair.

Purpose: Given the escalating prevalence of diabetes, the demand for specific bone graft materials is increasing, owing to the greater tendency towards bone defects and more difficult defect repair resulting from diabetic bone disease (DBD). Melatonin (MT), which is known for its potent antioxidant properties, has been shown to stimulate both osteogenesis and angiogenesis. Methods: MT was formulated into MT@PLGA nanoparticles (NPs), mixed with sodium alginate (SA) hydrogel, and contained within a 3D printing polycaprolactone/ß-Tricalcium phosphate (PCL/ß-TCP) scaffold. The osteogenic capacity of the MT nanocomposite scaffold under diabetic conditions was demonstrated via in vitro and in vivo studies and the underlying mechanisms were investigated. Results: Physicochemical characterization experiments confirmed the successful fabrication of the MT nanocomposite scaffold, which can achieve long-lasting sustained release of MT. The in vitro and in vivo studies demonstrated that the MT nanocomposite scaffold exhibited enhanced osteogenic capacity, which was elucidated by the dual angiogenesis effects activated through the NF-E2-related factor 2/Heme oxygenase 1 (Nrf2/HO-1) signaling pathway, including the enhancement of antioxidant enzyme activity to reduce the oxidative stress damage of vascular endothelial cells (VECs) and directly stimulating vascular endothelial growth factor (VEGF) production, which reversed the angiogenesis-osteogenesis uncoupling and promoted osteogenesis under diabetic conditions. Conclusion: This study demonstrated the research prospective and clinical implications of the MT nanocomposite scaffold as a novel bone graft for treating bone defect and enhancing bone fusion in diabetic individuals.

Transpedicular injection of rhBMP-2 with ß-tricalcium phosphate to reduce the proximal junctional kyphosis after adult spinal deformity correction: preliminary study.

The aim of this preliminary study was to assess the impact of injecting recombinant human bone morphogenetic protein-2 (rhBMP-2) with ß-tricalcium phosphate (ß-TCP) carrier into the uppermost instrumented vertebra (UIV) during surgery to prevent the development of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The 25 patients from study group had received 0.5 mg rhBMP-2 mixed with 1.5 g ß-TCP paste injection into the UIV during surgery. The control group consisted of 75 patients who underwent surgery immediately before the start of the study. The incidences of PJK and PJF were analyzed as primary outcomes. Spinopelvic parameters and patient-reported outcomes were analyzed as secondary outcomes. Hounsfield unit (HU) measurements were performed to confirm the effect of rhBMP-2 with ß-TCP on bone formation at preoperative and postoperative at computed tomography. PJK and PJF was more occurred in control group than study group (p = 0.02, 0.29, respectively). The HU of the UIV significantly increased 6 months after surgery. And the increment at the UIV was also significantly greater than that at the UIV-1 6 months after surgery. Injection of rhBMP-2 with ß-TCP into the UIV reduced PJK and PJF rates 6 months after surgery with new bone formation.

Dietary contribution of iron from limestone and dicalcium phosphate for broiler chickens.

Iron is routinely supplemented in broiler feeds aiming to prevent dietary deficiencies. Limestone and phosphates are very rich in Fe; however, its contribution from these sources have not been thoroughly investigated with chickens. The present research was conducted to evaluate live performance and blood parameters of broilers when using limestone and dicalcium phosphate as sources of Fe. A total of 576 one-day-old male Cobb x Cobb 500 were allocated into a total of 72 battery cages, 6 treatments with 12 replication cages of 8 chicks at placement. Chicks were fed diets formulated with corn, soybean meal (SBM) with laboratory grade calcium carbonate and phosphoric acid (having traces of Fe). All chicks were fed a common prestarter without Fe supplementation (analyzed total 58.2 ± 2.4 mg/kg Fe) from placement to 7 d. Allocation of birds to dietary treatments was completely randomized on day 8. Treatments had increasing Fe derived from commercial limestone and dicalcium phosphate (analyzed Fe 7,218 and 4,783 mg/kg, respectively) progressively replacing calcium carbonate and phosphoric acid to provide graded increases in total Fe (analyzed Fe in the feeds were 57.6 ± 2.1, 92.0 ± 2.3, 124.1 ± 2.7, 159.3 ± 3.1, 187.2 ± 3.2, 223.7 ± 3.6 mg/kg, respectively). There were no effects of dietary Fe on live performance, hematocrit, and hemoglobin the end of the study on day 28 (P > 0.05). Increasing dietary Fe from commercial limestone and dicalcium phosphate led to a linear reduction in the percent ileal digestible Fe. However, linear increments in Fe retention, serum ferritin and liver Fe occurred when compared to feeds without Fe derived from limestone and phosphate dicalcium. It is concluded that Fe from limestone and dicalcium phosphate can be partially utilized by broiler chickens. It was estimated that the Fe retained from limestone and dicalcium phosphate is of 1.9%. Broilers fed corn-soy feeds (58.2 mg/kg Fe) do not require supplemental Fe.

Electrophoretic Deposition of Calcium Phosphates on Carbon-Carbon Composite Implants: Morphology, Phase/Chemical Composition and Biological Reactions.

Despite a long period of application of metal implants, carbon-carbon medical composites are also widely used for bone defect prosthesis in surgery, dentistry, and oncology. Such implants might demonstrate excellent mechanical properties, but their biocompatibility and integration efficiency into the host should be improved. As a method of enhancing, the electrophoretic deposition of fine-dispersed hydroxyapatite (HAp) on porous carbon substrates might be recommended. With electron microscopy, energy dispersion X-ray and Raman spectroscopy, and X-ray diffraction, we found that the deposition and subsequent heat post-treatment (up to the temperature of 400 °C for 1 h) did not lead to any significant phase and chemical transformations of raw non-stoichometric HAp. The Ca/P ratio was ≈1.51 in the coatings. Their non-toxicity, cyto- and biocompatibility were confirmed by in vitro and in vivo studies and no adverse reactions and side effects had been detected in the test. The proposed coating and subsequent heat treatment procedures provided improved biological responses in terms of resorption and biocompatibility had been confirmed by histological, magnetic resonance and X-ray tomographic ex vivo studies on the resected implant-containing biopsy samples from the BDF1 mouse model. The obtained results are expected to be useful for modern medical material science and clinical applications.

Synergistic effects of calcium silicate/zinc silicate dual compounds andin-situinterconnected pores on promoting bone regeneration of composite scaffolds.

Rapid bone regeneration in implants is important for successful transplantation. In this regard, we report the development of calcium silicate/zinc silicate (CS/ZS) dual-compound-incorporated calcium phosphate cement (CPC) scaffolds with a three-dimensional poly (lactic-co-glycolic acid) network that synergistically promote bone regeneration.In vitroresults demonstrated that the incorporation of CS/ZS dual compounds into the CPC significantly promoted the osteogenic differentiation of stem cells compared to the addition of CS or ZS alone. Moreover, the bone-regeneration efficacy of the composite scaffolds was validated by filling in femur condyle defects in rabbits, which showed that the scaffolds with CS and ZS possessed a great bone repair effect, as evidenced by more new bone formation and a faster scaffold biodegradation compared to the scaffold with CS alone.

Biocompatibility and Osseointegration of the Biomimetically Coated and Water-Soluble Eggshell Membrane Protein Cross-Linked Ti Alloy Screws.

Background: The surface properties of dental and orthopedic implants are directly related to their osseointegration rate. Coating and/or modifying the implant surface might reduce the time of healing. In this study, we aimed to examine the effects of a hybrid surface consisting of a brushite surface coating and cross-linked water-soluble eggshell membrane protein on the osseointegration of titanium (Ti) screws under in vivo conditions. Methods: Twenty Ti alloy screws were implanted monocortically in anteromedial regions of New Zealand rabbit tibiae. Ten screws were untreated and used as controls. The remaining 10 screws were coated with calcium phosphate and following cross-linked with ostrich eggshell membrane protein. All rabbits were sacrificed six weeks after the surgery. Peri-screw tissues were evaluated by micro-computed tomography (µ-CT), histological and histomorphometrical methods. Results: The µ-CT assessments indicated that the experimental group had significantly higher mean bone surface area (BSA) and trabeculae number (TbN) than those of the control group (p ˂ 0.05). Bone surface area (BV), trabecular separation (TbSp), trabecular thickness (TbTh), and bone mineral density (BMD) scores of the control and experimental groups were quite similar (p > 0.05). The vascularization score of the experimental group was significantly higher than the control group (4.29 vs. 0.92%). No sign of the graft-versus-host reaction was observed. Conclusion: Our findings reveal that coating Ti alloy implants with calcium phosphate cross-linked with ostrich eggshell membrane protein increases the osseointegration of Ti alloy screws by increasing the bone surface area, number of trabeculae and vascularization in the implant site.