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In Situ Endoscopic Analysis of Vascular Supply and Regenerated Alveolar Bone in β-TCP Grafted and Ungrafted Postextraction Sites before Implant Placement: A Prospective Case Control Study.
Beltrán, V, Lazzarini, M, Figueroa, R, Sousa, V, Engelke, W
BioMed research international. 2019;:2797210
Abstract
BACKGROUND Endoscopy has seen a significant development over recent years in various medical fields with its application expanding from the support of minimal invasive surgery to in situ imaging. In this context, the application of endoscopic techniques to assess the quality of the regenerated bone in situ in the drill hole before implant placement is an appealing approach. AIM: The aim of this study was to use short distance support immersion endoscopy (SD-SIE) to compare the quality of regenerated bone in healed postextraction sites, which are grafted with an in situ hardening β-TCP, against ungrafted sites, before implant placement. This assessment was based on microscopic bone analysis in combination with the blood vessel count. METHOD 13 spontaneously healed and 13 grafted postextraction sites in 3 men and 6 women, aged 26-83 years, were evaluated using SD-SIE after 4-6 months. SD-SIE was applied in drill holes before implant placement, and videos were taken from representative central buccal areas. The video recordings were analyzed using Image J software for (1) number of blood vessels per area (NBV), (2) relative area of vessels (VA), (3) relative area of mineralized bone (MBA), (4) relative area of unmineralized bone (UMBA), and (5) relative area of bone substitute (BSA). RESULTS The grafted sites showed more (1) NBV as well as (2) VA (8.6 ± 1.1; 2.03 ± 0.28%) than the ungrafted sites (2.5 ± 0.6; 1.18 ± 0.36%) (independent t-test; p < 0.05); (3) MBA and (4) UMBA were similar to those in the grafted sites (86.3 ± 2.2 %; 13.7 ± 2.2 %) and to the ungrafted sites (89.5 ± 3.7%; 10.5 ± 3.6%) (independent t-test; p > 0.05); and (5) BSA in the grafted sites was 18.2 ± 5.4%. CONCLUSION SD-SIE is an interesting new approach for in situ assessment of bone quality and blood supply before implant placement. The regenerated bone in β-TCP grafted extraction sockets showed an increased vascularization compared to ungrafted sites providing a vital support for subsequent implant placement.
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Novel rechargeable calcium phosphate nanoparticle-filled dental cement.
Xie, X, Wang, L, Xing, D, Qi, M, Li, X, Sun, J, Melo, MAS, Weir, MD, Oates, TW, Bai, Y, et al
Dental materials journal. 2019;(1):1-10
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Abstract
The objectives were to develop a novel rechargeable cement containing amorphous calcium-phosphate nanoparticles (nanoACP) to suppress tooth decay. Five cements were made with: (1) 60% glass particles (experimental control); (2) 40% glass+20% nanoACP; (3) 30% glass+30% nanoACP; (4) 20% glass+40% nanoACP; (5) 10% glass+50% nanoACP. Groups 1-4 had enamel bond strengths similar to Transbond XT (3M) and Vitremer (3M) (p>0.1). The nanoACP cement had calcium and phosphate ion release which increased with increasing nanoACP fillers. The recharged cement had substantial ion re-release continuously for 14 days after a single recharge. Ion re-release did not decrease with increasing recharge/re-release cycles. Groups 3-5 maintained a safe pH of medium (>5.5); however, control cements had cariogenic pH of medium (<4.5) due to biofilm acid. Therefore, nanoACP cement (1) had good bond strength to enamel, (2) possessed calcium and phosphate ion recharge/re-release capability, and (3) raised biofilm pH to a safe level to inhibit caries.
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Masquelet technique and osteomyelitis: innovations and literature review.
Careri, S, Vitiello, R, Oliva, MS, Ziranu, A, Maccauro, G, Perisano, C
European review for medical and pharmacological sciences. 2019;(2 Suppl):210-216
Abstract
OBJECTIVE Wide diaphyseal bone defects, above all those infected, encounter into Masquelet technique a suitable treatment. The two-step procedure allows the surgeon to eliminate the infected tissues and then to promote new bone formation. We analyzed the literature about the use of the induced membrane technique in osteomyelitis and the innovations recently suggested. MATERIALS AND METHODS We reviewed some of the most common web databases using the key-words: Masquelet technique, induced membrane, and osteomyelitis. 66 studies were analyzed. RESULTS Comparing the Masquelet technique to other surgical procedures it shows better functional results in large bone defects due to infection. The induced membrane is like a biological chamber that protects the autograft and induces new bone formation promoting growth factors secretion. Different authors tried to improve one or more steps of the surgical procedure. Some studies focused on polymethyl methacrylate role and the possibility to use different materials instead of cement to induce the membrane. Others analyzed the autograft harvesting and placing techniques trying to reduce the amount of bone essential to fill the gap, like the RIA technique. Moreover, bone substitutes have been used, as beta-tricalcium phosphate, that showed an osteoconductive ability. CONCLUSIONS The survey is not a systematic review. Nevertheless, new concepts are introduced and analyzed identifying 6 areas of interest and induced membrane technique development.
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Recombinant Human Platelet-Derived Growth Factor BB in Combination With a Beta-Tricalcium Phosphate (rhPDGF-BB/β-TCP)-Collagen Matrix as an Alternative to Autograft.
Daniels, TR, Anderson, J, Swords, MP, Maislin, G, Donahue, R, Pinsker, E, Quiton, JD
Foot & ankle international. 2019;(9):1068-1078
Abstract
BACKGROUND Joint arthrodesis often employs autograft to promote union; graft harvesting can lead to perioperative morbidity. A Canadian randomized controlled trial (RCT) demonstrated that recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) combined with beta-tricalcium phosphate (β-TCP)-collagen was a safe, effective alternative to autograft. This multicenter North American RCT compared the safety and efficacy of rhPDGF-BB/β-TCP-collagen with autograft for ankle and hindfoot fusion. Subclassification using propensity scores (PS) incorporated patients from previous trials for enhanced statistical power for noninferiority testing and broader review of treatments. METHODS Patients requiring ankle or hindfoot arthrodesis and supplemental bone graft were treated with rhPDGF-BB/β-TCP-collagen (n = 69) or autograft (n = 35). Outcomes included joint fusion on computed tomography (24 weeks), clinical healing status, visual analog scale (VAS) pain, Short-Form 12 (SF-12), American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Foot Function Index (FFI) scores over 52 weeks. PS methodology addressed potential selection bias arising from pooling data among these patients and 2 previous RCTs with similar inclusion criteria, surgical techniques, graft harvest techniques, and outcomes. All 132 rhPDGF-BB/β-TCP-collagen-treated patients and 167 of 189 candidate autograft-treated controls were selected for comparison by an independent statistician blinded to outcomes. RESULTS In the PS subclassification, 68.1% treatment patients and 68.4% controls achieved >50% osseous bridging at fusion sites. Clinical healing status was achieved in 84.8% of treated patients and 90.7% of controls at 52 weeks. Clinical, functional, and quality of life results demonstrated noninferiority of rhPDGF-BB/β-TCP-collagen to autograft. Safety-related outcomes were equivalent. CONCLUSION PS subclassification analysis of 3 RCTs demonstrated that rhPDGF-BB/β-TCP-collagen was as effective as autograft for ankle and hindfoot fusions, with less pain and morbidity than treatment with autograft. LEVEL OF EVIDENCE Level I, prospective randomized study.
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Structure degradation and strength changes of sintered calcium phosphate bone scaffolds with different phase structures during simulated biodegradation in vitro.
Stastny, P, Sedlacek, R, Suchy, T, Lukasova, V, Rampichova, M, Trunec, M
Materials science & engineering. C, Materials for biological applications. 2019;:544-553
Abstract
The structure degradation and strength changes of calcium phosphate scaffolds after long-term exposure to an acidic environment simulating the osteoclastic activity were determined and compared. Sintered calcium phosphate scaffolds with different phase structures were prepared with a similar cellular pore structure and an open porosity of over 80%. Due to microstructural features the biphasic calcium phosphate (BCP) scaffolds had a higher compressive strength of 1.7 MPa compared with the hydroxyapatite (HA) and β-tricalcium phosphate (TCP) scaffolds, which exhibited a similar strength of 1.2 MPa. After exposure to an acidic buffer solution of pH = 5.5, the strength of the HA scaffolds did not change over 14 days. On the other hand, the strength of the TCP scaffolds decreased steeply in the first 2 days and reached a negligible value of 0.09 MPa after 14 days. The strength of the BCP scaffolds showed a steady decrease with a reasonable value of 0.5 MPa after 14 days. The mass loss, phase composition and microstructural changes of the scaffolds during degradation in the acidic environment were investigated and a mechanism of scaffold degradation was proposed. The BCP scaffold showed the best cell response in the in vitro tests. The BCP scaffold structure with the highly soluble phase (α-TCP) embedded in a less soluble matrix (β-TCP/HA) exhibited a controllable degradation with a suitable strength stability and with beneficial biological behavior it represented the preferred calcium phosphate structure for a resorbable bone scaffold.
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Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial.
Gómez-Barrena, E, Rosset, P, Gebhard, F, Hernigou, P, Baldini, N, Rouard, H, Sensebé, L, Gonzalo-Daganzo, RM, Giordano, R, Padilla-Eguiluz, N, et al
Biomaterials. 2019;:100-108
Abstract
BACKGROUND ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. METHODS Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. FINDINGS With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). INTERPRETATION Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. FUNDING EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).
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In vitro remineralization of artificial enamel caries with resin composites containing calcium phosphate particles.
Alania, Y, Natale, LC, Nesadal, D, Vilela, H, Magalhães, AC, Braga, RR
Journal of biomedical materials research. Part B, Applied biomaterials. 2019;(5):1542-1550
Abstract
The aim of the study was to evaluate the effect of experimental composites containing dicalcium phosphate dihydrate (DCPD) on remineralization of enamel lesions. Five resin-based composites containing equal parts (in mols) of bisphenol-A glycidyl dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA), and 60 vol % of fillers were manipulated. Filler phase was constituted by silanized barium glass and 0, 10, or 20 vol % of DPCD particles, either functionalized (F) or nonfunctionalized (NF) with TEGDMA. Artificial subsurface lesions were produced in human enamel fragments and divided according to the resin composite applied on the lesion (no DCPD, 20% NF, 20% F, 10% NF, 10% F) plus a group without composite build-up (nontreated, NT). Fragments were exposed to 16 days of pH cycling. Specimens were evaluated using transverse microradiography (TMR). Calcium and phosphate concentrations in pH-cycling solutions were determined by spectrophotometry. TMR and ionic concentrations were analyzed using one-way ANOVA/Tukey and Kruskal-Wallis/Dunn test, respectively (alpha: 0.05). All composite groups showed enamel remineralization (3%-23%). Higher mineral recovery in the middle (7%-11%) and bottom (2%-7%) thirds of the lesion was observed in groups with DCPD-containing composites compared to the "no DCPD" group (middle: 1%, bottom: -3%). Lesion depth was significantly reduced in groups using DCPD-containing composites compared to NT group. No noticeable increase in calcium and phosphate ions was observed in the pH-cycling solutions due to the presence of DCPD in the composites. In conclusion, composites with DCPD fractions as low as 10%, regardless of functionalization, were able to promote mineral recovery and reduce lesion depth of enamel lesions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1542-1550, 2019.
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Mathematical modeling of calcium phosphate precipitation in biologically relevant systems: scoping review.
Ostapienko, BI, Lopez, D, Komarova, SV
Biomechanics and modeling in mechanobiology. 2019;(2):277-289
Abstract
Biologically guided precipitation of calcium phosphates is important for the formation of calcified human tissues, such as bone and teeth, and is of practical significance in numerous industrial and agricultural processes, such as wastewater treatment and dairy ultrafiltration. Mineral precipitation is physicochemically complex and becomes even more complex in the presence of biological materials. The theoretical foundation of phase transition in general has been developed and is vital for many applications, such as metallurgy and weather prediction. The goal of this scoping review was to identify and evaluate established mathematical approaches developed to describe the formation of calcium precipitates in biological systems. A scoping review was conducted using MathSciNet, Scopus, and Web of Science databases to retrieve eligible mathematical modeling papers on calcium precipitates in biological systems. From the 2096 studies screened, 115 studies were included. The major biological systems of interest were tissues of the human body (49/115), water research (38/115), and agricultural and earth sciences applications (17/115). The majority of studies described precipitation of calcium phosphate (79/115), followed by calcium carbonate (22/115). Mathematical modeling of calcium precipitation was dominated by classical nucleation (64/115) and kinetic (38/115) theories. Only a minority of studies explicitly modeled chemical reactions in the aqueous phase (33/115). Biological components were explicitly described in 45/115 studies and included as physicochemical limitations in 70/115 studies. The majority of the studies (91/115) attempted to quantitatively compare the model predictions to the experimental data, with 59/115 reporting good to reasonable fit. This scoping review suggests that broad theories, such as classical nucleation and kinetic theories, may be adapted for modeling calcium precipitation in biologically relevant systems; however, detailed mathematical descriptions of biological, chemical, and physicochemical aspects of calcium precipitation are required.
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Development, Characterization and In Vitro Biological Properties of Scaffolds Fabricated From Calcium Phosphate Nanoparticles.
Morejón, L, Delgado, JA, Antunes Ribeiro, A, Varella de Oliveira, M, Mendizábal, E, García, I, Alfonso, A, Poh, P, van Griensven, M, Balmayor, ER
International journal of molecular sciences. 2019;(7)
Abstract
Ceramic materials mimic the mineral composition of native bone and feature osteoconductive properties; they are therefore used to regenerate bone tissue. Much research focuses on increasing the porosity and pore interconnectivity of ceramic scaffolds to increase osteoconductivity, cell migration and cell-cell interaction. We aimed to fabricate biocompatible 3D-scaffolds featuring macro- and microporous calcium phosphates with high pore interconnection. Nanoparticles of hydroxyapatite (HA) and calcium deficient hydroxyapatite (CDHA) were synthesized by wet chemical precipitation. Scaffolds were produced from them by the replication polymeric foam technique. Solid content and sintering temperature were varied. Nanoparticles and scaffolds were characterized regarding morphology, chemical and mineral composition, porosity and mechanical properties. Biocompatibility, cell attachment and distribution were evaluated in vitro with human adipose mesenchymal stem cells. Scaffolds with total porosity of 71%-87%, pores in the range of 280-550 µm and connectivity density up to 43 mm-3 were obtained. Smaller pore sizes were obtained at higher sintering temperature. High solid content resulted in a decrease of total porosity but increased interconnectivity. Scaffolds 50HA/50β-TCP featured superior interconnectivity and mechanical properties. They were bioactive and biocompatible. High HA solid content (40 wt.%) in the HA pure scaffolds was negative for cell viability and proliferation, while in the 50HA/50β-TCP composite scaffolds it resulted more biocompatible.
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Evaluation of the Efficacy of a 1:1 Mixture of β-TCP and rhPDGF-BB in the Surgical Management of Two- and Three-Wall Intraosseous Defects: A Prospective Clinical Trial.
Kavyamala, D, G, NVS, Dwarakanath, CD, Anudeep, M
The International journal of periodontics & restorative dentistry. 2019;(1):107-113
Abstract
The aim of this split-mouth clinical and radiographic study was to evaluate and compare the regenerative potential of a combination of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and beta tricalcium phosphate (β-TCP) to the established technique of bone grafting with β-TCP alone in the surgical management of intraosseous defects. A total of 24 sites in 12 subjects with intraosseous defects were included and randomly divided into test (rhPDGF-BB + β-TCP) and control (β-TCP alone) sites. Clinical parameters were recorded at baseline, 3 months, and 6 months. Radiographic parameters were evaluated at baseline and 6 months. Both groups showed statistically significant reductions of all clinical parameters. Intergroup comparison demonstrated a significantly greater probing pocket depth reduction and clinical attachment level gain in the test group. The mean percentage defect fill was significantly greater in the test group than in the control group at 3 and 6 months, and greater improvement in defect angle was also evident in the test group. Although both groups showed definitive improvements in all parameters, the test group showed significantly better results when used to treat human periodontal intraosseous defects.