Search results for: bone marrow macrophages

Authors: Dinara Ikramova, Karin A. Hing, Simon C. F. Rawlinson

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Silicate-substituted hydroxyapatite (SiHA) has been shown to enhance bone regeneration in vivo compared with phase pure stoichiometric hydroxyapatite. Evidence suggests that substrate chemistry dependent formation of a permissive protein layer on the surface of synthetic bone graft substitute materials is key for bioactivity and cell attachment. However, little information is available on whether the substrate chemistry may affect cell migration and recruitment. The aim of this study is to investigate whether or not human Mesenchymal Stem Cells (hMSCs) exhibit a chemotactic response to SiHA porous granules and if it can be linked to either the ion exchange or protein sequestering and enrichment on the surface of the material. 150mg of SiHA granules with 80% total porosity and 20% strut porosity were incubated in 1ml of either Serum Free Media (SFM) or 10% Serum Containing Media (SCM) under static cell culture conditions (37°C, 5% CO2) in absence of cells. Protein sequestering and exchange of calcium, phosphate and silicate ions were analysed at 0.5, 1, 2, 4, 8, 16 and 24 hours with n=12 per time point. Migration of hMSCs in the presence of 150mg of SiHA granules was assessed over 24 hours using a modified transwell migration system in either SFM or SCM (n=6) with 30% serum containing media acting as a positive control. At 24 hours protein sequestering and ionic exchange were analysed, and the number of cells was quantified using a high throughput confocal microscope (IN Cell Analyser 6000). In acellular condition, both calcium and phosphate ion concentrations in media showed a decrease at 24 hours which was greater in SFM than in SCM. This suggests possible formation and precipitation of a bone like apatite on the surface of SiHA. Reduction in this activity observed in SCM indicates that the presence of serum proteins is interfering with the ion exchange at the material and media interface. Adsorbed protein levels showed fluctuation over time followed by sharp decrease at 24 hours, suggesting a possible protein rearrangement on the surface of the material. The ion analysis performed on SFM and SCM after 24-hour incubation with cells in the presence of granules showed a greater reduction in phosphate concentration in both SFM and SCM compared to phosphate levels in acellular condition. Silicate concentration in SCM increased from 1.6mM (absence of cells) to 5.1mM (presence of cells). This indicates that the cells are promoting the uptake of phosphate and release of silicate ions. No significant change was seen in levels of adsorbed proteins in the presence and absence of cells. Further analysis is required to determine whether the species of these proteins change over time. The analysis of cell migration after 24-hour incubation showed more cells migrating towards the granules, 12.7% in SFM and 8.3% in SCM, than in positive control, 4.5% in SFM and 3.6% in SCM respectively. These results suggest that SiHA has a chemotactic activity independent of serum proteins. A property which has not previously been demonstrated for a synthetic bone graft material.

Keywords: cell migration, hMSCs, SiHA, transwell migration system

Procedia PDF Downloads 131

Authors: Alua Massalimova

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Situation analysis of Blood Service revealed that the strengths dominated over the weak 1.4 times. The possibilities dominate over the threats by 1.1 times. It follows that by using timely the possibility the Service, it is possible to strengthen its strengths and avoid threats. Priority directions of the resulting analysis are the use of subjective factors, such as personal management capacity managers of the Blood Center in the field of possibilities of legal activity of administrative decisions and the mobilization of stable staff in general market conditions. We have studied for the period 2011-2015 retrospectively indicators of Blood Service of Kazakhstan. Strengths of Blood Service of RK(Ps4,5): 1) indicators of donations for 1000 people is higher than in some countries of the CIS (in Russia 14, Kazakhstan - 17); 2) the functioning science centre of transfusiology; 3) the legal possibility of additional financing blood centers in the form of paid services; 4) the absence of competitors; 5) training on specialty Transfusiology; 6) the stable management staff of blood centers, a high level of competence; 7) increase in the incidence requiring transfusion therapy (oncohematology); 8) equipment upgrades; 9) the opening of a reference laboratory; 10) growth of the proportion of issued high-quality blood components; 11) governmental organization 'Drop of Life'; 12) the functioning bone marrow register; 13) equipped with modern equipment HLA-laboratory; 14) High categorization of average medical workers; 15) availability of own specialized scientific journal; 16) vivarium. The weaknesses (Ps = 3.5): 1) the incomplete equipping of blood centers and blood transfusion cabinets according to standards; 2) low specific weight of paid services of the CC; 3) low categorization of doctors; 4) high staff turnover; 5) the low scientific potential of industrial and clinical of transfusiology; 6) the low wages paid; 7) slight growth of harvested donor blood; 8) the weak continuity with offices blood transfusion; 9) lack of agitation work; 10) the formally functioning of Transfusion Association; 11) the absence of scientific laboratories; 12) high standard deviation from the average for donations in the republic. The possibilities (Ps = 2,7): 1): international grants; 2) organization of international seminars on clinical of transfusiology; 3) cross-sectoral cooperation; 4) to increase scientific research in the field of clinical of transfusiology; 5) reduce the share of donation unsuitable for transfusion and processing; 6) strengthening marketing management in the development of fee-based services; 7) advertising paid services; 8) strengthening the publishing of teaching aids; 9) team-building staff. The threats (Ps = 2.1): 1) an increase of staff turnover; 2) the risk of litigation; 3) reduction gemoprodukts based on evidence-based medicine; 4) regression of scientific capacity; 5) organization of marketing; 6) transfusiologist marketing; 7) reduction in the quality of the evidence base transfusions.

Keywords: blood service, healthcare, Kazakhstan, quantative swot analysis

Procedia PDF Downloads 228

Authors: Geliashvili T. M., Tyulyandina A. S., Valiev A. K., Kononets P. V., Kharatishvili T. K., Salkov A. G., Pronin A. I., Gadzhieva E. H., Parnas A. V., Ilyakov V. S.

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Aim/Introduction: Metastasis (Mts) to the sternum, while extremely rare in differentiated thyroid cancer (DTC) (1), requires a personalized, multidisciplinary treatment approach. In aggressively growing Mts to the sternum, which rapidly become unresectable, a comprehensive therapeutic and diagnostic approach is particularly important. Materials and methods: We present a clinical case of solitary Mts to the sternum as first manifestation of a papillary thyroid microcarcinoma in a 55-year-old man. Results: 18F-FDG PET/CT after thyroidectomy confirmed the solitary Mts to the sternum with extremely high FDG uptake (SUVmax=71,1), which predicted its radioiodine-refractory (RIR). Due to close attachment to the mediastinum and rapid growth, Mts was considered unresectable. During the next three months, the patient received targeted therapy with the tyrosine kinase inhibitor (TKI) Lenvatinib 24 mg per day. 1st course of radioiodine therapy (RIT) 6 GBq was also performed, the results of which confirmed the RIR of the tumor process. As a result of systemic therapy (targeted therapy combined with RIT and suppressive hormone therapy with L-thyroxine), there was a significant biochemical response (decrease of serum thyroglobulin level from 50,000 ng/ml to 550 ng/ml) and a partial response with decrease of tumor size (from 80x69x123 mm to 65x50x112 mm) and decrease of FDG accumulation (SUVmax from 71.1 to 63). All of this made possible to perform surgical treatment of Mts - sternal extirpation with its replacement by an individual titanium implant. At the control examination, the stimulated thyroglobulin level was only 134 ng/ml, and PET/CT revealed postoperative areas of 18F-FDG metabolism in the removed sternal Mts. Also, 18F-FDG PET/CT in the early (metabolic) stage revealed two new bone Mts (in the area of L3 SUVmax=17,32 and right iliac bone SUVmax=13,73), which, as well as the removed sternal Mts, appeared to be RIRs at the 2nd course of RIT 6 GBq. Subsequently, on 02.2022, external beam radiation therapy (EBRT) was performed on the newly identified oligometastatic bone foci. At present, the patient is under dynamic monitoring and in the process of suppressive hormone therapy with L-thyroxine. Conclusion: Thus, only due to the early prescription of targeted TKI therapy was it possible to perform surgical resection of Mts to the sternum, thereby improve the patient's quality of life and preserve the possibility of radical treatment in case of oligometastatic disease progression.

Keywords: differentiated thyroid cancer, metastasis to the sternum, radioiodine therapy, radioiodine-refractory cancer, targeted therapy, lenvatinib

Procedia PDF Downloads 105

Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

Procedia PDF Downloads 83

Authors: Farah El Mohtadi, Richard d'Arcy, Nicola Tirelli

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Since 40 years, poly (ethylene glycol) (PEG) has been the gold standard in biomaterials and drug delivery, because of its combination of chemical and biological inertness. However, the possibility of its breakdown under oxidative conditions and the demonstrated development of anti-PEG antibodies highlight the necessity to develop carriers based on materials with increased stability in a challenging biological environment. Here, we describe the synthesis of polysulfide via anionic ring-opening polymerization. In vitro, the synthesized polymer was characterized by low toxicity and a level of complement activation (in human plasma) and macrophage uptake slightly lower than PEG and poly (2‐methyl-2‐oxazoline) (PMOX), of a similar size. Importantly, and differently from PEG, on activated macrophages, the synthesized polymer showed a strong and dose-dependent ROS scavenging activity, which resulted in the corresponding reduction of cytokine production. Therefore, the results from these studies show that polysulfide is highly biocompatible and are potential candidates to be used as an alternative to PEG for various applications in nanomedicine.

Keywords: PEG, low toxicity, ROS scavenging, biocompatible

Procedia PDF Downloads 130

Authors: C. Gallottini, W. Di Mari, A. Amaddeo, K. Barbaro, A. Dolci, G. Dolci, L. Gallottini, G. Barraco, S. Eramo

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A group of 10 dogs (group A) with Periodontal Disease in the third stage, were subjected to regenerative therapy of periodontal tissues, by use of nano hydroxy apatite (NHA). These animals induced by general anesthesia, where treated by ultrasonic scaling, root planning, and at the end by a mucogingival flap in which it was applied NHA. The flap was closed and sutured with simple steps. Another group of 10 dogs (group B), control group, was treated only by scaling and root planning. No patient was subjected to antibiotic therapy. After three months, a check was made by inspection of the oral cavity, radiography and bone biopsy at the alveolar level. Group A showed a total restitutio ad integrum of the periodontal structures, and in group B still mild gingivitis in 70% of cases and 30% of the state remains unchanged. Numerous experimental studies both in animals and humans have documented that the grafts of porous hydroxyapatite are rapidly invaded by fibrovascular tissue which is subsequently converted into mature lamellar bone tissue by activating osteoblast. Since we acted on the removal of necrotic cementum and rehabilitating the root tissue by polishing without intervention in the ligament but only on anatomical functional interface of cement-blasts, we can connect the positive evolution of the clinical-only component of the cement that could represent this perspective, the only reason that Periodontal Disease become a Cement Disease, while all other clinical elements as nothing more than a clinical pathological accompanying.

Keywords: nanoidroxiaphatite, parodontal disease, cement disease, regenerative therapy

Procedia PDF Downloads 450

Authors: V. Schmidt, L. Janovák, N. Wiegand, B. Patczai, K. Turzó

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Large bone defects are not able to heal spontaneously. Bioactive glasses seem to be appropriate (bio)materials for bone reconstruction. Bioactive glasses are osteoconductive and osteoinductive, therefore, play a useful role in bony regeneration and repair. Because of their not optimal mechanical properties (e.g., brittleness, low bending strength, and fracture toughness), their applications are limited. Bioactive glass can be used as a coating material applied on metal surfaces. In this way -when using them as implants- the excellent mechanical properties of metals and the biocompatibility and bioactivity of glasses will be utilized. Furthermore, ion release effects of bioactive glasses regarding osteogenic and angiogenic responses have been shown. Silicate bioactive glasses (45S5 Bioglass) induce the release and exchange of soluble Si, Ca, P, and Na ions on the material surface. This will lead to special cellular responses inducing bone formation, which is favorable in the biointegration of the orthopedic prosthesis. The incorporation of other additional elements in the silicate network such as fluorine, magnesium, iron, silver, potassium, or zinc has been shown, as the local delivery of these ions is able to enhance specific cell functions. Although hip and knee prostheses present a high success rate, bacterial infections -mainly implant associated- are serious and frequent complications. Infection can also develop after implantation of hip prostheses, the elimination of which means more surgeries for the patient and additional costs for the clinic. Prosthesis-related infection is a severe complication of orthopedic surgery, which often causes prolonged illness, pain, and functional loss. While international efforts are made to reduce the risk of these infections, orthopedic surgical infections (SSIs) continue to occur in high numbers. It is currently estimated that up to 2.5% of primary hip and knee surgeries and up to 20% of revision arthroplasties are complicated by periprosthetic joint infection (PJIs). According to some authors, these numbers are underestimated, and they are also increasing. Staphylococcus aureus is the leading cause of both SSIs and PJIs, and the prevalence of methicillin-resistant S. aureus (MRSA) is on the rise, particularly in the United States. These deep infections lead to implant removal and consequently increase morbidity and mortality. The study targets this clinical problem using our experience so far with the Ag-doped polymer coatings on Titanium implants. Non-modified or modified (e.g., doped with antibacterial agents, like Ag) bioactive glasses could play a role in the prevention of infections or the therapy of infected tissues. Bioactive glasses have excellent biocompatibility, proved by in vitro cell culture studies of human osteoblast-like MG-63 cells. Ag-doped bioactive glass-scaffold has a good antibacterial ability against Escherichia coli and other bacteria. It may be concluded that these scaffolds have great potential in the prevention and therapy of implant-associated bone infection.

Keywords: antibacterial agents, bioactive glass, hip and knee prosthesis, medical implants

Procedia PDF Downloads 193

Authors: Mark T. Hanson, Alan T. Varughese

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Osteoporosis is a disease affecting bone quality which in turn can increase the risk of low energy fractures. Treatment of osteoporosis using Bisphosphonates has the beneficial effect of increasing bone mass while at the same time has been linked to the formation of atypical femoral fractures. This has led to the increased study of micro-fractures in bones of patients using Bisphosphonate treatment. One of the mechanics related issues which have been identified in this regard is the loss in stiffness of bones containing one or many micro-fractures. Different theories have been put forth using fracture mechanics to determine the effect of crack presence on elastic properties such as modulus. However, validation of these results in a deterministic way has not been forthcoming. The present analysis seeks to provide this deterministic evaluation of fracture’s effect on the elastic modulus. In particular, the effect of crack size, crack orientation and crack number on elastic modulus is investigated. In particular, the Finite Element method is used to explicitly determine the elastic modulus reduction caused by the presence of cracks in a representative volume element. Single cracks of various lengths and orientations are examined as well as cases of multiple cracks. Cracks in tension as well as under shear stress are considered. Although the focus is predominantly two-dimensional, some three-dimensional results are also presented. The results obtained show the explicit reduction in modulus caused by the parameters of crack size, orientation and number noted above. The present results allow the interpretation of the various theories which currently exist in the literature.

Keywords: cracks, elastic, fracture, modulus

Procedia PDF Downloads 109

Authors: A. Chari, A. El Bouari, B. Orayech, A. Faik, J. M. Igartua

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The phosphate is a natural resource of great importance in Morocco. In order to exploit this wealth, synthesis and studies of new a material based phosphate, were carried out. The apatite structure present o lot of characteristics, One of the main characteristics is to allow large and various substitutions for both cations and anions. Beside their biological importance in hard tissue (bone and teeth), apatites have been extensively studied for their potential use as fluorescent lamp phosphors or laser host materials.The apatite have interesting possible application fields such as in medicine as materials of bone filling, coating of dental implants, agro chemicals as artificial fertilizers. The LiPb2Ca2(PO4)3 was synthesized by the solid-state method, its crystal structure was investigated by Rietveld analysis using XRPD data. This material crystallizes with a structure of lacunar apatite anion deficit. The LiPb2Ca2(PO4)3 is hexagonal apatite at room temperature, adopting the space group P63/m (ITA No. 176), Rietveld refinements showed that the site 4f is shared by three cations Ca, Pb and Li. While the 6h is occupied by the Pb and Li cations. The structure can be described as built up from the PO4 tetrahedra and the sixfold coordination cavities, which delimit hexagonal tunnels along the c-axis direction. These tunnels are linked by the cations occupying the 4 f sites. Raman and Infrared spectroscopy analyses were carried out. The observed frequencies were assigned and discussed on the basis of unit-cell group analysis and by comparison to other apatite-type materials.

Keywords: apatite, Lacunar, crystal structure, Rietveldmethod, LiPb2Ca2(PO4)3, Phase transition

Procedia PDF Downloads 404

Authors: Natalia V. Minaeva, Natalia A. Zorina, Marina N. Khorobrikh, Philipp S. Sherstnev, Tatiana V. Krivokorytova, Alexander S. Luchinin, Maksim S. Minaev, Igor V. Paramonov

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Background. Over the last few decades, the Center for International Blood and Marrow Transplant Research (CIBMTR) and the World Marrow Donor Association (WMDA) have been actively working to ensure the safety of the hematopoietic stem cell (HSC) donation process. Registration of adverse events that may occur during the donation period and establishing a relationship between donation and side effects are included in the WMDA international standards. The level of blood serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is an early marker of myocardial stress. Due to the high analytical sensitivity and specificity, laboratory assessment of NT-proBNP makes it possible to objectively diagnose myocardial dysfunction. It is well known that the main stimulus for proBNP synthesis and secretion from atrial and ventricular cardiac myocytes is myocyte stretch and increasement of myocardial extensibility and pressure in the heart chambers. Аim. The aim of the study was to assess the dynamic changes in the levels of blood serum N-terminal pro-brain natriuretic peptide of unrelated donors at various stages of hematopoietic stem cell mobilization. Materials. We have examined 133 unrelated donors, including 92 men and 41 women, that have been included into the study. The NT-proBNP levels were measured before the start of mobilization, then on the day of apheresis, and after the donation of allogeneic HSC. The relationship between NT-proBNP levels and body mass index (BMI), ferritin, hemoglobin, and white blood cells (WBC) levels was assessed on the day of apheresis. The median age of donors was 34 years. Mobilization of HSCs was managed with filgrastim administration at a dose of 10 μg/kg daily for 4-5 days. The first leukocytapheresis was performed on day 4 from the start of filgrastim administration. Quantitative values of the blood serum NT-proBNP level are presented as a median (Me), first and third quartiles (Q1-Q3). Comparative analysis was carried out using the t-test and correlation analysis as well by Spearman method. Results. The baseline blood serum NT-proBNP levels in all 133 donors were within the reference values (<125 pg/ml) and equaled 21,6 (10,0; 43,3) pg/ml. At the same time, the level of NT-proBNP in women was significantly higher than that of men. On the day of the HSC apheresis, a significant increase of blood serum NT-proBNP levels was detected and equald 131,2 (72,6; 165,3) pg/ml (p<0,001), with higher rates in female donors. A statistically significant weak inverse correleation was established between the level of NT-proBNP and the BMI of donors (-0.18, p = 0,03), as well as the level of hemoglobin (-0.33, p <0,001), and ferritin levels (-0.19, p = 0,03). No relationship has been established between the magnitude of WBC levels achieved as a result of the mobilization of HSC on the day of leukocytapheresis. A day after the apheresis, the blood serum NT-proBNP levels still exceeded the reference values, but there was a decreasing tendency. Conclusion. An increase of the blood serum NT-proBNP level in unrelated donors during the mobilization of HSC was established. Future studies should clarify the reason for this phenomenon, as well as its effects on donors' long-term health.

Keywords: unrelated donors, mobilization, hematopoietic stem cells, N-terminal pro-brain natriuretic peptide

Procedia PDF Downloads 101

Authors: Janis Zarins, Kristaps Blums, Oskars Radzins, Renars Deksnis, Atis Svare, Santa Salaka

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Wide tumor resection remains the first choice method for tumors of the oral cavity. Nevertheless, remained tissue defect impacts patients functional and aesthetical outcome, which could be improved using microvascular tissue transfers. Mandibular reconstruction is challenging due to the complexity of composite tissue defects and occlusal relationships for normal eating, chewing, and pain free jaw motions. Individual 3-D virtual planning would provide better symmetry and functional outcome. The main goal of preoperative planning is to develop a customized surgical approach with patient specific cutting guides of the mandible, osteotomy guides of the fibula, pre-bended osteosynthesis plates to perform more precise reconstruction, to decrease the surgery time and reach the best outcome. Our study is based on the analysis of 32 patients operated on between 2019 to 2021. All patients underwent mandible reconstruction with vascularized fibula flaps. Patients characteristics, surgery profile, survival, functional outcome, and quality of life was evaluated. Preoperative planning provided a significant decrease of surgery time and the best arrangement of bone closely similar as before the surgery. In cases of bone asymmetry, deformity and malposition, a new mandible was created using 3D planning to restore the appearance of lower jaw anatomy and functionality.

Keywords: mandibular, 3D planning, cutting guides, fibula flap, reconstruction

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Authors: Sara Mercedes Barroso Pinzón, Antonio Javier Sanchéz Herencia, Begoña Ferrari, Álvaro Jesús Castro

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The current need for durable implants and bone substitutes characterised by biocompatibility, bioactivity and mechanical properties, without immunological rejection, is a major challenge for scientists. Hydroxyapatite (HAp) has been considered for decades as an ideal biomaterial for bone regeneration due to its chemical and crystallographic similarity to the mineral structure bioapatites. However, the lack of trace elements in the hydroxyapatite structure gives it very low mechanical and biological properties. In this sense, the objective of the research is to address the synthesis of hydroxyapatite with Mg from phosphate rock from sedimentary deposits in the central-eastern region of Colombia, taking advantage of the release of the species contained as natural precursors of Ca, P and Mg. The minerals present were studied, fluorapatite as the mineral of interest associated with mineralogical species of magnesium carbonates and quartz. The chemical and mineralogical composition was determined by X-ray fluorescence (XRF) and X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX); as well as the evaluation of the surface physicochemical properties of zeta potential (PZC), with the aim of studying the surface behaviour of the microconstituents present in the phosphate rock and to elucidate the synergistic mechanism between the minerals and establish the optimum conditions for the wet concentration process. From the products obtained and characterised by XRD, XRF, SEM, FTIR, RAMAN, HAp-Mg biocomposite scaffolds are fabricated and the influence of Mg on the morphometric parameters, mechanical and biological properties of the designed materials is evaluated.

Keywords: phosphate rock, hydroxyapatite, magnesium, biomaterials

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Authors: Priya Kulkarni, Soumya Koppikar, Datta Shinde, Shantanu Deshpande, Narendrakumar Wagh, Abhay Harsulkar

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Osteoarthritis (OA) is associated with multiple and overlapping aetiologies. IL-1β is produced by stressed tissue and known to aggravate disease pathologies. We selected 10 patients with elevated IL-1β in their synovial fluids (SF). We hypothesized IL-1β as nodal-point connecting different pathologies. IL-1β was higher in all meniscal tear (MT) patients perhaps as the earliest response to injury. Since MT above age of 30 leads to OA in less than 5 years, it is attributed that IL-1β modulates OA pathology. Among all bilateral OA patients, an interesting case operated for Total-Knee-Replacement revealed differential cartilage degeneration demonstrating strong association with higher IL-1β. Symptoms like acute-pain, effusion and redness were correlated with higher IL-1β and NO (Nitric-oxide). However, higher IL-1β was also found without typical-inflammation characterized by infiltration of neutrophils and macrophages. Cultured synoviocytes responded to IL-1β by releasing NO. In conclusion, IL-1β in SF acquires central position influencing different OA pathologies and aetiologies.

Keywords: IL-1β, meniscal tear, osteoarthritis, synovial fluid

Procedia PDF Downloads 596

Authors: Ramazan F. Akkoc, Elif Erdem, Nalan Kaya, Gonca Ozan, D. Özlem Dabak, Enver Ozan

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Maternal tobacco smoke exposure is known to cause growth retardation in the neonatal skeletal system. Alpha lipoic acid, a natural antioxidant found in some foods, limits the activities of osteoclasts and supports the osteoblast's bone formation mechanism. In this study, it was aimed to investigate the effects of alpha lipoic acid (ALA) on the height, long bones and tail lengths of pups exposed to maternal tobacco smoke. The rats were divided into four groups: 1) control group, 2) tobacco smoke group, 3) tobacco smoke + ALA group, and 4) ALA group. Rats in the group 2 (tobacco smoke), group 3 (tobacco smoke + ALA) were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group 3 (tobacco smoke + ALA). Only alpha lipoic acid was administered to the rats in the group 4. On day 21 postpartum, the height and tail lengths of the pups in all groups were measured, and the length of the extremity long bones was measured after decapitation. All morphometric measurements performed in group 2 (tobacco smoke) showed a significant decrease compared to group 1 (control), while all measurements in group 3 (tobacco smoke + ALA) showed a significant increase compared to group 2 (tobacco smoke). It has been shown that ALA has a protective effect against the regression of height, long bones and tail lengths of pups exposed to maternal tobacco smoke.

Keywords: alpha lipoic acid, bone, morphometry, rat, tobacco smoke

Procedia PDF Downloads 366

Authors: S. Alireza Mirghasemi, Javad Parvizi, Narges R. Gabaran, Shervin Rashidinia, Mahdi M. Bijanabadi, Dariush G. Savadkoohi

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Background: The anterior cruciate ligament is one of the most frequent ligament to be disrupted. Surgical reconstruction of the anterior cruciate ligament is a common practice to treat the disability or chronic instability of the knee. Several factors associated with success or failure of the ACL reconstruction including preoperative laxity of the knee, selection of the graft material, surgical technique, graft tension, and postoperative rehabilitation. We aimed to examine the biomechanical properties of any graft type and initial graft tensioning during ACL reconstruction using 3-dimensional computational finite element simulation. Methods: In this paper, 3-dimensional model of the knee was constructed to investigate the effect of graft tensioning on the knee joint biomechanics. Four different grafts were compared: 1) Bone-patellar tendon-bone graft (BPTB) 2) Hamstring tendon 3) BPTB and a band of gracilis4) Hamstring and a band of gracilis. The initial graft tension was set as “0, 20, 40, or 60N”. The anterior loading was set to 134 N. Findings: The resulting stress pattern and deflection in any of these models were compared to that of the intact knee. The obtained results showed that the combination of a band of gracilis with the former graft (BPTB or Hamstring) increases the structural stiffness of the knee. Conclusion: Required pretension during surgery decreases significantly by adding a band of gracilis to the proper graft.

Keywords: ACL reconstruction, deflection, finite element simulation, stress pattern

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Authors: Walaa Mohammed Saeed

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Studies suggest a crosstalk between bone and metabolism through Osteocalcin (OC), a bone-derived protein that plays an important role in regulating glucose and fat metabolism. Studies relate type II Diabetes Mellitus (DMII) with Homocysteine (Hcy) and cardiovascular diseases (CVD). This study investigates the relationship between levels of OC, Hcy, and DMII in 85 subjects of which 50 were diabetic female patients (29–65 years) and 35 healthy controls. OC and Hcy levels were measured in fasting blood samples using immunoassay analyzer. Fasting serum glucose, glycated hemoglobin, lipid profile, were estimated by automated Siemens Dimension XP auto-analyzer. A significant increase in the frequency of low OC levels (p < 0.001) and high Hcy levels (p < 0.001) was detected in diabetic patients compared to controls (chi-squared test). Using ANOVA test, patients were divided into tertiles based on plasma OC and Hcy levels; fasting serum glucose varied inversely with OC but directly with Hcy tertiles (p=0.049, p=0.033 respectively). Atherogenic Index of Plasma (AIP=Log TG/HDL) predicts that diabetic patients with 36% high and 15% intermediate cardiovascular risk had increased frequency of low OC levels compared to low-risk patients (p=0.047). Another group of diabetic patients with 39% high and 11% intermediate CVD risk had increased frequency of high Hcy levels (p=0.033). A significant negative correlation existed between OC and glucose (r = -0.318; p = 0.035) while correlation between glucose level and Hcy (r = 0.851 p=0.022) was positive. Hence, low serum OC levels and high Hcy levels were associated with impaired glucose metabolism that may increase cardiovascular risk in DMII.

Keywords: osteocalcin, homocysteine, type 2 diabetes, cardiovascular

Procedia PDF Downloads 155

Authors: Mariyah Poonawala, Selvan Ravindran, Anuradha Vaidya

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Despite much progress in understanding the regulatory factors and cytokines that support the maturation of the various cell lineages of the hematopoietic system, factors that govern the self-renewal and proliferation of hematopoietic stem cells (HSCs) is still a grey area of research. Hematopoietic stem cell transplantation (HSCT) has evolved over the years and gained tremendous importance in the treatment of both malignant and non-malignant diseases. However, factors such as graft rejection and multiple organ failure have challenged HSCT from time to time, underscoring the urgent need for development of milder processes for successful hematopoietic transplantation. An emerging concept in the field of stem cell biology states that the interactions between the bone-marrow micro-environment and the hematopoietic stem and progenitor cells is essential for regulation, maintenance, commitment and proliferation of stem cells. Understanding the role of mesenchymal stromal cells in modulating the functionality of HSCs is, therefore, an important area of research. Trans-resveratrol has been extensively studied for its various properties to combat and prevent cancer, diabetes and cardiovascular diseases etc. The aim of the present study was to understand the effect of trans-resveratrol on HSCs using single and co-culture systems. We have used KG1a cells since it is a well accepted hematopoietic stem cell model system. Our preliminary experiments showed that low concentrations of trans-resveratrol stimulated the HSCs to undergo proliferation whereas high concentrations of trans-resveratrol did not stimulate the cells to proliferate. We used a murine fibroblast cell line, M210B4, as a stromal feeder layer. On culturing the KG1a cells with M210B4 cells, we observed that the stimulatory as well as inhibitory effects of trans-resveratrol at low and high concentrations respectively, were enhanced. Our further experiments showed that low concentration of trans-resveratrol reduced the generation of reactive oxygen species (ROS) and nitric oxide (NO) whereas high concentrations increased the oxidative stress in KG1a cells. We speculated that perhaps the oxidative stress was imposing inhibitory effects at high concentration and the same was confirmed by performing an apoptotic assay. Furthermore, cell cycle analysis and growth kinetic experiments provided evidence that low concentration of trans-resveratrol reduced the doubling time of the cells. Our hypothesis is that perhaps at low concentration of trans-resveratrol the cells get pushed into the G0/G1 phase and re-enter the cell cycle resulting in their proliferation, whereas at high concentration the cells are perhaps arrested at G2/M phase or at cytokinesis and therefore undergo apoptosis. Liquid Chromatography-Quantitative-Time of Flight–Mass Spectroscopy (LC-Q-TOF MS) analyses indicated the presence of trans-resveratrol and its metabolite(s) in the supernatant of the co-cultured cells incubated with high concentration of trans-resveratrol. We conjecture that perhaps the metabolites of trans-resveratrol are responsible for the apoptosis observed at the high concentration. Our findings may shed light on the unsolved problems in the in vitro expansion of stem cells and may have implications in the ex vivo manipulation of HSCs for therapeutic purposes.

Keywords: co-culture system, hematopoietic micro-environment, KG1a cell line, M210B4 cell line, trans-resveratrol

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Authors: Z. Terzopoulou, I. Koliakou, D. Bikiaris

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Tissue engineering offers a new approach to regenerate diseased or damaged tissues such as bone. Great effort is devoted to eliminating the need of removing non-degradable implants at the end of their life span, with biodegradable polymers playing a major part. Poly(ε-caprolactone) (PCL) is one of the best candidates for this purpose due to its high permeability, good biodegradability and exceptional biocompatibility, which has stimulated extensive research into its potential application in the biomedical fields. However, PCL degrades much slower than other known biodegradable polymers and has a total degradation of 2-4 years depending on the initial molecular weight of the device. This is due to its relatively hydrophobic character and high crystallinity. Consequently, much attention has been given to the tunable degradation of PCL to meet the diverse requirements of biomedicine. Poly(ε-caprolactone) (PCL) is a biodegradable polyester that lacks bioactivity, so when used in bone tissue engineering, new bone tissue cannot bond tightly on the polymeric surface. Therefore, it is important to incorporate reinforcing fillers into PCL matrix in order to result in a promising combination of bioactivity, biodegradability, and strength. Natural clay halloysite nanotubes (HNTs) were incorporated into PCL polymeric matrix, via in situ ring-opening polymerization of caprolactone, in concentrations 0.5, 1 and 2.5 wt%. Both unmodified and modified with aminopropyltrimethoxysilane (APTES) HNTs were used in this study. The effect of nanofiller concentration and functionalization with end-amino groups on the physicochemical properties of the prepared nanocomposites was studied. Mechanical properties were found enhanced after the incorporation of nanofillers, while the modification increased further the values of tensile and impact strength. Thermal stability of PCL was not affected by the presence of nanofillers, while the crystallization rate that was studied by Differential Scanning Calorimetry (DSC) and Polarized Light Optical Microscopy (POM) increased. All materials were subjected to enzymatic hydrolysis in phosphate buffer in the presence of lipases. Due to the hydrophilic nature of HNTs, the biodegradation rate of nanocomposites was higher compared to neat PCL. In order to confirm the effect of hydrophilicity, contact angle measurements were also performed. In vitro biomineralization test confirmed that all samples were bioactive as mineral deposits were detected by X-ray diffractometry after incubation in SBF. All scaffolds were tested in relevant cell culture using osteoblast-like cells (MG-63) to demonstrate their biocompatibility

Keywords: biomaterials, nanocomposites, scaffolds, tissue engineering

Procedia PDF Downloads 316

Authors: Jatinder Pal Singh, Harpreet Singh, Gagandeep Singh Digra, Mandeep Kaur Sidhu, Pawan Kumar

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Introduction: Ganglion cyst is a benign condition in which there is a cystic lesion in relation to a joint or a tendon sheath arising from myxoid degeneration of fibrous connective tissue. These can be unilocular or multilocular. In rare cases, there may be multiple ganglion cysts, known as cystic ganglionosis. They can occur at any age but are commonly seen in adults. Clinically they may be asymptomatic or present as swelling or mass effect in adjacent structures. These are common in extremities such as hands and feet. Case Presentation: 11-year-old female child presented with slowly progressive painless swelling of her right hand since the age of 4. Antenatal and perinatal history was unremarkable. Her family history was negative. She denies fever, malaise, morning stiffness, weight loss, fatigue, restriction of joint movements, or any sensory and motor deficit. Lab parameters were negative for inflammatory or infectious etiology. No other joint or extremity involvement was present. On physical examination, the swelling was present on the dorsum and palmer aspect of the right hand and wrist. They were non-tender on palpation without any motor or sensory deficit. MRI hand revealed multiple well-defined fluid signal intensity cystic appearing lesions in periarticular/intraarticular locations in relation to distal radio-ulnar, radio-carpal, intercarpal, carpometacarpal, metacarpophalangeal and interphalangeal joints as well as peritendinous location around flexor tendons more so in the region of wrist, palm, 1st and 5th digit and along extensor tendons in the region of wrist, largest one noted along flexor pollicis longus tendon in thenar region and along 1st digit measuring approx. 4.6 x 1.2 x 1.2 centimeter. Pressure erosions and bone remodelling were noted in the bases of the 2nd to 5th metacarpals, capitate, trapezoid, the distal shaft of 1st metacarpal, and proximal phalanx of 1st digit. Marrow edema was noted in the base and proximal shaft of the 4th metacarpal and proximal shaft of the 3rd metacarpal – likely stress or pressure related. The patient was advised of aspiration, but the family refused the procedure. Therefore the patient was kept on conservative treatment. Conclusion: Cystic ganglionosis is a rare condition with very few cases reported in the medical literature. Its prevalence and association are not known because of the rarity of this condition. It should be considered as an important differential in patients presenting with soft tissue swelling in extremities. Treatment option includes conservative management, aspiration, and surgery. Aspiration has a high recurrence rate. Although surgery has a low recurrence rate, it carries a high rate of complications. Imaging with MRI is essential for confirmation of the cystic nature of lesions and their relation with the joint capsules or tendons. This helps in differentiating from other soft tissue lesions and presurgical planning.

Keywords: radiology, rare, cystic ganglionosis, child

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Authors: Mehrnaz Aminitabar, Moghan Amirhosseinian, Morteza Elsa

Abstract:

Bioactive glasses (BGs) are a group of surface-reactive biomaterials used in clinical applications as implants or filler materials in the human body to repair and replace diseased or damaged bone. Sol-gel technique was employed to prepare a SiO₂-CaO-P₂O₅ glass with nominal composition of 58S BG with the addition of Sr and Li modifiers which imparts special properties to the BG. The effect of simultaneous addition of Sr and Li on bioactivity and biocompatibility, proliferation, alkaline phosphatase (ALP) activity of osteoblast cell line MC3T3-E1 and antibacterial property against methicillin-resistant Staphylococcus aureus (MRSA) bacteria were examined. BGs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy before and after soaking the samples in the simulated body fluid (SBF) for different time intervals to characterize the formation of hydroxyapatite (HA) formed on the surface of BGs. Structural characterization indicated that the simultaneous presence of 5% Sr and 5% Li in 58S-BG composition not only did not retard HA formation because of opposite effect of Sr and Li of the dissolution of BG in the SBF but also, stimulated the differentiation and proliferation of MC3T3-E1s. Moreover, the presence of Sr and Li on dissolution of the ions resulted in an increase in the mean number of DAPI-labeled nuclei which was in good agreement with live/dead assay. The result of antibacterial tests revealed that Sr and Li-substituted 58S BG exhibited a potential antibacterial effect against MRSA bacteria. Because of optimal proliferation and ALP activity of MC3T3-E1cells, proper bioactivity and high antibacterial potential against MRSA, BG-5/5 is suggested as a multifunctional candidate for bone tissue engineering.

Keywords: antibacterial activity, bioactive glass, sol-gel, strontium

Procedia PDF Downloads 121

Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Elhamalsadat Ghaffari, Moghan Amirhosseinian, Amir Khaleghipour

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Multifunctional bioactive glasses (BGs) are designed with a focus on the provision of bactericidal and biological properties desired for angiogenesis, osteogenesis, and ultimately potential applications in bone tissue engineering. To achieve these, six sol-gel copper/magnesium substituted derivatives of 58S-BG, i.e. a mol% series of 60SiO₂-4P₂O₅-5CuO-(31-x) CaO/xMgO (where x=0, 1, 3, 5, 8, and 10), were synthesized. Afterwards, the effect of MgO/CaO substitution on the in vitro formation of nano-hydroxyapatite (HA), osteoblast-like cell responses and BGs antibacterial performance were studied. During the BGs synthesis, the elimination of nitrates was achieved at 700 °C that prevented the BGs crystallization and stabilized the obtained dried gels. The structural and morphological evaluations were performed with X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). These characterizations revealed that Cu-substituted 58S-BG consisting of 5 mol% MgO (BG-5/5) slightly had retarded the formation of HA. In addition, Cu-substituted 58S-BGs consisting 8 mol% and 10 mol% MgO (BG-5/8 and BG-5/10) displayed lower bioactivity probably due to the lower ion release rate of Ca–Si into the simulated body fluid (SBF). The determination of 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and alkaline phosphate (ALP) activities proved that the highest values of both differentiation and proliferation of MC3T3-E1 cells can be obtained from a 5 mol% MgO substituted BG, while the over addition of MgO (8 mol% and 10 mol%) decreased the bioactivity. Furthermore, these novel Cu/Mg-substituted 58S-BGs displayed antibacterial effect against methicillin-resistant Staphylococcus aureus bacteria. Taken together, the results suggest the equally-substituted BG-5/5 (i.e. the one consists of 5 mol% of both CuO and MgO) as a promising candidate for bone tissue engineering, among all newly designed BGs in this work, owing to its desirable cell proliferation, ALP activity and antibacterial properties.

Keywords: apatite, bioactivity, biomedical applications, sol-gel processes

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Authors: Z. S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Robnier Reyes, Andrew J. P. Marques, Joel Ramjist, Chris R. Pasarikovski, Victor X. D. Yang

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Over the past three decades, surgical robotic systems have demonstrated their ability to improve surgical outcomes. The LBR Med is a collaborative robotic arm that is meant to work with a surgeon to streamline surgical workflow. It has 7 degrees of freedom and thus can be easily oriented. Position and torque sensors at each joint allow it to maintain a position accuracy of 150 µm with real-time force and torque feedback, making it ideal for complex surgical procedures. Spinal fusion procedures involve the placement of as many as 20 pedicle screws, requiring a great deal of accuracy due to proximity to the spinal canal and surrounding vessels. Any deviation from intended path can lead to major surgical complications. Assistive surgical robotic systems are meant to serve as collaborative devices easing the workload of the surgeon, thereby improving pedicle screw placement by mitigating fatigue related inaccuracies. Moreover, robotic spinal systems have shown marked improvements over conventional freehanded techniques in both screw placement accuracy and fusion quality and have greatly reduced the need for screw revision, intraoperatively and post-operatively. However, current assistive spinal fusion robots, such as the ROSA Spine, are limited in functionality to positioning surgical instruments. While they offer a small degree of improvement in pedicle screw placement accuracy, they do not alleviate surgeon fatigue, nor do they provide real-time force and torque feedback during screw insertion. We propose a semi-autonomous surgical robot workflow for spinal fusion where the surgeon guides the robot to its initial position and orientation, and the robot drives the pedicle screw accurately into the vertebra. Here, we demonstrate feasibility by inserting pedicle screws into ex-vivo bovine rib bone. The robot monitors position, force and torque with respect to predefined values selected by the surgeon to ensure the highest possible spinal fusion quality. The workflow alleviates the strain on the surgeon by having the robot perform the screw placement while the ability to monitor the process in real-time keeps the surgeon in the system loop. The approach we have taken in terms of level autonomy for the robot reflects its ability to safely collaborate with the surgeon in the operating room without external navigation systems.

Keywords: ex vivo bovine bone, pedicle screw, surgical robot, surgical workflow

Procedia PDF Downloads 168

Authors: Hannah Nagel, Hayley Lang, Albert Sole Guitart, Natasha Lean, Rachel Allavena, Cleide Sprohnie-Barrera, Alex Young

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Aggressive neoplasia of the hoof is a rare occurrence in horses and has been only sporadically described in the literature. In the few cases reported intra-hoof wall, aggressive neoplasia has been documented radiographically and has been described with variable imaging characteristics. These include a well-defined osteolytic area, a smoothly outlined semi-circular defect, an extensive draining tract beneath the hoof wall, as well as an additional large area of osteolysis or an extensive central lytic region. A 20-year-old Quarterhorse gelding and a 10-year-old Thoroughbred gelding were both presented for chronic reoccurring lameness in the left forelimb and left hindlimb, respectively. Both of the cases displayed radiographic lesions that have been previously described but also displayed osteoproliferative expansile regions of additional bone formation. Changes associated with hoof neoplasia are often non-specific due to the nature and capacity of bone to react to pathological insult, which is either to proliferate or be absorbed. Both cases depict and describe imaging findings seen on radiography, contrast radiography, computed tomography, and magnetic resonance imaging before reaching a histological diagnosis of malignant melanoma and squamous cell carcinoma. Although aggressive hoof wall neoplasia is rare, there are some imaging features which may raise our index of suspicion for an aggressive hoof wall lesion. This case report documents two horses with similar imaging findings who underwent multiple assessments, surgical interventions, and imaging modalities with a final diagnosis of malignant neoplasia.

Keywords: horse, hoof, imaging, radiography, neoplasia

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Authors: O. O. Onafowokan, K. Anderson, M. R. Norton, R. G. Middleton

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Revision total hip arthroplasty (THA) is known to be a challenging procedure with potential for poor outcomes. Due to its lack of metaphyseal encroachment, hip resurfacing arthroplasty (HRA) is classified as a bone conserving procedure. Although the literature postulates that this is an advantage at time of revision surgery, there is no evidence to either support or refute this claim. We identified 129 hips that had undergone HRA and 129 controls undergoing first revision THA. We recorded the clinical assessment and survivorship of implants in a multi-surgeon, single centre, retrospective case control series for both arms. These were matched for age and sex. Data collected included demographics, indications for surgery, Oxford Hip Score (OHS), length of surgery, length of hospital stay, blood transfusion, implant complexity and further surgical procedures. Significance was taken as p < 0.05. Mean follow up was 7.5 years (1 to 15). There was a significant 6 point difference in postoperative OHS in favour of the revision resurfacing group (p=0.0001). The revision HRA group recorded 48 minutes less length of surgery (p<0.0001), 2 days less in length of hospital stay (p=0.018), a reduced need for blood transfusion (p=0.0001), a need for less complexity in revision implants (p=0.001) and a reduced probability of further surgery being required (P=0.003). Whilst we acknowledge the limitations of this study our results suggest that, in contrast to THA, the bone conservation element of HRA may make for a less traumatic revision procedure with better functional outcomes. Use of HRA has seen a dramatic decline as a result of concerns regarding metallosis. However, this information remains of relevance when counselling young active patients about their arthroplasty options and may become pertinent in the future if the promise of ceramic hip resurfacing is ever realized.

Keywords: hip resurfacing, metallosis, revision surgery, total hip arthroplasty

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Authors: Chih-Hsien Chen, Yi-Hung Ho, Chih-Wei Wang, Chih-Wei Chang, Yen-Nien Chen, Chih-Han Chang, Chun-Ting Li

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Laminotomy is a spinal decompression surgery compatible with a minimally invasive approach. However, the unilateral laminotomy for bilateral side decompression leads to more perioperative complications than the bilateral laminotomy. Although the unilateral laminotomy removes the least bone tissue among the spinal decompression surgeries, the difference of spinal stability between unilateral and bilateral laminotomy and laminectomy is rarely investigated. This study aims to compare the biomechanical effects of unilateral and bilateral laminotomy and laminectomy on the lumbar spine by finite element (FE) simulation. A three-dimensional FE model of the lumbar spine (L1–L5) was constructed with the vertebral body, discs, and ligaments, as well as the sacrum was constructed. Three different surgical methods, namely unilateral laminotomy, bilateral laminotomy and laminectomy, at L3–L4 and L4–L5 were considered. Partial pedicle and entire ligamentum flavum were removed to simulate bilateral decompression in laminotomy. The entire lamina and spinal processes from the lower L3 to upper L5 were detached in the laminectomy model. Then, four kinds of loadings, namely flexion, extension, lateral bending and rotation, were applied on the lumbar with various decompression conditions. The results indicated that the bilateral and unilateral laminotomy both increased the range of motion (ROM) compared with intact lumbar, while the laminectomy increased more ROM than both laminotomy did. The difference of ROM between the bilateral and unilateral laminotomy was very minor. Furthermore, bilateral laminotomy demonstrated similar poster element stress with unilateral laminotomy. Unilateral and bilateral laminotomy are equally suggested to bilateral decompression of lumbar spine with minimally invasive technique because limited effect was aroused due to more bone remove in the bilateral laminotomy on the lumbar stability. Furthermore, laminectomy is the last option for lumbar decompression.

Keywords: minimally invasive technique, lumbar decompression, laminotomy, laminectomy, finite element method

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Authors: Cristina Busuioc, Georgeta Voicu, Sorin-Ion Jinga

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The human bone presents in its dry form piezoelectric properties, which means that a mechanical stress results in electric polarization and an applied electric field causes strain. The immediate consequence was the revealing of piezoelectricity role in bone remodelling, as well as the integration of ceramic materials with piezoelectric behaviour in the composition of unitary or composite biomaterials. Thus, we prepared hydroxyapatite - collagen hybrid materials with barium titanate addition in order to achieve a better osseointegration. Barium titanate powder synthesized by a combined sol-gel-hydrothermal method, commercial hydroxyapatite and laboratory extracted collagen gel were employed as starting materials. Before the composites, fabrication, the powder with piezoelectric features was characterized in detail from the compositional, structural, morphological and electrical point of view. The next step was to elucidate the influence of barium titanate presence especially on the biological properties of the final materials. The biocompatibility of the hybrid supports without or with piezoelectric addition was investigated on mouse osteoblast cells through LDH cytotoxicity assay, LIVE/DEAD cell viability assay, and MTT cell proliferation assay. All results indicated that the analysed materials do not exert cytotoxic effects and present the ability to sustain cell survival and to promote their proliferation. In conclusion, barium titanate nanoparticles exhibit a good biocompatibility and osteoinductive properties, while the derived composite materials based on hydroxyapatite as oxide phase and collagen as polymeric phase can be successfully used for tissue engineering applications.

Keywords: barium titanate, hybrid composites, piezoelectricity, tissue engineering

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Authors: Ananya Hazare, Ranjit Kamble

Abstract:

Introduction: Patients with Cleft lip and palate (CL/P) can present with a maxillary retrution after cleft repair. Anterior Maxillary distraction osteogenesis (AMD) is a technique that provides simultaneous skeletal advancement and expansion of the soft tissues related to an anterior segment of the maxilla. This case presented is a case of AMD. The advantage of this technique is that the occlusion in the posterior segment can be maintained, and only the segment in cross bite is advanced for correction of the midfacial deficiency. The other alternative treatment is anterior movement by a Lefort 1 osteotomy. When a Lefort 1 osteotomy is compared with the Distraction osteogenesis or AMD, the disadvantages of the Le Fort 1 include a higher risk of morbidity, requirement of fixation, relapse tendency and unexpected changes in the nasal form. These complications were eliminated by AMD technique. This was followed by placement of the implant in the bone formed after AMD. Hence complete surgical, orthodontic and prosthodontics rehabilitation of the patient was done by an interdisciplinary approach. Methods: Patient presented with repaired UCL/P of the right side with midfacial retrusion. Intro-oral examination revealed a good occlusion in the posterior arch and anterior Crossbite from canine to canine. Patient's both maxillary lateral incisors were missing. The lower arch was well aligned with all teeth present. The study models when scored according to GOSLON yardstick received a score of 4. After pre-surgical orthodontic phase was completed an intraoral distractor was fabricated by modification of HYRAX expansion screw. After surgery, low subapical osteotomy cuts were placed and the distractor was fixed. The latency period of 5 days was observed after which the distraction was started. Distraction was done at a rate of 1 mm/day with a rhythm of 0.5mm in morning and 0.5mm in the evening. The total distraction of 12 mm was done. After a consolidation period, the distractor was removed, and retention by a removable partial denture was given. Radiographic examination confirmed mature bone formation in the distracted segment. Implants were placed and allowed to osseointegrate for approximately 4 months and were then loaded with abutments. Results: Total distraction done was 12mm and after relapse it was 8mm. After consolidation phase the radiographic examination revealed a B2 quality of bone according to the Misch's classification and sufficient height from the maxillary sinus. These findings were indicative for placement of implants in the distracted bone formed in premolar region. Implants were placed and after radiographic evidence of osseointegration was seen they were loaded with abutments. Thus resulting in a complete rehabilitation of a cleft patient by an interdisciplinary approach. Conclusion: Anterior maxillary distraction can be used as an alternative method instead of complete distraction osteogenesis or Lefort 1 advancement of maxilla in cases where the advancement needed is minimum. Use of HYRAX expansion screw modified as intra-oral distractor can be used in such cases, which significantly reduces the cost of treatment, as expensive distractors are not used. This technique is very useful and efficient in countries like India where the patient cannot afford expensive treatment options.

Keywords: cleft lip and palate, distraction osteogenesis, anterior maxillary distraction, orthodontics and dentofacial orthopaedics, hyrax expansion screw modification

Procedia PDF Downloads 256