Search results for: bone

Authors: Jyotsna Gupta, S. Ghosh, S. Aravindan

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The requirement of artificial prostheses (such as hip and knee joints) has increased with time. Many researchers are working to develop new implants with improved properties such as excellent biocompatibility with no tissue reactions, corrosion resistance in body fluid, high yield strength and low elastic modulus. Further, the morphological properties of the artificial implants should also match with that of the human bone so that cell adhesion, proliferation and transportation of the minerals and nutrition through body fluid can be obtained. Present study attempts to make porous Ti6Al15Mo alloys through powder metallurgy route using space holder technique. The alloy consists of 6wt% of Al which was taken as α phase stabilizer and 15wt% Mo was taken as β phase stabilizer with theoretical density 4.708. Ammonium hydrogen carbonate is used as a space holder in order to generate the porosity. The porosity of these fabricated porous alloys was controlled by adding the 0, 50, 70 vol.% of the space holder content. Three phases were found in the microstructure: α, α_2 and β phase of titanium. Kirkendall pores are observed to be decreased with increase of holding time during sintering and parallelly compressive strength and elastic modulus value increased slightly. Compressive strength and elastic modulus of porous Ti-6Al-15Mo alloy (1.17 g/cm3 density) is found to be suitable for cancellous bone. Released ions from Ti-6Al-15Mo alloy are far below from the permissible limits in human body.

Keywords: bone implant, powder metallurgy, sintering time, Ti-6Al-15Mo

Procedia PDF Downloads 118

Authors: Daniel Canales, Fabián Alvarez, Pablo Varela, Marcela Saavedra, Claudio García, Paula Zapata

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Calcium oxide nanoparticles (n-CaO) ca. 8 nm were obtained from eggshell waste. The n-CaO was incorporated into Poly(lactic acid) PLA matrix in 10 and 20 wt.% of filler content by electrospinning process to obtain PLA/n-CaO nanocomposite fibers as a potential use in scaffold for bone tissue regeneration. The fibers morphology and diameter were homogeneity, the PLA had a diameter of 2.2 ± 0.8 µm and, with the nanoparticles incorporation (20wt.%), reached ca. 2.9 ± 0.9 µm. The PLA/n-CaO nanocomposites fibers showed in vitro bioactivity, capable of inducing the precipitation of hydroxyapatite (HA) layer in the fiber surface after 7 days in Simulated Body Solution (SBF). The biocidal and biological properties of PLA/n-Cao with 20 wt.% were evaluated, showing a 30% reduction in bacterial viability against S. aureus and 11% for E. coli after 6 hours of bacterial suspensions exposure. Furthermore, the fibers did not show a cytotoxic effect on the bone marrow ST-2 cell line, permitting the cell adhesion and proliferation in Roswell Park Memorial Institute medium (RPMI). The PLA/n-CaO with 20 wt.% of nanoparticles showed a higher capacity to promote the osteogenic differentiation, significantly increasing the alkaline phosphatase (ALP) expression after 7 days compared to PLA and cell control. The in vivo analysis corroborated the biocompatibility of scaffolds prepared, the presence of n-CaO in PLA reduced the formation of fibrous encapsulation of the material improve the healing process.

Keywords: electrospun scaffolds, PLA based nanocomposites, calcium oxide nanoparticles, bioactive materials, tissue engineering

Procedia PDF Downloads 60

Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

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Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

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Authors: Reshma Jolly, Mohammad Shakir, Mohammad Shoeb Khan, Noor E. Iram

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A nanocomposite system integrating hydroxyapatite, chitin and starch (n-HA/CT/ST) has been synthesized via co-precipitation approach at room temperature, addressing the issues of biocompatibility, mechanical strength and cytotoxicity required for Bone tissue engineering. The interactions, crystallite size and surface morphology against n-HA/CT (nano-hydroxyapatite/chitin) nanocomposite have been obtained by correlating and comparing the results of FTIR, SEM, TEM and XRD. The comparative study of the bioactivity of n-HA/CT and n-HA/CT/ST nanocomposites revealed that the incorporation of starch as templating agent improved these properties in n-HA/CT/ST nanocomposite. The rise in thermal stability in n-HA/CT/ST nanocomposite as compared to n-HA/CT has been observed by comparing the TGA results. The comparison of SEM images of both the scaffolds indicated that the addition of ST influenced the surface morphology of n-HA/CT scaffold which appeared to be rougher and porous. The MTT assay on murine fibroblast L929 cells and in-vitro bioactivity of n-HA/CT/ST matrix referred superior non-toxic property of n-HA/CT/ST nanocomposite and higher possibility of osteo-integration in-vivo, respectively.

Keywords: bioactive, chitin, hyroxyapatite, nanocomposite

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Authors: Shakhawan K. Mawlood, Catriona Pickard, Benjamin Pickard

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In summer 2015 the remains of 800 children are among 1,967 bodies were exhumed by archaeologists at St Peter's Burial Ground in Blackburn, Lancashire. One hundred samples from these 19th century ancient bones were selected for DNA analysis. These comprised samples biased for those which prior osteological evidence indicated a potential for microbial infection by Mycobacterium tuberculosis (causing tuberculosis, TB) or Treponema pallidum (causing Syphilis) species, as well a random selection of other bones for which visual inspection suggested good preservation (and, therefore, likely DNA retrieval).They were subject to polymerase chain reaction (PCR) assays aimed at detecting traces of DNA from infecting mycobacteria, with the purpose both of confirming the palaeopathological diagnosis of tuberculosis and determining in individual cases whether disease and death was due to M. tuberculosis or other reasons. Our secondary goal was to determine sex determination and age prediction. The results demonstrated that extraction of vast majority ancient bones DNA samples succeeded.

Keywords: ancient bone, DNA, tuberculosis, age prediction

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Authors: Ramandeep Kaur, Makula Ajitha

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Fluvastatin has been reported for increasing bone mineral density in osteoporosis since last decade. Systemically administered drug undergoes extensive hepatic first-pass metabolism, thus very small amount of drug reaches the bone tissue which is highly insignificant. The present study aims to deliver fluvastatin in the form of nanoemulsion (NE) gel directly to the bone tissue through transdermal route thereby bypassing hepatic first pass metabolism. The NE formulation consisted of isopropyl myristate as oil, tween 80 as surfactant, transcutol as co-surfactant and water as the aqueous phase. Pseudoternary phase diagrams were constructed using aqueous titration method and NE’s obtained were subjected to thermodynamic-kinetic stability studies. The stable NE formulations were evaluated for their droplet size, zeta potential, and transmission electron microscopy (TEM). The nano-sized formulations were incorporated into 0.5% carbopol 934 gel matrix. Ex-vivo permeation behaviour of selected formulations through rat skin was investigated and compared with the conventional formulations (suspension and emulsion). Further, in-vivo pharmacokinetic study was carried using male Wistar rats. The optimized NE formulations mean droplet size was 11.66±3.2 nm with polydispersity index of 0.117. Permeation flux of NE gel formulations was found significantly higher than the conventional formulations i.e. suspension and emulsion. In vivo pharmacokinetic study showed significant increase in bioavailability (1.25 fold) of fluvastatin than oral formulation. Thus, it can be concluded that NE gel was successfully developed for transdermal delivery of fluvastatin for the treatment of osteoporosis.

Keywords: fluvastatin, nanoemulsion gel, osteoporosis, transdermal

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Authors: Elizabeta Sivevska, Sunchica Petrovska, Vaska Antevska, Lidija Todorovska, Sanja Manchevska, Beti Dejanova, Ivanka Karagjozova, Jasmina Pluncevic Gligoroska

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Introduction: Body composition plays an important role in the selection of young soccer players and it is associated with their successful performance. The most commonly used model of body composition divides the body into two compartments: fat components and fat-free mass (muscular and bone components). The aims of the study were to determine the body composition parameters of young male soccer players and to show the differences in age groups. Material and methods: A sample of 52 young male soccer players, with an age span from 9 to 14 years were divided into two groups according to the age (group 1 aged 9 to 12 years and group 2 aged 12 to 14 years). Anthropometric measurements were taken according to the method of Mateigka. The following measurements were made: body weight, body height, circumferences (arm, forearm, thigh and calf), diameters (elbow, knee, wrist, ankle) and skinfold thickness (biceps, triceps, thigh, leg, chest, abdomen). The measurements were used in Mateigka’s equations. Results: Body mass components were analyzed as absolute values (in kilograms) and as percentage values: the muscular component (MC kg and MC%), the bone component (BCkg and BC%) and the body fat (BFkg and BF%). The group up to 12 years showed the following mean values of the analyzed parameters: MM=21.5kg; MM%=46.3%; BC=8.1kg; BC%=19.1%; BF= 6.3kg; BF%= 15.7%. The second group aged 12-14 year had mean values of body composition parameters as follows: MM=25.6 kg; MM%=48.2%; BC = 11.4 kg; BC%=21.6%; BF= 8.5 kg; BF%= 14. 7%. Conclusions: The young soccer players aged 12 up to 14 years who are in the pre-pubertal phase of growth and development had higher bone component (p<0.05) compared to younger players. There is no significant difference in muscular and fat body component between the two groups of young soccer players.

Keywords: body composition, young soccer players, body fat, fat-free mass

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Authors: Anja Kurz, Marc Flynn, Tobias Good, Marco Caversaccio, Martin Kompis

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Bone Anchored Hearing Implants (BAHI) are routinely used in patients with conductive or mixed hearing loss, e.g. if conventional air conduction hearing aids cannot be used. New sound processors and new fitting software now allow the adjustment of parameters such as loudness compression ratios or maximum power output separately. Today it is unclear, how the choice of these parameters influences aided speech understanding in BAHI users. In this prospective experimental study, the effect of varying the compression ratio and lowering the maximum power output in a BAHI were investigated. Twelve experienced adult subjects with a mixed hearing loss participated in this study. Four different compression ratios (1.0; 1.3; 1.6; 2.0) were tested along with two different maximum power output settings, resulting in a total of eight different programs. Each participant tested each program during two weeks. A blinded Latin square design was used to minimize bias. For each of the eight programs, speech understanding in quiet and in noise was assessed. For speech in quiet, the Freiburg number test and the Freiburg monosyllabic word test at 50, 65, and 80 dB SPL were used. For speech in noise, the Oldenburg sentence test was administered. Speech understanding in quiet and in noise was improved significantly in the aided condition in any program, when compared to the unaided condition. However, no significant differences were found between any of the eight programs. In contrast, on a subjective level there was a significant preference for medium compression ratios of 1.3 to 1.6 and higher maximum power output.

Keywords: Bone Anchored Hearing Implant, baha, compression, maximum power output, speech understanding

Procedia PDF Downloads 349

Authors: Suraj Muke, Vikas Mankumare, Sadhana Sathaye

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Osteoporosis is the most common metabolic bone disease which affects an estimated 25 million people worldwide, leading to 1 million fractures, 40,000 annual deaths and health costs of billions of dollars. It is estimated that about 80% of total osteoporosis patients are women, amongst which majority are above the age of 45 years. Postmenopausal osteoporosis is associated with lack of intestinal calcium absorption, increasing pro-oxidant and inflammatory mediators. Lawsonia inermis is a biennial dicotyledonous herbaceous shrub is reported to possess a high flavonoid, high phenolic and Inhibitors of osteoclastogenesis like Daphneside and Daphnorin. The present study aimed to screen osteoprotective effect of methanolic extract of Lawsonia inermis (LIM) in rat model along with its antioxidant activity. LIM shows phenolic content 146.3Milligrams of Gallic acid equivalent present per gram of extract and 19.8 Milligrams of rutin per gram of extract of Total flavonoid content with IC50 value 42.99μg/ml. bilateral ovariectomized rat model in which Healthy female wistar rats were used for screening. Treatment with LIM was carried out using graded doses of 25mg/kg, 50mg/kg and 100mg/kg for period of 28 days. The negative control group comprised of ovariectomized rats along with saline treatment for four weeks whereas sham operated rats were used as positive control.LIM showed a decrease in bone turnover by preventing loss of urinary calcium and phosphorous moreover it decreased the alkaline phosphatase levels and loss of bone density is prevented by LIM suggesting decrease in osteoclast activity.

Keywords: antioxidant, osteoclast, osteoporosis, ovariectomized

Procedia PDF Downloads 378

Authors: Pinar Erturk, Sevde Altuntas, Fatih Buyukserin

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In order to obtain an effective integration between an implant and a bone, implant surfaces should have similar properties to bone tissue surfaces. Especially mimicry of the chemical, mechanical and topographic properties of the implant to the bone is crucial for fast and effective osseointegration. Titanium-based biomaterials are more preferred in clinical use, and there are studies of coating these implants with oxide layers that have chemical/nanotopographic properties stimulating cell interactions for enhanced osseointegration. There are low success rates of current implantations, especially in craniofacial implant applications, which are large and vital zones, and the oxide layer coating increases bone-implant integration providing long-lasting implants without requiring revision surgery. Our aim in this study is to examine bone-cell behavior on titanium implants with an aluminum oxide layer (AAO) on effective osseointegration potential in the deformation of large zones with difficult spontaneous healing. In our study, aluminum layer coated titanium surfaces were anodized in sulfuric, phosphoric, and oxalic acid, which are the most common used AAO anodization electrolytes. After morphologic, chemical, and mechanical tests on AAO coated Ti substrates, viability, adhesion, and mineralization of adult bone cells on these substrates were analyzed. Besides with atomic layer deposition (ALD) as a sensitive and conformal technique, these surfaces were coated with pure alumina (5 nm); thus, cell studies were performed on ALD-coated nanoporous oxide layers with suppressed ionic content too. Lastly, in order to investigate the effect of the topography on the cell behavior, flat non-porous alumina layers on silicon wafers formed by ALD were compared with the porous ones. Cell viability ratio was similar between anodized surfaces, but pure alumina coated titanium and anodized surfaces showed a higher viability ratio compared to bare titanium and bare anodized ones. Alumina coated titanium surfaces, which anodized in phosphoric acid, showed significantly different mineralization ratios after 21 days over other bare titanium and titanium surfaces which anodized in other electrolytes. Bare titanium was the second surface that had the highest mineralization ratio. Otherwise, titanium, which is anodized in oxalic acid electrolyte, demonstrated the lowest mineralization. No significant difference was shown between bare titanium and anodized surfaces except AAO titanium surface anodized in phosphoric acid. Currently, osteogenic activities of these cells on the genetic level are investigated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis results of RUNX-2, VEGF, OPG, and osteopontin genes. Also, as a result of the activities of the genes mentioned before, Western Blot will be used for protein detection. Acknowledgment: The project is supported by The Scientific and Technological Research Council of Turkey.

Keywords: alumina, craniofacial implant, MG-63 cell line, osseointegration, oxalic acid, phosphoric acid, sulphuric acid, titanium

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Authors: Gulsharat A. Baigonakova, Ekaterina S. Marchenko, Venera R. Luchsheva

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The preferred materials for bone grafting are titanium-nickel alloys. They have a porous, permeable structure similar to that of bone tissue, can withstand long-term physiological stress in the body, and retain the scaffolding function for bone tissue ingrowth. Despite the excellent functional properties of these alloys, there is a possibility of post-operative infectious complications that prevent the newly formed bone tissue from filling the spaces created in a timely manner and prolong the rehabilitation period of patients. In order to minimise such consequences, it is necessary to use biocompatible materials capable of simultaneously fulfilling the function of a long-term functioning implant and an osteoreplacement carrier saturated with drugs. Methods to modify the surface by saturation with bioactive substances, in particular macrocyclic compounds, for the controlled release of drugs, biologically active substances, and cells are becoming increasingly important. This work is dedicated to the functionalisation of the surface of porous titanium nickelide by the deposition of macrocyclic compounds in order to provide titanium nickelide with antibacterial activity and accelerated osteogenesis. The paper evaluates the effect of macrocyclic compound deposition methods on the continuity, structure, and cytocompatibility of the surface properties of porous titanium nickelide. Macrocyclic compounds were deposited on the porous surface of titanium nickelide under the influence of various physical effects. Structural research methods have allowed the evaluation of the surface morphology of titanium nickelide and the nature of the distribution of these compounds. The method of surface functionalisation of titanium nickelide influences the size of the deposited bioactive molecules and the nature of their distribution. The surface functionalisation method developed has enabled titanium nickelide to be deposited uniformly on the inner and outer surfaces of the pores, which will subsequently enable the material to be uniformly saturated with various drugs, including antibiotics and inhibitors. The surface-modified porous titanium nickelide showed high biocompatibility and low cytotoxicity in in vitro studies. The research was carried out with financial support from the Russian Science Foundation under Grant No. 22-72-10037.

Keywords: biocompatibility, NiTi, surface, porous structure

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Authors: Mehieddine Bouatrous

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Recently bioactive ceramic materials have been applied in the biomedical field as bulk, granular, or coating materials for more than half a century. More recently, bone tissue engineering scaffolds made of highly porous bioactive ceramic, glass-ceramic, and composite materials have also been created. As a result, recent bioactive ceramic structures have a high bioactivity rate, an open pores network, and good mechanical characteristics simulating cortical bone. Cyclowollastonite frameworks are also suggested for use as a graft material. As a porogenous agent, various amounts of the polymethyl methacrylate (PMMA) powders were used in this study successfully to synthesize a highly interrelated, nanostructured porous cyclowollastonite with a large specific surface area where the morphology and porosity were investigated. Porous cyclowollastonite bioactive ceramics were synthesized with a cost-effective and eco-friendly wet chemical method. The synthesized biomaterial is bioactive according to in vitro tests and can be used for bone tissue engineering scaffolds where cyclowollastonite sintered dense discs were submerged in simulated body fluid (S.B.F.) for various periods of time (1-4 weeks), resulting in the formation of a dense and consistent layer of hydroxyapatite on the surface of the ceramics, indicating its good in vitro bioactivity. Therefore, the cyclowollastonite framework exhibits good in vitro bioactivity due to its highly interconnecting porous structure and open macropores. The results demonstrate that even after soaking for several days, the surface of cyclowollastonite ceramic can generate a dense and consistent layer of hydroxyapatite. The results showed that cyclowollastonite framework exhibits good in vitro bioactivity due to highly interconnecting porous structure and open macropores.

Keywords: porous, bioactive, biomaterials, S.B.F, cyclowollastonite, biodegradability

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Authors: Seyedmahdi Mousavihashemi

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Natural Akermanite (NAM) has been successfully prepared by a modified sol-gel method. Optimization in calcination temperature and mechanical ball milling resulted in a pure and nano-sized powder which characterized by means of scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared Spectroscopy (FT–IR). We hypothesized that nano-sized Akermanite (AM) would mimic more efficiently the nanocrystal structure and function of natural bone apatite, owing to the higher surface area, compare to conventional micron-size Akermanite (AM). Accordingly, we used the unique advantage of nanotechnology to improve novel nano akermanite particles as a potential candidate for bone tissue regeneration whether as a per implant filling powder or in combination with other biomaterials as a composite scaffold. Pure Akermanite (PAM) powders were successfully obtained via a simple sol-gel method followed by calcination at 1250 °C. Mechanical grinding in a ceramic ball mill for 7 hours resulted in akermanite (AM) nanoparticles in the range of about 30- 45 nm.

Keywords: biomedical engineering, nano composite, SEM, TEM

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Authors: G. Voicu, C. D. Ghitulica, A. Cucuruz, C. Busuioc

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In the field of tissue engineering, the compositional and microstructural features of the employed materials play an important role, with implications on the mechanical and biological behaviour of the medical devices. In this context, the development of calcium phosphate-natural biopolymer composites represents a choice of many scientific groups. Thus, tricalcium phosphate powders were synthesized by a wet method, namely co-precipitation, starting from high purity reagents. Moreover, the substitution of calcium with magnesium have been approached, in the 5-10 wt.% range. Afterwards, the phosphate powders were integrated into two types of composites with chitosan, different from morphological point of view. First, 3D porous scaffolds were obtained by a freeze-drying procedure. Second, uniform compact films were achieved by film casting. The influence of chitosan molecular weight (low, medium and high), as well as phosphate powder to polymer ratio (1:1 and 1:2) on the morphological properties, were analysed in detail. In conclusion, the reported biocomposites, prepared by a straightforward route are suitable for bone substitution or repairing applications.

Keywords: bone reconstruction, chitosan, composite scaffolds, tricalcium phosphate

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Authors: Cecília M. Antão, Paulo Jorge Nogueira

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Breast cancer (BC) is the first cause of cancer mortality among Portuguese women. This retrospective observational study aimed at identifying comorbidities associated with BC female patients admitted to Portuguese public hospitals (2010-2018), investigating the effect of comorbidities on BC mortality rate, and building a predictive model using logistic regression. Results showed that the BC mortality in Portugal decreased in this period and reached 4.37% in 2018. Adjusted odds ratio indicated that secondary malignant neoplasms of liver, of bone and bone marrow, congestive heart failure, and diabetes were associated with an increased chance of dying from breast cancer. Although the Lisbon district (the most populated area) accounted for the largest percentage of BC patients, the logistic regression model showed that, besides patient’s age, being resident in Bragança, Castelo Branco, or Porto districts was directly associated with an increase of the mortality rate.

Keywords: breast cancer, comorbidities, logistic regression, adjusted odds ratio

Procedia PDF Downloads 54

Authors: Trad Khodja Rafik, Mahtout Amine, Ghoul Rachid, Benbouali Amine, Boulahlib Amine, Hariza Abdelmalik

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Cranioplasty with custom implant realized using 3D printing technology. Cranioplasty is a surgical act that aims restoring cranial bone losses in order to protect the brain from external aggressions and to improve the patient aesthetic appearance. This objective can be achieved with taking advantage of the current technological development in computer science and biomechanics. The objective of this paper it to present an approach for the realization of high precision biocompatible cranial implants using new 3D printing technologies at the lowest cost. The proposed method is to reproduce the missing part of the skull by referring to its healthy contralateral part. Once the model is validated by the neurosurgeons, a mold is 3D printed for the production of a biocompatible implant in Poly-Methyl-Methacrylate (PMMA) acrylic cement. Using this procedure four patients underwent this procedure with excellent aesthetic results.

Keywords: cranioplasty, cranial bone loss, 3D printing technology, custom-made implants, PMMA

Procedia PDF Downloads 78

Authors: Predrag Kavaric, Vladimir L. Jubic, Maxim Cadenovic

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The patient was transferred from his dentist to our tertiary medical institution. In anamnesis, we got information that his dental intervention was two years ago when he got dental implants but because of the coronavirus pandemic event, he didn’t finish the whole procedure. After two years, he decided that he will continue his work at his dentist, then his dentist noticed that there is no earlier inserted implant in the upper jaw on the right side. They do Panoramic X-ray and find that the implant is all in the maxillary sinus cavity. The flour of the maxilla was intact without any fistula on the place where the implant was inserted in the maxilla bone, After that initial diagnostic they sent the patient to maxillofacial surgery and otorhinolaryngology. We asked for a CT scan of paranasal sinuses, which confirmed the foreign body in the right maxillary sinus. The plan was that in general anesthesia we do FESS and try to find a foreign body in the maxillary sinus or in case of failure to do Caldwel Luc on that side. After preoperative preparation in GA, we do FESS. In inspection, we find small polyps and chronically changed mucosa of osteomeatal complex and right maxillary sinus. After removing polyps we did uncinectomy and medial maxillectomy. With Heuweiser Antrum grasping forceps after several attempts we managed to extract a foreign body from the bottom of the right maxillary sinus. On the first postoperative day we did detamponade, and then we discharge the patient from hospital. The Covid pandemic has contributed to the postponement of a large number of planned operations, which has resulted in various complications in the treatment of a number of patients. In this case, it happened that the implant was most likely rejected by the bone but in the direction of the maxillary sinus, which is not a common cause. On the other hand, the success was that less traumatic intervention was able to remove the foreign body from the maxillary sinus in which it was located. Since the sinus floor is free of bone defects, it can be continued relatively quickly with dental procedures.

Keywords: x-ray, surgery, maxillar sinus, complication, fees

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Authors: Ane Escobar, Paula Angelomé, Mihaela Delcea, Marek Grzelczak, Sergio Enrique Moya

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The antibacterial capacity of bone-anchoring implants can be improved by the use of antibiotics that can be delivered to the media after the surgery. Mesoporous films have shown great potential in drug delivery for orthopedic applications, since pore size and thickness can be tuned to produce different surface area and free volume inside the material. This work shows the synthesis of mesoporous titania films (MTF) by sol-gel chemistry and evaporation-induced self-assembly (EISA) on top of glass substrates. Pores with a diameter of 12nm were observed by Transmission Electron Microscopy (TEM). A film thickness of 100 nm was measured by Scanning Electron Microscopy (SEM). Gentamicin was used to study the antibiotic delivery from the film by means of High-performance liquid chromatography (HPLC). The Staphilococcus aureus strand was used to evaluate the effectiveness of the penicillin loaded films toward inhibiting bacterial colonization. MC3T3-E1 pre-osteoblast cell proliferation experiments proved that MTFs have a good biocompatibility and are a suitable surface for MC3T3-E1 cell proliferation. Moreover, images taken by Confocal Fluorescence Microscopy using labeled vinculin, showed good adhesion of the MC3T3-E1 cells to the MTFs, as well as complex actin filaments arrangement. In order to improve cell proliferation Bone Morphogenetic Protein-2 (BMP-2) was adsorbed on top of the mesoporous film. The deposition of the protein was proved by measurements in the contact angle, showing an increment in the hydrophobicity while the protein concentration is higher. By measuring the dehydrogenase activity in MC3T3-E1 cells cultured in dually functionalized mesoporous titatina films with gentamicin and BMP-2 is possible to find an improvement in cell proliferation. For this purpose, the absorption of a yellow-color formazan dye, product of a water-soluble salt (WST-8) reduction by the dehydrogenases, is measured. In summary, this study proves that by means of the surface modification of MTFs with proteins and loading of gentamicin is possible to achieve an antibacterial effect and a cell growth improvement.

Keywords: antibacterial, biocompatibility, bone morphogenetic protein-2, cell proliferation, gentamicin, implants, mesoporous titania films, osteoblasts

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Authors: H. Maachou, A. Chagnes, G. Cote

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The present work reports the properties of chitosan/hydroxyapatite (Cs/HA: 100/00, 70/30 and 30/70) composite microspheres obtained by emulsification processing route. The morphology of chitosane microspheres was observed by a scanning electron microscope (SEM) which shows an aggregate of spherical microspheres with a particle size, determined by optical microscope, ranged from 4 to 10 µm. Thereafter, a biomimetic approach was used to study the in vitro biomineralization of these composites. It concerns the composites immersion in simulated body fluid (SBF) for different times. The deposited calcium phosphate was studied using X-ray diffraction analysis (XRD), FTIR spectroscopy and ICP analysis of phosphorus. In fact, the mineral formed on Cs/HA microspheres was a mixture of carbonated HA and β-TCP as showed by FTIR peaks at 1419,5 and 871,8 cm-1 and XRD peak at 29,5°. This formation was induced by the presence of HA in chitosan microspheres. These results are confirmed by SEM micrographs which chow the Ca-P crystals growth in form of cauliflowers. So, these materials are of great interest for bone regeneration applications due to their ability to nucleate calcium phosphates in presence of simulated body fluid (SBF).

Keywords: hydroxyapatite, chitosan, microsphere, composite, bone regeneration

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Authors: Ahmad Nazrun Shuid, Isa Naina Mohamed, Nurul Izzah Ibrahim, Norazlina Mohamed

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Studies have shown that oral tocotrienol, a potent vitamin E, promoted fracture healing of osteoporotic bone. In this study, tocotrienol was combined with a polymer carrier (PLGA), and injected to the fracture site. The slow and constant release of tocotrienol particles would promote fracture healing of post-menopausal osteoporosis rat model. Fracture healing was assessed using micro-CT. Twenty-four Sprague-Dawley rats were ovariectomised or sham-operated and the left tibiae were fractured and fixed with plate and screws. The fractures were created at the upper third of the left tibiae. The rats were divided into 3 groups: sham-operated (SO), ovariectomised-control (OVxC) and PLGA-incorporated tocotrienol treatment (OVx + TT) groups. After 4 weeks, the OVx + TT group showed significantly better callus fracture healing than the OVxC group. In conclusion, tocotrienol-incorporated PLGA was able to promote fracture healing of osteoporotic bone.

Keywords: osteoporosis, micro-CT, tocotrienol, PLGA, fracture

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Authors: Georgeta Voicu, Cristina Daniela Ghitulica, Andreia Cucuruz, Cristina Busuioc

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In the field of tissue engineering, the compositional and microstructural features of the employed materials play an important role, with implications on the mechanical and biological behaviour of the medical devices. In this context, the development of apatite - natural biopolymer composites represents a choice of many scientific groups. Thus, hydroxyapatite powders were synthesized by a wet method, namely co-precipitation, starting from high purity reagents (CaO, MgO, and H3PO4). Moreover, the substitution of calcium with magnesium have been approached, in the 5 - 10 wt.% range. Afterward, the phosphate powders were integrated in two types of composites with chitosan, different from morphological point of view. First, 3D porous scaffolds were obtained by a freeze-drying procedure. Second, uniform, compact films were achieved by film casting. The influence of chitosan molecular weight (low, medium and high), as well as apatite powder to polymer ratio (1:1 and 1:2) on the morphological properties, were analysed in detail. In conclusion, the reported biocomposites, prepared by a straightforward route are suitable for bone substitution or repairing applications.

Keywords: bone reconstruction, chitosan, composite scaffolds, hydroxyapatite

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Authors: D. Ficai, A. Ficai, D. Gudovan, I. A. Gudovan, I. Ardelean, R. Trusca, E. Andronescu, V. Mitran, A. Cimpean

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In the last years, scientists struggled hardly to mimic bone structures to develop implants and biostructures which present higher biocompatibility and reduced rejection rate. One way to obtain this goal is to use similar materials as that of bone, namely collagen/hydroxyapatite composite materials. However, it is very important to tailor both compositions but also the microstructure of the bone that would ensure both the optimal osteointegartion and the mechanical properties required by the application. In this study, new collagen/hydroxyapatites composite materials doped with Cu, Li, Mn, Zn were successfully prepared. The synthesis method is described below: weight the Ca(OH)₂ mass, i.e., 7,3067g, and ZnCl₂ (0.134g), CuSO₄ (0.159g), LiCO₃ (0.133g), MnCl₂.4H₂O (0.1971g), and suspend in 100ml distilled water under magnetic stirring. The solution thus obtained is added a solution of NaH₂PO₄*H2O (8.247g dissolved in 50ml distilled water) under slow dropping of 1 ml/min followed by adjusting the pH to 9.5 with HCl and finally filter and wash until neutral pH. The as-obtained slurry was dried in the oven at 80°C and then calcined at 600°C in order to ensure a proper purification of the final product of organic phases, also inducing a proper sterilization of the mixture before insertion into the collagen matrix. The collagen/hydroxyapatite composite materials are tailored from morphological point of view to optimize their biocompatibility and bio-integration against mechanical properties whereas the addition of the dopants is aimed to improve the biological activity of the samples. The addition of transitional metals can improve the biocompatibility and especially the osteoblasts adhesion (Mn²⁺) or to induce slightly better osteoblast differentiation of the osteoblast, Zn²⁺ being a cofactor for many enzymes including those responsible for cell differentiation. If the amount is too high, the final material can become toxic and lose all of its biocompatibility. In order to achieve a good biocompatibility and not reach the cytotoxic effect, the amount of transitional metals added has to be maintained at low levels (0.5% molar). The amount of transitional metals entering into the elemental cell of HA will be verified using inductively-coupled plasma mass spectrometric system. This highly sensitive technique is necessary, because, at such low levels of transitional metals, the difference between biocompatible and cytotoxic is a very thin line, thus requiring proper and thorough investigation using a precise technique. In order to determine the structure and morphology of the obtained composite materials, IR spectroscopy, X-Ray diffraction (XRD), scanning electron microscopy (SEM), and Energy Dispersive X-Ray Spectrometry (EDS) were used. Acknowledgment: The present work was possible due to the EU-funding grant POSCCE-A2O2.2.1-2013-1, Project No. 638/12.03.2014, code SMIS-CSNR 48652. The financial contribution received from the national project “Biomimetic porous structures obtained by 3D printing developed for bone tissue engineering (BIOGRAFTPRINT), No. 127PED/2017 is also highly acknowledged.

Keywords: collagen, composite materials, hydroxyapatite, bone tissue engineering

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Authors: Adil Elrayah, Jie Weng, Esra Suliman

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The mineral in human bone is not pure stoichiometric calcium phosphate (Ca/P) as it is partially substituted by in organic elements. In this study, the copper ions (Cu²⁺) substituted hydroxyapatite (CuHA) powder has been synthesized by the co-precipitation method. The CuHA powder has been used to fabricate CuHA fiber scaffolds by sol-gel process and the following sinter process. The resulted CuHA fibers have slightly different microstructure (i.e. porosity) compared to HA fiber scaffold, which is denser. The mechanical properties test was used to evaluate CuHA, and the results showed decreases in both compression strength and hardness tests. Moreover, the in vitro used endothelial cells to evaluate the angiogenesis of CuHA. The result illustrated that the viability of endothelial cell on CuHA fiber scaffold surfaces tends to antigenic behavior. The results obtained with CuHA scaffold give this material benefit in biological applications such as antimicrobial, antitumor, antigens, compacts, filling cavities of the tooth and for the deposition of metal implants anti-tumor, anti-cancer, bone filler, and scaffold.

Keywords: fiber scaffold, copper ions, hydroxyapatite, in vitro, mechanical property

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Authors: Mayur Chaudhari, Ashutosh Gaikwad, Shubham Kavathale, Aditya Mule, Dilip Panchal, Puja Verma

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The purpose of this investigation was to locate restorative bio-materials for the manufacture of implants and crowns. A three-dimensional (3D) finite element analysis (FEA) was carried out to evaluate the stress distribution in the implant and abutment with several types of bio-materials and various prosthetic crowns. While the dental implant, abutment, and screw were subjected to a vertical impact force, the effects of mechanical characteristics such as Young's modulus and Poisson's ratio were evaluated and contrasted. Crowns are made from zirconia, cobalt, ceramic, acrylic resin, and porcelain materials. Implants are made from materials such as titanium, zirconia, PEEK, and CFR-PEEK. SolidWorks was used to create the 3D geometry, and Ansys Software was used to analyze it. The results show that using CFR-PEEK implants and an acrylic resin crown resulted in less bone stress than using alternative materials. In order to reduce the amount of stress on the bone and possibly prevent implant failure, the study's findings support the use of a CFR PEEK implant, abutment, and crown in bruxism patients.

Keywords: biomaterials, implant, crown, abutment

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Authors: Neelesh Papineni

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Aim: Piezosurgery is a relatively new technique for osteotomy and osteoplasty that uses ultrasonic vibration. The conventional method of treating periodontal cases are by conventional surgeries. However, in this advancing field the use of motor-driven instruments is being considered less invasive. Out of these motor-driven instruments, piezo-electric device has been introduced to the field of periodontics and oral implantology. This article discusses about the wide range of application of piezo-electric device in periodontology, its advantages over conventional surgical therapies and other motor-driven instruments. Results: Piezo- electric has shown better results in aspect of osteotomy, osteoplasty, implants, and any procedure which includes conserving the bone. Also piezo-electric does not cause any kind of damage to the surrounding soft tissue and eliminates the risk of bone necrosis which is a risk factor in other motor driven instruments. Conclusion: In this era of modern dentistry , a successful periodontal and implant surgery requires a sound osseous support. This review gives a pictorial representation about the wide range of application of piezo-electric device in periodontology.

Keywords: piezo-electric, osteotomy, osteoplasty, implantology

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Authors: Sadam Elayah

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Background: One of the most critical competencies in advanced dentistry is alveolar ridge preservation after exodontia. The aim of this clinical trial was to assess the impact of autologous concentrated growth factor (CGF) as a socket-filling material and its ridge preservation properties following the lower third molar extraction. Materials and Methods: A total of 60 sides of 30 participants who had completely symmetrical bilateral impacted lower third molars were enrolled. The short-term outcome variables were wound healing, swelling and pain, clinically assessed at different time intervals (1st, 3rd & 7th days). While the long-term outcome variables were bone height & width, bone density and socket surface area in the coronal section. Cone beam computed tomography images were obtained immediately after surgery and three months after surgery as a temporal measure. Randomization was achieved by opaque, sealed envelopes. Follow-up data were compared to baseline using Paired & Unpaired t-tests. Results: The wound healing index was significantly better in the test sides (P =0.001). Regarding the facial swelling, the test sides had significantly fewer values than the control sides, particularly on the 1st (1.01±.57 vs 1.55 ±.56) and 3rd days (1.42±0.8 vs 2.63±1.2) postoperatively. Nonetheless, the swelling disappeared within the 7th day on both sides. The pain scores of the visual analog scale were not a statistically significant difference between both sides on the 1st day; meanwhile, the pain scores were significantly lower on the test sides compared with the control sides, especially on the 3rd (P=0.001) and 7th days (P˂0.001) postoperatively. Regarding long-term outcomes, CGF sites had higher values in height and width when compared to Control sites (Buccal wall 32.9±3.5 vs 29.4±4.3 mm, Lingual wall 25.4±3.5 vs 23.1±4 mm, and Alveolar bone width 21.07±1.55vs19.53±1.90 mm) respectively. Bone density showed significantly higher values in CGF sites than in control sites (Coronal half 200±127.3 vs -84.1±121.3, Apical half 406.5±103 vs 64.2±158.6) respectively. There was a significant difference between both sites in reducing periodontal pockets. Conclusion: CGF application following surgical extraction provides an easy, low-cost, and efficient option for alveolar ridge preservation. Thus, dentists may encourage using CGF during dental extractions, particularly when alveolar ridge preservation is required.

Keywords: platelet, extraction, impacted teeth, alveolar ridge, regeneration, CGF

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Authors: Patricia Shirley Almeida Prado, Selma Paixão Argollo, Maria De Fátima Teixeira Guimarães, Leticia Matos Sobrinho

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Skeletal differential diagnosis is essential in forensic anthropology in order to differentiate skeletal trauma from normal osseous variation and pathological processes. Thus, part of forensic anthropological field is differentiate skeletal criminal injuries from the normal skeletal variation (bone fusion or nonunion, transitional vertebrae and other non-metric traits), non-traumatic skeletal pathology (myositis ossificans, arthritis, bone metastasis, osteomyelitis) from traumatic skeletal pathology (myositis ossificans traumatic) avoiding misdiagnosis. This case shows the importance of effective pathological diagnosis in order to accelerate the identification process of skeletonized human remains. THE CASE: An unidentified skeletal remains at the medico legal institute Nina Rodrigues-Salvador, of a male young adult (29 to 40 years estimated) showing a massive heterotopic ossification on its right tibia at upper epiphysis and adjacent articular femur surface; an extensive ossification on the right clavicle (at the sternal extremity) also presenting an heterotopic ossification at right scapulae (upper third of scapulae lateral margin and infraglenoid tubercule) and at the head of right humerus at the shoulder joint area. Curiously, this case also shows an unusual porosity in certain vertebrae´s body and in some tarsal and carpal bones. Likewise, his left fifth metacarpal bones (right and left) showed a healed fracture which led both bones distorted. Based on identification, of pathological conditions in human skeletal remains literature and protocols these alterations can be misdiagnosed and this skeleton may present more than one pathological process. The anthropological forensic lab at Medico-legal Institute Nina Rodrigues in Salvador (Brazil) adopts international protocols to ancestry, sex, age and stature estimations, also implemented well-established conventions to identify pathological disease and skeletal alterations. The most compatible diagnosis for this case is hematogenous osteomyelitis due to following findings: 1: the healed fracture pattern at the clavicle showing a cloaca which is a pathognomonic for osteomyelitis; 2: the metacarpals healed fracture does not present cloaca although they developed a periosteal formation. 3: the superior articular surface of the right tibia shows an extensive inflammatory healing process that extends to adjacent femur articular surface showing some cloaca at tibia bone disease. 4: the uncommon porosities may result from hematogenous infectious process. The fractures probably have occurred in a different moments based on the healing process; the tibia injury is more extensive and has not been reorganized, while metacarpals and clavicle fracture is properly healed. We suggest that the clavicle and tibia´s fractures were infected by an existing infectious disease (syphilis, tuberculosis, brucellosis) or an existing syndrome (Gorham’s disease), which led to the development of osteomyelitis. This hypothesis is supported by the fact that different bones are affected in diverse levels. Like the metacarpals that do not show the cloaca, but then a periosteal new bone formation; then the unusual porosities do not show a classical osteoarthritic processes findings as the marginal osteophyte, pitting and new bone formation, they just show an erosive process without bone formation or osteophyte. To confirm and prove our hypothesis we are working on different clinical approaches like DNA, histopathology and other image exams to find the correct diagnostic.

Keywords: bone disease, forensic anthropology, hematogenous osteomyelitis, human identification, human remains

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Authors: Carlos Amnael Orozco-Diaz, Robert David Moorehead, Gwendolen Reilly, Fiona Gilchrist, Cheryl Ann Miller

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The current gold-standard for maxillofacial reconstruction surgery (MRS) utilizes auto-grafted cancellous bone as a filler. This study was aimed towards developing a polylactic-acid/hydroxyapatite (PLA-HA) composite suitable for fused-deposition 3D printing. Functionalization of the polymer through the addition of HA was directed to promoting bone-regeneration properties so that the material can rival the performance of cancellous bone grafts in terms of bone-lesion repair. This kind of composite enables the production of MRS implants based off 3D-reconstructions from image studies – namely computed tomography – for anatomically-correct fitting. The present study encompassed in-vitro degradation and in-vitro biocompatibility profiling for 3D-printed PLA and PLA-HA composites. PLA filament (Verbatim Co.) and Captal S hydroxyapatite micro-scale HA powder (Plasma Biotal Ltd) were used to produce PLA-HA composites at 5, 10, and 20%-by-weight HA concentration. These were extruded into 3D-printing filament, and processed in a BFB-3000 3D-Printer (3D Systems Co.) into tensile specimens, and were mechanically challenged as per ASTM D638-03. Furthermore, tensile specimens were subjected to accelerated degradation in phosphate-buffered saline solution at 70°C for 23 days, as per ISO-10993-13-2010. This included monitoring of mass loss (through dry-weighing), crystallinity (through thermogravimetric analysis/differential thermal analysis), molecular weight (through gel-permeation chromatography), and tensile strength. In-vitro biocompatibility analysis included cell-viability and extracellular matrix deposition, which were performed both on flat surfaces and on 3D-constructs – both produced through 3D-printing. Discs of 1 cm in diameter and cubic 3D-meshes of 1 cm3 were 3D printed in PLA and PLA-HA composites (n = 6). The samples were seeded with 5000 MG-63 osteosarcoma-like cells, with cell viability extrapolated throughout 21 days via resazurin reduction assays. As evidence of osteogenicity, collagen and calcium deposition were indirectly estimated through Sirius Red staining and Alizarin Red staining respectively. Results have shown that 3D printed PLA loses structural integrity as early as the first day of accelerated degradation, which was significantly faster than the literature suggests. This was reflected in the loss of tensile strength down to untestable brittleness. During degradation, mass loss, molecular weight, and crystallinity behaved similarly to results found in similar studies for PLA. All composite versions and pure PLA were found to perform equivalent to tissue-culture plastic (TCP) in supporting the seeded-cell population. Significant differences (p = 0.05) were found on collagen deposition for higher HA concentrations, with composite samples performing better than pure PLA and TCP. Additionally, per-cell-calcium deposition on the 3D-meshes was significantly lower when comparing 3D-meshes to discs of the same material (p = 0.05). These results support the idea that 3D-printable PLA-HA composites are a viable resorbable material for artificial grafts for bone-regeneration. Degradation data suggests that 3D-printing of these materials – as opposed to other manufacturing methods – might result in faster resorption than currently-used PLA implants.

Keywords: bone regeneration implants, 3D-printing, in vitro testing, biocompatibility, polymer degradation, polymer-ceramic composites

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Authors: Nurul Izzah Ibrahim, Isa Naina Mohamed, Norazlina Mohamed, Ahmad Nazrun Shuid

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Osteoporosis disease delays fracture healing. Statins have shown potential for osteoporosis and to promote fracture healing. The effects of statin can be further potentiated by combining it with a carrier known as poly-(DL-lactide), which would provide persistent release of statin to the fracture site. This study was designed to investigate the effects of direct injection of poly-(DL-lactide)-incorporated lovastatin on fracture healing of postmenopausal osteoporosis rat model. Twenty-four Sprague-Dawley female rats were divided into 3 groups: sham-operated (SO), ovariectomized-control rats (OVxC) and poly-(DL-lactide)-incorporated lovastatin (OVx+Lov) groups. The OVx+Lov group was given a single injection of 750 µg/kg lovastatin particles incorporated with poly-(DL-lactide). After 4 weeks, the fractured tibiae were dissected out for biomechanical assessments of the callus. The OVx+Lov group showed significantly better callus strength than the OVxC group (p<0.05). In conclusion, a single injection of lovastatin-incorporated poly-(DL-lactide) was able to promote better fracture healing of osteoporotic bone.

Keywords: statins, fracture healing, osteoporosis, poly-(DL-lactide)

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Authors: S. Ghalem, M. Mesmoudi, I. Daoudand, H. Allali

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The nitrogen-containing bisphosphonates (N-BPs) are well established as the treatments of choice for disorders of excessive bone resorption, myeloma and bone metastases, and osteoporosis. They inhibit farnesyl pyrophosphate synthase (FFPS), a key enzyme in the mevalonate pathway, resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton, adhesion/spreading, and invasion of cancer cells. A very few examples for synthesis of α-amino bisphosphonates based on several amino acids are known from the literature. In the present work, esters of aminoacid react with ketophsophonate (or their analog acid or acyl) to afford the desired products, α-iminophosphonates. The reaction of imine with dimethyl phosphate in the presence of catalytic amount of I2 give ester of α-aminobisphosphonate as sole product in good yield. Finally, we used computational docking methods to predict how several α-aminobisphosphonates bind to FPPS and how R and X influence. Pamidronate, β-aminobisphosphonate already marketed, was used as reference. These results are of interest since they represent a new and simple way to sythesize α-aminobisphosphonates with a free COOH group increased by R2 functionalisable and opening up the possibility of using the molecular docking to facilitate the design of other, novel FFPS inhibitors.

Keywords: drug research, cancer, α-amino bisphosphonates, molecular docking

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