Search results for: bone scaffold

Authors: MyungGu Yeo, JongHan Ha, Gi-Hoon Yang, JaeYoon Lee, SeungHyun Ahn, Hyeongjin Lee, HoJun Jeon, YongBok Kim, Minseong Kim, GeunHyung Kim

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Tissue engineering is a rapidly growing interdisciplinary research area that may provide options for treating damaged tissues and organs. As a promising technique for regenerating various tissues, this technology requires biomedical scaffolds, which serve as an artificial extracellular matrix (ECM) to support neotissue growth. Electrospun micro/nanofibers have been used widely in tissue engineering because of their high surface-area-to-volume ratio and structural similarity to extracellular matrix. However, low mechanical sustainability, low 3D shape-ability, and low cell infiltration have been major limitations to their use. In this work, we propose new hybrid scaffolds interlayered with cell-laden electrospun micro/nano fibers and poly(caprolactone) microstructures. Also, we applied various concentrations of alginate and electric field strengths to determine optimal conditions for the cell-electrospinning process. The combination of cell-laden bioink (2 ⅹ 10^5 osteoblast-like MG63 cells/mL, 2 wt% alginate, 2 wt% poly(ethylene oxide), and 0.7 wt% lecithin) and a 0.16 kV/mm electric field showed the highest cell viability and fiber formation in this process. Using these conditions and PCL microstructures, we achieved mechanically stable hybrid scaffolds. In addition, the cells embedded in the fibrous structure were viable and proliferated. We suggest that the cell-embedded hybrid scaffolds fabricated using the cell-electrospinning process may be useful for various soft- and hard-tissue regeneration applications.

Keywords: bioink, cell-laden scaffold, micro/nanofibers, poly(caprolactone)

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Authors: R. Trad Khodja, A. Guessmi, R. Ghoul, A. Mahtout, S. A. Benbouali, M. A. Boulahlib

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Cranioplasty is a surgical act that aims to restore cranial bone losses in order to protect the brain from external aggressions and to improve the patient's aesthetic appearance. This objective can be achieved by taking advantage of the current technological development in computer science and biomechanics. The objective of this paper is 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, ten patients underwent this procedure with excellent aesthetic results.

Keywords: cranioplasty, cranial defect, PMMA, 3d printing, custom made implants

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Authors: Abdul Aziz, Muhammad Qamar Masood, Saadia Sattar, Saira Fatima, Najmul Islam

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Introduction: The most common endocrine tumor is thyroid cancer. Follicular Thyroid Carcinoma (FTC) accounts for 5%–10% of all thyroid cancers. Patients with FTC frequently present with more advanced stage diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery, while radioactive iodine therapy is the main adjuvant therapy as per ATA guidelines. In many developing countries, surgical facilities and radioactive iodine are in short supply; therefore, understanding follicular thyroid cancer trends may help developing countries plan and use resources more effectively. Methodology: It was a retrospective observational study of FTC patients of age 18 years and above conducted at Aga Khan University Hospital, Karachi, from 1st January 2010 to 31st December 2019. Results: There were 404 patients with thyroid carcinoma, out of which forty (10.1%) were FTC. 50% of the patients were in the 41-60 years age group, and the female to male ratio was 1.5: 1. Twenty-four patients (60%) presented with complain of neck swelling followed by metastasis (20%) and compressive symptoms (20%). The most common site of metastasis was bone (87.5%), followed by lung (12.5%). The pre-operative thyroglobulin level was done in six out of eight metastatic patients (75%) in which it was elevated. This emphasizes the importance of checking thyroglobulin level in unusual presentation (bone pain, fractures) of a patient having neck swelling also to help in establishing the primary source of tumor. There was no complete documentation of ultrasound features of the thyroid gland in all the patients, which is an important investigation done in the initial evaluation of thyroid nodule. On FNAC, 50% (20 patients) had Bethesda category III-IV nodules, while 10% ( 4 patients ) had Bethesda category II. In sixteen patients, FNAC was not done as they presented with compressive symptoms or metastasis. Fifty percent had a total thyroidectomy and 50% had subtotal followed by completion thyroidectomy, plus ten patients had lymph node dissection, out of which seven had histopathological lymph node involvement. On histopathology, twenty-three patients (57.5%) had minimally invasive, while seventeen (42.5%) had widely invasive follicular thyroid carcinoma. The capsular invasion was present in thirty-three patients (82.5%); one patient had no capsular invasion, but there was a vascular invasion. Six patients' histopathology had no record of capsular invasion. In contrast, the lymphovascular invasion was present in twenty-six patients (65%). In this study, 65 % of the patients had clinical stage 1 disease, while 25% had stage 2 and 10% had clinical stage 4. Seventeen patients (42.5%) had received RAI 30-100 mCi, while ten patients (25%) received more than 100 mCi. Conclusion: FTC demographic and clinicopathological presentation are the same in Pakistan as compared to other countries. Surgery followed by RAI is the mainstay of treatment. Thus understanding the trend of FTC and proper planning and utilization of the resources will help the developing countries in effectively treating the FTC.

Keywords: thyroid carcinoma, follicular thyroid carcinoma, clinicopathological features, developing countries

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Authors: Sudhir Kumar Sharma, Abiy D. Woldetsadik, Mazin Magzoub, Ramesh Jagannathan

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It is well known that bioactive ceramics exhibit specific biological affinities, especially in the area of tissue re-generation. In this context, we report the development of an eminently scalable, novel, supercritical CO₂ based process for the fabrication of hierarchically porous 'soft' CaCO₃ scaffolds. Porosity at the macro, micro, and nanoscales was obtained through process optimization of the so-called 'coffee-ring effect'. Exposure of these CaCO₃ scaffolds to monocytic THP-1 cells yielded negligible levels of tumor necrosis factor-alpha (TNF-α) thereby confirming the lack of immunogenicity of the scaffolds. ECM protein treatment of the scaffolds showed enhanced adsorption comparable to standard control such as glass. In vitro studies using osteoblast precursor cell line, MC3T3, also demonstrated the cytocompatibility of hierarchical porous CaCO₃ scaffolds.

Keywords: supercritical CO2, CaCO3 scaffolds, coffee-ring effect, ECM proteins

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Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel

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Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.

Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant

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Authors: Przemyslaw Nogly, Tobias Weinert, Daniel James, Sergio Carbajo, Dmitry Ozerov, Antonia Furrer, Dardan Gashi, Veniamin Borin, Petr Skopintsev, Kathrin Jaeger, Karol Nass, Petra Bath, Robert Bosman, Jason Koglin, Matthew Seaberg, Thomas Lane, Demet Kekilli, Steffen Brünle, Tomoyuki Tanaka, Wenting Wu, Christopher Milne, Thomas A. White, Anton Barty, Uwe Weierstall, Valerie Panneels, Eriko Nango, So Iwata, Mark Hunter, Igor Schapiro, Gebhard Schertler, Richard Neutze, Jörg Standfuss

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Ultrafast isomerization of retinal is the primary step in a range of photoresponsive biological functions including vision in humans and ion-transport across bacterial membranes. We studied the sub-picosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin using an X-ray laser. Twenty snapshots with near-atomic spatial and temporal resolution in the femtosecond regime show how the excited all-trans retinal samples conformational states within the protein binding pocket prior to passing through a highly-twisted geometry and emerging in the 13-cis conformation. The aspartic acid residues and functional water molecules in proximity of the retinal Schiff base respond collectively to formation and decay of the initial excited state and retinal isomerization. These observations reveal how the protein scaffold guides this remarkably efficient photochemical reaction.

Keywords: bacteriorhodopsin, free-electron laser, retinal isomerization mechanism, time-resolved crystallography

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Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak

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Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.

Keywords: cancer, MyD88, TIR domains, Toll-like receptors

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Authors: Thuy Phuong Nhat Tran, Ashutosh Thakur, Toshiaki Taniike

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Recently, covalently linked graphene oxide frameworks (GOFs) have attracted considerable attention in gas absorbance and water purification as well-defined microporous materials. In spite of their potential advantages such as a controllable pore dimension, adjustable hydrophobicity, and structural stability, these materials have been scarcely employed in heterogeneous catalysis. Here we demonstrate a novel and facile method to synthesize Pd nanoparticles (NPs) confined in a GOF (Pd@GOF). The GOF with uniform interlayer space was obtained by the intercalation of diboronic acid between graphene oxide layers. It was found that Pd NPs were generated inside the graphitic gallery spaces of the GOF, and thus, formed Pd NPs were well-dispersed with a narrow particle size distribution. The synthesized Pd@GOF emerged as an efficient nanocatalyst based on its superior performance (product yield and recyclability) toward Suzuki-Miyaura cross-coupling reaction in both polar and apolar solvents, which has been hardly observed for previously reported graphene-based Pd nanocatalysts. Furthermore, the rational comparison of the catalytic performance between two kinds of Pd@GOF (Pd NPs encapsulated in a diboronic ester-intercalated GOF and in a monoboronic ester-intercalated GOF) firmly confirmed the essential role of a rigid framework design in the stabilization of Pd NPs. Based on these results, the covalently assembled GOF was proposed as a promising scaffold for hosting noble metal NPs to construct desired metal@GOF nanocatalysts with improved activity and durability.

Keywords: graphene oxide framework, palladium nanocatalyst, pore confinement, Suzuki-Miyaura cross-coupling reaction

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Authors: I. Gkolfinopoulos, N. Chijiwa

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To evaluate the remaining capacity in concrete tensioned members, it is important to accurately estimate damage in precast concrete tendons. In this research Johnson-Cook model and damage parameters of high-strength steel material were calculated by static and dynamic uniaxial tensile tests. Replication of experimental results was achieved through finite element analysis for both single 8-noded three-dimensional element as well as the full-scale dob-bone shaped model and relevant model parameters are proposed. Finally, simulation results in terms of strain and deformation were verified using digital image correlation analysis.

Keywords: DIC analysis, Johnson-Cook, quasi-static, dynamic, rupture, tendon

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Authors: Sara Grazhdani, Alma Cili, Arben Ivanaj

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Immune Thrombocytopenic Purpura is an autoimmune disease characterized by the destruction of platelets by immune mediators, their deficient production in the red bone marrow and increased splenic sequestration, leading to the appearance of thrombocytopenia and increased risk of hemorrhage. Treatment is indicated in patients with low platelet counts (<30 x 10 9 /L) who present clinically with hemorrhagic events or are at increased risk for hemorrhage. The goal of the treatment remains (I) prevention of hemorrhagic events and deaths resulting from them, (II) reaching an adequate level of the number of platelets, (III) treatment of patients with as few toxic effects as possible. Corticosteroid therapy remains the first choice in the treatment of patients with Primary Immune Thrombocytopenic Purpura. Rituximab (Mabthera) remains the first choice in the second line in the treatment of patients with Immune Thrombocytopenic Purpura, refractory to the use of cortisones.

Keywords: ITP, rituximab, prednisolone, relapse

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Authors: Devadrita Dey Sarkar

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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

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Authors: Thi Thi Zin, Pyke Tin, Ikuo Kobayashi, Yoichiro Horii

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Today dairy farm experts and farmers have well recognized the importance of dairy cow Body Condition Score (BCS) since these scores can be used to optimize milk production, managing feeding system and as an indicator for abnormality in health even can be utilized to manage for having healthy calving times and process. In tradition, BCS measures are done by animal experts or trained technicians based on visual observations focusing on pin bones, pin, thurl and hook area, tail heads shapes, hook angles and short and long ribs. Since the traditional technique is very manual and subjective, the results can lead to different scores as well as not cost effective. Thus this paper proposes an algebraic geometric imaging approach for an automatic dairy cow BCS system. The proposed system consists of three functional modules. In the first module, significant landmarks or anatomical points from the cow image region are automatically extracted by using image processing techniques. To be specific, there are 23 anatomical points in the regions of ribs, hook bones, pin bone, thurl and tail head. These points are extracted by using block region based vertical and horizontal histogram methods. According to animal experts, the body condition scores depend mainly on the shape structure these regions. Therefore the second module will investigate some algebraic and geometric properties of the extracted anatomical points. Specifically, the second order polynomial regression is employed to a subset of anatomical points to produce the regression coefficients which are to be utilized as a part of feature vector in scoring process. In addition, the angles at thurl, pin, tail head and hook bone area are computed to extend the feature vector. Finally, in the third module, the extracted feature vectors are trained by using Markov Classification process to assign BCS for individual cows. Then the assigned BCS are revised by using multiple regression method to produce the final BCS score for dairy cows. In order to confirm the validity of proposed method, a monitoring video camera is set up at the milk rotary parlor to take top view images of cows. The proposed method extracts the key anatomical points and the corresponding feature vectors for each individual cows. Then the multiple regression calculator and Markov Chain Classification process are utilized to produce the estimated body condition score for each cow. The experimental results tested on 100 dairy cows from self-collected dataset and public bench mark dataset show very promising with accuracy of 98%.

Keywords: algebraic geometric imaging approach, body condition score, Markov classification, polynomial regression

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Authors: Aboussalih Amira, Zarza Tahar, Fedaoui Kamel, Baroura Lazhar, Hammoudi Salah

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316 L steel is a stainless steel frequently used in orthopedic surgery; in the design of implants (hip, knee, shoulder, ankle, etc.), in dental surgery, cardiology, ophthalmology. Before any use, it is essential to predict the macroscopic phenomenological behavior of the material, and to analyze its response. The behavior of 316 L steel in low cycle fatigue, under uniaxial cyclic loading of tension/compression, producing significant plastic deformations leading to material damage. This investigation allowed us to characterize the behavior of the 316L steel employed in the locking of the compression plates (LCP), of which they are generally used in orthopedics to stabilize the fractured bone parts. And to perceive the phenomenon of Ratcheting leading to the damage of LCP by an excess of plastic deformation under nonsymmetrical alternated imposed constraint in low cycle fatigue.

Keywords: 316L SS, locking compression plate, low cycle fatigue, ratcheting

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Authors: Mohamad Saeed Ahrari-Khafi, Abutorab Tabatabai-Naini, Niloofar Ajvadi

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Scapular fracture is not common in horses, due to the proper protection of scapular muscles. However, if it happens, it can cause lameness in horses. Because of the overlapping of the scapula on the contralateral scapula and the thorax, usually radiography cannot be helpful in evaluation, except in small amount of its ventral part. Although ultrasonography is mainly used for diagnosis of soft tissue injuries, it also can be used for evaluation of bone surface abnormalities. This study was intended to document the normal ultrasonographic appearance of the equine scapula. Right forelimb of six horses was used. To facilitate the image assessment, a zoning system was developed. Ultrasonography was performed by using a 5-11 MHz linear array transducer. Ultrasonographic anatomy of scapula in different parts and planes was imaged and documented, hoping to help practitioners to diagnose fractures and injuries. Results showed that ultrasonography is capable to depict different parts of the scapula and regional muscles, and can be used for detecting fractures and other abnormalities.

Keywords: horse, scapula, scapular fracture, ultrasonography

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Authors: Lewis Mehl-Madrona, Josephine Conte, Barbara Mainguy

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We explore the historical connection of Andrew Taylor Still with the aboriginal nations placed in Missouri, notably the Shawnee, Pawnee, Kickapoo, Cherokee, and the Pottowattomy. Still was fluent in Shawnee and himself was part Native American (Lumbee). These nations had well-developed forms of hands-on healing as well as practicing lightning bone setting. They were more sophisticated than their European-derived neighbors in treating fractures and discolocations. We trace Still’s writings as evidence for his connectedness with these people and respect for their traditions. We explore the traditional hands-on therapies of these nations and discover that they are quite similar to osteopathy. We propose that Still was a translator of traditional manual medicine of the nations into the mainstream of American society. While, surely, he made his own personal contributions to manual medicine, he did not invent osteopathy de novo but relied on methods that were well-developed across centuries for his inspiration.

Keywords: indigenous healing, indigenous bodywork, American osteopathy, Andrew Taylor Still, Cherokee, Shawnee

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Authors: Jinho Hur, Minjung Shin, Heekyu Kim

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In many places, new railway constructions in the city are being used to build a viaduct station to take advantage of the space below the line, for difficulty of securing railway site and disconnections of areas. The space under the viaduct has limited to use by noise and vibration. In order to use it for various purposes, reducing noise and vibration is required. The vibration reduction method for new structures is recently developed enough to use as accommodation, but the reduction method for existing structures is still far-off. In this study, it suggests vibration reduction method by filling vibration reduction material to column members which is path of structure-bone-noise from trains run. Because most of railroad stations are reinforced concrete structures. It compares vibration reduction of station applied the method and original station by FEM analysis. As a result, reduction of vibration acceleration level in bandwidth 15~30Hz can be reduced. Therefore, using this method for viaduct railroad station, vibration of station is expected to be reduced.

Keywords: structure borne noise, TPU, viaduct rail station, vibration reduction method

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Authors: Simone F. Medeiros, Isabela F. Santos, Rodolfo M. Moraes, Jaspreet K. Kular, Marcus A. Johns, Ram Sharma, Amilton M. Santos

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Tissue engineering aims to develop alternatives to treat damaged tissues by promoting their regeneration. Its basic principle is to place cells on a scaffold capable of promoting cell functions, and for this purpose, polymeric nanoparticles have been successfully used due to the ability of some macro chains to mimic the extracellular matrix and influence cell functions. In general, nanoparticles require surface chemical modification to achieve cell adhesion, and recent advances in their synthesis include methods for modifying the ligand density and distribution onto nanoparticles surface. However, this work reports the development of biodegradable polymeric nanoparticles capable of promoting cellular adhesion without any surface chemical modification by ligands. Biocompatible and biodegradable nanoparticles based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) were synthesized by solvent evaporation method. The produced nanoparticles were small in size (85 and 125 nm) and colloidally stable against time in aqueous solution. Morphology evaluation showed their spherical shape with small polydispersity. Human osteoblast-like cells (MG63) were cultured in the presence of PHBHV nanoparticles, and growth kinetics were compared to those grown on tissue culture polystyrene (TCPS). Cell attachment on non-tissue culture polystyrene (non-TCPS) pre-coated with nanoparticles was assessed and compared to attachment on TCPS. These findings reveal the potential of PHBHV nanoparticles for cell adhesion and growth, without requiring a matrix ligand to support cells, to be used as scaffolds, in tissue engineering applications.

Keywords: tissue engineering, PHBHV, stem cells, cellular attachment

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Authors: S. F. Fakhouri, M.M. Shimano, D. Maranho, C. A. Araújo, M. V. Guimarães, A. C. Shimano, J. B. Volpon

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Pathological deviations of the mechanical axis of the lower limbs deeply alter the stress distributions on the femur and tibia and the hip, knee, and ankle articulations. The purpose of this research was to assess the effects of pathological deviations in different levels of the lower limbs in the distribution of stress in the proximal femur region using photoelasticity of plane transmission. For most of the types of deviations studied, the results showed that the internal stress was generally higher in the calcar region than in the trochanteric region, followed by the third distal of the femur head. This study allowed for the development of better criteria for the correction of angular deviations and helped identify the deviations that are most harmful to the mechanical axis in terms of the effects on the bone and the articular effort of the lower limbs. These results will lead to future improvements in studies on prostheses.

Keywords: alignment, deviations, inferior limbs, mechanical axis, photoelasticity, stress

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Authors: Mohammad ASadian, Samira RajiAsadabadi

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Osteoporosis is very common, particularly in post-menopausal women and is characterized by a decrease in bone mass and strength. Osteoporosis also affects the jawbone and it is considered a potential contraindication to the placement of dental implants. The present paper reviews the literature regarding the effect of osteoporosis on the osseointegration of implants. Experimental models have shown that osteoporosis affects the process of osseointegration, which can be reversed by treatment. However, studies in subjects with osteoporosis have shown no differences in the survival of the implants compared to healthy individuals. Therefore, osteoporosis cannot be considered a contraindication for implant placement. Oral bisphosphonates are the most commonly used pharmacological agents in the treatment of osteoporosis. Although there have been cases of osteonecrosis of the jaw in patients treated with bisphosphonates, they are very rare and it is more usually associated with intravenous bisphosphonates in patients with neoplasms or other serious diseases. Nevertheless, patients treated with bisphosphonates must be informed in writing about the possibility of this complication and must give informed consent. Ceasing to use of bisphosphonates before implant placement does not seem to be necessary.

Keywords: Osteoporosis, dental implant, bisphosphonates, survival

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Katerina Bakela, Ioanna Zerva, Irene Athanassakis

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Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression (incretion of MDSCs cells and Tregs, imbalance of inflammatory/anti-inflammatory cytokines) and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS. Such protocol allowed longer survival, necessary in the prospect of the therapeutic treatment application. The so-called vaccine-on-chip consists of a 3-dimensional laser micro-texture Si-scaffold loaded with BALB/c mouse macrophages and activated in vitro with 1μg/ml PG, which exert its action upon subcutaneous implantation. The LPS treatment significantly decreased CD4+, CD8+, CD3z+, and CD19+ cells, while increasing myeloid-derived suppressor cells (MDSCs), CD25+, and Foxp3+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and production of IL-6, TNF-a, and IL-18 while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated vaccine-on chip significantly decreased the percent of CD11b+, Gr1+, CD25+, Foxp3+ cells, and arginase-1 activity in the spleen of LPS-treated animals, while decreasing IL-6 and TNF-a in the serum, allowing survival to all animals tested and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a promising mode of action of PG pre-activated vaccine-on chip in LPS endotoxemia, strengthening; thus, the use of treatment is septic patients.

Keywords: myeloid-derived suppressor cells, peptidoglycan, sepsis, Si-scaffolds

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Authors: Sergei Kosarev

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Wrong treatment tactics for hand and wrist sport-related injuries can lead to the inability to play sports in the future. It is especially important for professional athletes. The members of the Russian Olympic Team are treated in our hospital -Federal Clinical Research Center (Moscow). For their treatment, we use minimally invasive methods such as wrist arthroscopy and also orthobiologics procedures. In 2022 we had cases with scaphoid fracture and TFCC injuries. In all the cases, we were using the arthroscopy technic for treatment. The scaphoid fracture was fixed by K-wires with free bone grafting. For TFCC injures we used transossal sutures. Rehabilitation started the next day after surgery. Rehabilitation included hand therapy and physiotherapy. All athletes returned to the sport after 8-12 weeks after surgery. One of them had pain in the wrist after 12 weeks after surgery, not more than 4 point VAS. Pain syndrome was blocked after 2 PRP injections in the ulnar side of the wrist.

Keywords: sport trauma, wrist arthroscopy, wrist pain, scaphoid fracture

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Authors: C. L Popa, C.S. Ciobanu, S. L. Iconaru, P. Chapon, A. Costescu, P. Le Coustumer, D. Predoi

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In this paper, the preparation and characterization of silver doped hydroxyapatite thin films and their antimicrobial activity characterized is reported. The resultant Ag: HAp films coated on commercially pure Si disks substrates were systematically characterized by Scanning Electron Microscopy (SEM) coupled with X-ray Energy Dispersive Spectroscopy detector (X-EDS), Glow Discharge Optical Emission Spectroscopy (GDOES) and Fourier Transform Infrared spectroscopy (FT-IR). GDOES measurements show that a substantial Ag content has been deposited in the films. The X-EDS and GDOES spectra revealed the presence of a material composed mainly of phosphate, calcium, oxygen, hydrogen and silver. The antimicrobial efficiency of Ag:HAp thin films against Escherichia coli and Staphylococcus aureus bacteria was demonstrated. Ag:HAp thin films could lead to a decrease of infections especially in the case of bone and dental implants by surface modification of implantable medical devices.

Keywords: silver, hydroxyapatite, thin films, GDOES, SEM, FTIR, antimicrobial effect

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Authors: Khaled Saeed Ali

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This study was conducted with 3 week old domestic chicken to determine the effect of supplementation of cadmium to dietary. 10 mg/kg Cadmium chloride added to maize- sesame cake meal diet for 4 weeks. The additional cadmium to the diet induced a decreasing body weight and changes in biochemical parameters of chicken. Chicken were divided into two groups. The first group was given a diet containing the concentration of 10 mg cadmium /kg daily for a period of 30 days and the second group was given diet without cadmium and used as a control group. The result revealed decrease in the body weight of treated chicken by 12.7 % compared to control group, whose body weight increased. The plasma glucose concentration, creatinine, aspartate aminotranseferase (AST), and alanine aminotransferase (ALT) were increased significantly (P<0.05) in Cd treated chicken in comparison to the control group. Cadmium accumulation was observed in the intestine, kidney, liver and bone. The accumulation of cadmium was markedly higher (3-4 times) in cadmium-treated animals compared to the control.

Keywords: cadmium, biochemical parameters, body weight, chicken

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Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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Authors: Chih-Chang Yeh, Min-Fang Yang, Hsin-I Chang

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Chitosan is a cationic polysaccharide derived from the partial deacetylation of chitin. Hyaluronic acid (HA), chondroitin sulfate (CS) and heparin (HP) are anionic glycosaminoglycans (GCGs) which can regulate osteogenic activity. In this study, chitosan membranes were prepared by glutaraldehyde crosslinking reaction and then complexed with three different types of GCGs. 7F2 osteoblasts-like cells and macrophages Raw264.7 were used as models to study the influence of chitosan membranes on osteometabolism. Although chitosan membranes are highly hydrophilic, the membranes associated with GCG-chitosan complexes showed about 60-70% cell attachment. Furthermore, the membranes associated with HP-chitosan complexes could increase ALP activity in comparison with chitosan films only. Three types of the membranes associated with GCG-chitosan complexes could significantly inhibit LPS induced-nitric oxide expression. In addition, chitosan membranes associated with HP and HA can down-regulate tartrate-resistant acid phosphatase (TRAP) activity but not CS-chitosan complexes. Based on these results, we conclude that chitosan membranes associated with HP can increase ALP activity in osteoblasts and chitosan membranes associated with HP and HA reduce TRAP activity in osteoclasts.

Keywords: osteoblast, osteoclast, chitosan, glycosaminoglycan

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Authors: Ji Hyung Park, Dong-Hyun Seo, Young-Jin Jung, Han Sung Kim

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The aim of this study is to evaluate the effects of the laser and partial vibration stimulation on the mice tibia with morphological characteristics. Twenty female C57BL/6 mice (12 weeks old) were used for the experiment. The study was carried out on four groups of animals each consisting of five mice. Four groups of mice were ovariectomized. Animals were scanned at 0 and 2 weeks after ovariectomy by using micro-computed tomography to estimate morphological characteristics of tibial trabecular bone. Morphological analysis showed that structural parameters of multi-stimuli group appear significantly better phase in BV/TV, BS/BV, Tb.Th, Tb.N, Tb.Sp, and Tb.pf than single stimulation groups. However, single stimulation groups didn’t show significant effect on tibia with Sham group. This study suggests that multi-stimuli may restrain the change as the degenerate phase on osteoporosis in the mice tibia.

Keywords: laser, partial vibration, osteoporosis, in-vivo micro-CT, mice

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Authors: Masoud Nasiri Sarvi, Yunhua Luo

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Low-trauma hip fracture, usually caused by fall from standing height, has become a main source of morbidity and mortality for the elderly. Factors affecting hip fracture include sex, race, age, body weight, height, body mass distribution, etc., and thus, hip fracture risk in fall differs widely from subject to subject. It is therefore necessary to develop a subject-specific biomechanical model to predict hip fracture risk. The objective of this study is to develop a two-level, image-based, subject-specific biomechanical model consisting of a whole-body dynamics model and a proximal-femur finite element (FE) model for more accurately assessing the risk of hip fracture in lateral falls. Required information for constructing the model is extracted from a whole-body and a hip DXA (Dual Energy X-ray Absorptiometry) image of the subject. The proposed model considers all parameters subject-specifically, which will provide a fast, accurate, and non-expensive method for predicting hip fracture risk.

Keywords: bone mineral density, hip fracture risk, impact force, sideways falls

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Authors: Ashish Thakur

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This technical paper was written in view of focusing the biomaterials and its various applications in modern industries. Author tires to elaborate not only the medical, infect plenty of application in other industries. The scope of the research area covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. Biomaterials are invariably in contact with living tissues. Thus, interactions between the surface of a synthetic material and biological environment must be well understood. This paper reviews the benefits and challenges associated with surface modification of the metals in biomedical applications. The paper also elaborates how the surface characteristics of metallic biomaterials, such as surface chemistry, topography, surface charge, and wettability, influence the protein adsorption and subsequent cell behavior in terms of adhesion, proliferation, and differentiation at the biomaterial–tissue interface. The chapter also highlights various techniques required for surface modification and coating of metallic biomaterials, including physicochemical and biochemical surface treatments and calcium phosphate and oxide coatings. In this review, the attention is focused on the biomaterial-associated infections, from which the need for anti-infective biomaterials originates. Biomaterial-associated infections differ markedly for epidemiology, aetiology and severity, depending mainly on the anatomic site, on the time of biomaterial application, and on the depth of the tissues harbouring the prosthesis. Here, the diversity and complexity of the different scenarios where medical devices are currently utilised are explored, providing an overview of the emblematic applicative fields and of the requirements for anti-infective biomaterials. In addition to this, chapter introduces nanomedicine and the use of both natural and synthetic polymeric biomaterials, focuses on specific current polymeric nanomedicine applications and research, and concludes with the challenges of nanomedicine research. Infection is currently regarded as the most severe and devastating complication associated to the use of biomaterials. Osteoporosis is a worldwide disease with a very high prevalence in humans older than 50. The main clinical consequences are bone fractures, which often lead to patient disability or even death. A number of commercial biomaterials are currently used to treat osteoporotic bone fractures, but most of these have not been specifically designed for that purpose. Many drug- or cell-loaded biomaterials have been proposed in research laboratories, but very few have received approval for commercial use. Polymeric nanomaterial-based therapeutics plays a key role in the field of medicine in treatment areas such as drug delivery, tissue engineering, cancer, diabetes, and neurodegenerative diseases. Advantages in the use of polymers over other materials for nanomedicine include increased functionality, design flexibility, improved processability, and, in some cases, biocompatibility.

Keywords: nanomedicine, tissue, infections, biomaterials

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Authors: Farusil Najeeb Mullaveettil, Rolanas Dauksevicius

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Cellular structures produced by additive manufacturing have earned wide research attention due to their unique specific strength and energy absorption potentiality. The literature review concludes that pattern type and density are vital parameters that affect the mechanical properties of parts formed by additive manufacturing techniques and have an influence on printing time and material consumption. Fused deposition modeling technique (FDM) is used here to produce Polyvinylidene fluoride (PVDF) parts. In this work, patterns are based on triply periodic minimal surfaces (TPMS) produced by PVDF-based filaments using the FDM technique. PVDF homopolymer filament Fluorinar-H™ and PVDF copolymer filament Fluorinar-C™ are printed with three types of TPMS patterns. The patterns printed are Gyroid, Schwartz diamond, and Schwartz primitive. Tensile, flexural, and compression tests under quasi-static loading conditions are performed in compliance with ISO standards. The investigation elucidates the deformation mechanisms and a study that establishes a relationship between the printed and nominal specimens' dimensional accuracy. In comparison to the examined TPMS pattern, Schwartz diamond showed a higher relative elastic modulus and strength than the other patterns in tensile loading, and the Gyroid pattern showed the highest mechanical characteristics in flexural loading. The concluded results could be utilized to produce informed cellular designs for biomedical and mechanical applications.

Keywords: additive manufacturing, FDM, PVDF, gyroid, schwartz primitive, schwartz diamond, TPMS, tensile, flexural

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