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Authors:José Pinto, João R. C. Ramos, Rafael S. Costa, Sergio Rossell, Patrick Dumas, Rui Oliveira Abstract: Introduction: Hybrid modeling combining First-Principles with machine learning is becoming a pivotal methodology for Biopharma 4.0 enactment. Chinese Hamster Ovary (CHO) cells, being the workhorse for industrial glycoproteins production, have been the object of several hybrid modeling studies. Most previous studies pursued a shallow hybrid modeling approach based on three-layered Feedforward Neural Networks (FFNNs) combined with macroscopic material balance equations. Only recently, the hybrid modeling field is incorporating deep learning into its framework with significant gains in descriptive and predictive power.Methods: This study compares, for the first time, deep and shallow hybrid modeling in a CHO process development context. Data of 24 fed-batch cultivations of a CHO-K1 cell line expressing a target glycoprotein, comprising 30 measured state variables over time, were used to compare both methodologies. Hybrid models with varying FFNN depths (3-5 layers) were systematically compared using two training methodologies. The classical training is based on the Levenberg-Marquardt algorithm, indirect sensitivity equations and cross-validation. The deep learning is based on the Adaptive Moment Estimation Method (ADAM), stochastic regularization and semidirect sensitivity equations.Results and conclusion: The results point to a systematic generalization improvement of deep hybrid models over shallow hybrid models. Overall, the training and testing errors decreased by 14.0% and 23.6% respectively when applying the deep methodology. The Central Processing Unit (CPU) time for training the deep hybrid model increased by 31.6% mainly due to the higher FFNN complexity. The final deep hybrid model is shown to predict the dynamics of the 30 state variables within the error bounds in every test experiment. Notably, the deep hybrid model could predict the metabolic shifts in key metabolites (e.g., lactate, ammonium, glutamine and glutamate) in the test experiments. We expect deep hybrid modeling to accelerate the deployment of high-fidelity digital twins in the biopharma sector in the near future. PubDate: 2023-09-08T00:00:00Z
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Authors:Ye Luo, Zhuman Li, Mengling Hu, Ling Zhang, Feng Li, Shaobai Wang Abstract: Objective: Fatigue can affect the ankle kinematic characteristics of landing movements. Traditional marker-based motion capture techniques have difficulty in accurately obtaining the kinematics of the talocrural and subtalar joints. This study aimed to investigate the effects of fatigue on the talocrural and subtalar joints during the landing using dual fluoroscopic imaging system (DFIS).Methods: This study included fourteen healthy participants. The foot of each participant was scanned using magnetic resonance imaging to create 3D models. High-speed DFIS was used to capture images of the ankle joint during participants performing a single-leg landing jump from a height of 40 cm. Fatigue was induced by running and fluoroscopic images were captured before and after fatigue. Kinematic data were obtained by 3D/2D registration in virtual environment software. The joint kinematics in six degrees of freedom and range of motion (ROM) were compared between the unfatigued and fatigued conditions.Results: During landing, after the initial contact with the ground, the main movement of the talocrural joint is extension and abduction, while the subtalar joint mainly performs extension, eversion, and abduction. Compared to unfatigued, during fatigue the maximum medial translation (1.35 ± 0.45 mm vs. 1.86 ± 0.69 mm, p = 0.032) and medial-lateral ROM (3.19 ± 0.60 mm vs. 3.89 ± 0.96 mm, p = 0.029) of the talocrural joint significantly increased, the maximum flexion angle (0.83 ± 1.24°vs. 2.11° ± 1.80°, p = 0.037) of the subtalar joint significantly increased, and the flexion-extension ROM (6.17° ± 2.21° vs. 7.97° ± 2.52°, p = 0.043) of the subtalar joint significantly increased.Conclusion: This study contributes to the quantitative understanding of the normal function of the talocrural and subtalar joints during high-demand activities. During landing, the main movement of the talocrural joint is extension and abduction, while the subtalar joint mainly performs extension, eversion, and abduction. Under fatigue conditions, the partial ROM of the talocrural and subtalar joints increases. PubDate: 2023-09-08T00:00:00Z
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Authors:Jigar Vyas, Isha Shah, Sudarshan Singh, Bhupendra G. Prajapati Abstract: Three-dimensional (3D)/four-dimensional (4D) printing, also known as additive manufacturing or fast prototyping, is a manufacturing technique that uses a digital model to generate a 3D/4D solid product. The usage of biomaterials with 3D/4D printers in the pharma and healthcare industries is gaining significant popularity. 3D printing has mostly been employed in the domain of otolaryngology to build portable anatomical models, personalized patient-centric implants, biologic tissue scaffolds, surgical planning in individuals with challenging conditions, and surgical training. Although identical to 3D printing technology in this application, 4D printing technology comprises a fourth dimension of time. With the use of 4D printing, a printed structure may alter over time under various stimuli. Smart polymeric materials are also generally denoted as bioinks are frequently employed in tissue engineering applications of 3D/4D printing. In general, 4D printing could significantly improve the safety and efficacy of otolaryngology therapies. The use of bioprinting in otolaryngology has an opportunity to transform the treatment of diseases influencing the ear, nose, and throat as well as the field of tissue regeneration. The present review briefs on polymeric material including biomaterials and cells used in the manufacturing of patient centric 3D/4D bio-printed products utilized in management of otolaryngology. PubDate: 2023-09-08T00:00:00Z
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Authors:Kai Wang, Brian J. Shriver, Roozbeh Aschar-Sobbi, Alex Y. Yi, Nicole T. Feric, Michael P. Graziano Abstract: Introduction: The development of patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offers an opportunity to study genotype-phenotype correlation of hypertrophic cardiomyopathy (HCM), one of the most common inherited cardiac diseases. However, immaturity of the iPSC-CMs and the lack of a multicellular composition pose concerns over its faithfulness in disease modeling and its utility in developing mechanism-specific treatment.Methods: The Biowire platform was used to generate 3D engineered cardiac tissues (ECTs) using HCM patient-derived iPSC-CMs carrying a β-myosin mutation (MYH7-R403Q) and its isogenic control (WT), withal ECTs contained healthy human cardiac fibroblasts. ECTs were subjected to electro-mechanical maturation for 6 weeks before being used in HCM phenotype studies.Results: Both WT and R403Q ECTs exhibited mature cardiac phenotypes, including a lack of automaticity and a ventricular-like action potential (AP) with a resting membrane potential < −75 mV. Compared to WT, R403Q ECTs demonstrated many HCM-associated pathological changes including increased tissue size and cell volume, shortened sarcomere length and disorganized sarcomere structure. In functional assays, R403Q ECTs showed increased twitch amplitude, slower contractile kinetics, a less pronounced force-frequency relationship, a smaller post-rest potentiation, prolonged AP durations, and slower Ca2+ transient decay time. Finally, we observed downregulation of calcium handling genes and upregulation of NPPB in R403Q vs. WT ECTs. In an HCM phenotype prevention experiment, ECTs were treated for 5-weeks with 250 nM mavacamten or a vehicle control. We found that chronic mavacamten treatment of R403Q ECTs: (i) shortened relaxation time, (ii) reduced APD90 prolongation, (iii) upregulated ADRB2, ATP2A2, RYR2, and CACNA1C, (iv) decreased B-type natriuretic peptide (BNP) mRNA and protein expression levels, and (v) increased sarcomere length and reduced sarcomere disarray.Discussion: Taken together, we demonstrated R403Q ECTs generated in the Biowire platform recapitulated many cardiac hypertrophy phenotypes and that chronic mavacamten treatment prevented much of the pathology. This demonstrates that the Biowire ECTs are well-suited to phenotypic-based drug discovery in a human-relevant disease model. PubDate: 2023-09-08T00:00:00Z
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Authors:Herbert P. Jennissen Abstract: The constant release of human bone morphogenetic protein 2 (rhBMP-2) in the picomolar range (Pico-Stat) from PDLLA-biohybrids led to the detection of intrinsic novel pro- and anti-angiogenic functions of this cytokine. As integrant part in this perspective of previous work, first evidence for the binding of rhBMP-2, as an inverse agonist, to allosteric angiogenic receptors in cocultures of human endothelial cells is reported. PubDate: 2023-09-07T00:00:00Z
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Authors:Yang Wang, Yang Liu, Aobo Zhang, Qing Han, Jianhang Jiao, Hao Chen, Xuqiang Gong, Wangwang Luo, Jing Yue, Xue Zhao, Jincheng Wang, Minfei Wu Abstract: Introduction: Anterior cervical discectomy and fusion (ACDF) is a standard procedure for treating symptomatic cervical degenerative disease. The cage and plate constructs (CPCs) are widely employed in ACDF to maintain spinal stability and to provide immediate support. However, several instrument-related complications such as dysphagia, cage subsidence, and adjacent segment degeneration have been reported in the previous literature. This study aimed to design a novel individualized zero-profile (NIZP) cage and evaluate its potential to enhance the biomechanical performance between the instrument and the cervical spine.Methods: The intact finite element models of C3-C7 were constructed and validated. A NIZP cage was designed based on the anatomical parameters of the subject’s C5/6. The ACDF procedure was simulated and the CPCs and NIZP cage were implanted separately. The range of motion (ROM), intradiscal pressure (IDP), and peak von Mises stresses of annulus fibrosus were compared between the two surgical models after ACDF under four motion conditions. Additionally, the biomechanical performance of the CPCs and NIZP cage were evaluated.Results: Compared with the intact model, the ROM of the surgical segment was significantly decreased for both surgical models under four motion conditions. Additionally, there was an increase in IDP and peak von Mises stress of annulus fibrosus in the adjacent segment. The NIZP cage had a more subtle impact on postoperative IDP and peak von Mises stress of annulus fibrosus in adjacent segments compared to CPCs. Meanwhile, the peak von Mises stresses of the NIZP cage were reduced by 90.0–120.0 MPa, and the average von Mises stresses were reduced by 12.61–17.56 MPa under different motion conditions. Regarding the fixation screws, the peak von Mises stresses in the screws of the NIZP cage increased by 10.0–40.0 MPa and the average von Mises stresses increased by 2.37–10.10 MPa.Conclusion: The NIZP cage could effectively reconstruct spinal stability in ACDF procedure by finite element study. Compared with the CPCs, the NIZP cage had better biomechanical performance, with a lower stress distribution on the cage and a more moderate effect on the adjacent segmental discs. Therefore, the NIZP cage could prevent postoperative dysphagia as well as decrease the risk of subsidence and adjacent disc degeneration following ACDF. In addition, this study could serve as a valuable reference for the development of personalized instruments. PubDate: 2023-09-07T00:00:00Z
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Authors:Yinong Wang, Wufan Chen, Qing Wang Abstract: Introduction: The estimation of myocardial motion abnormalities has great potential for the early diagnosis of myocardial infarction (MI). This study aims to quantitatively analyze the segmental and transmural myocardial motion in MI rats by incorporating two novel strategies of algorithm parameter optimization and transmural motion index (TMI) calculation.Methods: Twenty-one rats were randomly divided into three groups (n = 7 per group): sham, MI, and ischemia–reperfusion (IR) groups. Ultrasound radio-frequency (RF) signals were acquired from each rat heart at 1 day and 28 days after animal model establishment; thus, a total of six datasets were represented as Sham1, Sham28, MI1, MI28, IR1, and IR28. The systolic cumulative displacement was calculated using our previously proposed vectorized normalized cross-correlation (VNCC) method. A semiautomatic regional and layer-specific myocardium segmentation framework was proposed for transmural and segmental myocardial motion estimation. Two novel strategies were proposed: the displacement-compensated cross-correlation coefficient (DCCCC) for algorithm parameter optimization and the transmural motion index (TMI) for quantitative estimation of the cross-wall transmural motion gradient.Results: The results showed that an overlap value of 80% used in VNCC guaranteed a more accurate displacement calculation. Compared to the Sham1 group, the systolic myocardial motion reductions were significantly detected (p < 0.05) in the middle anteroseptal (M-ANT-SEP), basal anteroseptal (B-ANT-SEP), apical lateral (A-LAT), middle inferolateral (M-INF-LAT), and basal inferolateral (B-INF-LAT) walls as well as a significant TMI drop (p < 0.05) in the M-ANT-SEP wall in the MI1 rats; significant motion reductions (p < 0.05) were also detected in the B-ANT-SEP and A-LAT walls in the IR1 group. The motion improvements (p < 0.05) were detected in the M-INF-LAT wall in the MI28 group and the apical septal (A-SEP) wall in the IR28 group compared to the MI1 and IR1 groups, respectively.Discussion: Our results show that the MI-induced reductions and reperfusion-induced recovery in systolic myocardial contractility could be successfully evaluated using our method, and most post-MI myocardial segments could recover systolic function to various extents in the remodeling phase. In conclusion, the ultrasound-based quantitative estimation framework for estimating segmental and transmural motion of the myocardium proposed in our study has great potential for non-invasive, novel, and early MI detection. PubDate: 2023-09-07T00:00:00Z
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Authors:Jinming Zhao, Jingxing Yang, Jian Jiao, Xiangdong Wang, Yan Zhao, Luo Zhang Abstract: Intranasal administration offers a feasible, non-invasive method of delivering therapeutic drugs to the brain, allowing therapeutic pharmaceuticals to be administered directly to the central nervous system by bypassing the blood-brain barrier. Furthermore, exosomes are naturally occurring cell-derived nanovesicles that can serve as carriers for a variety of chemical compounds. Many studies have focused on artificial exosomes as innovative medication delivery methods. As a result, trans-nasal delivery of artificial exosomes might be employed to treat brain illnesses in a novel method. This review will outline the drug delivery mechanism of artificial extracellular vesicles, emphasize its advantages as a nasal drug carrier, particularly its application as a novel nanocarriers in brain diseases, and focus on its prospective application in chronic inflammatory nose disorders. Finally, artificial exosomes may become a unique drug delivery mode for clinical therapeutic usage. PubDate: 2023-09-07T00:00:00Z
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Authors:Fabian Haase, Carsten Siemers, Joachim Rösler Abstract: Laser powder bed fusion (LPBF) of titanium or titanium alloys allows fabrication of geometrically more complex and, possibly, individualized implants or osteosynthesis products and could thus improve the outcome of medical treatments considerably. However, insufficient LPBF process parameters can result in substantial porosity, decreasing mechanical properties and requiring post-treatment. Furthermore, texturized parts with anisotropic properties are usually obtained after LPBF processing, limiting their usage in medical applications. The present study addresses both: first, a design of experiments is used in order to establish a set of optimized process parameters and a process window for LPBF printing of small commercially pure (CP) titanium parts with minimized volume porosity. Afterward, the first results on the development of a biocompatible titanium alloy designed for LPBF processing of medical implants with improved solidification and more isotropic properties are presented on the basis of conventionally melted alloys. This development was performed on the basis of Ti-0.44O-0.5Fe-0.08C-0.4Si-0.1Au, a near-α alloy presented by the authors for medical applications and conventional manufacturing, with yttrium and boron additions as additional growth restriction solutes. In terms of LPBF processing of CP titanium grade 1 powder, a high relative density of approximately 99.9% was obtained in the as-printed state of the volume of a small cubical sample by using optimized laser power, scanning speed, and hatch distance in combination with a rotating scanning pattern. Moreover, tensile specimens processed with these volume settings and tested in the as-printed milled state exhibited a high average yield and ultimate tensile strength of approximately 663 and 747 N/mm2, respectively, combined with a high average ductility of approximately 24%. X-ray diffraction results suggest anisotropic mechanical properties, which are, however, less pronounced in terms of the tested specimens. Regarding alloy development, the results show that yttrium additions lead to a considerable microstructure refinement but have to be limited due to the occurrence of a large amount of precipitations and a supposed higher propensity for the formation of long columnar prior β-grains. However, phase/texture and microstructure analyses indicate that Ti-0.44O-0.5Fe-0.08C-0.4Si-0.1Au-0.1B-0.1Y is a promising candidate to achieve lower anisotropy during LPBF processing, but further investigations on LPBF printing and Y2O3 formation are necessary. PubDate: 2023-09-07T00:00:00Z
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Authors:Fengzhen Zheng, Abdul Basit, Zhiyue Zhang, Huan Zhuang, Jun Chen, Jianfen Zhang Abstract: Mannan, a highly abundant and cost-effective natural resource, holds great potential for the generation of high-value compounds such as bioactive polysaccharides and biofuels. In this study, we successfully enhanced the expression of constructed GH5 β-mannanase (TaMan5) from Trichoderma asperellum ND-1 by employing propeptide in Pichia pastoris. By replacing the α-factor with propeptide (MGNRALNSMKFFKSQALALLAATSAVA), TaMan5 activity was significantly increased from 67.5 to 91.7 U/mL. It retained higher activity in the presence of 20% ethanol and 15% NaCl. When incubated with a high concentration of mannotriose or mannotetraose, the transglycosylation action of TaMan5 can be detected, yielding the corresponding production of mannotetraose or mannooligosaccharides. Moreover, the unique mechanism whereby TaMan5 catalyzes the degradation of mannan into mannobiose involves the transglycosylation of mannose to mannotriose or mannotetraose as a substrate to produce a mannotetraose or mannopentose intermediate, respectively. Additionally, the production of soluble sugars from lignocellulose is a crucial step in bioethanol development, and it is noteworthy that TaMan5 could synergistically yield fermentable sugars from corn stover and bagasse. These findings offered valuable insights and strategies for enhancing β-mannanase expression and efficient conversion of lignocellulosic biomass, providing cost-effective and sustainable approaches for high-value biomolecule and biofuel production. PubDate: 2023-09-07T00:00:00Z
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Authors:Joana Campos, Henrik Almqvist, Jie Bao, Ola Wallberg, Gunnar Lidén Abstract: Optically pure lactic acid (LA) is needed in PLA (poly-lactic acid) production to build a crystalline structure with a higher melting point of the biopolymer than that of the racemic mixture. Lignocellulosic biomass can be used as raw material for LA production, in a non-food biorefinery concept. In the present study, genetically engineered P. acidilactici ZP26 was cultivated in a simultaneous saccharification and fermentation (SSF) process using steam pretreated softwood solids as a carbon source to produce optically pure D-LA. Given the low concentrations of identifiable inhibitory compounds from sugar and lignin degradation, the fermentation rate was expected to follow the rate of enzymatic hydrolysis. However, added pretreated solids (7% on weight (w/w) of water-insoluble solids [WIS]) significantly and immediately affected the process performance, which resulted in a long lag phase (more than 40 h) before the onset of the exponential phase of the fermentation. This unexpected delay was also observed without the addition of enzymes in the SSF and in a model fermentation with glucose and pretreated solids without added enzymes. Experiments showed that it was possible to overcome the extended lag phase in the presence of pretreated softwood solids by allowing the microorganism to initiate its exponential phase in synthetic medium, and subsequently adding the softwood solids and enzymatic blend to proceed to an SSF with D-LA production. PubDate: 2023-09-07T00:00:00Z
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Authors:Wenhang Liu, Youwei Zhang, Yongtao Lyu, Sergei Bosiakov, Yadong Liu Abstract: Introduction: Triply periodic minimal surface (TPMS) is widely used in the design of bone scaffolds due to its structural advantages. However, the current approach to designing bone scaffolds using TPMS structures is limited to a forward process from microstructure to mechanical properties. Developing an inverse bone scaffold design method based on the mechanical properties of bone structures is crucial.Methods: Using the machine learning and genetic algorithm, a new inverse design model was proposed in this research. The anisotropy of bone was matched by changing the number of cells in different directions. The finite element (FE) method was used to calculate the TPMS configuration and generate a back propagation neural network (BPNN) data set. Neural networks were used to establish the relationship between microstructural parameters and the elastic matrix of bone. This relationship was then used with regenerative genetic algorithm (RGA) in inverse design.Results: The accuracy of the BPNN-RGA model was confirmed by comparing the elasticity matrix of the inverse-designed structure with that of the actual bone. The results indicated that the average error was below 3.00% for three mechanical performance parameters as design targets, and approximately 5.00% for six design targets.Discussion: The present study demonstrated the potential of combining machine learning with traditional optimization method to inversely design anisotropic TPMS bone scaffolds with target mechanical properties. The BPNN-RGA model achieves higher design efficiency, compared to traditional optimization methods. The entire design process is easily controlled. PubDate: 2023-09-07T00:00:00Z
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Authors:Rupak Dua, Onessa Sharufa, Joi Terry, William Dunn, Indu Khurana, Jagasivamani Vadivel, Yue Zhang, Henry J. Donahue Abstract: Polyether-ether-ketone (PEEK) is increasingly becoming popular in medicine because of its excellent mechanical strength, dimensional stability, and chemical resistance properties. However, PEEK being bioinert, has weak bone osseointegration properties, limiting its clinical applications. In this study, a porous PEEK structure was developed using a chemical etching method with 98 wt% sulfuric acids and three post-treatments were performed to improve bone cell adhesion and proliferation. Four groups of PEEK samples were prepared for the study: Control (untreated; Group 1); Etched with sulfuric acid and washed with distilled water (Group 2); Etched with sulfuric acid and washed with acetone and distilled water (Group 3); and Etched with sulfuric acid and washed with 4 wt% sodium hydroxide and distilled water (Group 4). Surface characterization of the different groups was evaluated for surface topology, porosity, roughness, and wettability using various techniques, including scanning electron microscopy, profilometer, and goniometer. Further chemical characterization was done using Energy-dispersive X-ray spectroscopy to analyze the elements on the surface of each group. Bone cell studies were conducted using cell toxicity and alkaline phosphatase activity (ALP) assays. The SEM analysis of the different groups revealed porous structures in the treatment groups, while the control group showed a flat topology. There was no statistically significant difference between the pore size within the treated groups. This was further confirmed by the roughness values measured with the profilometer. We found a statistically significant increase in the roughness from 7.22 × 10−3 μm for the control group to the roughness range of 0.1 µm for the treated groups (Groups 2–4). EDX analysis revealed the presence of a 0.1% weight concentration of sodium on the surface of Group 4, while sulfur weight percentage concentration was 1.1%, 0.1%, and 1.4% in groups 2, 3, and 4, respectively, indicating different surface chemistry on the surface due to different post-treatments. Cell toxicity decreased, and ALP activity increased in groups 3 and 4 over 7 days compared with the control group. It is demonstrated that the surface modification of PEEK using a chemical etching method with post-processing with either acetone or sodium hydroxide provides a nano-porous structure with improved properties, leading to enhanced osteoblastic cell differentiation and osteogenic potential. PubDate: 2023-09-07T00:00:00Z
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Authors:Jing Gao, Lulu Jiang, Baohong Zhao Abstract: Mandibular flexure, characterized by unique biomechanical behaviors such as elastic bending and torsion under functional loading, has emerged as a crucial factor in oral clinical diagnosis and treatment. This paper presents a comprehensive review of the current research status on mandibular flexure, drawing insights from relevant studies retrieved from the PubMed database (www.ncbi.nlm.nih.gov/pubmed), including research conclusions, literature reviews, case reports, and authoritative reference books. This paper thoroughly explores the physiological mechanisms underlying mandibular flexure, discussing different concurrent deformation types and the essential factors influencing this process. Moreover, it explores the profound implications of mandibular flexure on clinical aspects such as bone absorption around dental implants, the precision of prosthesis fabrication, and the selection and design of superstructure materials. Based on the empirical findings, this review provides crucial clinical recommendations. Specifically, it is recommended to exert precise control over the patients mouth opening during impression-taking. Those with a high elastic modulus or bone-tissue-like properties should be prioritized when selecting superstructure materials. Moreover, this review underscores the significance of customizing framework design to accommodate individual variations in facial morphology and occlusal habits. Future research endeavors in this field have the potential to advance clinical diagnosis and treatment approaches, providing opportunities for improvement. PubDate: 2023-09-07T00:00:00Z
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Authors:Xuan Mu, Reza Amouzandeh, Hannah Vogts, Elise Luallen, Milad Arzani Abstract: Silk spinning, observed in spiders and insects, exhibits a remarkable biological source of inspiration for advanced polymer fabrications. Because of the systems design, silk spinning represents a holistic and circular approach to sustainable polymer fabrication, characterized by renewable resources, ambient and aqueous processing conditions, and fully recyclable “wastes.” Also, silk spinning results in structures that are characterized by the combination of monolithic proteinaceous composition and mechanical strength, as well as demonstrate tunable degradation profiles and minimal immunogenicity, thus making it a viable alternative to most synthetic polymers for the development of advanced biomedical devices. However, the fundamental mechanisms of silk spinning remain incompletely understood, thus impeding the efforts to harness the advantageous properties of silk spinning. Here, we present a concise and timely review of several essential features of silk spinning, including the molecular designs of silk proteins and the solvent cues along the spinning apparatus. The solvent cues, including salt ions, pH, and water content, are suggested to direct the hierarchical assembly of silk proteins and thus play a central role in silk spinning. We also discuss several hypotheses on the roles of solvent cues to provide a relatively comprehensive analysis and to identify the current knowledge gap. We then review the state-of-the-art bioinspired fabrications with silk proteins, including fiber spinning and additive approaches/three-dimensional (3D) printing. An emphasis throughout the article is placed on the universal characteristics of silk spinning developed through millions of years of individual evolution pathways in spiders and silkworms. This review serves as a stepping stone for future research endeavors, facilitating the in vitro recapitulation of silk spinning and advancing the field of bioinspired polymer fabrication. PubDate: 2023-09-06T00:00:00Z
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Authors:Dong-Sung Won, Yubeen Park, Chu Hui Zeng, Dae Sung Ryu, Ji Won Kim, Jeon Min Kang, Song Hee Kim, Hyung-Sik Kim, Sang Soo Lee, Jung-Hoon Park Abstract: Background: In-stent restenosis caused by tissue hyperplasia and tumor growth through the wire meshes of an implanted self-expandable metallic stent (SEMS) remains an unresolved obstacle. This study aimed to investigate the safety and efficacy of SEMS-mediated radiofrequency ablation (RFA) for treating stent-induced tissue hyperplasia in a rat gastric outlet obstruction model.Methods: The ablation zone was investigated using extracted porcine liver according to the ablation time. The optimal RFA parameters were evaluated in the dissected rat gastric outlet. We allocated 40 male rats to four groups of 10 rats as follows: group A, SEMS placement only; group B, SEMS-mediated RFA at 4 weeks; group C, SEMS-mediated RFA at 4 weeks and housed until 8 weeks; and group D, SEMS-mediated RFA at 4 and 8 weeks. Endoscopy and fluoroscopy for in vivo imaging and histological and immunohistochemical analysis were performed to compare experimental groups.Results: Stent placement and SEMS-mediated RFA with an optimized RFA parameter were technically successful in all groups. Granulation tissue formation-related variables were significantly higher in group A than in groups B–D (all p < 0.05). Endoscopic and histological findings confirmed that the degrees of stent-induced tissue hyperplasia in group D were significantly lower than in groups B and C (all p < 0.05). Hsp70 and TUNEL expressions were significantly higher in groups B–D than in group A (all p < 0.001).Conclusion: The implanted SEMS-mediated RFA successfully managed stent-induced tissue hyperplasia, and repeated or periodic RFA seems to be more effective in treating in-stent restenosis in a rat gastric outlet obstruction model. PubDate: 2023-09-06T00:00:00Z
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Authors:Kaicheng Wu, Xiaole Sun, Dongqiang Ye, Faning Zhang, Shen Zhang, Weijie Fu Abstract: Existing studies on the biomechanical characteristics of the first metatarsophalangeal joint (1st MTPJ) during shod running are limited to sagittal plane assessment and rely on skin marker motion capture, which can be affected by shoes wrapping around the 1st MTPJ and may lead to inaccurate results. This study aims to investigate the in vivo effects of different habitual foot strike patterns (FSP) on the six degrees of freedom (6DOF) values of the 1st MTPJ under shod condition by utilizing a dual-fluoroscopic imaging system (DFIS). Long-distance male runners with habitual forefoot strike (FFS group, n = 15) and rearfoot strike (RFS group, n = 15) patterns were recruited. All participants underwent foot computed tomography (CT) scan to generate 3D models of their foot. The 6DOF kinematics of the 1st MTPJ were collected using a DFIS at 100 Hz when participants performed their habitual FSP under shod conditions. Independent t-tests and one-dimensional statistical parametric mapping (1-d SPM) were employed to analyze the differences between the FFS and RFS groups’ 1st MTPJ 6DOF kinematic values during the stance phase. FFS exhibited greater superior translation (3.5–4.9 mm, p = 0.07) during 51%–82% of the stance and higher extension angle (8.4°–10.1°, p = 0.031) during 65%–75% of the stance in the 1st MTPJ than RFS. Meanwhile, FFS exhibited greater maximum superior translation (+3.2 mm, p = 0.022), maximum valgus angle (+6.1°, p = 0.048) and varus–valgus range of motion (ROM) (+6.5°, p = 0.005) in the 1st MTPJ during stance. The greater extension angle of the 1st MTPJ in the late stance suggested that running with FFS may enhance the propulsive effect. However, the higher maximum valgus angle and the ROM of varus–valgus in FFS may potentially lead to the development of hallux valgus. PubDate: 2023-09-06T00:00:00Z
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Authors:Angela S. P. Lin, David S. Reece, Tanushree Thote, Sanjay Sridaran, Hazel Y. Stevens, Nick J. Willett, Robert E. Guldberg Abstract: Background: Micronized dehydrated human amnion/chorion membrane (mdHACM) has reduced short term post-traumatic osteoarthritis (PTOA) progression in rats when delivered 24 h after medial meniscal transection (MMT) and is being investigated for clinical use as a disease modifying therapy. Much remains to be assessed, including its potential for longer-term therapeutic benefit and treatment effects after onset of joint degeneration.Objectives: Characterize longer-term effects of acute treatment with mdHACM and determine whether treatment administered to joints with established PTOA could slow or reverse degeneration. Hypotheses: Acute treatment effects will be sustained for 6 weeks, and delivery of mdHACM after onset of joint degeneration will attenuate structural osteoarthritic changes.Methods: Rats underwent MMT or sham surgery (left leg). mdHACM was delivered intra-articularly 24 h or 3 weeks post-surgery (n = 5–7 per group). Six weeks post-surgery, animals were euthanized and left tibiae scanned using equilibrium partitioning of an ionic contrast agent microcomputed tomography (EPIC-µCT) to structurally quantify joint degeneration. Histology was performed to examine tibial plateau cartilage.Results: Quantitative 3D µCT showed that cartilage structural metrics (thickness, X-ray attenuation, surface roughness, exposed bone area) for delayed mdHACM treatment limbs were significantly improved over saline treatment and not significantly different from shams. Subchondral bone mineral density and thickness for the delayed treatment group were significantly improved over acute treated, and subchondral bone thickness was not significantly different from sham. Marginal osteophyte degenerative changes were decreased with delayed mdHACM treatment compared to saline. Acute treatment (24 h post-surgery) did not reduce longer-term joint tissue degeneration compared to saline. Histology supported µCT findings and further revealed that while delayed treatment reduced cartilage damage, chondrocytes displayed qualitatively different morphologies and density compared to sham.Conclusion: This study provides insight into effects of intra-articular delivery timing relative to PTOA progression and the duration of therapeutic benefit of mdHACM. Results suggest that mdHACM injection into already osteoarthritic joints can improve joint health, but a single, acute mdHACM injection post-injury does not prevent long term osteoarthritis associated with meniscal instability. Further work is needed to fully characterize the durability of therapeutic benefit in stable osteoarthritic joints and the effects of repeated injections. PubDate: 2023-09-06T00:00:00Z
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Authors:Xiaodong Hu, Chunhai Ke, Jiaqi Zhong, Yujiong Chen, Jieyang Dong, Mingming Hao, Qi Chen, Jiahua Ni, Zhaoxiang Peng Abstract: Osteosarcoma, the most common primary malignant bone tumor, is characterized by malignant cells producing osteoid or immature bone tissue. Most osteosarcoma patients require reconstructive surgery to restore the functional and structural integrity of the injured bone. Metal orthopedic implants are commonly used to restore the limb integrity in postoperative patients. However, conventional metal implants with a bioinert surface cannot inhibit the growth of any remaining cancer cells, resulting in a higher risk of cancer recurrence. Herein, we fabricate a selenium-doped TiO2 nanotube array (Se-doped TNA) film to modify the surface of medical pure titanium substrate, and evaluate the anti-tumor effect and biocompatibility of Se-doped TNA film. Moreover, we further explore the anti-tumor potential mechanism of Se-doped TNA film by studying the behaviors of human osteosarcoma cells in vitro. We provide a new pathway for achieving the anti-tumor function of orthopedic implants while keeping the biocompatibility, aiming to suppress the recurrence of osteosarcoma. PubDate: 2023-09-05T00:00:00Z
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Authors:Devon E. Anderson, Katherine G. Broun, Paromita Kundu, Xingyu Jing, Xiang Tang, Christopher Lu, Alexander Kotelsky, Sandeep Mannava, Whasil Lee Abstract: Introduction: A massive rotator cuff tear (RCT) leads to glenohumeral joint destabilization and characteristic degenerative changes, termed cuff tear arthropathy (CTA). Understanding the response of articular cartilage to a massive RCT will elucidate opportunities to promote homeostasis following restoration of joint biomechanics with rotator cuff repair. Mechanically activated calcium-permeating channels, in part, modulate the response of distal femoral chondrocytes in the knee against injurious loading and inflammation. The objective of this study was to investigate PIEZO1-mediated mechanotransduction of glenohumeral articular chondrocytes in the altered biomechanical environment following RCT to ultimately identify potential therapeutic targets to attenuate cartilage degeneration after rotator cuff repair.Methods: First, we quantified mechanical susceptibility of chondrocytes in mouse humeral head cartilage ex vivo with treatments of specific chemical agonists targeting PIEZO1 and TRPV4 channels. Second, using a massive RCT mouse model, chondrocytes were assessed for mechano-vulnerability, PIEZO1 expression, and calcium signaling activity 14-week post-injury, an early stage of CTA.Results: In native humeral head chondrocytes, chemical activation of PIEZO1 (Yoda1) significantly increased chondrocyte mechanical susceptibility against impact loads, while TRPV4 activation (GSK101) significantly decreased impact-induced chondrocyte death. A massive RCT caused morphologic and histologic changes to the glenohumeral joint with decreased sphericity and characteristic bone bruising of the posterior superior quadrant of the humeral head. At early CTA, chondrocytes in RCT limbs exhibit a significantly decreased functional expression of PIEZO1 compared with uninjured or sham controls.Discussion: In contrast to the hypothesis, PIEZO1 expression and activity is not increased, but rather downregulated, after massive RCT at the early stage of cuff tear arthropathy. These results may be secondary to the decreased axial loading after glenohumeral joint decoupling in RCT limbs. PubDate: 2023-09-05T00:00:00Z
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