Pub Date : 2022-04-07DOI: 10.3389/fmedt.2022.846065
N. Milosevic, M. Rütter, A. David
Endothelial cell adhesion molecules have long been proposed as promising targets in many pathologies. Despite promising preclinical data, several efforts to develop small molecule inhibitors or monoclonal antibodies (mAbs) against cell adhesion molecules (CAMs) ended in clinical-stage failure. In parallel, many well-validated approaches for targeting CAMs with nanomedicine (NM) were reported over the years. A wide range of potential applications has been demonstrated in various preclinical studies, from drug delivery to the tumor vasculature, imaging of the inflamed endothelium, or blocking immune cells infiltration. However, no NM drug candidate emerged further into clinical development. In this review, we will summarize the most advanced examples of CAM-targeted NMs and juxtapose them with known traditional drugs against CAMs, in an attempt to identify important translational hurdles. Most importantly, we will summarize the proposed strategies to enhance endothelial CAM targeting by NMs, in an attempt to offer a catalog of tools for further development.
{"title":"Endothelial Cell Adhesion Molecules- (un)Attainable Targets for Nanomedicines","authors":"N. Milosevic, M. Rütter, A. David","doi":"10.3389/fmedt.2022.846065","DOIUrl":"https://doi.org/10.3389/fmedt.2022.846065","url":null,"abstract":"Endothelial cell adhesion molecules have long been proposed as promising targets in many pathologies. Despite promising preclinical data, several efforts to develop small molecule inhibitors or monoclonal antibodies (mAbs) against cell adhesion molecules (CAMs) ended in clinical-stage failure. In parallel, many well-validated approaches for targeting CAMs with nanomedicine (NM) were reported over the years. A wide range of potential applications has been demonstrated in various preclinical studies, from drug delivery to the tumor vasculature, imaging of the inflamed endothelium, or blocking immune cells infiltration. However, no NM drug candidate emerged further into clinical development. In this review, we will summarize the most advanced examples of CAM-targeted NMs and juxtapose them with known traditional drugs against CAMs, in an attempt to identify important translational hurdles. Most importantly, we will summarize the proposed strategies to enhance endothelial CAM targeting by NMs, in an attempt to offer a catalog of tools for further development.","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82103128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-05DOI: 10.3389/fmedt.2022.856412
Swapna Sasi, Basabdatta Sen Bhattacharya
We have studied brain connectivity using a biologically inspired in silico model of the visual pathway consisting of the lateral geniculate nucleus (LGN) of the thalamus, and layers 4 and 6 of the primary visual cortex. The connectivity parameters in the model are informed by the existing anatomical parameters from mammals and rodents. In the base state, the LGN and layer 6 populations in the model oscillate with dominant alpha frequency, while the layer 4 oscillates in the theta band. By changing intra-cortical hyperparameters, specifically inhibition from layer 6 to layer 4, we demonstrate a transition to alpha mode for all the populations. Furthermore, by increasing the feedforward connectivities in the thalamo-cortico-thalamic loop, we could transition into the beta band for all the populations. On looking closely, we observed that the origin of this beta band is in the layer 6 (infragranular layers); lesioning the thalamic feedback from layer 6 removed the beta from the LGN and the layer 4. This agrees with existing physiological studies where it is shown that beta rhythm is generated in the infragranular layers. Lastly, we present a case study to demonstrate a neurological condition in the model. By changing connectivities in the network, we could simulate the condition of significant (P < 0.001) decrease in beta band power and a simultaneous increase in the theta band power, similar to that observed in Schizophrenia patients. Overall, we have shown that the connectivity changes in a simple visual thalamocortical in silico model can simulate state changes in the brain corresponding to both health and disease conditions.
{"title":"In silico Effects of Synaptic Connections in the Visual Thalamocortical Pathway","authors":"Swapna Sasi, Basabdatta Sen Bhattacharya","doi":"10.3389/fmedt.2022.856412","DOIUrl":"https://doi.org/10.3389/fmedt.2022.856412","url":null,"abstract":"We have studied brain connectivity using a biologically inspired in silico model of the visual pathway consisting of the lateral geniculate nucleus (LGN) of the thalamus, and layers 4 and 6 of the primary visual cortex. The connectivity parameters in the model are informed by the existing anatomical parameters from mammals and rodents. In the base state, the LGN and layer 6 populations in the model oscillate with dominant alpha frequency, while the layer 4 oscillates in the theta band. By changing intra-cortical hyperparameters, specifically inhibition from layer 6 to layer 4, we demonstrate a transition to alpha mode for all the populations. Furthermore, by increasing the feedforward connectivities in the thalamo-cortico-thalamic loop, we could transition into the beta band for all the populations. On looking closely, we observed that the origin of this beta band is in the layer 6 (infragranular layers); lesioning the thalamic feedback from layer 6 removed the beta from the LGN and the layer 4. This agrees with existing physiological studies where it is shown that beta rhythm is generated in the infragranular layers. Lastly, we present a case study to demonstrate a neurological condition in the model. By changing connectivities in the network, we could simulate the condition of significant (P < 0.001) decrease in beta band power and a simultaneous increase in the theta band power, similar to that observed in Schizophrenia patients. Overall, we have shown that the connectivity changes in a simple visual thalamocortical in silico model can simulate state changes in the brain corresponding to both health and disease conditions.","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84216927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-05DOI: 10.3389/fmedt.2022.859498
P. Rangaiah, Bappaditya Mandal, E. Avetisyan, A. Chezhian, B. Augustine, M. Pérez, Robin Augustine
The European “Senseburn” project aims to develop a smart, portable, non-invasive microwave early effective diagnostic tool to assess the depth(d) and degree of burn. The objective of the work is to design and develop a convenient non-invasive microwave sensor for the analysis of the burn degree on burnt human skin. The flexible and biocompatible microwave sensor is developed using a magnetically coupled loop probe with a spiral resonator (SR). The sensor is realized with precise knowledge of the lumped element characteristics (resistor (R), an inductor (L), and a capacitor (C) RLC parameters). The estimated electrical equivalent circuit technique relies on a rigorous method enabling a comprehensive characterization of the sensor (loop probe and SR). The microwave resonator sensor with high quality factor (Q) is simulated using a CST studio suite, AWR microwave office, and fabricated on the RO 3003 substrate with a standard thickness of 0.13 mm. The sensor is prepared based on the change in dielectric property variation in the burnt skin. The sensor can detect a range of permittivity variations (εr 3–38). The sensor is showing a good response in changing resonance frequency between 1.5 and 1.71 GHz for (εr 3 to 38). The sensor is encapsulated with PDMS for the biocompatible property. The dimension of the sensor element is length (L) = 39 mm, width (W) = 34 mm, and thickness (T) = 1.4 mm. The software algorithm is prepared to automate the process of burn analysis. The proposed electromagnetic (EM) resonator based sensor provides a non-invasive technique to assess burn degree by monitoring the changes in resonance frequency. Most of the results are based on numerical simulation. We propose the unique circuit set up and the sensor device based on the information generated from the simulation in this article. The clinical validation of the sensor will be in our future work, where we will understand closely the practical functioning of the sensor based on burn degrees. The senseburn system is designed to support doctors to gather vital info of the injuries wirelessly and hence provide efficient treatment for burn victims, thus saving lives.
{"title":"Preliminary Analysis of Burn Degree Using Non-invasive Microwave Spiral Resonator Sensor for Clinical Applications","authors":"P. Rangaiah, Bappaditya Mandal, E. Avetisyan, A. Chezhian, B. Augustine, M. Pérez, Robin Augustine","doi":"10.3389/fmedt.2022.859498","DOIUrl":"https://doi.org/10.3389/fmedt.2022.859498","url":null,"abstract":"The European “Senseburn” project aims to develop a smart, portable, non-invasive microwave early effective diagnostic tool to assess the depth(d) and degree of burn. The objective of the work is to design and develop a convenient non-invasive microwave sensor for the analysis of the burn degree on burnt human skin. The flexible and biocompatible microwave sensor is developed using a magnetically coupled loop probe with a spiral resonator (SR). The sensor is realized with precise knowledge of the lumped element characteristics (resistor (R), an inductor (L), and a capacitor (C) RLC parameters). The estimated electrical equivalent circuit technique relies on a rigorous method enabling a comprehensive characterization of the sensor (loop probe and SR). The microwave resonator sensor with high quality factor (Q) is simulated using a CST studio suite, AWR microwave office, and fabricated on the RO 3003 substrate with a standard thickness of 0.13 mm. The sensor is prepared based on the change in dielectric property variation in the burnt skin. The sensor can detect a range of permittivity variations (εr 3–38). The sensor is showing a good response in changing resonance frequency between 1.5 and 1.71 GHz for (εr 3 to 38). The sensor is encapsulated with PDMS for the biocompatible property. The dimension of the sensor element is length (L) = 39 mm, width (W) = 34 mm, and thickness (T) = 1.4 mm. The software algorithm is prepared to automate the process of burn analysis. The proposed electromagnetic (EM) resonator based sensor provides a non-invasive technique to assess burn degree by monitoring the changes in resonance frequency. Most of the results are based on numerical simulation. We propose the unique circuit set up and the sensor device based on the information generated from the simulation in this article. The clinical validation of the sensor will be in our future work, where we will understand closely the practical functioning of the sensor based on burn degrees. The senseburn system is designed to support doctors to gather vital info of the injuries wirelessly and hence provide efficient treatment for burn victims, thus saving lives.","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88716643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-04DOI: 10.3389/fmedt.2022.783460
Farrukh Khalil, J. Onyango
Patent expiry or loss of exclusivity exposes innovator pharmaceutical companies to changes in the market dynamics brought about by increased production of generics by rival companies after patent expiration. This current study focused on the effect of generic products manufacturing and competitive market pressures, price changes, and changes in sales volumes and profitability of innovator multinational pharmaceutical companies after patent expiry. The methodology of this study involved a descriptive survey design and utilized both qualitative and quantitative techniques for data collection, analysis, and presentation. Primary data were collected using the key informants' in-depth interviews and survey questionnaires. The top management, including regional managers, general managers, and directors of each of the eight companies participating in this study, were interviewed to gather the qualitative data. Thirty-six respondents comprising of Product Development Managers and Business Supervising Managers responded to a survey questionnaire through purposive sampling. Findings depicted a significant effect of patent expiry on the generic production and subsequent decline in the performance of multinational innovator companies in the pharmaceutical industry. This study recommends that multinational innovator companies operating in low-income countries, such as Kenya, develop strategic policies to tap into the market by leveraging generic production through collaborative manufacturing with generic companies to share revenues.
{"title":"Effect of Patent Expiry on the Performance of Innovator Multinational Pharmaceutical Companies in a Low Middle Income Country","authors":"Farrukh Khalil, J. Onyango","doi":"10.3389/fmedt.2022.783460","DOIUrl":"https://doi.org/10.3389/fmedt.2022.783460","url":null,"abstract":"Patent expiry or loss of exclusivity exposes innovator pharmaceutical companies to changes in the market dynamics brought about by increased production of generics by rival companies after patent expiration. This current study focused on the effect of generic products manufacturing and competitive market pressures, price changes, and changes in sales volumes and profitability of innovator multinational pharmaceutical companies after patent expiry. The methodology of this study involved a descriptive survey design and utilized both qualitative and quantitative techniques for data collection, analysis, and presentation. Primary data were collected using the key informants' in-depth interviews and survey questionnaires. The top management, including regional managers, general managers, and directors of each of the eight companies participating in this study, were interviewed to gather the qualitative data. Thirty-six respondents comprising of Product Development Managers and Business Supervising Managers responded to a survey questionnaire through purposive sampling. Findings depicted a significant effect of patent expiry on the generic production and subsequent decline in the performance of multinational innovator companies in the pharmaceutical industry. This study recommends that multinational innovator companies operating in low-income countries, such as Kenya, develop strategic policies to tap into the market by leveraging generic production through collaborative manufacturing with generic companies to share revenues.","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"180 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73935817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.3389/fmedt.2022.851927
A. Sakes, Menno Lageweg, R. van Starkenburg, Saurabh Sontakke, J. Spronck
With the ongoing miniaturization of surgical instruments, the ability to apply large forces on tissues for resection becomes challenging and the risk of buckling becomes more real. In an effort to allow for high force application in slender instruments, in this study, we have investigated using a hydraulic pressure wave (COMSOL model) and developed an innovative 5F cardiac catheter (L = 1,000 mm) that allows for applying high forces up to 9.0 ± 0.2 N on target tissues without buckling. The catheter uses high-speed pressure waves to transfer high-force impulses through a slender flexible shaft consisted of a flat wire coil, a double braid, and a nylon outer coating. The handle allows for single-handed operation of the catheter with easy adjusting of the input impulse characteristic, including frequency (1–10 Hz), time and number of strokes using a solenoid actuator, and easy connection of an off-the-shelf inflator for catheter filling. In a proof-of-principle experiment, we illustrated that the Wave catheter was able to penetrate a phantom model of a coronary Chronic Total Occlusion (CTO) manufactured out of hydroxyapatite and gelatin. It was found that the time until puncture decreased from 80 ± 5.4 s to 7.8 ± 0.4 s, for a stroke frequency of 1–10 Hz, respectively. The number of strikes until puncture was approximately constant at 80 ± 5.4, 76.7 ± 2.6, and 77.7 ± 3.9 for the different stroke frequencies. With the development of the Wave catheter, first steps have been made toward high force application through slender shafts.
{"title":"Crossing Total Occlusions Using a Hydraulic Pressure Wave: Development of the Wave Catheter","authors":"A. Sakes, Menno Lageweg, R. van Starkenburg, Saurabh Sontakke, J. Spronck","doi":"10.3389/fmedt.2022.851927","DOIUrl":"https://doi.org/10.3389/fmedt.2022.851927","url":null,"abstract":"With the ongoing miniaturization of surgical instruments, the ability to apply large forces on tissues for resection becomes challenging and the risk of buckling becomes more real. In an effort to allow for high force application in slender instruments, in this study, we have investigated using a hydraulic pressure wave (COMSOL model) and developed an innovative 5F cardiac catheter (L = 1,000 mm) that allows for applying high forces up to 9.0 ± 0.2 N on target tissues without buckling. The catheter uses high-speed pressure waves to transfer high-force impulses through a slender flexible shaft consisted of a flat wire coil, a double braid, and a nylon outer coating. The handle allows for single-handed operation of the catheter with easy adjusting of the input impulse characteristic, including frequency (1–10 Hz), time and number of strokes using a solenoid actuator, and easy connection of an off-the-shelf inflator for catheter filling. In a proof-of-principle experiment, we illustrated that the Wave catheter was able to penetrate a phantom model of a coronary Chronic Total Occlusion (CTO) manufactured out of hydroxyapatite and gelatin. It was found that the time until puncture decreased from 80 ± 5.4 s to 7.8 ± 0.4 s, for a stroke frequency of 1–10 Hz, respectively. The number of strikes until puncture was approximately constant at 80 ± 5.4, 76.7 ± 2.6, and 77.7 ± 3.9 for the different stroke frequencies. With the development of the Wave catheter, first steps have been made toward high force application through slender shafts.","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79166027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-21DOI: 10.3389/fmedt.2022.834856
D. Krist, D. Linz, U. Schotten, S. Zeemering, Dwayne Leenen
Aim This proof-of-concept study aimed to investigate atrial and ventricular lesion formation by a 20-mm linear laser ablation catheter, regarding lesion depth and tissue damage. Methods In total, 6 female swines underwent standard femoral vein access to introduce a novel 20-mm linear laser ablation catheter in the right atrium to perform endocardial cavotricuspid isthmus (CTI) ablations. The navigation took place under fluoroscopy with additional visualization by intracardiac echocardiograph. Via a sternotomy, epicardial ablations were performed on the surface of the left ventricle (LV), right ventricle (RV), and right atrial appendage (RAA). Procedural safety was assessed by registration of intraprocedural adverse events and by macroscopic examination of the excised hearts for the presence of charring or tissue disruption at the lesion site. Results Altogether 39 lesions were created, including 8 endocardial CTI (mean lesion length 20.6 ± 1.65 mm), 26 epicardial ventricle (mean lesion length LV: 25.3 ± 1.35 mm, RV: 24.9 ± 2.40 mm), and 5 epicardial appendage ablations (mean lesion length RAA: 26.0 ± 3.16 mm). Transmurality was achieved in all CTI and atrial appendage ablations, in 62% of the RV ablations and in none of the LV ablations. No perforation or steam pop occurred, and no animal died during the procedure. Conclusion In this porcine study, the 20-mm linear laser ablation catheter has shown excellent results for endocardial cavotricuspid isthmus ablation, and it resulted in acceptable lesion depth during atrial and ventricular epicardial ablation. The absence of tissue charring, steam pops, or microbubbles under the experimental conditions suggests a high degree of procedural safety.
目的:本概念验证研究旨在探讨20毫米线性激光消融导管对心房和心室病变形成的影响，包括病变深度和组织损伤。方法6头母猪经标准股静脉入路，在右心房置入新型20mm线性激光消融导管，行心内膜腔尖峡部(CTI)消融。导航在x线透视下进行，并通过心内超声心动图进行额外的可视化。经胸骨切开，在左心室(LV)、右心室(RV)和右心房附件(RAA)表面进行心外膜消融。通过登记术中不良事件和对切除的心脏进行宏观检查以确定病变部位是否存在炭化或组织破坏来评估手术安全性。结果共形成39个病灶，其中心内膜CTI 8个(平均病灶长度20.6±1.65 mm)，心外膜室26个(平均病灶长度LV: 25.3±1.35 mm, RV: 24.9±2.40 mm)，心外膜附件消融5个(平均病灶长度RAA: 26.0±3.16 mm)。所有CTI和心房附件消融均实现了透性，62%的右心室消融和左心室消融均未实现。没有穿孔或蒸汽爆裂发生，也没有动物在手术过程中死亡。结论在猪的研究中，20mm线性激光消融导管对心内膜腔三尖瓣峡部的消融有很好的效果，在心房和心室心外膜消融时病灶深度可接受。在实验条件下，没有组织炭化，蒸汽爆裂或微气泡表明高度的程序安全性。
{"title":"A Novel Laser Energy Ablation Catheter for Endocardial Cavo-Tricuspid Isthmus Ablation and Epicardial Ventricular Lesion Formation: An in vivo Proof-of-Concept Study","authors":"D. Krist, D. Linz, U. Schotten, S. Zeemering, Dwayne Leenen","doi":"10.3389/fmedt.2022.834856","DOIUrl":"https://doi.org/10.3389/fmedt.2022.834856","url":null,"abstract":"Aim This proof-of-concept study aimed to investigate atrial and ventricular lesion formation by a 20-mm linear laser ablation catheter, regarding lesion depth and tissue damage. Methods In total, 6 female swines underwent standard femoral vein access to introduce a novel 20-mm linear laser ablation catheter in the right atrium to perform endocardial cavotricuspid isthmus (CTI) ablations. The navigation took place under fluoroscopy with additional visualization by intracardiac echocardiograph. Via a sternotomy, epicardial ablations were performed on the surface of the left ventricle (LV), right ventricle (RV), and right atrial appendage (RAA). Procedural safety was assessed by registration of intraprocedural adverse events and by macroscopic examination of the excised hearts for the presence of charring or tissue disruption at the lesion site. Results Altogether 39 lesions were created, including 8 endocardial CTI (mean lesion length 20.6 ± 1.65 mm), 26 epicardial ventricle (mean lesion length LV: 25.3 ± 1.35 mm, RV: 24.9 ± 2.40 mm), and 5 epicardial appendage ablations (mean lesion length RAA: 26.0 ± 3.16 mm). Transmurality was achieved in all CTI and atrial appendage ablations, in 62% of the RV ablations and in none of the LV ablations. No perforation or steam pop occurred, and no animal died during the procedure. Conclusion In this porcine study, the 20-mm linear laser ablation catheter has shown excellent results for endocardial cavotricuspid isthmus ablation, and it resulted in acceptable lesion depth during atrial and ventricular epicardial ablation. The absence of tissue charring, steam pops, or microbubbles under the experimental conditions suggests a high degree of procedural safety.","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83784220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-17DOI: 10.3389/fmedt.2022.834123
Michael C. Yang, A. O’Connor, B. Kalionis, D. Heath
Decellularized extracellular matrix (dECM) deposited by mesenchymal stromal cells (MSCs) has emerged as a promising substrate for improved expansion of MSCs. To date, essentially all studies that have produced dECM for MSC expansion have done so on tissue culture plastic or glass. However, substrate surface chemistry has a profound impact on the adsorption of proteins that mediate cell-material interactions, and different surface chemistries can cause changes in cell behavior, ECM deposition, and the in vivo response to a material. This study tested the hypothesis that substrate surface chemistry impacts the deposition of ECM and its subsequent bioactivity. This hypothesis was tested by producing glass surfaces with various surface chemistries (amine, carboxylic acid, propyl, and octyl groups) using silane chemistry. ECM was deposited by an immortalized MSC line, decellularized, and characterized through SDS-PAGE and immunofluorescence microscopy. No significant difference was observed in dECM composition or microarchitecture on the different surfaces. The decellularized surfaces were seeded with primary MSCs and their proliferation and differentiation were assessed. The presence of dECM improved the proliferation of primary MSCs by ~100% in comparison to surface chemistry controls. Additionally, the adipogenesis increased by 50–90% on all dECM surfaces in comparison to surface chemistry controls, and the osteogenesis increased by ~50% on the octyl-modified surfaces when dECM was present. However, no statistically significant differences were observed within the set of dECM surfaces or control surfaces. These results support the null hypothesis, meaning surface chemistry (over the range tested in this work) is not a key regulator of the composition or bioactivity of MSC-derived dECM. These results are significant because they provide an important insight into regenerative engineering technologies. Specifically, the utilization of dECM in stem cell manufacturing and tissue engineering applications would require the dECM to be produced on a wide variety of substrates. This work indicates that it can be produced on materials with a range of surface chemistries without undesired changes in the bioactivity of the dECM.
{"title":"Improvement of Mesenchymal Stromal Cell Proliferation and Differentiation via Decellularized Extracellular Matrix on Substrates With a Range of Surface Chemistries","authors":"Michael C. Yang, A. O’Connor, B. Kalionis, D. Heath","doi":"10.3389/fmedt.2022.834123","DOIUrl":"https://doi.org/10.3389/fmedt.2022.834123","url":null,"abstract":"Decellularized extracellular matrix (dECM) deposited by mesenchymal stromal cells (MSCs) has emerged as a promising substrate for improved expansion of MSCs. To date, essentially all studies that have produced dECM for MSC expansion have done so on tissue culture plastic or glass. However, substrate surface chemistry has a profound impact on the adsorption of proteins that mediate cell-material interactions, and different surface chemistries can cause changes in cell behavior, ECM deposition, and the in vivo response to a material. This study tested the hypothesis that substrate surface chemistry impacts the deposition of ECM and its subsequent bioactivity. This hypothesis was tested by producing glass surfaces with various surface chemistries (amine, carboxylic acid, propyl, and octyl groups) using silane chemistry. ECM was deposited by an immortalized MSC line, decellularized, and characterized through SDS-PAGE and immunofluorescence microscopy. No significant difference was observed in dECM composition or microarchitecture on the different surfaces. The decellularized surfaces were seeded with primary MSCs and their proliferation and differentiation were assessed. The presence of dECM improved the proliferation of primary MSCs by ~100% in comparison to surface chemistry controls. Additionally, the adipogenesis increased by 50–90% on all dECM surfaces in comparison to surface chemistry controls, and the osteogenesis increased by ~50% on the octyl-modified surfaces when dECM was present. However, no statistically significant differences were observed within the set of dECM surfaces or control surfaces. These results support the null hypothesis, meaning surface chemistry (over the range tested in this work) is not a key regulator of the composition or bioactivity of MSC-derived dECM. These results are significant because they provide an important insight into regenerative engineering technologies. Specifically, the utilization of dECM in stem cell manufacturing and tissue engineering applications would require the dECM to be produced on a wide variety of substrates. This work indicates that it can be produced on materials with a range of surface chemistries without undesired changes in the bioactivity of the dECM.","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81973480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-11DOI: 10.3389/fmedt.2022.782756
Talha Iqbal, A. Elahi, W. Wijns, A. Shahzad
Over the past decade, there has been a significant development in wearable health technologies for diagnosis and monitoring, including application to stress monitoring. Most of the wearable stress monitoring systems are built on a supervised learning classification algorithm. These systems rely on the collection of sensor and reference data during the development phase. One of the most challenging tasks in physiological or pathological stress monitoring is the labeling of the physiological signals collected during an experiment. Commonly, different types of self-reporting questionnaires are used to label the perceived stress instances. These questionnaires only capture stress levels at a specific point in time. Moreover, self-reporting is subjective and prone to inaccuracies. This paper explores the potential feasibility of unsupervised learning clustering classifiers such as Affinity Propagation, Balanced Iterative Reducing and Clustering using Hierarchies (BIRCH), K-mean, Mini-Batch K-mean, Mean Shift, Density-Based Spatial Clustering of Applications with Noise (DBSCAN) and Ordering Points To Identify the Clustering Structure (OPTICS) for implementation in stress monitoring wearable devices. Traditional supervised machine learning (linear, ensembles, trees, and neighboring models) classifiers require hand-crafted features and labels while on the other hand, the unsupervised classifier does not require any labels of perceived stress levels and performs classification based on clustering algorithms. The classification results of unsupervised machine learning classifiers are found comparable to supervised machine learning classifiers on two publicly available datasets. The analysis and results of this comparative study demonstrate the potential of unsupervised learning for the development of non-invasive, continuous, and robust detection and monitoring of physiological and pathological stress.
{"title":"Exploring Unsupervised Machine Learning Classification Methods for Physiological Stress Detection","authors":"Talha Iqbal, A. Elahi, W. Wijns, A. Shahzad","doi":"10.3389/fmedt.2022.782756","DOIUrl":"https://doi.org/10.3389/fmedt.2022.782756","url":null,"abstract":"Over the past decade, there has been a significant development in wearable health technologies for diagnosis and monitoring, including application to stress monitoring. Most of the wearable stress monitoring systems are built on a supervised learning classification algorithm. These systems rely on the collection of sensor and reference data during the development phase. One of the most challenging tasks in physiological or pathological stress monitoring is the labeling of the physiological signals collected during an experiment. Commonly, different types of self-reporting questionnaires are used to label the perceived stress instances. These questionnaires only capture stress levels at a specific point in time. Moreover, self-reporting is subjective and prone to inaccuracies. This paper explores the potential feasibility of unsupervised learning clustering classifiers such as Affinity Propagation, Balanced Iterative Reducing and Clustering using Hierarchies (BIRCH), K-mean, Mini-Batch K-mean, Mean Shift, Density-Based Spatial Clustering of Applications with Noise (DBSCAN) and Ordering Points To Identify the Clustering Structure (OPTICS) for implementation in stress monitoring wearable devices. Traditional supervised machine learning (linear, ensembles, trees, and neighboring models) classifiers require hand-crafted features and labels while on the other hand, the unsupervised classifier does not require any labels of perceived stress levels and performs classification based on clustering algorithms. The classification results of unsupervised machine learning classifiers are found comparable to supervised machine learning classifiers on two publicly available datasets. The analysis and results of this comparative study demonstrate the potential of unsupervised learning for the development of non-invasive, continuous, and robust detection and monitoring of physiological and pathological stress.","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"23 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72606050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-10DOI: 10.3389/fmedt.2022.856067
L. Petrini, G. Pennati, D. Fotiadis
{"title":"Editorial: Verification and Validation of in silico Models for Biomedical Implantable Devices","authors":"L. Petrini, G. Pennati, D. Fotiadis","doi":"10.3389/fmedt.2022.856067","DOIUrl":"https://doi.org/10.3389/fmedt.2022.856067","url":null,"abstract":"","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85763694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-09DOI: 10.3389/fmedt.2022.693148
Dulshani Kankanige, L. Liyanage, M. O’Connor
Protein interaction pathways and networks are critically-required for a vast range of biological processes. Improved discovery of candidate druggable proteins within specific cell, tissue and disease contexts will aid development of new treatments. Predicting protein interaction networks from gene expression data can provide valuable insights into normal and disease biology. For example, the resulting protein networks can be used to identify potentially druggable targets and drug candidates for testing in cell and animal disease models. The advent of whole-transcriptome expression profiling techniques—that catalogue protein-coding genes expressed within cells and tissues—has enabled development of individual algorithms for particular tasks. For example,: (i) gene ontology algorithms that predict gene/protein subsets involved in related cell processes; (ii) algorithms that predict intracellular protein interaction pathways; and (iii) algorithms that correlate druggable protein targets with known drugs and/or drug candidates. This review examines approaches, advantages and disadvantages of existing gene expression, gene ontology, and protein network prediction algorithms. Using this framework, we examine current efforts to combine these algorithms into pipelines to enable identification of druggable targets, and associated known drugs, using gene expression datasets. In doing so, new opportunities are identified for development of powerful algorithm pipelines, suitable for wide use by non-bioinformaticians, that can predict protein interaction networks, druggable proteins, and related drugs from user gene expression datasets.
{"title":"Application of Transcriptomics for Predicting Protein Interaction Networks, Drug Targets and Drug Candidates","authors":"Dulshani Kankanige, L. Liyanage, M. O’Connor","doi":"10.3389/fmedt.2022.693148","DOIUrl":"https://doi.org/10.3389/fmedt.2022.693148","url":null,"abstract":"Protein interaction pathways and networks are critically-required for a vast range of biological processes. Improved discovery of candidate druggable proteins within specific cell, tissue and disease contexts will aid development of new treatments. Predicting protein interaction networks from gene expression data can provide valuable insights into normal and disease biology. For example, the resulting protein networks can be used to identify potentially druggable targets and drug candidates for testing in cell and animal disease models. The advent of whole-transcriptome expression profiling techniques—that catalogue protein-coding genes expressed within cells and tissues—has enabled development of individual algorithms for particular tasks. For example,: (i) gene ontology algorithms that predict gene/protein subsets involved in related cell processes; (ii) algorithms that predict intracellular protein interaction pathways; and (iii) algorithms that correlate druggable protein targets with known drugs and/or drug candidates. This review examines approaches, advantages and disadvantages of existing gene expression, gene ontology, and protein network prediction algorithms. Using this framework, we examine current efforts to combine these algorithms into pipelines to enable identification of druggable targets, and associated known drugs, using gene expression datasets. In doing so, new opportunities are identified for development of powerful algorithm pipelines, suitable for wide use by non-bioinformaticians, that can predict protein interaction networks, druggable proteins, and related drugs from user gene expression datasets.","PeriodicalId":94015,"journal":{"name":"Frontiers in medical technology","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90634374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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