@article{dewey_mahmood_abello_sultana_jones_gluck_budhathoki-uprety_2024, title={Development of Optical Nanosensors for Detection of Potassium Ions and Assessment of Their Biocompatibility with Corneal Epithelial Cells}, volume={6}, ISSN={["2470-1343"]}, url={https://doi.org/10.1021/acsomega.4c01867}, DOI={10.1021/acsomega.4c01867}, abstractNote={Imbalance of potassium-ion levels in the body can lead to physiological dysfunctions, which can adversely impact cardiovascular, neurological, and ocular health. Thus, quantitative measurement of potassium ions in a biological system is crucial for personal health monitoring. Nanomaterials can be used to aid in disease diagnosis and monitoring therapies. Optical detection technologies along with molecular probes emitting within the near-infrared (NIR) spectral range are advantageous for biological measurements due to minimal interference from light scattering and autofluorescence within this spectral window. Herein, we report the development of NIR fluorescent nanosensors, which can quantitatively detect potassium ions under biologically relevant conditions. The optical nanosensors were developed by using photoluminescent single-walled carbon nanotubes (SWCNTs) encapsulated in polymers that contain potassium chelating moieties. The nanosensors, polystyrene sulfonate [PSS-SWCNTs, nanosensor 1 (NS1)] or polystyrene-}, journal={ACS OMEGA}, author={Dewey, Hannah M. and Mahmood, Nasif and Abello, Sofia Mariapaz and Sultana, Nigar and Jones, Jaron and Gluck, Jessica M. and Budhathoki-Uprety, Januka}, year={2024}, month={Jun} } @article{wang_mahmood_budhathoki-uprety_brown_king_gluck_2024, title={Preparation and Characterization of Hydrogels Fabricated From Chitosan and Poly(vinyl alcohol) for Tissue Engineering Applications}, volume={7}, ISSN={["2576-6422"]}, url={https://doi.org/10.1021/acsabm.4c00642}, DOI={10.1021/acsabm.4c00642}, abstractNote={In this study, we report on the preparation, characterization, and cytocompatibility of hydrogels for biomedical applications made from two different molecular weights of chitosan (CS) blended with poly(vinyl alcohol) (PVA) and chemically cross-linked with tetraethyl orthosilicate (TEOS) followed by freeze-drying. A series of CS-PVA hydrogels were synthesized with different amounts of chitosan (1%, 2%, and 3% by weight). The structure of these CS-PVA hydrogels was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The hydrogel samples were also characterized for tensile strength, contact angle, swelling behavior, and degradation at physiological body temperature. Their physicochemical properties, biocompatibility, and cell viability when cultured with human dermal fibroblasts were assessed using alamarBlue and live/dead assays and compared to optimize their functionality. SEM analysis showed that the concentration and molecular weight of the chitosan component affected the pore size. Furthermore, the contact angle decreased with increasing chitosan content, indicating that chitosan increased its hydrophilic properties. The}, journal={ACS APPLIED BIO MATERIALS}, author={Wang, Ziyu and Mahmood, Nasif and Budhathoki-Uprety, Januka and Brown, Ashley C. and King, Martin W. and Gluck, Jessica M.}, year={2024}, month={Jul} } @article{zhang_tao_gluck_wang_daneshmand_king_2023, title={A textile-reinforced composite vascular graft that modulates macrophage polarization and enhances endothelial cell migration, adhesion and proliferation in vitro}, volume={1}, ISSN={["1744-6848"]}, url={https://doi.org/10.1039/D2SM01190E}, DOI={10.1039/D2SM01190E}, abstractNote={We engineered a textile-reinforced hydrogel vascular graft. The textile provides robustness while the hydrogel promotes endothelial cell attachment and growth. The composite enhanced macrophage activation, which increased endothelial cell migration.}, journal={SOFT MATTER}, author={Zhang, Fan and Tao, Hui and Gluck, Jessica M. and Wang, Lu and Daneshmand, Mani A. and King, Martin W.}, year={2023}, month={Jan} } @article{mahmood_sefat_roberts_gilger_gluck_2023, title={Application of Noggin-Coated Electrospun Scaffold in Corneal Wound Healing}, volume={12}, ISSN={2164-2591}, url={http://dx.doi.org/10.1167/tvst.12.8.15}, DOI={10.1167/tvst.12.8.15}, abstractNote={Purpose The objective of this study is to develop and characterize electrospun corneal bandage infused with Noggin protein and evaluate its therapeutic potential in the treatment of superficial nonhealing corneal ulceration. Methods Electrospun nanofibrous scaffolds were created with different blend ratios of polycaprolactone and gelatin and coated with different concentrations of Noggin protein. Morphologic, mechanical, degradation, and surface chemistry of the developed scaffold was assessed. Biocompatibility of the developed scaffold with corneal epithelial cells was evaluated by looking at cell viability, proliferation, and immunostaining. In vitro wound healing in the presence of Noggin-coated scaffold was evaluated by measuring wound closure rate after scratch. Results Uniform nanofibrous scaffolds coated with Noggin were constructed through optimization of electrospinning parameters and demonstrated mechanical properties better than or similar to commercially available contact lenses used in corneal wound healing. In the presence of Noggin-coated scaffold, corneal epithelial cells showed higher proliferation and wound-healing rate. Conclusions This Noggin-coated electrospun scaffold represents a step toward, expanding treatment options for patients with indolent corneal ulcers. Translational Relevance In this study, the feasibility of Noggin-coated electrospun scaffold as a therapeutic for indolent corneal ulcer was evaluated. This study also provides a better perspective for understanding electrospun scaffolds as a tunable platform to infuse topical therapeutics and use as a corneal bandage.}, number={8}, journal={Translational Vision Science & Technology}, publisher={Association for Research in Vision and Ophthalmology (ARVO)}, author={Mahmood, Nasif and Sefat, Eelya and Roberts, Darby and Gilger, Brian C. and Gluck, Jessica M.}, year={2023}, month={Aug}, pages={15} } @article{mcgarry_sefat_suh_ali_gluck_2023, title={Comparison of NIH 3T3 Cellular Adhesion on Fibrous Scaffolds Constructed from Natural and Synthetic Polymers}, volume={8}, ISSN={["2313-7673"]}, url={https://doi.org/10.3390/biomimetics8010099}, DOI={10.3390/biomimetics8010099}, abstractNote={Polymer scaffolds are increasingly ubiquitous in the field of tissue engineering in improving the repair and regeneration of damaged tissue. Natural polymers exhibit better cellular adhesion and proliferation than biodegradable synthetics but exhibit inferior mechanical properties, among other disadvantages. Synthetic polymers are highly tunable but lack key binding motifs that are present in natural polymers. Using collagen and poly(lactic acid) (PLA) as models for natural and synthetic polymers, respectively, an evaluation of the cellular response of embryonic mouse fibroblasts (NIH 3T3 line) to the different polymer types was conducted. The samples were analyzed using LIVE/DEAD™, alamarBlue™, and phalloidin staining to compare cell proliferation on, interaction with, and adhesion to the scaffolds. The results indicated that NIH3T3 cells prefer collagen-based scaffolds. PLA samples had adhesion at the initial seeding but failed to sustain long-term adhesion, indicating an unsuitable microenvironment. Structural differences between collagen and PLA are responsible for this difference. Incorporating cellular binding mechanisms (i.e., peptide motifs) utilized by natural polymers into biodegradable synthetics offers a promising direction for biomaterials to become biomimetic by combining the advantages of synthetic and natural polymers while minimizing their disadvantages.}, number={1}, journal={BIOMIMETICS}, author={McGarry, Katarina and Sefat, Eelya and Suh, Taylor C. and Ali, Kiran M. and Gluck, Jessica M.}, year={2023}, month={Mar} } @article{hoque_mahmood_ali_sefat_huang_petersen_harrington_fang_gluck_2023, title={Development of a Pneumatic-Driven Fiber-Shaped Robot Scaffold for Use as a Complex 3D Dynamic Culture System}, volume={8}, ISSN={["2313-7673"]}, url={https://doi.org/10.3390/biomimetics8020170}, DOI={10.3390/biomimetics8020170}, abstractNote={Cells can sense and respond to different kinds of continuous mechanical strain in the human body. Mechanical stimulation needs to be included within the in vitro culture system to better mimic the existing complexity of in vivo biological systems. Existing commercial dynamic culture systems are generally two-dimensional (2D) which fail to mimic the three-dimensional (3D) native microenvironment. In this study, a pneumatically driven fiber robot has been developed as a platform for 3D dynamic cell culture. The fiber robot can generate tunable contractions upon stimulation. The surface of the fiber robot is formed by a braiding structure, which provides promising surface contact and adequate space for cell culture. An in-house dynamic stimulation using the fiber robot was set up to maintain NIH3T3 cells in a controlled environment. The biocompatibility of the developed dynamic culture systems was analyzed using LIVE/DEAD™ and alamarBlue™ assays. The results showed that the dynamic culture system was able to support cell proliferation with minimal cytotoxicity similar to static cultures. However, we observed a decrease in cell viability in the case of a high strain rate in dynamic cultures. Differences in cell arrangement and proliferation were observed between braided sleeves made of different materials (nylon and ultra-high molecular weight polyethylene). In summary, a simple and cost-effective 3D dynamic culture system has been proposed, which can be easily implemented to study complex biological phenomena in vitro.}, number={2}, journal={BIOMIMETICS}, author={Hoque, Muh Amdadul and Mahmood, Nasif and Ali, Kiran M. and Sefat, Eelya and Huang, Yihan and Petersen, Emily and Harrington, Shane and Fang, Xiaomeng and Gluck, Jessica M.}, year={2023}, month={Jun} } @article{zhang_gluck_brown_zaharoff_king_2023, title={Heparin Affinity-Based IL-4 Delivery to Modulate Macrophage Phenotype and Endothelial Cell Activity In Vitro}, volume={15}, ISSN={1944-8244 1944-8252}, url={http://dx.doi.org/10.1021/acsami.3c00489}, DOI={10.1021/acsami.3c00489}, abstractNote={Macrophages play a pivotal role in wound healing and tissue regeneration, as they are rapidly recruited to the site of injury or implanted foreign material. Depending on their interaction with the material, macrophages can develop different phenotypes, with the M1 pro-inflammatory and M2 pro-regenerative phenotypes being highly involved in tissue regeneration. M2 macrophages mitigate inflammation and promote tissue regeneration and extracellular matrix remodeling. In this study, we engineered a gelatin-heparin-methacrylate (GelMA-HepMA) hydrogel that gradually releases interleukin-4 (IL-4), a cytokine that modulates macrophages to adopt the M2 phenotype. Methacrylation of heparin improved the retention of both heparin and IL-4 within the hydrogel. The GelMA-HepMA hydrogel and IL-4 synergistically downregulated M1 gene expression and upregulated M2 gene expression in macrophages within 48 h of in vitro cell culture. However, the M2-like macrophage phenotype induced by the GelMA-HepMA-IL-4 hydrogel did not necessarily further improve endothelial cell proliferation and migration in vitro.}, number={23}, journal={ACS Applied Materials & Interfaces}, publisher={American Chemical Society (ACS)}, author={Zhang, Fan and Gluck, Jessica M. and Brown, Ashley C. and Zaharoff, David A. and King, Martin W.}, year={2023}, month={Jun}, pages={27457–27470} } @article{wang_amanah_ali_payne_kisthardt_scholle_ormond_mathur_gluck_2022, title={A standardized procedure for quantitative evaluation of residual viral activity on antiviral treated textiles}, volume={11}, ISSN={["1746-7748"]}, url={https://doi.org/10.1177/00405175221126532}, DOI={10.1177/00405175221126532}, abstractNote={ The SARS-CoV-2 pandemic has increased the demand for antiviral technologies to mitigate or prevent the risk of viral transmission. Antiviral treated textiles have the potential to save lives, especially in healthcare settings that rely on reusable patient-care textiles and personal protective equipment. Currently, little is known about the role of textiles in cross-contamination and pathogen transmission, despite the wealth of information on hard surfaces and fomites harboring viruses that remain viable in certain circumstances. In addition, there is no international standard method for evaluating residual viral activity on textiles, which would allow a thorough investigation of the efficacy of antiviral textile products. Therefore, this pilot study aims to develop and refine a standardized protocol to quantitatively evaluate residual viral activity on antiviral textiles. Specifically, we focused on general textiles, such as bed linens, commonly used in healthcare settings for patient care. The Tissue Culture Infectious Dose 50 (TCID50) method is frequently used to quantitatively evaluate viral infectivity on textiles, but has not been established as a standard. This procedure involves observing the cytopathic effect of a given virus on cells grown in a 96-well plate after several days of incubation to determine the infectivity titer. We used HCoV-229E and Huh-7 human liver cancer cells for this investigation. We worked to improve the TCID50 method through variations of different steps within the protocol to attain reproducible results. Our proposed optimized hybrid protocol has shown evidence that the protocol is technically simpler and more efficient, and provides successful, consistent results. The analysis showed a significant difference between the treated fabric compared with controls. }, journal={TEXTILE RESEARCH JOURNAL}, author={Wang, Ziyu and Amanah, Alaowei Y. and Ali, Kiran M. and Payne, Lucy C. and Kisthardt, Samantha and Scholle, Frank and Ormond, R. Bryan and Mathur, Kavita and Gluck, Jessica M.}, year={2022}, month={Nov} } @article{zhang_scull_gluck_brown_king_2022, title={Effects of sterilization methods on gelatin methacryloyl hydrogel properties and macrophage gene expression in vitro}, volume={18}, ISSN={1748-6041 1748-605X}, url={http://dx.doi.org/10.1088/1748-605X/aca4b2}, DOI={10.1088/1748-605X/aca4b2}, abstractNote={Abstract To assure the long-term safety and functional performance after implantation, it is of critical importance to completely sterilize a biomaterial implant. Ineffective sterilization can cause severe inflammation and infection at the implant site, leading to detrimental events of morbidity and even mortality. Macrophages are pivotal players in the inflammatory and foreign body response after implanting a biomaterial in the body. However, the relationship between the sterilization procedure and macrophage response has not been established. In this study, three commonly used sterilization methods, including autoclaving, ethylene oxide gas and ethanol treatment, were used to sterilize a gelatin methacryloyl hydrogel. The impacts of different sterilization methods on the structure and physical properties of the hydrogel were compared. Macrophage responses to the sterilized hydrogel were analyzed based on their morphology, viability and in vitro gene expression. It was found that the sterilization methods only marginally altered the hydrogel morphology, swelling behavior and elastic modulus, but significantly impacted macrophage gene expression within 48 h and over 7 d in vitro. Therefore, when selecting sterilization methods for GelMA hydrogel, not only the sterility and hydrogel properties, such as material destruction and degradation caused by temperature and moisture, should be taken into consideration, but also the cellular responses to the sterilized material which could be substantially different.}, number={1}, journal={Biomedical Materials}, publisher={IOP Publishing}, author={Zhang, Fan and Scull, Grant and Gluck, Jessica M and Brown, Ashley C and King, Martin W}, year={2022}, month={Dec}, pages={015015} } @article{suh_twiddy_mahmood_ali_lubna_bradford_daniele_gluck_2022, title={Electrospun Carbon Nanotube-Based Scaffolds Exhibit High Conductivity and Cytocompatibility for Tissue Engineering Applications}, volume={7}, ISSN={["2470-1343"]}, url={https://doi.org/10.1021/acsomega.2c01807}, DOI={10.1021/acsomega.2c01807}, abstractNote={Carbon nanotubes (CNTs) are known for their excellent conductive properties. Here, we present two novel methods, “sandwich” (sCNT) and dual deposition (DD CNT), for incorporating CNTs into electrospun polycaprolactone (PCL) and gelatin scaffolds to increase their conductance. Based on CNT percentage, the DD CNT scaffolds contain significantly higher quantities of CNTs than the sCNT scaffolds. The inclusion of CNTs increased the electrical conductance of scaffolds from 0.0 ± 0.00 kS (non-CNT) to 0.54 ± 0.10 kS (sCNT) and 5.22 ± 0.49 kS (DD CNT) when measured parallel to CNT arrays and to 0.25 ± 0.003 kS (sCNT) and 2.85 ± 1.12 (DD CNT) when measured orthogonally to CNT arrays. The inclusion of CNTs increased fiber diameter and pore size, promoting cellular migration into the scaffolds. CNT inclusion also decreased the degradation rate and increased hydrophobicity of scaffolds. Additionally, CNT inclusion increased Young’s modulus and failure load of scaffolds, increasing their mechanical robustness. Murine fibroblasts were maintained on the scaffolds for 30 days, demonstrating high cytocompatibility. The increased conductivity and high cytocompatibility of the CNT-incorporated scaffolds make them appropriate candidates for future use in cardiac and neural tissue engineering.}, number={23}, journal={ACS OMEGA}, publisher={American Chemical Society (ACS)}, author={Suh, Taylor C. and Twiddy, Jack and Mahmood, Nasif and Ali, Kiran M. and Lubna, Mostakima M. and Bradford, Philip D. and Daniele, Michael A. and Gluck, Jessica M.}, year={2022}, month={Jun}, pages={20006–20019} } @article{ali_huang_amanah_mahmood_suh_gluck_2022, title={In Vitro Biocompatibility and Degradation Analysis of Mass-Produced Collagen Fibers}, volume={14}, ISSN={["2073-4360"]}, url={https://doi.org/10.3390/polym14102100}, DOI={10.3390/polym14102100}, abstractNote={Automation and mass-production are two of the many limitations in the tissue engineering industry. Textile fabrication methods such as electrospinning are used extensively in this field because of the resemblance of the extracellular matrix to the fiber structure. However, electrospinning has many limitations, including the ability to mass-produce, automate, and reproduce products. For this reason, this study evaluates the potential use of a traditional textile method such as spinning. Apart from mass production, these methods are also easy, efficient, and cost-effective. This study uses bovine-derived collagen fibers to create yarns using the traditional ring spinning method. The collagen yarns are proven to be biocompatible. Enzymatic biodegradability was also confirmed for its potential use in vivo. The results of this study prove the safety and efficacy of the material and the fabrication method. The material encourages higher cell proliferation and migration compared to tissue culture-treated plastic plates. The process is not only simple but is also streamlined and replicable, resulting in standardized products that can be reproduced.}, number={10}, journal={POLYMERS}, author={Ali, Kiran M. and Huang, Yihan and Amanah, Alaowei Y. and Mahmood, Nasif and Suh, Taylor C. and Gluck, Jessica M.}, year={2022}, month={May} } @article{mahmood_suh_ali_sefat_jahan_huang_gilger_gluck_2022, title={Induced Pluripotent Stem Cell-Derived Corneal Cells: Current Status and Application}, volume={8}, ISSN={["2629-3277"]}, url={https://doi.org/10.1007/s12015-022-10435-8}, DOI={10.1007/s12015-022-10435-8}, abstractNote={Deficiency and dysfunction of corneal cells leads to the blindness observed in corneal diseases such as limbal stem cell deficiency (LSCD) and bullous keratopathy. Regenerative cell therapies and engineered corneal tissue are promising treatments for these diseases [1]. However, these treatments are not yet clinically feasible due to inadequate cell sources. The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka has provided a multitude of opportunities in research because iPSCs can be generated from somatic cells, thus providing an autologous and unlimited source for corneal cells. Compared to other stem cell sources such as mesenchymal and embryonic, iPSCs have advantages in differentiation potential and ethical concerns, respectively. Efforts have been made to use iPSCs to model corneal disorders and diseases, drug testing [2], and regenerative medicine [1]. Autologous treatments based on iPSCs can be exorbitantly expensive and time-consuming, but development of stem cell banks with human leukocyte antigen (HLA)- homozygous cell lines can provide cost- and time-efficient allogeneic alternatives. In this review, we discuss the early development of the cornea because protocols differentiating iPSCs toward corneal lineages rely heavily upon recapitulating this development. Differentiation of iPSCs toward corneal cell phenotypes have been analyzed with an emphasis on feeder-free, xeno-free, and well-defined protocols, which have clinical relevance. The application, challenges, and potential of iPSCs in corneal research are also discussed with a focus on hurdles that prevent clinical translation.}, journal={STEM CELL REVIEWS AND REPORTS}, author={Mahmood, Nasif and Suh, Taylor Cook and Ali, Kiran M. and Sefat, Eelya and Jahan, Ummay Mowshome and Huang, Yihan and Gilger, Brian C. and Gluck, Jessica M.}, year={2022}, month={Aug} } @article{wang_hamedi_zhang_el-shafei_brown_gluck_king_2022, title={Plasma-Induced Diallyldimethylammonium Chloride Antibacterial Hernia Mesh}, volume={5}, ISSN={2576-6422 2576-6422}, url={http://dx.doi.org/10.1021/acsabm.2c00695}, DOI={10.1021/acsabm.2c00695}, abstractNote={A hernia is a pathological condition caused by a defect or opening in the muscle wall, which leads to organs pushing through the opening or defect. Hernia recurrence, seroma, persistent pain, tissue adhesions, and wound infection are common complications following hernia repair surgery. Infection after hernia mesh implantation is the third major complication leading to hernia recurrence. In order to reduce the incidence of late infections, we developed a polypropylene mesh with antibacterial properties. In this study, knitted polypropylene meshes were exposed to radio-frequency plasma to activate their surfaces. The antibacterial monomer diallyldimethylammonium chloride (DADMAC) was then grafted onto the mesh surface using pentaerythritol tetraacrylate as the cross-linker since it is able to engage all four functional groups to form a high-density cross-linked network. The subsequent antibacterial performance showed a 2.9 log reduction toward Staphylococcus aureus and a 0.9 log reduction for Escherichia coli.}, number={12}, journal={ACS Applied Bio Materials}, publisher={American Chemical Society (ACS)}, author={Wang, Ziyu and Hamedi, Hamid and Zhang, Fan and El-Shafei, Ahmed and Brown, Ashley C. and Gluck, Jessica M. and King, Martin W.}, year={2022}, month={Nov}, pages={5645–5656} } @article{yin_xiang_zhang_tao_gluck_chiu_lam_2021, title={Cleaner production of mulberry spun silk yarns via a shortened and gassing-free production route}, volume={278}, url={https://doi.org/10.1016/j.jclepro.2020.123690}, DOI={10.1016/j.jclepro.2020.123690}, abstractNote={Abstract The green production of textiles via an eco-friendly approach has recently gained considerable interest. As a derivative industry of silk manufacturing, spun silk utilizes waste materials generated in different processes of silk production, which is considered as the re-use of silk waste. The spun silk industry is facing several problems now, including environmental pollution, low production efficiency, increased labor intensity, significant material waste, and excessive energy consumption. This study presents an environment-friendly production route to produce mulberry spun silk yarns, by eliminating the gassing process that burns away surface hairs and neps. The gassing process not only generates odors, dust, and gas discharges but also results in significant material wastage and high production cost. The key is a modified ring spinning technology to achieve low yarn hairiness and neps; thus the yarn produced no longer requires gassing. The number of processing steps is also reduced to nine from twelve compared to the traditional silk spinning system. The modified 60 Nm mulberry spun silk yarns show a comparable tenacity of 26.33 cN/tex, evenness of 9.96%, neps (+200%) of 18 per 1 km, and a slightly worse hairiness S3 value of 74 per 100 m, compared with the conventional gassed ones. The plain knitted fabrics made by the modified yarns also reveal a 1.5 grade higher pilling resistance, similar mechanical and thermal properties, and a slightly hairier surface appearance than the conventional ones. The new processing route greatly reduces carbon footprint and achieves significant savings in materials, manpower, and energy, which may shed new light on the industrial manufacturing of mulberry spun silk yarns.}, journal={Journal of Cleaner Production}, publisher={Elsevier BV}, author={Yin, R. and Xiang, Y.F. and Zhang, Z.H. and Tao, X.M. and Gluck, J.M. and Chiu, K. and Lam, W.}, year={2021}, month={Jan}, pages={123690} } @article{suh_amanah_gluck_2020, title={Electrospun Scaffolds and Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Cardiac Tissue Engineering Applications}, volume={7}, url={https://www.mdpi.com/2306-5354/7/3/105}, DOI={10.3390/bioengineering7030105}, abstractNote={Tissue engineering (TE) combines cells, scaffolds, and growth factors to assemble functional tissues for repair or replacement of tissues and organs. Cardiac TE is focused on developing cardiac cells, tissues, and structures—most notably the heart. This review presents the requirements, challenges, and research surrounding electrospun scaffolds and induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) towards applications to TE hearts. Electrospinning is an attractive fabrication method for cardiac TE scaffolds because it produces fibers that demonstrate the optimal potential for mimicking the complex structure of the cardiac extracellular matrix (ECM). iPSCs theoretically offer the capacity to generate limitless numbers of CMs for use in TE hearts, however these iPSC-CMs are electrophysiologically, morphologically, mechanically, and metabolically immature compared to adult CMs. This presents a functional limitation to their use in cardiac TE, and research aiming to address this limitation is presented in this review.}, number={3}, journal={Bioengineering}, publisher={MDPI AG}, author={Suh, Taylor Cook and Amanah, Alaowei Y. and Gluck, Jessica M.}, year={2020}, month={Sep}, pages={105} } @article{gluck_herren_yechikov_kao_khan_phinney_chiamvimonvat_chan_lieu_2017, title={Biochemical and biomechanical properties of the pacemaking sinoatrial node extracellular matrix are distinct from contractile left ventricular matrix.}, volume={12}, url={http://europepmc.org/abstract/med/28934329}, DOI={10.1371/journal.pone.0185125}, abstractNote={Extracellular matrix plays a role in differentiation and phenotype development of its resident cells. Although cardiac extracellular matrix from the contractile tissues has been studied and utilized in tissue engineering, extracellular matrix properties of the pacemaking sinoatrial node are largely unknown. In this study, the biomechanical properties and biochemical composition and distribution of extracellular matrix in the sinoatrial node were investigated relative to the left ventricle. Extracellular matrix of the sinoatrial node was found to be overall stiffer than that of the left ventricle and highly heterogeneous with interstitial regions composed of predominantly fibrillar collagens and rich in elastin. The extracellular matrix protein distribution suggests that resident pacemaking cardiomyocytes are enclosed in fibrillar collagens that can withstand greater tensile strength while the surrounding elastin-rich regions may undergo deformation to reduce the mechanical strain in these cells. Moreover, basement membrane-associated adhesion proteins that are ligands for integrins were of low abundance in the sinoatrial node, which may decrease force transduction in the pacemaking cardiomyocytes. In contrast to extracellular matrix of the left ventricle, extracellular matrix of the sinoatrial node may reduce mechanical strain and force transduction in pacemaking cardiomyocytes. These findings provide the criteria for a suitable matrix scaffold for engineering biopacemakers.}, number={9}, journal={PloS one}, author={Gluck, JM and Herren, AW and Yechikov, S and Kao, HKJ and Khan, A and Phinney, BS and Chiamvimonvat, N and Chan, JW and Lieu, DK}, year={2017}, month={Sep} } @article{dedifferentiated adipocytes improve heart function post-myocardial infarction_2017, url={http://dx.doi.org/10.4172/2325-9620.1000135}, DOI={10.4172/2325-9620.1000135}, abstractNote={Background:The development of pluripotent stem cell-based strategies for regenerative medicine offers hope of one day having a limitless source of therapeutic cells for the repairing of damaged cardiac tissue resulting from myocardial infarction (MI). Dedifferentiated adipose cells (DFAT) have recently gained attention in this regard for their in vitro and in vivo ability to express vascular and cardiac-specific markers. To date, there is limited knowledge with respect to their capacity to improve cardiac function and contractility when introduced into the myocardium after the onset of MI. To that end, this study investigated the in vivo potential of intramyocardially injected mouse DFAT (mDFAT) cells to differentiate towards cardiovascular lineages and enhance cardiac function in a murine model of MI. Methods: Mature adipocytes were harvested from GFP-transgenic mice and dedifferentiated in vitro to produce pluripotent mDFAT cells. Mice that underwent LAD ligation surgery were injected intramyocardially with a dose of therapeutic mDFAT cells (n=6) shortly after the confirmation of successful MI. Results: Consistent with previous findings by the authors, we observed an immunofluorescent stain pattern in the infarct area of mDFAT cells adjacent to or co-localized with Troponin T, Cx-43, CD31, isolectin B4 and α-SMA up to eight weeks after cell transplantation. Furthermore, echocardiography and hemodynamic catheterization measurements indicated an overall improvement in global cardiac function, including ejection fraction, fractional shortening and contractility. Conclusions: This study is the first to report that the transplantation of mDFAT cells into a murine model of MI can preserve cardiac function up to eight weeks after the onset of infarction, suggesting a potential role for DFAT cells as a therapeutic pluripotent cell source in cardiovascular tissue repair.}, journal={Journal of Regenerative Medicine}, year={2017} } @article{yechikov_copaciu_gluck_deng_chiamvimonvat_chan_lieu_2016, title={Same-Single-Cell Analysis of Pacemaker-Specific Markers in Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Subtypes Classified by Electrophysiology.}, volume={11}, url={http://europepmc.org/abstract/med/27434649}, DOI={10.1002/stem.2466}, abstractNote={Abstract Insights into the expression of pacemaker-specific markers in human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte subtypes can facilitate the enrichment and track differentiation and maturation of hiPSC-derived pacemaker-like cardiomyocytes. To date, no study has directly assessed gene expression in each pacemaker-, atria-, and ventricular-like cardiomyocyte subtype derived from hiPSCs since currently the subtypes of these immature cardiomyocytes can only be identified by action potential profiles. Traditional acquisition of action potentials using patch-clamp recordings renders the cells unviable for subsequent analysis. We circumvented these issues by acquiring the action potential profile of a single cell optically followed by assessment of protein expression through immunostaining in that same cell. Our same-single-cell analysis for the first time revealed expression of proposed pacemaker-specific markers—hyperpolarization-activated cyclic nucleotide-modulated (HCN)4 channel and Islet (Isl)1—at the protein level in all three hiPSC-derived cardiomyocyte subtypes. HCN4 expression was found to be higher in pacemaker-like hiPSC-derived cardiomyocytes than atrial- and ventricular-like subtypes but its downregulation over time in all subtypes diminished the differences. Isl1 expression in pacemaker-like hiPSC-derived cardiomyocytes was initially not statistically different than the contractile subtypes but did become statistically higher than ventricular-like cells with time. Our observations suggest that although HCN4 and Isl1 are differentially expressed in hiPSC-derived pacemaker-like relative to ventricular-like cardiomyocytes, these markers alone are insufficient in identifying hiPSC-derived pacemaker-like cardiomyocytes.}, number={11}, journal={Stem cells (Dayton, Ohio)}, author={Yechikov, S and Copaciu, R and Gluck, JM and Deng, W and Chiamvimonvat, N and Chan, JW and Lieu, DK}, year={2016}, month={Jul}, pages={2670–2680} } @article{full_delman_gluck_abdmaulen_shemin_heydarkhan-hagvall_2015, title={Effect of fiber orientation of collagen-based electrospun meshes on human fibroblasts for ligament tissue engineering applications}, volume={103}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84918775504&partnerID=MN8TOARS}, DOI={10.1002/jbm.b.33153}, abstractNote={Within the past two decades polylactic-co-glycolic acid (PLGA) has gained considerable attention as a biocompatible and biodegradable polymer that is suitable for tissue engineering and regenerative medicine. In this present study, we have investigated the potential of PLGA, collagen I (ColI), and polyurethane (PU) scaffolds for ligament tissue regeneration. Two different ratios of PLGA (50:50 and 85:15) were used to determine the effects on mechanical tensile properties and cell adhesion. The Young's modulus, tensile stress at yield, and ultimate tensile strain of PLGA(50:50)-ColI-PU scaffolds demonstrated similar tensile properties to that of ligaments found in the knee. Whereas, scaffolds composed of PLGA(85:15)-ColI-PU had lower tensile properties than that of ligaments. Furthermore, we investigated the effect of fiber orientation on mechanical properties and our results indicate that aligned fiber scaffolds demonstrate higher tensile properties than scaffolds with random fiber orientation. Also, human fibroblasts attached and proliferated with no need for additional surface modifications to the presented electrospun scaffolds in both categories. Collectively, our investigation demonstrates the effectiveness of electrospun PLGA scaffolds as a suitable candidate for regenerative medicine, capable of being manipulated and combined with other polymers to create three-dimensional microenvironments with adjustable tensile properties to mimic native tissues.}, number={1}, journal={Journal of Biomedical Materials Research - Part B Applied Biomaterials}, author={Full, SM and Delman, C and Gluck, JM and Abdmaulen, R and Shemin, RJ and Heydarkhan-Hagvall, S}, year={2015}, pages={39–46} } @article{gluck_delman_chyu_maclellan_shemin_heydarkhan-hagvall_2014, title={Microenvironment influences vascular differentiation of murine cardiovascular progenitor cells.}, volume={11}, url={http://europepmc.org/abstract/med/24687591}, DOI={10.1002/jbm.b.33155}, abstractNote={AbstractWe examined the effects of the microenvironment on vascular differentiation of murine cardiovascular progenitor cells (CPCs). We isolated CPCs and seeded them in culture exposed to the various extracellular matrix (ECM) proteins in both two‐dimensional (2D) and 3D culture systems. To better understand the contribution of the microenvironment to vascular differentiation, we analyzed endothelial and smooth muscle cell differentiation at both day 7 and day 14. We found that laminin and vitronectin enhanced vascular endothelial cell differentiation while fibronectin enhanced vascular smooth muscle cell differentiation. We also observed that the effects of the 3D electrospun scaffolds were delayed and not noticeable until the later time point (day 14), which may be due to the amount of time necessary for the cells to migrate to the interior of the scaffold. The study characterized the contributions of both ECM proteins and the addition of a 3D culture system to continued vascular differentiation. Additionally, we demonstrated the capability bioengineer a CPC‐derived vascular graft. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1730–1739, 2014.}, number={8}, journal={Journal of biomedical materials research. Part B, Applied biomaterials}, author={Gluck, JM and Delman, C and Chyu, J and MacLellan, WR and Shemin, RJ and Heydarkhan-Hagvall, S}, year={2014}, month={Mar}, pages={1730–1739} } @article{hyaluronan-based three-dimensional microenvironment potently induces cardiovascular progenitor cell populations_2013, url={http://dx.doi.org/10.1155/2013/752620}, DOI={10.1155/2013/752620}, abstractNote={The relationship between stem cell niches in vivo and their surrounding microenvironment is still relatively unknown. Recent advances have indicated that extrinsic factors within the cardiovascular progenitor cell niche influence maintenance of a multipotent state as well as drive cell-fate decisions. We have previously shown the direct effects of extracellular matrix (ECM) proteins and have now investigated the effects of dimension on the induction of a cardiovascular progenitor cell (CPC) population. We have shown here that the three-dimensionality of a hyaluronan-based hydrogel greatly induces a CPC population, as marked by Flk-1. We have compared the effects of a 3D microenvironment to those of conventional 2D cell culture practices and have found that the 3D microenvironment potently induces a progenitor cell state.}, journal={ISRN Tissue Engineering}, year={2013} } @article{stem cell extracellular matrix interactions in three- dimensional system via integrins_2012, url={http://dx.doi.org/10.4172/2325-9620.1000107}, DOI={10.4172/2325-9620.1000107}, abstractNote={Stem Cell Extracellular Matrix Interactions in Three- Dimensional System via Integrins Cells of all types interact with the extracellular matrix (ECM) through integrin-mediated interactions. Adhesion of embryonic stem (ES) cells is necessary for differentiation. We have characterized integrin expression of undifferentiated mES cells and established a system of evaluating the ECM-integrin interactions in three-dimension (3D) using electrospun scaffolds. We observed a higher proliferation rate at early time points in conventional 2D culture with various ECM proteins (collagen IV, laminin, fibronectin, vitronectin) as compared to 3D conditions. At later time points, we observed higher proliferations in 3D culture conditions compared to 2D culture conditions. We also detected the importance of α5, αV, β1, β5 and αVβ5 integrin subunits for cellular adhesion in 3D conditions using a cellular adhesion assay.}, journal={Journal of Regenerative Medicine}, year={2012} } @article{gluck_rahgozar_ingle_rofail_petrosian_cline_jordan_roos_maclellan_shemin_et al._2011, title={Hybrid coaxial electrospun nanofibrous scaffolds with limited immunological response created for tissue engineering.}, volume={10}, url={http://europepmc.org/abstract/med/21732530}, DOI={10.1002/jbm.b.31885}, abstractNote={AbstractElectrospinning using synthetic and natural polymers is a promising technique for the fabrication of scaffolds for tissue engineering. Numerous synthetic polymers are available to maximize durability and mechanical properties (polyurethane) versus degradability and cell adhesion (polycaprolactone). In this study, we explored the feasibility of creating scaffolds made of bicomponent nanofibers from both polymers using a coaxial electrospinning system. We used a core of poly(urethane) and a sheath of a mixture of poly(ε‐caprolactone) and gelatin, all dissolved in 1,1,1,3,3,3‐hexafluror‐2‐propanol. These nanofibrous scaffolds were then evaluated to confirm their core–sheath nature and characterize their morphology and mechanical properties under static and dynamic conditions. Furthermore, the antigenicity of the scaffolds was studied to confirm that there is no significant foreign body response to the scaffold itself that would preclude its use in vivo. The results show the advantages of combining both natural and synethic polymers to create a coaxial scaffold capable of withstanding dynamic culture conditions and encourage cellular migration to the interior of the scaffold for tissue‐engineering applications. Also, the results show that there is no significant immunoreactivity in vivo to the components of the scaffolds. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.}, number={1}, journal={Journal of biomedical materials research. Part B, Applied biomaterials}, author={Gluck, JM and Rahgozar, P and Ingle, NP and Rofail, F and Petrosian, A and Cline, MG and Jordan, MC and Roos, KP and Maclellan, WR and Shemin, RJ and et al.}, year={2011}, month={Jul}, pages={180–190} } @article{schenke-layland_nsair_van_angelis_gluck_votteler_goldhaber_mikkola_kahn_maclellan_2011, title={Recapitulation of the embryonic cardiovascular progenitor cell niche.}, volume={4}, url={http://europepmc.org/abstract/med/21257198}, DOI={10.1016/j.biomaterials.2010.12.046}, abstractNote={Stem or progenitor cell populations are often established in unique niche microenvironments that regulate cell fate decisions. Although niches have been shown to be critical for the normal development of several tissues, their role in the cardiovascular system is poorly understood. In this study, we characterized the cardiovascular progenitor cell (CPC) niche in developing human and mouse hearts, identifying signaling pathways and extracellular matrix (ECM) proteins that are crucial for CPC maintenance and expansion. We demonstrate that collagen IV (ColIV) and β-catenin-dependent signaling are essential for maintaining and expanding undifferentiated CPCs. Since niches are three-dimensional (3D) structures, we investigated the impact of a 3D microenvironment that mimics the in vivo niche ECM. Employing electrospinning technologies, 3D in vitro niche substrates were bioengineered to serve as culture inserts. The three-dimensionality of these structures increased mouse embryonic stem cell differentiation into CPCs when compared to 2D control cultures, which was further enhanced by incorporation of ColIV into the substrates. Inhibiting p300-dependent β-catenin signals with the small molecule IQ1 facilitated further expansion of CPCs. Our study represents an innovative approach to bioengineer cardiac niches that can serve as unique 3D in vitro systems to facilitate CPC expansion and study CPC biology.}, number={11}, journal={Biomaterials}, author={Schenke-Layland, K and Nsair, A and Van, Handel B and Angelis, E and Gluck, JM and Votteler, M and Goldhaber, JI and Mikkola, HK and Kahn, M and Maclellan, WR}, year={2011}, month={Jan}, pages={2748–2756} } @article{heydarkhan-hagvall_gluck_delman_jung_ehsani_full_shemin_2012, title={The effect of vitronectin on the differentiation of embryonic stem cells in a 3D culture system}, volume={33}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84855723930&partnerID=MN8TOARS}, DOI={10.1016/j.biomaterials.2011.11.065}, abstractNote={While stem cell niches in vivo are complex three-dimensional (3D) microenvironments, the relationship between the dimensionality of the niche to its function is unknown. We have created a 3D microenvironment through electrospinning to study the impact of geometry and different extracellular proteins on the development of cardiac progenitor cells (Flk-1(+)) from resident stem cells and their differentiation into functional cardiovascular cells. We have investigated the effect of collagen IV, fibronectin, laminin and vitronectin on the adhesion and proliferation of murine ES cells as well as the effects of these proteins on the number of Flk-1(+) cells cultured in 2D conditions compared to 3D system in a feeder free condition. We found that the number of Flk-1(+) cells was significantly higher in 3D scaffolds coated with laminin or vitronectin compared to colIV-coated scaffolds. Our results show the importance of defined culture systems in vitro for studying the guided differentiation of pluripotent embryonic stem cells in the field of cardiovascular tissue engineering and regenerative medicine.}, number={7}, journal={Biomaterials}, author={Heydarkhan-Hagvall, S and Gluck, JM and Delman, C and Jung, M and Ehsani, N and Full, S and Shemin, RJ}, year={2012}, pages={2032–2040} } @article{schenke-layland_rofail_heydarkhan_gluck_ingle_angelis_choi_maclellan_beygui_shemin_et al._2009, title={The use of three-dimensional nanostructures to instruct cells to produce extracellular matrix for regenerative medicine strategies.}, volume={9}, url={http://europepmc.org/abstract/med/19524289}, DOI={10.1016/j.biomaterials.2009.05.033}, abstractNote={Synthetic polymers or naturally-derived extracellular matrix (ECM) proteins have been used to create tissue engineering scaffolds; however, the need for surface modification in order to achieve polymer biocompatibility and the lack of biomechanical strength of constructs built using proteins alone remain major limitations. To overcome these obstacles, we developed novel hybrid constructs composed of both strong biosynthetic materials and natural human ECM proteins. Taking advantage of the ability of cells to produce their own ECM, human foreskin fibroblasts were grown on silicon-based nanostructures exhibiting various surface topographies that significantly enhanced ECM protein production. After 4 weeks, cell-derived sheets were harvested and histology, immunochemistry, biochemistry and multiphoton imaging revealed the presence of collagens, tropoelastin, fibronectin and glycosaminoglycans. Following decellularization, purified sheet-derived ECM proteins were mixed with poly(epsilon-caprolactone) to create fibrous scaffolds using electrospinning. These hybrid scaffolds exhibited excellent biomechanical properties with fiber and pore sizes that allowed attachment and migration of adipose tissue-derived stem cells. Our study represents an innovative approach to generate strong, non-cytotoxic scaffolds that could have broad applications in tissue regeneration strategies.}, number={27}, journal={Biomaterials}, author={Schenke-Layland, K and Rofail, F and Heydarkhan, S and Gluck, JM and Ingle, NP and Angelis, E and Choi, CH and MacLellan, WR and Beygui, RE and Shemin, RJ and et al.}, year={2009}, month={Jun}, pages={4665–4675} }