Publications

2022
151., Huibin Chang, Qihan Liu, John F. Zimmerman, Keel Yong Lee, Qianru Jin, Michael M. Peters, Michael Rosnach, Suji Choi, Sean L. Kim, Herdeline Ann M. Ardoña, Luke A. MacQueen, Christophe O. Chantre, Sarra E. Motta, Elizabeth M. Cordoves, and Kevin Kit Parker. 7/7/2022. “Recreating the Heart’s Helical Structure-Function Relationship with Focused Rotary Jet Spinning.” Science, 377, 6602, Pp. 180-185. Publisher's VersionAbstract
Helical alignments within the heart’s musculature have been speculated to be important in achieving physiological pumping efficiencies. Testing this possibility is difficult, however, because it is challenging to reproduce the fine spatial features and complex structures of the heart’s musculature using current techniques. Here we report focused rotary jet spinning (FRJS), an additive manufacturing approach that enables rapid fabrication of micro/nanofiber scaffolds with programmable alignments in three-dimensional geometries. Seeding these scaffolds with cardiomyocytes enabled the biofabrication of tissue-engineered ventricles, with helically aligned models displaying more uniform deformations, greater apical shortening, and increased ejection fractions compared with circumferential alignments. The ability of FRJS to control fiber arrangements in three dimensions offers a streamlined approach to fabricating tissues and organs, with this work demonstrating how helical architectures contribute to cardiac performance.
Recreating the Hearts Helical Structure-Function Relationship with Focused Rotary Jet Spinning
150., Huibin Chang, Jie Xu, Luke A. MacQueen, Zeynep Aytac, Michael M. Peters, John F. Zimmerman, Tao Xu, Philip Demokritou, and Kevin Kit Parker. 6/20/2022. “High-Throughput Coating with Biodegradable Anitmicrobial Pullulan Fibres Extends Shelf Life and Reduces Weight Loss in an Avocado.” Nature Food, 3, Pp. 428-436. Publisher's VersionAbstract

Food waste and food safety motivate the need for improved food packaging solutions. However, current films/coatings addressing these issues are often limited by inefficient release dynamics that require large quantities of active ingredients. Here we developed antimicrobial pullulan fibre (APF)-based packaging that is biodegradable and capable of wrapping food substrates, increasing their longevity and enhancing their safety. APFs were spun using a high-throughput system, termed focused rotary jet spinning, with water as the only solvent, allowing the incorporation of naturally derived antimicrobial agents. Using avocados as a representative example, we demonstrate that APF-coated samples had their shelf life extended by inhibited proliferation of natural microflora, and lost less weight than uncoated control samples. This work offers a promising technique to produce scalable, low-cost and environmentally friendly biodegradable antimicrobial packaging systems.

High-Throughput Coating with Biodegradable Anitmicrobial Pullulan Fibres Extends Shelf Life and Reduces Weight Loss in an Avocado
149., Dilip Thomas, Suji Choi, Christina Alamana, Kevin Kit Parker, and Joseph C. Wu. 6/9/2022. “Cellular and Engineered Organoids for Cardiovascular Models.” Circulation Research, 130, 12, Pp. 1780-1802. Publisher's VersionAbstract

An ensemble of in vitro cardiac tissue models has been developed over the past several decades to aid our understanding of complex cardiovascular disorders using a reductionist approach. These approaches often rely on recapitulating single or multiple clinically relevant end points in a dish indicative of the cardiac pathophysiology. The possibility to generate disease-relevant and patient-specific human induced pluripotent stem cells has further leveraged the utility of the cardiac models as screening tools at a large scale. To elucidate biological mechanisms in the cardiac models, it is critical to integrate physiological cues in form of biochemical, biophysical, and electromechanical stimuli to achieve desired tissue-like maturity for a robust phenotyping. Here, we review the latest advances in the directed stem cell differentiation approaches to derive a wide gamut of cardiovascular cell types, to allow customization in cardiac model systems, and to study diseased states in multiple cell types. We also highlight the recent progress in the development of several cardiovascular models, such as cardiac organoids, microtissues, engineered heart tissues, and microphysiological systems. We further expand our discussion on defining the context of use for the selection of currently available cardiac tissue models. Last, we discuss the limitations and challenges with the current state-of-the-art cardiac models and highlight future directions.

Cellular and Engineered Organoids for Cardiovascular Models
148., Herdeline Ann M. Ardoña, John F. Zimmerman, Kevin Shani, Su Hwan Kim, Feyisayo Eweje, Dimitrios Bitounis, Dorsa Parviz, Evan Casalino, Michael Strano, Philip Demokritou, and Kevin Kit Parker. 4/2022. “Differential Modulation of Endothelial Cytoplasmic Protrusions After Exposure to Graphene-Family Nanomaterials.” NanoImpact, 26. Publisher's VersionAbstract

Engineered nanomaterials offer the benefit of having systematically tunable physicochemical characteristics (e.g., size, dimensionality, and surface chemistry) that highly dictate the biological activity of a material. Among the most promising engineered nanomaterials to date are graphene-family nanomaterials (GFNs), which are 2-D nanomaterials (2DNMs) with unique electrical and mechanical properties. Beyond engineering new nanomaterial properties, employing safety-by-design through considering the consequences of cell-material interactions is essential for exploring their applicability in the biomedical realm. In this study, we asked the effect of GFNs on the endothelial barrier function and cellular architecture of vascular endothelial cells. Using micropatterned cell pairs as a reductionist in vitro model of the endothelium, the progression of cytoskeletal reorganization as a function of GFN surface chemistry and time was quantitatively monitored. Here, we show that the surface oxidation of GFNs (graphene, reduced graphene oxide, partially reduced graphene oxide, and graphene oxide) differentially affect the endothelial barrier at multiple scales; from the biochemical pathways that influence the development of cellular protrusions to endothelial barrier integrity. More oxidized GFNs induce higher endothelial permeability and the increased formation of cytoplasmic protrusions such as filopodia. We found that these changes in cytoskeletal organization, along with barrier function, can be potentiated by the effect of GFNs on the Rho/Rho-associated kinase (ROCK) pathway. Specifically, GFNs with higher surface oxidation elicit stronger ROCK2 inhibitory behavior as compared to pristine graphene sheets. Overall, findings from these studies offer a new perspective towards systematically controlling the surface-dependent effects of GFNs on cytoskeletal organization via ROCK2 inhibition, providing insight for implementing safety-by-design principles in GFN manufacturing towards their targeted biomedical applications.

Differential Modulation of Endothelial Cytoplasmic Protrusions After Exposure to Graphene-Family Nanomaterials
147 -, K. Y. Lee, S.-J. Park, D. G. Matthews, S. L. Kim, C. A. Marquez, J. F. Zimmerman, H. A. Ardoña, A. G. Kleber, G. Lauder, and K. K. Parker. 2/10/2022. “An autonomously swimming biohybrid fish designed with human cardiac biophysics.” Science, 375, 6581, Pp. 639–647. Publisher's VersionAbstract
Biohybrid systems have been developed to better understand the design principles and coordination mechanisms of biological systems. We consider whether two functional regulatory features of the heart—mechanoelectrical signaling and automaticity—could be transferred to a synthetic analog of another fluid transport system: a swimming fish. By leveraging cardiac mechanoelectrical signaling, we recreated reciprocal contraction and relaxation in a muscular bilayer construct where each contraction occurs automatically as a response to the stretching of an antagonistic muscle pair. Further, to entrain this closed-loop actuation cycle, we engineered an electrically autonomous pacing node, which enhanced spontaneous contraction. The biohybrid fish equipped with intrinsic control strategies demonstrated self-sustained body–caudal fin swimming, highlighting the role of feedback mechanisms in muscular pumps such as the heart and muscles.
An autonomously swimming biohybrid fish designed with human cardiac biophysics
146 -, Lee KY, Nguyen HT, Setiawati A, Nam S-J, Kim M, Ko I-G, Jung WH, Parker KK, Kim C-J, and Shin KW. 2/2022. “An Extracellular Matrix-Liposome Composite, a Novel Extracellular Matrix Delivery System for Accelerated Tissue Regeneration.” Advanced Healthcare Materials. Publisher's VersionAbstract
The unfolded states of fibronectin (FN) subsequently induce the formation of an extracellular matrix (ECM) fibrillar network, which is necessary to generate new substitutive tissues. Here, the authors demonstrate that negatively charged small unilamellar vesicles (SUVs) qualify as candidates for FN delivery due to their remarkable effects on the autonomous binding and unfolding of FN, which leads to increased tissue regeneration. In vitro experiments revealed that the FN-SUV complex remarkably increased the attachment, differentiation, and migration of fibroblasts. The potential utilization of this complex in vivo to treat inflammatory colon diseases is also described based on results obtained for ameliorated conditions in rats with ulcerative colitis (UC) that had been treated with the FN-SUV complex. Their findings provide a new ECM-delivery platform for ECM-based therapeutic applications and suggest that properly designed SUVs may be an unprecedented FN-delivery system that is highly effective in treating UC and inflammatory bowel diseases.
An Extracellular Matrix-Liposome Composite, a Novel Extracellular Matrix Delivery System for Accelerated Tissue Regeneration
2021
145 -, Ziad AT, Zimmerman JF, Rao J, Sieiro D, McNamara HM, Cherrier T, Rodriguez-delaRosa A, Hick-Colin A, Bousson F, Fugier-Schmucker C, Marchianoi F, Habermanni B, Chala J, Nesmith AP, Gapon, Svetlana, Wagner E, Gupta VA, Bassel-Dubyk R, Olsonk EN, Cohen AE, and Parker KK. 7/2021. “Prednisolone Rescues Duchenne Muscular Dystrophy Phenotypes in Human Pluripotent Stem Cell–Derived Skeletal Muscle in Vitro.” Proceedings of the National Academy of Sciences of the United States of America, 118, 28, Pp. 1-12. Publisher's VersionAbstract
Duchenne muscular dystrophy (DMD) is a devastating genetic disease leading to degeneration of skeletal muscles and premature death. How dystrophin absence leads to muscle wasting remains unclear. Here, we describe an optimized protocol to differentiate human induced pluripotent stem cells (iPSC) to a late myogenic stage. This allows us to recapitulate classical DMD phenotypes (mislocalization of proteins of the dystrophin-associated glycoprotein complex, increased fusion, myofiber branching, force contraction defects, and calcium hyperactivation) in isogenic DMD-mutant iPSC lines in vitro. Treatment of the myogenic cultures with prednisolone (the standard of care for DMD) can dramatically rescue force contraction, fusion, and branching defects in DMD iPSC lines. This argues that prednisolone acts directly on myofibers, challenging the largely prevalent view that its beneficial effects are caused by antiinflammatory properties. Our work introduces a human in vitro model to study the onset of DMD pathology and test novel therapeutic approaches.
Prednisolone Rescues Duchenne Muscular Dystrophy Phenotypes in Human Pluripotent Stem Cell–Derived Skeletal Muscle in Vitro
144 -, Glieberman AL, Pope BD, Melton DA, and Parker KK. 2/2021. “Building Biomimetic Potency Tests for Islet Transplantation.” Diabetes, 70, 2, Pp. 347-363. Publisher's VersionAbstract
Diabetes is a disease of insulin insufficiency, requiring many to rely on exogenous insulin with constant monitoring to avoid a fatal outcome. Islet transplantation is a recent therapy that can provide insulin independence, but the procedure is still limited by both the availability of human islets and reliable tests to assess their function. While stem cell technologies are poised to fill the shortage of transplantable cells, better methods are still needed for predicting transplantation outcome. To ensure islet quality, we propose that the next generation of islet potency tests should be biomimetic systems that match glucose stimulation dynamics and cell microenvironmental preferences and rapidly assess conditional and continuous insulin secretion with minimal manual handing. Here, we review the current approaches for islet potency testing and outline technologies and methods that can be used to arrive at a more predictive potency test that tracks islet secretory capacity in a relevant context. With the development of potency tests that can report on islet secretion dynamics in a context relevant to their intended function, islet transplantation can expand into a more widely accessible and reliable treatment option for individuals with diabetes.
Building Biomimetic Potency Tests for Islet Transplantation
143 -, Badrossamay MR, McIlwee HA, Goss JA, and Parker KK. 1/2021. “Nanofiber assembly by rotary jet spinning.” Publisher, 10, 6, Pp. 2257-2261. Publisher's VersionAbstract
High-voltage electrical fields and low production rate limit electrospinning, the electrical charging of polymer liquids, as a means of nanofiber fabrication. Here, we show a facile method of fabrication of aligned three-dimensional nanofiber structures by utilizing high-speed, rotating polymer solution jets to extrude fibers. Termed rotary jet-spinning, fiber morphology, diameter, and web porosity can be controlled by varying nozzle geometry, rotation speed, and polymer solution properties. We demonstrate the utility of this technique for tissue engineering by building anisotropic arrays of biodegradable polymer fibers and seeding the constructs with neonatal rat ventricular cardiomyocytes. The myocytes used the aligned fibers to orient their contractile cytoskeleton and to self-organize into a beating, multicellular tissue that mimics the laminar, anisotropic architecture of the heart muscle. This technique may prove advantageous for building uniaxially aligned nanofiber structures for polymers which are not amenable to fabrication by electrospinning.
Nanofiber assembly by rotary jet spinning
2020
142 - and K. K. Parker. 11/6/2020. “Some Data Is Hard To Get-Some Data You Have to Be Hard to Get.” Matter, 3, 3, Pp. 623–627. Publisher's VersionAbstract
My second tour of duty in the Global War on Terror took me, an Army reservist, from my research and teaching at Harvard to the mountainous valleys of eastern Afghanistan. My job on this tour, working for the Center for Army Lessons Learned, was to try to understand how we were trying to rid the battlefield of improvised explosive devices, or IEDs, which were causing most of the Coalition casualties. A field-grade officer with no troops under my command, I roamed my area of operation attached to tactical units to collect data. One such group was Route Clearance Patrol 13 (RCP13), an amalgam of combat engineers, explosive specialists, and specialized teams, clearing roads of IEDs (Figure 1). On these missions, I sat strapped into its Buffalo, a motorized beast whose extraordinary size and robotic arm capabilities were designed to directly engage the explosive devices in lieu of dispatching someone to check it out themselves.
Some Data Is Hard To Get-Some Data You Have to Be Hard to Get
141 -, Parker KK, Longobardi L, and Sulicz A. 11/5/2020. “Welcome to Biophysics Reviews, a big tent for the biophysics community.” Biophysics Reviews, 1, 1, Pp. 010401. Publisher's VersionAbstract
It is our pleasure to welcome you to the first issue of Biophysics Reviews (BPR), a new journal from AIP Publishing covering the diverse field of biophysics. The journal expands on the tradition of excellence set by Applied Physics Reviews (APR) by publishing high impact, cutting edge research and reviews that are valuable for both emerging and experienced researchers.
Welcome to Biophysics Reviews, a big tent for the biophysics community
140 -, Yadid M, Lind JU, Ardoña HAM, Sheehy SP, Dickinson LE, Eweje F, Bastings MCB, Pope B, O’Connor BB, Straubhaar JR, and Kleb Budnik B. 10/14/2020. “Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip.” Science Translational Medicine, 12, 565, Pp. eaax8005.Abstract
Extracellular vesicles, small membrane-bound particles released from cells, have been shown to have cardioprotective effects. Here, Yadid et al. analyzed the proteins contained in vesicles released from endothelial cells under normoxia and hypoxia and investigated cardioprotective effects on cardiac tissues in vitro. Using a human heart-on-chip composed of cardiomyocytes, the authors showed that endothelial cell–derived vesicles supported metabolic function, tissue contraction, and viability during ischemia-reperfusion injury. This study helps to elucidate the mechanism by which vesicles are cardioprotective in human tissue.
Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip
139 -, Aytac Z, Huang R, Vaze N, Xu T, Eitzer BD, Krol W, MacQueen LA, Chang H, Bousfield DW, Chan-Park MB, Ng KW, Parker KK, White JC, and Demokritou P. 9/21/2020. “Development of biodegradable and antimicrobial electrospun zein fibers for food packaging.” ACS Sustainable Chemistry & Engineering, 8, 40, Pp. 15354-15365. Publisher's VersionAbstract
There is an urgent need to develop biodegradable and nontoxic materials from biopolymers and nature-derived antimicrobials to enhance food safety and quality. In this study, electrospinning was used as a one-step, scalable, green synthesis approach to engineer antimicrobial fibers from zein using nontoxic organic solvents and a cocktail of nature-derived antimicrobials which are all FDA-classified Generally Recognized as Safe (GRAS) for food use. Morphological and physicochemical properties of fibers, as well as the dissolution kinetics of antimicrobials were assessed along with their antimicrobial efficacy using state of the art analytical and microbiological methods. A cocktail of nature-derived antimicrobials was developed and included thyme oil, citric acid, and nisin. Its ability to inactivate a broad-spectrum of with food-related pathogens was demonstrated. Morphological characterization of the electrospun antimicrobial fibers revealed bead-free fibers with a small average diameter of 165 nm, whereas physicochemical characterization showed high surface area-to-volume ratio (specific surface area:21.91 m2/g) and presence of antimicrobial analytes in the fibers. The antimicrobials exhibited initial rapid release from the fibers in 2 h into various food simulants. Furthermore, the antimicrobial fibers effectively reduced E. coli and L. innocua populations by ∼5 logs for after 24 h and 1 h of exposure, respectively. More importantly, due to the small diameter and high surface area-to-volume ratio of the fibers, only miniscule quantities of fiber mass and antimicrobials per surface area (2.50 mg/cm2 of fibers) are needed for pathogen inactivation. The scalability of this fiber synthesis process was also demonstrated using a multineedle injector with production yield up to 1 g/h. This study shows the potential of using nature-derived biopolymers and antimicrobials to synthesize fibers for sustainable food packaging materials.
Development of biodegradable and antimicrobial electrospun zein fibers for food packaging
138 -, Pope BD, Warren CR, Dahl MO, Pizza CV, Henze DE, Sinatra NR, Gonzalez GM, Chang H, Liu Q, Gleiberman AL, Ferrier JP, Cowan CA, and Parker KK. 9/21/2020. “Fattening chips: hypertrophy, feeding, and fasting of human white adipocytes in vitro.” Lab on a Chip, 22. Publisher's VersionAbstract
Adipose is a distributed organ that performs vital endocrine and energy homeostatic functions. Hypertrophy of white adipocytes is a primary mode of both adaptive and maladaptive weight gain in animals and predicts metabolic syndrome independent of obesity. Due to the failure of conventional culture to recapitulate adipocyte hypertrophy, technology for production of adult-size adipocytes would enable applications such as in vitro testing of weight loss therapeutics. To model adaptive adipocyte hypertrophy in vitro, we designed and built fat-on-a-chip using fiber networks inspired by extracellular matrix in adipose tissue. Fiber networks extended the lifespan of differentiated adipocytes, enabling growth to adult sizes. By micropatterning preadipocytes in a native cytoarchitecture and by adjusting cell-to-cell spacing, rates of hypertrophy were controlled independent of culture time or differentiation efficiency. In vitro hypertrophy followed a nonlinear, nonexponential growth model similar to human development and elicited transcriptomic changes that increased overall similarity with primary tissue. Cells on the chip responded to simulated meals and starvation, which potentiated some adipocyte endocrine and metabolic functions. To test the utility of the platform for therapeutic development, transcriptional network analysis was performed, and retinoic acid receptors were identified as candidate drug targets. Regulation by retinoid signaling was suggested further by pharmacological modulation, where activation accelerated and inhibition slowed hypertrophy. Altogether, this work presents technology for mature adipocyte engineering, addresses the regulation of cell growth, and informs broader applications for synthetic adipose in pharmaceutical development, regenerative medicine, and cellular agriculture.
137 -, Fioretta ES, Motta SE, Lintas Valentina, Loerakker S, Parker KK, Baaijens FPT, Falk V, Hoerstrup SP, and Emmert MY. 9/9/2020. “Next-generation tissue-engineered heart valves with repair, remodelling and regeneration capacity.” Nature Reviews Cardiology, 18, Pp. 92–116. Publisher's VersionAbstract
Valvular heart disease is a major cause of morbidity and mortality worldwide. Surgical valve repair or replacement has been the standard of care for patients with valvular heart disease for many decades, but transcatheter heart valve therapy has revolutionized the field in the past 15 years. However, despite the tremendous technical evolution of transcatheter heart valves, to date, the clinically available heart valve prostheses for surgical and transcatheter replacement have considerable limitations. The design of next-generation tissue-engineered heart valves (TEHVs) with repair, remodelling and regenerative capacity can address these limitations, and TEHVs could become a promising therapeutic alternative for patients with valvular disease. In this Review, we present a comprehensive overview of current clinically adopted heart valve replacement options, with a focus on transcatheter prostheses. We discuss the various concepts of heart valve tissue engineering underlying the design of next-generation TEHVs, focusing on off-the-shelf technologies. We also summarize the latest preclinical and clinical evidence for the use of these TEHVs and describe the current scientific, regulatory and clinical challenges associated with the safe and broad clinical translation of this technology.
Next-generation tissue-engineered heart valves with repair, remodelling and regeneration capacity
136 -, Gonzalez GM, Ward J, Song J, Swana K, Fossey SA, Palmer JL, Zhang FW, Lucian VM, Cera L, Zimmerman JF, Burpo FJ, and Parker KK. 9/2/2020. “para-Aramid Fiber Sheets for Simultaneous Mechanical and Thermal Protection in Extreme Environments.” Matter, 3, 3, Pp. 742-758. Publisher's VersionAbstract
First responders and military personnel working under extreme conditions require protection against multiple hazards, including thermal and ballistic protection. However, traditional materials lack multiple types of protection in a single protective layer. By controlling the chemical and structural makeup of high-performance fibers across multiple length scales, this work demonstrates a multifunctional sheet capable of providing simultaneous thermal and ballistic protection. These sheets are composed of long, continuous fibers to resist a mechanical load and large pores to limit heat transfer. By combining these structure-function properties, these fibers overcome traditional trade-offs, providing mechanical performance equivalent to commercially available ballistic fibers while providing 20-fold insulation capability. Overcoming previous limitations, this approach enables simultaneous thermal and mechanical protection for astronauts, bomb disposal experts, and warfighters.
para-Aramid Fiber Sheets for Simultaneous Mechanical and Thermal Protection in Extreme Environments
135 -, Cera L, Gonzalez GM, Liu Q, Choi S, Chantre CO, Lee J, Gabardi R, Choi MC, Shin K, and Parker KK. 8/31/2020. “A bioinspired and hierarchically structured shape-memory material.” Nature Materials, 20, Pp. 242–249. Publisher's VersionAbstract
Shape-memory polymeric materials lack long-range molecular order that enables more controlled and efficient actuation mechanisms. Here, we develop a hierarchical structured keratin-based system that has long-range molecular order and shape-memory properties in response to hydration. We explore the metastable reconfiguration of the keratin secondary structure, the transition from α-helix to β-sheet, as an actuation mechanism to design a high-strength shape-memory material that is biocompatible and processable through fibre spinning and three-dimensional (3D) printing. We extract keratin protofibrils from animal hair and subject them to shear stress to induce their self-organization into a nematic phase, which recapitulates the native hierarchical organization of the protein. This self-assembly process can be tuned to create materials with desired anisotropic structuring and responsiveness. Our combination of bottom-up assembly and top-down manufacturing allows for the scalable fabrication of strong and hierarchically structured shape-memory fibres and 3D-printed scaffolds with potential applications in bioengineering and smart textiles.
A bioinspired and hierarchically structured shape-memory material
134 -, Herland A, Maoz BM, Fitzgerald EA, Grevesse T, Vidoudez C, Sheehy SP, Budnik N, Dauth S, Mannix R, Budnik B, Parker KK, and Ingber DE. 8/3/2020. “Proteomic and Metabolomic Characterization of Human Neurovascular Unit Cells in Response to Methamphetamine.” Advanced Biosystems, 4, 9, Pp. e1900230. Publisher's VersionAbstract
The functional state of the neurovascular unit (NVU), composed of the blood–brain barrier and the perivasculature that forms a dynamic interface between the blood and the central nervous system (CNS), plays a central role in the control of brain homeostasis and is strongly affected by CNS drugs. Human primary brain microvascular endothelium, astrocyte, pericyte, and neural cell cultures are often used to study NVU barrier functions as well as drug transport and efficacy; however, the proteomic and metabolomic responses of these different cell types are not well characterized. Culturing each cell type separately, using deep coverage proteomic analysis and characterization of the secreted metabolome, as well as measurements of mitochondrial activity, the responses of these cells under baseline conditions and when exposed to the NVU-impairing stimulant methamphetamine (Meth) are analyzed. These studies define the previously unknown metabolic and proteomic profiles of human brain pericytes and lead to improved characterization of the phenotype of each of the NVU cell types as well as cell-specific metabolic and proteomic responses to Meth.
Proteomic and Metabolomic Characterization of Human Neurovascular Unit Cells in Response to Methamphetamine
133 -, O’Connor BB, Pope B, Peters MM, Ris-Stalpers C, and Parker KK. 7/1/2020. “The role of extracellular matrix in normal and pathological pregnancy: Future applications of microphysiological systems in reproductive medicine.” Experimental Biology and Medicine, 245, 13, Pp. 1163-1174. Publisher's VersionAbstract
Extracellular matrix in the womb regulates the initiation, progression, and completion of a healthy pregnancy. The composition and physical properties of extracellular matrix in the uterus and at the maternal-fetal interface are remodeled at each gestational stage, while maladaptive matrix remodeling results in obstetric disease. As in vitro models of uterine and placental tissues, including micro-and milli-scale versions of these organs on chips, are developed to overcome the inherent limitations of studying human development in vivo, we can isolate the influence of cellular and extracellular components in healthy and pathological pregnancies. By understanding and recreating key aspects of the extracellular microenvironment at the maternal-fetal interface, we can engineer microphysiological systems to improve assisted reproduction, obstetric disease treatment, and prenatal drug safety.
The role of extracellular matrix in normal and pathological pregnancy: Future applications of microphysiological systems in reproductive medicine
132 -, Ahn S, Chantre CO, Ardoña HAM, Gonzalez GM, Campbell PH, and Parker KK. 5/28/2020. “Biomimetic and estrogenic fibers promote tissue repair in mice and human skin via estrogen receptor β.” Biomaterials, 255, Pp. 120149. Publisher's VersionAbstract
The dynamic changes in estrogen levels throughout aging and during the menstrual cycle influence wound healing. Elevated estrogen levels during the pre-ovulation phase accelerate tissue repair, whereas reduced estrogen levels in post-menopausal women lead to slow healing. Although previous reports have shown that estrogen may potentiate healing by triggering the estrogen receptor (ER)-β signaling pathway, its binding to ER-α has been associated with severe collateral effects and has therefore limited its use as a therapeutic agent. To this end, soy phytoestrogens, which preferentially bind to the ER-β, are currently being explored as a safer therapeutic alternative to estrogen. However, the development and evaluation of phytoestrogen-based materials as local ER-β modulators remains largely unexplored. Here, we engineered biomimetic and estrogenic nanofiber wound dressings built from soy protein isolate (SPI) and hyaluronic acid (HA) using immersion rotary jet spinning. These engineered scaffolds were shown to successfully recapitulate the native dermal architecture, while delivering an ER-β-triggering phytoestrogen (genistein). When tested in ovariectomized mouse and ex vivo human skin tissues, HA/SPI scaffolds outperformed controls (no treatment or HA only scaffolds) towards promoting cutaneous tissue repair. These improved healing outcomes were prevented when the ER-β pathway was genetically or chemically inhibited. Our findings suggest that estrogenic fibrous scaffolds facilitate skin repair by ER-β activation.
Biomimetic and estrogenic fibers promote tissue repair in mice and human skin via estrogen receptor β

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