Kevin Kit Parker

• PhD
• Professor at Harvard University

N-terminal acetyltransferases including NAA10 catalyze N-terminal acetylation, an evolutionarily conserved co- and post-translational modification. However, little is known about the role of N-terminal acetylation in cardiac homeostasis. To gain insight into cardiac-dependent NAA10 function, we studied a previously unidentified NAA10 variant p.(Arg...

In biomimetic design, researchers recreate existing biological structures to form functional devices. For biohybrid robotic swimmers assembled with tissue engineering, this is problematic because most devices operate at different length scales than their naturally occurring counterparts, resulting in reduced performance. To overcome these challenge...

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) lack nanoscale structures essential for efficient excitation–contraction coupling. Such nanostructures, known as dyads, are frequently disrupted in heart failure. Here we show that the reduced expression of cardiomyopathy-associated 5 (CMYA5), a master protein that establi...

Human iPSC-derived cardiomyocytes (hiPSC-CMs) have proven invaluable for cardiac disease modeling and regeneration. Challenges with quality, inter-batch consistency, cryopreservation and scale remain, reducing experimental reproducibility and clinical translation. Here, we report a robust stirred suspension cardiac differentiation protocol, and we...

Studying the behavior of electroactive cells, such as firing dynamics and chemical secretion, is crucial for developing human disease models and therapeutics. Following the recent advances in cell culture technology, traditional monolayers are optimized to resemble more 3D, organ‐like structures. The biological and electrochemical complexity of the...

Electrolytes are essential parts of the environment for all life forms, where proteins, water, and solutes interplay to support vital activities. However, a fundamental understanding of the effect of ionic solutes on proteins remains elusive for more than a century. Here we show how some ionic solutes can serve as potent denaturants despite the abs...

In the last decade human iPSC-derived cardiomyocytes (hiPSC-CMs) proved to be valuable for cardiac disease modeling and cardiac regeneration, yet challenges with scale, quality, inter-batch consistency, and cryopreservation remain, reducing experimental reproducibility and limiting clinical translation. Here, we report a robust cardiac differentiat...

In tissues and organs, the extracellular matrix (ECM) helps maintain inter-and intracellular architectures that sustain the structure-function relationships defining physiological homeostasis. Combining fiber scaffolds and cells to form engineered tissues is a means of replicating these relationships. Engineered tissues' fiber scaffolds are designe...

N-terminal-acetyltransferases including NAA10 catalyze N-terminal acetylation (Nt-acetylation), an evolutionarily conserved co-translational modification. Little is known about the role of Nt-acetylation in cardiac homeostasis. To gain insights, we studied a novel NAA10 variant (p.R4S) segregating with QT-prolongation, cardiomyopathy and developmen...

Hydrogels are attractive materials for tissue engineering, but efforts to date have shown limited ability to produce the microstructural features necessary to promote cellular self-organization into hierarchical three-dimensional (3D) organ models. Here we develop a hydrogel ink containing prefabricated gelatin fibres to print 3D organ-level scaffo...

BACKGROUND N-terminal-acetyltransferases catalyze N-terminal acetylation (Nt-acetylation), an evolutionarily conserved co-translational modification. Nt-acetylation regulates diverse signaling pathways, yet little is known about its effects in the heart. To gain insights, we studied NAA10-related syndrome, in which mutations in NAA10, which catalyz...

The past ten years have seen the rapid expansion of the field of biohybrid robotics. By combining engineered, synthetic components with living biological materials, new robotics solutions have been developed that harness the adaptability of living muscles, the sensitivity of living sensory cells, and even the computational abilities of living neuro...

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 ro...

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 possibilit...

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 w...

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 (2D...

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 leverag...

Wound Healing A new platform for the delivery of extracellular matrix (ECM) that can rapidly heal damaged tissues is developed. In article number 2101599, Kevin K. Parker, Chang‐Ju Kim, Kwanwoo Shin, and co‐workers, confirm that when unfolded fibronectins are delivered by binding to small unilamellar vesicles with negative charges, they are very ef...

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 au...

For more than fifty years, it has been hypothesized that the helical alignment of the heart gives rise to its mechanical function. Testing this hypothesis in an engineered environment is difficult, as the fine spatial features and complex three-dimensional (3D) structures of the cardiac musculature are challenging to reproduce using current biofabr...

Significance Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutation in the X-linked dystrophin gene, resulting in skeletal muscle loss and patient premature death. Here, we present an improved protocol for the differentiation of human pluripotent stem cells to the skeletal muscle lineage. Using this protocol for the different...

The unfolded states of fibronectin (FN) subsequently induce the formation of the extracellular matrix (ECM) fibrillar network, which is necessary to generate new substitutive tissues. Here, we demonstrate that negatively charged small unilamellar vesicles (SUVs) qualify as candidates for FN delivery due to their remarkable effects on the autonomous...

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...

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...

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 to recapitulate...

Extracellular vesicles (EVs) derived from various stem cell sources induce cardioprotective effects during ischemia-reperfusion injury (IRI). These have been attributed mainly to the antiapoptotic, proangiogenic, microRNA (miRNA) cargo within the stem cell–derived EVs. However, the mechanisms of EV-mediated endothelial signaling to cardiomyocytes,...

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-d...

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 tr...

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, astroc...

Impact statement: 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....

The multiscale organization of protein-based fibrillar materials is a hallmark of many organs, but the recapitulation of hierarchal structures down to fibrillar scales, which is a requirement for withstanding physiological loading forces, has been challenging. We present a microfluidic strategy for the continuous, large-scale formation of strong, h...

Personnel operating in extreme environments require equipment that protects against multiple hazards. Currently, protection against both thermal and ballistic threats requires the combination of multiple high-performance materials that increases equipment weight and complexity. Here, we hypothesized we could achieve simultaneous protection by manuf...

The multiscale organization of protein-based fibrillar materials is a hallmark of many organs, but the recapitulation of hierarchal structures down to fibrillar scales, which is a requirement for withstanding physiological loading forces, has been challenging. We present a microfluidic strategy for the continuous, large-scale formation of strong, h...

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...

Analyses of drug pharmacokinetics (PKs) and pharmacodynamics (PDs) performed in animals are often not predictive of drug PKs and PDs in humans, and in vitro PK and PD modelling does not provide quantitative PK parameters. Here, we show that physiological PK modelling of first-pass drug absorption, metabolism and excretion in humans—using computatio...

Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ‘interrogator’ that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, f...

The blood–brain barrier plays a critical role in delivering oxygen and nutrients to the brain while preventing the transport of neurotoxins. Predicting the ability of potential therapeutics and neurotoxicants to modulate brain barrier function remains a challenge due to limited spatial resolution and geometric constraints offered by existing in vit...

Increasing numbers of commercial skincare products are being manufactured with engineered nanomaterials (ENMs), prompting a need to fully understand how ENMs interact with the dermal barrier as a major biodistribution entry route. Although animal studies show that certain nanomaterials can cross the skin barrier, physiological differences between h...

Bioprocessing applications that derive meat products from animal cell cultures require food-safe culture substrates that support volumetric expansion and maturation of adherent muscle cells. Here we demonstrate scalable production of microfibrous gelatin that supports cultured adherent muscle cells derived from cow and rabbit. As gelatin is a natur...

Recent reports suggest the utility of extracellular matrix (ECM) molecules as raw components in scaffolding of engineered materials. However, rapid and tunable manufacturing of ECM molecules into fibrous structures remains poorly developed. Here we report on an immersion rotary jet-spinning (iRJS) method to show high-throughput manufacturing (up to...

Background: Current differentiation protocols to produce cardiomyocytes from human induced pluripotent stem cells (iPSCs) are capable of generating highly pure cardiomyocyte populations as determined by expression of cardiac troponin T. However, these cardiomyocytes remain immature, more closely resembling the fetal state, with a lower maximum con...

Engineered nanomaterials (ENMs) are increasingly used in consumer products due to their unique physicochemical properties, but the specific hazards they pose to the structural and functional integrity of endothelial barriers remain elusive. When assessing the effects of ENMs on vascular barrier function, endothelial cell monolayers are commonly use...

Pancreatic β cell function is compromised in diabetes and is typically assessed by measuring insulin secretion during glucose stimulation. Traditionally, measurement of glucose-stimulated insulin secretion involves manual liquid handling, heterogeneous stimulus delivery, and enzyme-linked immunosorbent assays that require large numbers of islets an...

Here, we present ultragentle soft robotic actuators capable of grasping delicate specimens of gelatinous marine life. Although state-of-the-art soft robotic manipulators have demonstrated gentle gripping of brittle animals (e.g., corals) and echinoderms (e.g., sea cucumbers) in the deep sea, they are unable to nondestructively grasp more fragile so...

Engineering bioscaffolds for improved cutaneous tissue regeneration remains a healthcare challenge due to the increasing number of patients suffering from acute and chronic wounds. To help address this problem, we propose to utilize alfalfa, an ancient medicinal plant that contains antibacterial/oxygenating chlorophylls and bioactive phytoestrogens...

Background: Modeling of human arrhythmias using induced pluripotent stem cell-derived cardiomyocytes has focused on single cell phenotypes. However, arrhythmias are the emergent properties of cells assembled into tissues, and the impact of inherited arrhythmia mutations on tissue-level properties of human heart tissue has not been reported. Metho...

A spoof fingerprint was fabricated on paper and applied for a spoofing attack to unlock a smartphone on which a capacitive array of sensors had been embedded with a fingerprint recognition algorithm. Using an inkjet printer with an ink made of carbon nanotubes (CNTs), we printed a spoof fingerprint having an electrical and geometric pattern of ridg...

Development of biomimetic and instructive materials is emerging as a promising approach for redirecting fibrotic wound healing into a regenerative process. In nature, complete tissue regeneration can transpire in certain organ substructures, during embryogenesis and, remarkably, in some organisms in which whole limbs can regrow. These regenerative...

Here we describe of an Interrogator instrument that uses liquid-handling robotics, a custom software package, and an integrated mobile microscope to enable automated culture, perfusion, medium addition, fluidic linking, sample collection, and in situ microscopic imaging of up to 10 Organ Chips inside a standard tissue culture incubator. The automat...

Understanding the uptake and transport dynamics of engineered nanomaterials (ENMs) by mammalian cells is an important step in designing next-generation drug delivery systems. However, to track these materials and their cellular interactions, current studies often depend on surface-bound fluorescent labels which have the potential to alter native ce...

Laboratory studies of the heart use cell and tissue cultures to dissect heart function yet rely on animal models to measure pressure and volume dynamics. Here, we report tissue-engineered scale models of the human left ventricle, made of nanofibrous scaffolds that promote native-like anisotropic myocardial tissue genesis and chamber-level contracti...

The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contribution...

Complex deformation of a polymer jet appears in many manufacturing processes, such as 3D printing, electrospinning, blow spinning, and rotary jet spinning. In these applications, a polymer melt or solution is first extruded through an orifice and forms a jet. The polymer jet is then dynamically deformed until the polymer solidifies. The final produ...

Inside cells, complex metabolic reactions are distributed across the modular compartments of organelles1,2. Reactions in organelles have been recapitulated in vitro by reconstituting functional protein machineries into membrane systems3,4,5. However, maintaining and controlling these reactions is challenging. Here we designed, built, and tested a s...

Soft pneumatic actuators are promising candidates for micro-manipulation and delicate gripping due to their wide range of motion and ease of fabrication. While existing elastomer-based devices have attracted attention due to their compliant structures, there is a need for materials that combine flexibility, controllable actuation, and robustness. T...

Due to the unique physicochemical properties exhibited by materials with nanoscale dimensions, there is currently a continuous increase in the number of engineered nanomaterials (ENMs) used in consumer goods. However, several reports associate ENM exposure to negative health outcomes such as cardiovascular diseases. Therefore, understanding the pat...

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tis...

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Wounds in the fetus can heal without scarring. Consequently, biomaterials that attempt to recapitulate the biophysical and biochemical properties of fetal skin have emerged as promising pro-regenerative strategies. The extracellular matrix (ECM) protein fibronectin (Fn) in particular is believed to play a crucial role in directing this regenerative...

The extracellular matrix (ECM) consists of polymerized protein monomers that form a unique fibrous network providing stability and structural support to surrounding cells. We harnessed the fibrillogenesis mechanisms of naturally occurring ECM proteins to produce artificial fibers with a heterogeneous protein makeup. Using ECM proteins as fibril bui...

Historically, soy protein and extracts have been used extensively in foods due to their high protein and mineral content. More recently, soy protein has received attention for a variety of its potential health benefits, including enhanced skin regeneration. It has been reported that soy protein possesses bioactive molecules similar to extracellular...

Organ-on-chip platforms aim to improve preclinical models for organ-level responses to novel drug compounds. Heart-on-a-chip assays in particular require tissue engineering techniques that rely on labor-intensive photolithographic fabrication or resolution-limited 3D printing of micropatterned substrates, which limits turnover and flexibility of pr...

Actuation is essential for artificial machines to interact with their surrounding environment and to accomplish the functions for which they are designed. Over the past few decades, there has been considerable progress in developing new actuation technologies. However, controlled motion still represents a considerable bottleneck for many applicatio...

Microphysiological systems and organs-on-chips promise to accelerate biomedical and pharmaceutical research by providing accurate in vitro replicas of human tissue. Aside from addressing the physiological accuracy of the model tissues, there is a pressing need for improving the throughput of these platforms. To do so, scalable data acquisition stra...

The mechanisms underlying the spatial organization of self-assembled myofibrils in cardiac tissues remain incompletely understood. By modeling cells as elastic solids under active cytoskeletal contraction, we found a good correlation between the predicted maximal principal stress directions and the in vitro myofibril orientations in individual card...

Biodegradable scaffold matrixes form the basis of any in vitro tissue engineering approach by acting as a temporary matrix for cell proliferation and extracellular matrix deposition until the scaffold is replaced by neo-tissue. In this context several synthetic polymers have been investigated, however a concise systematic comparative analyses is mi...

Millimeter-long conducting fibers can be fabricated from carbon nanomaterials via a simple method involving the release of a prestrained protein layer. This study shows how a self-rolling process initiated by polymerization of a micropatterned layer of fibronectin (FN) results in the production of carbon nanomaterial-based microtubular fibers. The...

Here we demonstrate that microfluidic cell culture devices, known as Organs-on-a-Chips can be fabricated with multifunctional, real-time, sensing capabilities by integrating both Multi-Electrode Arrays (MEAs) and electrodes for Transepithelial Electrical Resistance (TEER) measurements into the chips during their fabrication. To prove proof-of-conce...

Tissue engineered scaffolds have emerged as a promising solution for heart valve replacement because of their potential for regeneration. However, traditional heart valve tissue engineering has relied on resource-intensive, cell-based manufacturing, which increases cost and hinders clinical translation. To overcome these limitations, in situ tissue...

In vitro studies of cardiac physiology and drug response have traditionally been performed on individual isolated cardiomyocytes or isotropic monolayers of cells that may not mimic desired physiological traits of the laminar adult myocardium. Recent studies have reported a number of advances to Heart-on-a-Chip platforms for the fabrication of more...

The assembly of natural and synthetic polymers into fibrous nanomaterials has applications ranging from textiles, tissue engineering, photonics, and catalysis. However, rapid manufacturing of these materials is challenging, as the state of the art in nanofiber assembly remains limited by factors such as solution polarity, production rate, applied e...

Front Cover: Pull spinning is a new nanofiber manufacturing technique that uses a high-speed rotating bristle to draw anisotropic nanofibers from a polymer solution. The versatile structure and composition of scaffolds formed using pull spinning enables a wide range of applications, including muscle tissue engineering and textile design. This is re...

Front Cover: Utilizing a precipitant vortex, a novel nanofiber platform produces Kevlar, nylon, DNA, and alginate nanofibers for high-performance composites and tissue engineering applications. The artwork provided is original to our lab. This is reported by Grant M. Gonzalez, Luke A. MacQueen, Johan U. Lind, Stacey A. Fitzgibbons, Christophe O. Ch...

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: The scarcity of comparative data for ce...

Efficient contractions of the left ventricle are ensured by the continuous transfer of adenosine triphosphate (ATP) from energy production sites, the mitochondria, to energy utilization sites, such as ionic pumps and the force-generating sarcomeres. To minimize the impact of intracellular ATP trafficking, sarcomeres and mitochondria are closely pac...

To date, clinical success of cardiac cell-therapies remains limited. To enhance the cardioreparative properties of stem cells, the concept of lineage-specification through cardiopoietic-guidance has been recently suggested. However, so far, only results from murine studies and from a clinical pilot-trial in chronic heart-failure (CHF) are available...

Smoking represents a major risk factor for chronic obstructive pulmonary disease (COPD), but it is difficult to characterize smoke-induced injury responses under physiological breathing conditions in humans due to patient-to-patient variability. Here, we show that a small airway-on-a-chip device lined by living human bronchiolar epithelium from nor...

Biomedical research has relied on animal studies and conventional cell cultures for decades. Recently, microphysiological systems (MPS), also known as organs-on-chips, that recapitulate the structure and function of native tissues in vitro, have emerged as a promising alternative. However, current MPS typically lack integrated sensors and their fab...

A class of novel therapies leverages regenerative cell types in disease microenvironments. This complex interplay challenges established good manufacturing practices, as standards and analytical tools to measure regenerative potency are missing. That is, we can build the product right, but we do not know if we are building the right product. Here,...