Scholars@Duke
Sharon Gerecht

Sharon Gerecht

Paul M. Gross Distinguished Professor
Biomedical Engineering

Selected Publications

CaMKK2 Regulates Macrophage Polarization Induced by Matrix Stiffness: Implications for Shaping the Immune Response in Stiffened Tissues.

Journal Article Adv Sci (Weinh) · April 2025 Macrophages are essential for immune responses and maintaining tissue homeostasis, exhibiting a wide range of phenotypes depending on their microenvironment. The extracellular matrix (ECM) is a vital component that provides structural support and organizat ... Full text Link to item Cite

Engineering the Microstructure and Spatial Bioactivity of MAP Scaffolds Instructs Vasculogenesis In Vitro and Modifies Vessel Formation In Vivo

Journal Article Advanced Functional Materials · January 15, 2025 In tissues where the vasculature is either lacking or abnormal, biomaterials can be designed to promote vessel formation and enhance tissue repair. In this work, the microstructure and bioactivity of microporous annealed particle (MAP) scaffolds are indepe ... Full text Cite

Acute Three-Dimensional Hypoxia Regulates Angiogenesis.

Journal Article Advanced healthcare materials · January 2025 Hypoxia elicits a multitude of tissue responses depending on the severity and duration of the exposure. While chronic hypoxia is shown to impact development, regeneration, and cancer, the understanding of the threats of acute (i.e., short-term) hypoxia is ... Full text Cite

Automated 3D Segmentation of Hydrogel-Treated Mice Wounds Using Optical Coherence Tomography and Deep Learning

Conference Progress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2025 Optical coherence tomography (OCT) is a powerful non-invasive imaging technique, providing high-resolution three-dimensional images of biological tissues. However, accurately segmenting regions-of-interest from large 3D images is challenging and often reli ... Full text Cite

Cell-Material Interactions in Vascular Tissue Engineering

Journal Article Accounts of Materials Research · January 1, 2025 The vascular system, encompassing blood and lymphatic vessels, is essential for nutrient transport, waste elimination, and homeostasis regulation. Composed of endothelial cells and mural cells, such as smooth muscle cells and pericytes, the vasculature is ... Full text Cite

Generation of an induced pluripotent stem cell line, JHUi005-A, from a Marfan Syndrome patient harboring a pathogenic c.3338-2A>C intronic splicing variant.

Journal Article Stem cell research · September 2024 Marfan Syndrome, a connective tissue disorder caused by Fibrillin-1 (FBN1) gene mutations, induces disease in the ocular, musculoskeletal, and cardiovascular systems and increases aortic vulnerability to rupture associated with high mortality rates. We des ... Full text Cite

Engineered Biomaterials and Model Systems to Study YAP/TAZ in Cancer.

Journal Article ACS biomaterials science & engineering · September 2024 The transcriptional coactivators yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are master regulators involved in a multitude of cancer types and a wide range of tumorigenic events, including cancer stem cell rene ... Full text Cite

Functional profiling of resident cells during vascular aging

Conference Physiology · May 2024 Introduction: Depending on surrounding cell types, substrate mechanics, and chemical agonists, vascular cell types – including endothelial (ECs) and smooth muscle cells (VSMC) — modulate their behavior to maintain homeostasis. Aging perturbs this ... Full text Cite

Oncogene-induced matrix reorganization controls CD8+ T cell function in the soft-tissue sarcoma microenvironment.

Journal Article The Journal of clinical investigation · April 2024 CD8+ T cell dysfunction impedes antitumor immunity in solid cancers, but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; howeve ... Full text Cite

Age-dependent loss of HAPLN1 erodes vascular integrity via indirect upregulation of endothelial ICAM1 in melanoma.

Journal Article Nature aging · March 2024 Melanoma, the most lethal form of skin cancer, often has worse outcomes in older patients. We previously demonstrated that an age-related decrease in the secreted extracellular matrix (ECM) protein HAPLN1 has a role in slowing melanoma progression. Here we ... Full text Cite

Cytoplasmic accumulation and plasma membrane association of anillin and Ect2 promote confined migration and invasion.

Journal Article Res Sq · January 10, 2024 Cells migrating in confinement experience mechanical challenges whose consequences on cell migration machinery remain only partially understood. Here, we demonstrate that a pool of the cytokinesis regulatory protein anillin is retained during interphase in ... Full text Link to item Cite

In Vivo Evaluation of Hydrogel-Mediated Wound Healing Using Optical Coherence Tomography

Conference Optical Coherence Tomography, OCT 2024 in Proceedings Optica Biophotonics Congress: Biomedical Optics 2024, Translational, Microscopy, OCT, OTS, BRAIN - Part of Optica Biophotonics Congress: Biomedical Optics · January 1, 2024 We demonstrate in vivo monitoring of wound healing dynamics in mice treated with hydrogels of varying stiffness using OCT. Distinct cellular responses were visualized and tracked, revealing the potential of OCT for optimizing hydrogel-based treatments. ... Cite

In Vivo Evaluation of Hydrogel-Mediated Wound Healing Using Optical Coherence Tomography

Conference Optical Coherence Tomography, OCT 2024 in Proceedings Optica Biophotonics Congress: Biomedical Optics 2024, Translational, Microscopy, OCT, OTS, BRAIN - Part of Optica Biophotonics Congress: Biomedical Optics · January 1, 2024 We demonstrate in vivo monitoring of wound healing dynamics in mice treated with hydrogels of varying stiffness using OCT. Distinct cellular responses were visualized and tracked, revealing the potential of OCT for optimizing hydrogel-based treatments. ... Full text Cite

Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis.

Journal Article Nature communications · December 2023 The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as ... Full text Cite

Engineering biomaterials to tailor the microenvironment for macrophage–endothelium interactions

Journal Article Nature Reviews Materials · October 1, 2023 Macrophages and endothelial cells (ECs) have essential roles in physiological and pathological conditions by regulating inflammation, vascularization and tissue remodelling. Although the interactions between macrophages and ECs in tissue homeostasis and di ... Full text Cite

Downregulation of YAP Activity Restricts P53 Hyperactivation to Promote Cell Survival in Confinement.

Journal Article Advanced science (Weinheim, Baden-Wurttemberg, Germany) · August 2023 Cell migration through confining three dimensional (3D) topographies can lead to loss of nuclear envelope integrity, DNA damage, and genomic instability. Despite these detrimental phenomena, cells transiently exposed to confinement do not usually die. Whet ... Full text Cite

Hydrogels to Recapture Extracellular Matrix Cues That Regulate Vascularization.

Journal Article Arteriosclerosis, thrombosis, and vascular biology · August 2023 The ECM (extracellular matrix) is a 3-dimensional network that supports cellular responses and maintains structural tissue integrity in healthy and pathological conditions. The interactions between ECM and cells trigger signaling cascades that lead to phen ... Full text Cite

Collagen VI deposition mediates stromal T cell trapping through inhibition of T cell motility in the prostate tumor microenvironment.

Journal Article Matrix biology : journal of the International Society for Matrix Biology · August 2023 The tumor extracellular matrix (ECM) is a barrier to anti-tumor immunity in solid tumors by disrupting T cell-tumor cell interaction underlying the need for elucidating mechanisms by which specific ECM proteins impact T cell motility and activity within th ... Full text Cite

The extracellular matrix mechanics in the vasculature.

Journal Article Nature cardiovascular research · August 2023 Mechanical stimuli from the extracellular matrix (ECM) modulate vascular differentiation, morphogenesis and dysfunction of the vasculature. With innovation in measurements, we can better characterize vascular microenvironment mechanics in health and diseas ... Full text Cite

Reconstructing the ageing extracellular matrix

Journal Article Nature Reviews Bioengineering · July 1, 2023 The extracellular matrix (ECM) is a key component of the stem-cell niche, and undergoes profound changes during ageing, affecting tissue mechanics and structure. Here, we argue that ECM alterations can be leveraged to engineer biomaterials to investigate a ... Full text Cite

Effect of ECM and mechanical strain on vascular cell plasticity

Conference Physiology · May 2023 Introduction: Depending on surrounding cell types, substrate mechanics, and chemical agonists, vascular smooth muscle cells (VSMCs) alternate between a contractile and synthetic phenotype. While endothelial cells (ECs) do not modulate their phenot ... Full text Cite

Vascular stiffening in aging females with a hypertension-induced HIF2A gain-of-function mutation.

Journal Article Bioengineering & translational medicine · March 2023 Pulmonary arterial hypertension (PAH) is more prevalent in females than males; the causes of this sex difference have not been adequately explored. Gain-of-function (GOF) mutations in hypoxia-inducible factor 2α (HIF2A) lead to PAH and thrombotic consequen ... Full text Cite

BEYOND THE ENDOTHELIUM: THE ROLE OF MURAL CELLS IN VASCULAR BIOLOGY: In vitro systems to study endothelial/pericyte cell interactions.

Journal Article Vascular biology (Bristol, England) · February 2023 The vasculature is crucial for tissue development and survival, and the stability of blood vessels to perform these functions relies on the interplay between endothelial cells (ECs) and mural cells. Pericytes are a subtype of mural cells found in the micro ... Full text Cite

Engineering of the microenvironment to accelerate vascular regeneration.

Journal Article Trends in molecular medicine · January 2023 Blood vessels are crucial for tissue development, functionality, and homeostasis and are typically a determinant in the progression of healing and regeneration. The tissue microenvironment provides physicochemical cues that affect cellular function, and th ... Full text Cite

Looking on the horizon; potential and unique approaches to developing radiation countermeasures for deep space travel.

Journal Article Life Sci Space Res (Amst) · November 2022 Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human heal ... Full text Link to item Cite

Off-the-shelf, heparinized small diameter vascular graft limits acute thrombogenicity in a porcine model.

Journal Article Acta biomaterialia · October 2022 Thrombogenicity poses a challenge to the clinical translation of engineered grafts. Previously, small-diameter vascular grafts (sdVG) composed of fibrin hydrogel microfiber tubes (FMT) with an external poly(ε-caprolactone) (PCL) sheath supported long-term ... Full text Cite

Nanoparticle-based modulation of CD4+ T cell effector and helper functions enhances adoptive immunotherapy.

Journal Article Nature communications · October 2022 Helper (CD4+) T cells perform direct therapeutic functions and augment responses of cells such as cytotoxic (CD8+) T cells against a wide variety of diseases and pathogens. Nevertheless, inefficient synthetic technologies for expansio ... Full text Cite

Engineering Smooth Muscle to Understand Extracellular Matrix Remodeling and Vascular Disease.

Journal Article Bioengineering (Basel, Switzerland) · September 2022 The vascular smooth muscle is vital for regulating blood pressure and maintaining cardiovascular health, and the resident smooth muscle cells (SMCs) in blood vessel walls rely on specific mechanical and biochemical signals to carry out these functions. Any ... Full text Cite

Stiffening Matrix Induces Age-Mediated Microvascular Phenotype Through Increased Cell Contractility and Destabilization of Adherens Junctions.

Journal Article Advanced science (Weinheim, Baden-Wurttemberg, Germany) · August 2022 Aging is a major risk factor in microvascular dysfunction and disease development, but the underlying mechanism remains largely unknown. As a result, age-mediated changes in the mechanical properties of tissue collagen have gained interest as drivers of en ... Full text Cite

Tissue Engineering Approaches to Uncover Therapeutic Targets for Endothelial Dysfunction in Pathological Microenvironments.

Journal Article International journal of molecular sciences · July 2022 Endothelial cell dysfunction plays a central role in many pathologies, rendering it crucial to understand the underlying mechanism for potential therapeutics. Tissue engineering offers opportunities for in vitro studies of endothelial dysfunction in pathol ... Full text Cite

Hypoxia-induced blood-brain barrier dysfunction is prevented by pericyte-conditioned media via attenuated actomyosin contractility and claudin-5 stabilization.

Journal Article FASEB journal : official publication of the Federation of American Societies for Experimental Biology · May 2022 The blood-brain barrier (BBB) regulates molecular and cellular entry from the cerebrovasculature into the surrounding brain parenchyma. Many diseases of the brain are associated with dysfunction of the BBB, where hypoxia is a common stressor. However, the ... Full text Cite

Intrinsic epigenetic control of angiogenesis in induced pluripotent stem cell-derived endothelium regulates vascular regeneration.

Journal Article NPJ Regenerative medicine · May 2022 Human-induced pluripotent stem cell-derived endothelial cells (iECs) provide opportunities to study vascular development and regeneration, develop cardiovascular therapeutics, and engineer model systems for drug screening. The differentiation and character ... Full text Cite

Erratum: Regenerative and durable small-diameter graft as an arterial conduit(Proceedings of the National Academy of Sciences of the United States of America (2019) 116 (12710–12719) DOI: 10.1073/pnas.1905966116)

Journal Article Proceedings of the National Academy of Sciences of the United States of America · September 14, 2021 The authors note that the image shown in Fig. 1D, ii is an inadvertent duplication of an image that was published previously (1). The authors have provided a revised figure that includes the correct image for ii in Fig. 1D. The corrected figure and its leg ... Full text Cite

Discretizing Three-Dimensional Oxygen Gradients to Modulate and Investigate Cellular Processes.

Journal Article Advanced science (Weinheim, Baden-Wurttemberg, Germany) · July 2021 With the increased realization of the effect of oxygen (O2 ) deprivation (hypoxia) on cellular processes, recent efforts have focused on the development of engineered systems to control O2 concentrations and establish biomimetic O Full text Cite

The next generation of endothelial differentiation: Tissue-specific ECs.

Journal Article Cell stem cell · July 2021 Endothelial cells (ECs) sense and respond to fluid flow and regulate immune cell trafficking in all organs. Despite sharing the same mesodermal origin, ECs exhibit heterogeneous tissue-specific characteristics. Human pluripotent stem cells (hPSCs) can pote ... Full text Cite

HIF2A gain-of-function mutation modulates the stiffness of smooth muscle cells and compromises vascular mechanics.

Journal Article iScience · April 2021 Heterozygous gain-of-function (GOF) mutations of hypoxia-inducible factor 2α (HIF2A), a key hypoxia-sensing regulator, are associated with erythrocytosis, thrombosis, and vascular complications that account for morbidity and mortality of patients. We demon ... Full text Cite

Modeling metastasis: Engineering approaches to study the metastatic cascade

Journal Article Progress in Biomedical Engineering · February 5, 2021 Tumor progression and metastasis requires a complex interplay between tumor cells and their surrounding environment. Conventional 2D and 3D tissue culture models lack the precision and spatiotemporal control required to accurately model the complexity of t ... Full text Cite

Hydrogel Network Dynamics Regulate Vascular Morphogenesis.

Journal Article Cell stem cell · November 2020 Matrix dynamics influence how individual cells develop into complex multicellular tissues. Here, we develop hydrogels with identical polymer components but different crosslinking capacities to enable the investigation of mechanisms underlying vascular morp ... Full text Cite

Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization.

Journal Article Science advances · July 2020 Biologically active ligands (e.g., RGDS from fibronectin) play critical roles in the development of chemically defined biomaterials. However, recent decades have shown only limited progress in discovering novel extracellular matrix-protein-derived ligands ... Full text Cite

Vascular Phenotype is Compromised in Dynamically Stiffening Hydrogel

Conference The FASEB Journal · April 2020 Cardiovascular diseases are one of the leading causes of death worldwide with age mediated endothelial dysfunction as one of the major risk factors. Endothelial dysfunction is caused by a variety of reasons, such as oxidative ... Full text Cite

iPSC-derived endothelial cell response to hypoxia via SDF1a/CXCR4 axis facilitates incorporation to revascularize ischemic retina.

Journal Article JCI insight · March 2020 Ischemic retinopathies are major causes of blindness worldwide. Local hypoxia created by loss of vascular supply leads to tissue injury and aberrant neovascularization in the retina. There is a great need for therapies that enhance revascularization of hyp ... Full text Cite

Early Vascular Cells Improve Microvascularization Within 3D Cardiac Spheroids.

Journal Article Tissue engineering. Part C, Methods · February 2020 Introduction: A key obstacle in the creation of engineered cardiac tissues of clinically relevant sizes is limited diffusion of oxygen and nutrients. Thus, there is a need for organized vascularization within a three-dimensional (3D) tissue e ... Full text Cite

Collagen fiber structure guides 3D motility of cytotoxic T lymphocytes.

Journal Article Matrix biology : journal of the International Society for Matrix Biology · January 2020 Lymphocyte motility is governed by a complex array of mechanisms, and highly dependent on external microenvironmental cues. Tertiary lymphoid sites in particular have unique physical structure such as collagen fiber alignment, due to matrix deposition and ... Full text Cite

Reconstructing the Vascular Developmental Milieu In Vitro.

Journal Article Trends in cell biology · January 2020 Understanding human development has fascinated scientists for centuries. With advancements in stem cell technologies, this understanding has expanded beyond fascination to application towards informing the design of therapeutics in regenerative medicine. A ... Full text Cite

Embryonic stem cells as a cell source for tissue engineering

Chapter · January 1, 2020 Tissue engineering could generate off-the-shelf organs for transplantation to treat a variety of debilitating ailments such as diabetes or Parkinson’s disease. One of the major barriers to the realization of this enormous potential is the lack of renewable ... Full text Cite

Hydrogel vehicles for sequential delivery of protein drugs to promote vascular regeneration.

Journal Article Advanced drug delivery reviews · September 2019 In recent years, as the mechanisms of vasculogenesis and angiogenesis have been uncovered, the functions of various pro-angiogenic growth factors (GFs) and cytokines have been identified. Therefore, therapeutic angiogenesis, by delivery of GFs, has been so ... Full text Cite

Senescent Cells with Augmented Cytokine Production for Microvascular Bioengineering and Tissue Repairs.

Journal Article Advanced biosystems · August 2019 Controlled delivery of cytokines and growth factors has been an area of intense research interest for molecular and cellular bioengineering, immunotherapy, and regenerative medicine. In this study, we show that primary human lung fibroblasts chemically ind ... Full text Cite

Engineering an Artificial T-Cell Stimulating Matrix for Immunotherapy.

Journal Article Advanced materials (Deerfield Beach, Fla.) · June 2019 T cell therapies require the removal and culture of T cells ex vivo to expand several thousand-fold. However, these cells often lose the phenotype and cytotoxic functionality for mediating effective therapeutic responses. The extracellular matrix (ECM) has ... Full text Cite

Regenerative and durable small-diameter graft as an arterial conduit.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · June 2019 Despite significant research efforts, clinical practice for arterial bypass surgery has been stagnant, and engineered grafts continue to face postimplantation challenges. Here, we describe the development and application of a durable small-diameter vascula ... Full text Cite

Chipping Away at Blood-Brain-Barrier Modeling.

Journal Article Cell stem cell · June 2019 In this issue, Vatine et al. (2019) present a fully human blood-brain barrier chip that accurately predicts drug permeability and can be perfused with whole blood. Utilizing patient-derived tissue, they recapitulate disease-specific defects and establish a ... Full text Cite

Role of iPSC-derived pericytes on barrier function of iPSC-derived brain microvascular endothelial cells in 2D and 3D.

Journal Article Fluids and barriers of the CNS · June 2019 BackgroundPericytes of the blood-brain barrier (BBB) are embedded within basement membrane between brain microvascular endothelial cells (BMECs) and astrocyte end-feet. Despite the direct cell-cell contact observed in vivo, most in vitro BBB model ... Full text Cite

Acellular and cellular approaches to improve diabetic wound healing.

Journal Article Advanced drug delivery reviews · June 2019 Chronic diabetic wounds represent a huge socioeconomic burden for both affected individuals and the entire healthcare system. Although the number of available treatment options as well as our understanding of wound healing mechanisms associated with diabet ... Full text Cite

Engineered Heart Slice Model of Arrhythmogenic Cardiomyopathy Using Plakophilin-2 Mutant Myocytes.

Journal Article Tissue engineering. Part A · May 2019 Impact statementGenetic heart diseases such as arrhythmogenic cardiomyopathy (AC), a common genetic cause of sudden cardiac death, can be modeled using patient-specific induced pluripotent stem cell-derived cardiac myocytes (CMs). However, it is i ... Full text Cite

A Feedback Loop between Hypoxia and Matrix Stress Relaxation Increases Oxygen-Axis Migration and Metastasis in Sarcoma.

Journal Article Cancer research · April 2019 Upregulation of collagen matrix crosslinking directly increases its ability to relieve stress under the constant strain imposed by solid tumor, a matrix property termed stress relaxation. However, it is unknown how rapid stress relaxation in response to in ... Full text Cite

Hypoxia and matrix viscoelasticity sequentially regulate endothelial progenitor cluster-based vasculogenesis.

Journal Article Science advances · March 2019 Vascular morphogenesis is the formation of endothelial lumenized networks. Cluster-based vasculogenesis of endothelial progenitor cells (EPCs) has been observed in animal models, but the underlying mechanism is unknown. Here, using O2-controllab ... Full text Cite

Hydrogels with self-healing abilities as injectable carriers for vasculogenesis

Conference Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium · January 1, 2019 Statement of Purpose: Transplantation of therapeutic vasculature has been proposed as a treatment for many vascular disorders. Endothelial colony-forming cells (ECFCs) are sought as a potential therapeutic for treating vascular disease and generating engin ... Cite

A self-healing hydrogel as an injectable instructive carrier for cellular morphogenesis.

Journal Article Biomaterials · December 2018 Transplantation of progenitor cells can accelerate tissue healing and regenerative processes. Nonetheless, direct cell delivery fails to support survival of transplanted cells or long-term treatment of vascular related diseases due to compromised vasculatu ... Full text Cite

Cytoskeletal tension regulates mesodermal spatial organization and subsequent vascular fate.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · August 2018 Morphogenesis during human development relies on the interplay between physiochemical cues that are mediated in part by cellular density and cytoskeletal tension. Here, we interrogated these factors on vascular lineage specification during human-induced pl ... Full text Cite

Microfluidic platform for the real time measurement and observation of endothelial barrier function under shear stress.

Journal Article Biomicrofluidics · July 2018 Electric cell-substrate impedance sensing (ECIS) is a quickly advancing field to measure the barrier function of endothelial cells. Most ECIS systems that are commercially available use gold electrodes, which are opaque and do not allow for real-time imagi ... Full text Cite

Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells.

Journal Article Cell reports · July 2018 The role of primary cilia in mechanosensation is essential in endothelial cell (EC) shear responsiveness. Here, we find that venous, capillary, and progenitor ECs respond to shear stress in vitro in a cilia-dependent manner. We then demonstrate that primar ... Full text Cite

Sex differences in the mitochondrial bioenergetics of astrocytes but not microglia at a physiologically relevant brain oxygen tension.

Journal Article Neurochemistry international · July 2018 Biological sex is thought to influence mitochondrial bioenergetic function. Previous respiration measurements examining brain mitochondrial sex differences were made at atmospheric oxygen using isolated brain mitochondria. Oxygen is 160 mm Hg (21%) in the ... Full text Cite

Oxygen in cancer and neovascularization

Conference Free Radical Biology and Medicine · May 2018 Full text Cite

Extracellular Matrix Regulation of Stem Cell Fate

Journal Article Current Stem Cell Reports · March 1, 2018 Purpose of Review: The extracellular matrix (ECM) presents a complex myriad of biochemical and physical cues in the stem cell niche and is able to modulate stem cell fate and function. This review summarizes engineering approaches that have exploited natur ... Full text Cite

Let's get physical: Biomechanical influences on human pluripotent stem cell differentiation towards vascular engineering

Journal Article Current Opinion in Biomedical Engineering · March 1, 2018 Regenerative medicine provides a promising avenue of research in which tissue lost from disease, trauma and congenital defects can be replaced from substitutes created in the laboratory. Human pluripotent stem cells (hPSCs) are of great interest in the fie ... Full text Cite

Collagen Fiber Architecture Regulates Hypoxic Sarcoma Cell Migration.

Journal Article ACS biomaterials science & engineering · February 2018 Collagen is prevalent in the microenvironment of many cancer types and has been demonstrated to play an important role during disease progression. We previously showed the importance of hypoxic gradients in sarcoma cell migration. Here, we utilized an oxyg ... Full text Cite

Pericytes Derived from Human Pluripotent Stem Cells.

Journal Article Advances in experimental medicine and biology · January 2018 Pericytes wrap blood microvessels and are believed to play important roles in vascular morphogenesis, maturation, and stability. In addition, pericytes have emerged as candidates for targeting cancer growth and for wound healing. In order to model these pr ... Full text Cite

Human Pluripotent Stem Cells to Engineer Blood Vessels.

Journal Article Advances in biochemical engineering/biotechnology · January 2018 Development of pluripotent stem cells (PSCs) is a remarkable scientific advancement that allows scientists to harness the power of regenerative medicine for potential treatment of disease using unaffected cells. PSCs provide a unique opportunity to study a ... Full text Cite

Integrin binding: Sticking around vessels.

Journal Article Nature materials · August 2017 Full text Cite

O2-controllable hydrogels for studying cellular responses to hypoxic gradients in three dimensions in vitro and in vivo.

Journal Article Nature protocols · August 2017 Oxygen (O2) acts as a potent upstream regulator of cell function. In both physiological and pathophysiological microenvironments, the O2 concentration is not uniformly distributed but instead follows a gradient that depends on distanc ... Full text Cite

Dual Cross-Linked Biofunctional and Self-Healing Networks to Generate User-Defined Modular Gradient Hydrogel Constructs.

Journal Article Advanced healthcare materials · August 2017 Gradient hydrogels have been developed to mimic the spatiotemporal differences of multiple gradient cues in tissues. Current approaches used to generate such hydrogels are restricted to a single gradient shape and distribution. Here, a hydrogel is designed ... Full text Cite

Abstract 5477: Hydrogels to study ECM-oxygen gradient interactions for sarcoma cell migration

Conference Cancer Research · July 1, 2017 AbstractHypoxia is a critical factor in the progression and metastasis of many cancers, including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in tumors as they grow beyond their vascular ... Full text Cite

Bioinspired Hydrogels to Engineer Cancer Microenvironments.

Journal Article Annual review of biomedical engineering · June 2017 Recent research has demonstrated that tumor microenvironments play pivotal roles in tumor development and metastasis through various physical, chemical, and biological factors, including extracellular matrix (ECM) composition, matrix remodeling, oxygen ten ... Full text Cite

Compliant substratum guides endothelial commitment from human pluripotent stem cells.

Journal Article Science advances · May 2017 The role of mechanical regulation in driving human induced pluripotent stem cell (hiPSC) differentiation has been minimally explored. Although endothelial cell (EC) fate from hiPSCs has been demonstrated using small molecules to drive mesoderm induction, t ... Full text Cite

Engineering Niches for Blood Vessel Regeneration

Chapter · April 14, 2017 Although there is a vast amount of literature describing molecular cues governing vascular maturation, recreating vascular networks for therapeutic application, specific to a variety of tissue and organ sites, remains elusive. To address this issue, the fi ... Full text Cite

Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

Journal Article Acta biomaterialia · April 2017 Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in ... Full text Cite

Micropattern size-dependent endothelial differentiation from a human induced pluripotent stem cell line.

Journal Article Journal of tissue engineering and regenerative medicine · March 2017 The multifaceted extracellular milieu presents biochemical and biophysical stimuli that influence stem cell differentiation. Two-dimensional (2D) micropatterned substrates allow the presentation of these cues in spatially defined geometries that have been ... Full text Cite

Editorial overview: Biological engineering: Stem cell engineering

Journal Article Current Opinion in Chemical Engineering · February 1, 2017 Full text Cite

Abstract B61: Intratumoral oxygen gradients mediate sarcoma cell invasion

Conference Cancer Research · January 15, 2017 AbstractHypoxia is a critical factor in the progression and metastasis of many cancers including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in tumors as they grow beyond their vascular s ... Full text Cite

Engineering the human blood-brain barrier in vitro.

Journal Article Journal of biological engineering · January 2017 The blood-brain barrier (BBB) is the interface between the vasculature and the brain, regulating molecular and cellular transport into the brain. Endothelial cells (ECs) that form the capillary walls constitute the physical barrier but are dependent on int ... Full text Cite

Bridging the gap: induced pluripotent stem cell derived endothelial cells for 3D vascular assembly

Journal Article Current Opinion in Chemical Engineering · January 1, 2017 As cardiovascular disease continues to take the lives of so many patients, it is paramount that scientists and engineers construct reliable, lasting vascular therapies. Stem cell therapies for cardiovascular disease have the potential to provide patient-sp ... Full text Cite

Diffusing Colloidal Probes of kT-Scale Biomaterial-Cell Interactions.

Journal Article Langmuir : the ACS journal of surfaces and colloids · November 2016 In the optimization of applied biomaterials, measurements of their interactions with cell surfaces are important to understand their influence on specific and nonspecific cell surface adhesion, internalization pathways, and toxicity. In this study, a novel ... Full text Cite

Stem Cell Fate Is a Touchy Subject.

Journal Article Cell stem cell · September 2016 Uncoupling synergistic interactions between physio-chemical cues that guide stem cell fate may improve efforts to direct their differentiation in culture. Using supramolecular hydrogels, Alakpa et al. (2016) demonstrate that mesenchymal stem cell different ... Full text Cite

Engineered human vascularized constructs accelerate diabetic wound healing.

Journal Article Biomaterials · September 2016 Stem cell-based therapy is emerging as a promising approach for chronic diabetic wounds, but strategies for optimizing both cellular differentiation and delivery remain as major obstacles. Here, we study bioengineered vascularized constructs as a therapeut ... Full text Cite

Intratumoral oxygen gradients mediate sarcoma cell invasion.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · August 2016 Hypoxia is a critical factor in the progression and metastasis of many cancers, including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in tumors as they grow beyond their vascular supply, leading to heterogeneous areas of O2 depletion. H ... Full text Cite

Three-dimensional culture of small-diameter vascular grafts.

Journal Article Journal of materials chemistry. B · May 2016 In this review we analyze a representative sample of efforts to engineer three dimensional small-diameter (<6 mm) vascular grafts, concentrating on biomaterial substrates, cellular choices, and biomechanical stimulation. Natural or synthetic scaffolds for ... Full text Cite

Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering.

Journal Article Biochemical and biophysical research communications · May 2016 Proper blood vessel networks are necessary for constructing and re-constructing tissues, promoting wound healing, and delivering metabolic necessities throughout the body. Conversely, an understanding of vascular dysfunction has provided insight into the p ... Full text Cite

Microfluidics and biomaterials to study angiogenesis

Journal Article Current Opinion in Chemical Engineering · February 1, 2016 Toward the design of lab-on-a-chip technologies to recapitulate angiogenesis, chemical and mechanical cues in the vascular microenvironment are being considered. The goal is to develop platforms with control over shear stress, spatial architecture, and nut ... Full text Cite

Engineered Biopolymeric Scaffolds for Chronic Wound Healing.

Journal Article Frontiers in physiology · January 2016 Skin regeneration requires the coordinated integration of concomitant biological and molecular events in the extracellular wound environment during overlapping phases of inflammation, proliferation, and matrix remodeling. This process is highly efficient d ... Full text Cite

Derivation of Endothelial Cells and Pericytes from Human Pluripotent Stem Cells.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2016 Blood vessels serve as the lifeline of nearly all living tissue. Vascular cells derived from human pluripotent stem cells hold great potential for clinical use in the regeneration of diseased vasculature and construction of blood vessels in engineered tiss ... Full text Cite

Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis.

Journal Article PloS one · January 2016 The extracellular matrix (ECM) has been demonstrated to facilitate angiogenesis. In particular, fibronectin has been documented to activate endothelial cells, resulting in their transition from a quiescent state to an active state in which the cells exhibi ... Full text Cite

To Serve and Protect: Hydrogels to Improve Stem Cell-Based Therapies.

Journal Article Cell stem cell · January 2016 Harsh environments within damaged and diseased tissues and limited retention and survival of injected stem cells pose major challenges for stem cell therapeutics today. Here, we discuss promising hydrogel-based strategies for improving engraftment and viab ... Full text Cite

Human Brain Microvascular Endothelial Cells Derived from the BC1 iPS Cell Line Exhibit a Blood-Brain Barrier Phenotype.

Journal Article PloS one · January 2016 The endothelial cells that form capillaries in the brain are highly specialized, with tight junctions that minimize paracellular transport and an array of broad-spectrum efflux pumps that make drug delivery to the brain extremely challenging. One of the ma ... Full text Cite

Endothelial progenitor cell recruitment in a microfluidic vascular model.

Journal Article Biofabrication · December 2015 During vessel injury, endothelial progenitors cells (EPCs) are recruited from bone marrow and directed to the hypoxic injury site. The hypoxic conditions in the damaged blood vessel promote TNF-α, which upregulates intercellular adhesion molecule-1 (ICAM-1 ... Full text Cite

Three-Dimensional Vascular Network Assembly From Diabetic Patient-Derived Induced Pluripotent Stem Cells.

Journal Article Arteriosclerosis, thrombosis, and vascular biology · December 2015 ObjectiveIn diabetics, hyperglycemia results in deficient endothelial progenitors and cells, leading to cardiovascular complications. We aim to engineer 3-dimensional (3D) vascular networks in synthetic hydrogels from type 1 diabetes mellitus (T1D ... Full text Cite

Review: in vitro microvessel models.

Journal Article Lab on a chip · November 2015 A wide range of perfusable microvessel models have been developed, exploiting advances in microfabrication, microfluidics, biomaterials, stem cell technology, and tissue engineering. These models vary in complexity and physiological relevance, but provide ... Full text Cite

Designer Hydrogels for Precision Control of Oxygen Tension and Mechanical Properties.

Journal Article Journal of materials chemistry. B · October 2015 Oxygen levels and mechanical properties provide vital cues to regulate myriad cellular functions and stem cell fate decisions. Here, we present a hybrid hydrogel system in which we can control independently oxygen levels and mechanical properties. We desig ... Full text Cite

Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.

Journal Article The Journal of investigative dermatology · October 2015 Currently available skin grafts and skin substitutes for healing following third-degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a ... Full text Cite

Biomechanical strain induces elastin and collagen production in human pluripotent stem cell-derived vascular smooth muscle cells.

Journal Article American journal of physiology. Cell physiology · August 2015 Blood vessels are subjected to numerous biomechanical forces that work harmoniously but, when unbalanced because of vascular smooth muscle cell (vSMC) dysfunction, can trigger a wide range of ailments such as cerebrovascular, peripheral artery, and coronar ... Full text Cite

Abstract 960: Deregulation of the Hippo pathway in soft tissue sarcoma promotes FOXM1 expression and tumorigenesis

Conference Cancer Research · August 1, 2015 AbstractThe genetic aberrations responsible for soft tissue sarcoma formation in adults are largely unknown, and targeted therapies are sorely needed for this complex and heterogeneous family of diseases. He ... Full text Cite

Fabrication of 3-dimensional multicellular microvascular structures.

Journal Article FASEB journal : official publication of the Federation of American Societies for Experimental Biology · August 2015 Despite current advances in engineering blood vessels over 1 mm in diameter and the existing wealth of knowledge regarding capillary bed formation, studies for the development of microvasculature, the connecting bridge between them, have been extremely lim ... Full text Cite

Stochasticity and Spatial Interaction Govern Stem Cell Differentiation Dynamics.

Journal Article Scientific reports · July 2015 Stem cell differentiation underlies many fundamental processes such as development, tissue growth and regeneration, as well as disease progression. Understanding how stem cell differentiation is controlled in mixed cell populations is an important step in ... Full text Cite

Polymeric hydrogels as artificial extracellular microenvironments for cancer research

Journal Article European Polymer Journal · June 29, 2015 An emerging trend in cancer research is to design in vitro tissue culture models that can accurately guide clinical trials to improve their therapeutic outcomes. Particularly, recent studies in cancer research have focused on utilizing three-dimensional (3 ... Full text Cite

Deregulation of the Hippo pathway in soft-tissue sarcoma promotes FOXM1 expression and tumorigenesis.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · June 2015 Genetic aberrations responsible for soft-tissue sarcoma formation in adults are largely unknown, with targeted therapies sorely needed for this complex and heterogeneous family of diseases. Here we report that that the Hippo pathway is deregulated in many ... Full text Cite

Acellular implantable and injectable hydrogels for vascular regeneration.

Journal Article Biomedical materials (Bristol, England) · March 2015 In recent years, therapeutic angiogenesis has been sought as a treatment for many vascular disorders, including peripheral artery disease and coronary artery disease. As mechanisms of angiogenesis and vasculogenesis have been elucidated, the functions of i ... Full text Cite

Hypoxia and free radicals: role in tumor progression and the use of engineering-based platforms to address these relationships.

Journal Article Free radical biology & medicine · February 2015 Hypoxia is a feature of all solid tumors, contributing to tumor progression and therapy resistance. Through stabilization of the hypoxia-inducible factor 1 alpha (HIF-1α), hypoxia activates the transcription of a number of genes that sustain tumor progress ... Full text Cite

Characterizing human pluripotent-stem-cell-derived vascular cells for tissue engineering applications.

Journal Article Stem cells and development · February 2015 Tissue-engineered constructs are rendered useless without a functional vasculature owing to a lack of nutrients and oxygen. Cell-based approaches to reconstruct blood vessels can yield structures that mimic native vasculature and aid transplantation. Vascu ... Full text Cite

Controlling Microvascular Assembly

Conference TISSUE ENGINEERING PART A · 2015 Cite

Hydrogels to model 3D in vitro microenvironment of tumor vascularization.

Journal Article Advanced drug delivery reviews · December 2014 A growing number of failing clinical trials for cancer therapy are substantiating the need to upgrade the current practice in culturing tumor cells and modeling tumor angiogenesis in vitro. Many attempts have been made to engineer vasculature in vitro by u ... Full text Cite

Biomaterials as Artificial Niches for Pluripotent Stem Cell Engineering

Chapter · November 10, 2014 Human pluripotent stem (PSCs) cells are potentially useful platforms for tissue regenerative medicine and cell-based therapies due to their pluripotent nature and self-renewal capacity. However, controlling human PSC differentiation for generation of funct ... Full text Cite

The design of dextran-based hypoxia-inducible hydrogels via in situ oxygen-consuming reaction.

Journal Article Macromolecular rapid communications · November 2014 Hypoxia plays a critical role in the development and wound healing process, as well as a number of pathological conditions. Here, dextran-based hypoxia-inducible (Dex-HI) hydrogels formed with in situ oxygen consumption via a laccase-medicated reaction are ... Full text Cite

Harnessing developmental processes for vascular engineering and regeneration.

Journal Article Development (Cambridge, England) · July 2014 The formation of vasculature is essential for tissue maintenance and regeneration. During development, the vasculature forms via the dual processes of vasculogenesis and angiogenesis, and is regulated at multiple levels: from transcriptional hierarchies an ... Full text Cite

Efficient and scalable expansion of human pluripotent stem cells under clinically compliant settings: a view in 2013.

Journal Article Annals of biomedical engineering · July 2014 Human pluripotent stem cells (hPSCs) hold great promise for revolutionizing regenerative medicine for their potential applications in disease modeling, drug discovery, and cellular therapy. Many their applications require robust and scalable expansion of h ... Full text Cite

Hypoxia-inducible hydrogels.

Journal Article Nature communications · June 2014 Oxygen is vital for the existence of all multicellular organisms, acting as a signalling molecule regulating cellular activities. Specifically, hypoxia, which occurs when the partial pressure of oxygen falls below 5%, plays a pivotal role during developmen ... Full text Cite

Defining differences among perivascular cells derived from human pluripotent stem cells.

Journal Article Stem cell reports · May 2014 Distinguishing between perivascular cell types remains a hurdle in vascular biology due to overlapping marker expressions and similar functionalities. Clarifying and defining heterogeneities in vitro among perivascular cells could lead to improved cell-bas ... Full text Cite

Recapitulating physiological and pathological shear stress and oxygen to model vasculature in health and disease.

Journal Article Scientific reports · May 2014 Studying human vascular disease in conventional cell cultures and in animal models does not effectively mimic the complex vascular microenvironment and may not accurately predict vascular responses in humans. We utilized a microfluidic device to recapitula ... Full text Cite

Hyaluronic acid hydrogel stiffness and oxygen tension affect cancer cell fate and endothelial sprouting.

Journal Article Biomaterials science · May 2014 Three-dimensional (3D) tissue culture models may recapitulate aspects of the tumorigenic microenvironment in vivo, enabling the study of cancer progression in vitro. Both hypoxia and matrix stiffness are known to regulate tumor growth. Using ... Full text Cite

Low oxygen tension enhances endothelial fate of human pluripotent stem cells.

Journal Article Arteriosclerosis, thrombosis, and vascular biology · April 2014 ObjectiveA critical regulator of the developing or regenerating vasculature is low oxygen tension. Precise elucidation of the role of low oxygen environments on endothelial commitment from human pluripotent stem cells necessitates controlled in vi ... Full text Cite

Creating polymer hydrogel microfibres with internal alignment via electrical and mechanical stretching.

Journal Article Biomaterials · March 2014 Hydrogels have been widely used for 3-dimensional (3D) cell culture and tissue regeneration due to their tunable biochemical and physicochemical properties as well as their high water content, which resembles the aqueous microenvironment of the natural ext ... Full text Cite

Going with the flow: microfluidic platforms in vascular tissue engineering.

Journal Article Current opinion in chemical engineering · February 2014 Vascularization of tissue-engineered constructs, requiring the transport of oxygen, nutrients and waste through a thick and cellular dense meshwork, continues to hamper the success of the technology in addressing the donor organ shortage crisis. Microfluid ... Full text Cite

Derivation and network formation of vascular cells from human pluripotent stem cells.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2014 As the lifeline of almost all living tissues, blood vessels are a major focus of tissue-regenerative therapies. Rebuilding blood vessels has vast implications for the study of vascular growth and treatment of diseases in which vascular function is compromi ... Full text Cite

Vascular Development and Morphogenesis in Biomaterials

Chapter · January 1, 2014 There are a vast number of materials that have been used to promote vascular development in vitro, in growth, and anastomosis in vivo, as well as to differentiate stem cells into vascular cells for blood vessel regeneration. Some of these materials have be ... Full text Cite

Cell-biomaterial interactions for blood vessel formation

Chapter · January 1, 2014 Our knowledge of human vascular development and growth has been considerably augmented by biomaterial-based approaches. This chapter first discusses the architecture of the vasculature, from its cellular to extracellular matrix components. In the following ... Full text Cite

Micropatterned surfaces for the study of cancer and endothelial cell interactions with hyaluronic acid

Journal Article Israel Journal of Chemistry · December 1, 2013 Hyaluronic acid (HA) is a glycosaminoglycan component of the extracellular matrix. Studies have shown that various cancers exhibit high levels of HA content, and that an increased amount of HA corresponds to poor patient prognosis. HA has been implicated i ... Full text Cite

Scalable expansion of human induced pluripotent stem cells in the defined xeno-free E8 medium under adherent and suspension culture conditions.

Journal Article Stem cell research · November 2013 Large-scale production of human induced pluripotent stem cells (hiPSCs) by robust and economic methods has been one of the major challenges for translational realization of hiPSC technology. Here we demonstrate a scalable culture system for hiPSC expansion ... Full text Cite

ANGIOGENESIS BIOMIMETIC: EXTRACELLULAR MATRIX AND OXYGEN

Conference Free Radical Biology and Medicine · November 2013 Full text Cite

Fast and furious: the mass and motion of stem cells.

Journal Article Biophysical journal · August 2013 Full text Cite

Self-organized vascular networks from human pluripotent stem cells in a synthetic matrix.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · July 2013 The success of tissue regenerative therapies is contingent on functional and multicellular vasculature within the redeveloping tissue. Although endothelial cells (ECs), which compose the vasculature's inner lining, are intrinsically able to form nascent ne ... Full text Cite

Recent progress in the use of induced pluripotent stem cells in vascular regeneration.

Journal Article Expert review of cardiovascular therapy · June 2013 Full text Cite

Perivascular cells in blood vessel regeneration.

Journal Article Biotechnology journal · April 2013 Vascular engineering seeks to design and construct functional blood vessels comprising endothelial cells (ECs) and perivascular cells (PCs), with the ultimate goal of clinical translation. While EC behavior has been extensively investigated, PCs play an eq ... Full text Cite

Integration and regression of implanted engineered human vascular networks during deep wound healing.

Journal Article Stem cells translational medicine · April 2013 The ability of vascularized constructs to integrate with tissues may depend on the kinetics and stability of vascular structure development. This study assessed the functionality and durability of engineered human vasculatures from endothelial progenitors ... Full text Cite

Derivation and maturation of synthetic and contractile vascular smooth muscle cells from human pluripotent stem cells.

Journal Article Cardiovascular research · February 2013 AimsEmbryonic vascular smooth muscle cells (vSMCs) have a synthetic phenotype; in adults, they commit to the mature contractile phenotype. Research shows that human pluripotent stem cells (hPSCs) differentiate into vSMCs, but nobody has yet docume ... Full text Cite

Vascular tissue engineering: biodegradable scaffold platforms to promote angiogenesis.

Journal Article Stem cell research & therapy · January 2013 The ability to understand and regulate human vasculature development and differentiation has the potential to benefit patients suffering from a variety of ailments, including cardiovascular disease, peripheral vascular disease, ischemia, and burn wounds. C ... Full text Cite

A novel in vitro model for microvasculature reveals regulation of circumferential ECM organization by curvature.

Journal Article PloS one · January 2013 In microvascular vessels, endothelial cells are aligned longitudinally whereas several components of the extracellular matrix (ECM) are organized circumferentially. While current three-dimensional (3D) in vitro models for microvasculature have allowed the ... Full text Cite

Hypoxia Affects the Structure of Breast Cancer Cell-Derived Matrix to Support Angiogenic Responses of Endothelial Cells.

Journal Article Journal of carcinogenesis & mutagenesis · January 2013 Hypoxia, a common feature of the tumor environment and participant in tumor progression, is known to alter gene and protein expression of several Extracellular Matrix (ECM) proteins, many of which have roles in angiogenesis. Previously, we reported that EC ... Full text Cite

Spatially defined microenvironments to study tumor angiogensis

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · 2013 Cite

A physical sciences network characterization of non-tumorigenic and metastatic cells.

Journal Article Scientific reports · January 2013 To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastati ... Full text Cite

Acrylated hyaluronic acid hydrogels to study cancer angiogenesis

Conference Food, Pharmaceutical and Bioengineering Division 2013 - Core Programming Area at the 2013 AIChE Annual Meeting: Global Challenges for Engineering a Sustainable Future · January 1, 2013 Cite

Human Vascular Progenitor Cells

Chapter · January 1, 2013 Full text Cite

Engineering approaches for investigating tumor angiogenesis: exploiting the role of the extracellular matrix.

Journal Article Cancer research · December 2012 A major paradigm shift in cancer research is the emergence of multidisciplinary approaches to investigate complex cell behaviors, to elucidate regulatory mechanisms and to identify therapeutic targets. Recently, efforts are focused on the engineering of co ... Full text Cite

The extracellular matrix is a novel attribute of endothelial progenitors and of hypoxic mature endothelial cells.

Journal Article FASEB journal : official publication of the Federation of American Societies for Experimental Biology · December 2012 Extracellular matrix (ECM) production is critical to preserve the function and integrity of mature blood vessels. Toward the engineering of blood vessels, studies have centered on ECM production by supporting cells, whereas few studies implicate endothelia ... Full text Cite

Patterning microscale extracellular matrices to study endothelial and cancer cell interactions in vitro.

Journal Article Lab on a chip · November 2012 The extracellular matrix (ECM) of the tumor niche provides support to residing and migrating cells and presents instructive cues that influence cellular behaviours. The ECM protein fibronectin (Fn) enables vascular network formation, while hyaluronic acid ... Full text Cite

Spatial control of cell-mediated degradation to regulate vasculogenesis and angiogenesis in hyaluronan hydrogels.

Journal Article Biomaterials · September 2012 Matrix remodeling is crucial for neovascularization, however its utilization to control this process in synthetic biomaterials has been limited. Here, we utilized hyaluronic acid (HA) hydrogels to spatially control cellular remodeling during vascular netwo ... Full text Cite

Endothelial cell responses to micropillar substrates of varying dimensions and stiffness.

Journal Article Journal of biomedical materials research. Part A · June 2012 In the vascular niche, the extracellular matrix (ECM) provides a structural scaffold with a rich ligand landscape of essential matrix proteins that supports the organization and stabilization of endothelial cells (ECs) into functional blood vessels. Many o ... Full text Cite

Breast cancer cell-derived matrix supports vascular morphogenesis.

Journal Article American journal of physiology. Cell physiology · April 2012 The extracellular matrix (ECM), important for maintaining tissue homeostasis, is abnormally expressed in mammary tumors and additionally plays a crucial role in angiogenesis. We hypothesize that breast cancer cells (BCCs) deposit ECM that supports unique p ... Full text Cite

Microbioreactors to manipulate oxygen tension and shear stress in the microenvironment of vascular stem and progenitor cells.

Journal Article Biotechnology and applied biochemistry · March 2012 The dynamics of dissolved oxygen (DO) and shear stress in the vasculature microenvironment play a major role in determining the fate of stem cells in adults and during early embryonic development. In this study, we present a microbioreactor (MBR) that prov ... Full text Cite

Design and development of microbioreactors for long-term cell culture in controlled oxygen microenvironments.

Journal Article Biomedical microdevices · February 2012 The ability to control the oxygen level to which cells are exposed in tissue culture experiments is crucial for many applications. Here, we design, develop and test a microbioreactor (MBR) for long-term cell culture studies with the capability to accuratel ... Full text Cite

Human Vascular Progenitor Cells

Chapter · January 1, 2012 Full text Cite

Development of a biodegradable, temperature-sensitive dextran-based polymer as a cell-detaching substrate.

Journal Article Macromolecular bioscience · January 2012 A biodegradable, temperature-sensitive dextran-allyl isocyanate-ethylamine (TSDAIE) as a nonenzymatic cell detachment polymeric substrate for human endothelial progenitor cells (EPCs) is developed and examined. The lower critical solution temperature of TS ... Full text Cite

The differential formation of the LINC-mediated perinuclear actin cap in pluripotent and somatic cells.

Journal Article PloS one · January 2012 The actin filament cytoskeleton mediates cell motility and adhesion in somatic cells. However, whether the function and organization of the actin network are fundamentally different in pluripotent stem cells is unknown. Here we show that while conventional ... Full text Cite

Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · December 2011 Neovascularization is a critical determinant of wound-healing outcomes for deep burn injuries. We hypothesize that dextran-based hydrogels can serve as instructive scaffolds to promote neovascularization and skin regeneration in third-degree burn wounds. D ... Full text Cite

Biomaterials approaches in vascular engineering: A review of past and future trends

Chapter · December 1, 2011 Creating functional vasculatures remains one of the fundamental challenges that must be addressed before large, complex tissue-engineered constructs can be used in clinical applications. Our current understanding of stem cell biology and vascular morphogen ... Full text Cite

Unforeseen decreases in dissolved oxygen levels affect tube formation kinetics in collagen gels.

Journal Article American journal of physiology. Cell physiology · August 2011 The availability of oxygen (O(2)) is a critical parameter affecting vascular tube formation. In this study, we hypothesize that dissolved oxygen (DO) levels in collagen gels change during the three-dimensional (3D) culture of human umbilical vein endotheli ... Full text Cite

Controlled activation of morphogenesis to generate a functional human microvasculature in a synthetic matrix.

Journal Article Blood · July 2011 Understanding the role of the extracellular matrix (ECM) in vascular morphogenesis has been possible using natural ECMs as in vitro models to study the underlying molecular mechanisms. However, little is known about vascular morphogenesis in synthetic matr ... Full text Cite

Hyaluronic Acid hydrogels support cord-like structures from endothelial colony-forming cells.

Journal Article Tissue engineering. Part A · May 2011 The generation of functional vascular networks has the potential to improve treatment for vascular diseases and to facilitate successful organ transplantation. Endothelial colony-forming cells (ECFCs) have robust proliferative potential and can form vascul ... Full text Cite

Reconstructing the differentiation niche of embryonic stem cells using biomaterials.

Journal Article Macromolecular bioscience · January 2011 The biochemical cues and topographical architecture of the extracellular environment extensively influence ES cell fate. The microenvironment surrounding the developing embryo presents these instructive cues in a complex and interactive manner in order to ... Full text Cite

Functional neovascularization of biodegradable dextran hydrogels with multiple angiogenic growth factors.

Journal Article Biomaterials · January 2011 Slow vascularization of functional blood limits the transplantation of tissue constructs and the recovery of ischemic and wounded tissues. Despite the widespread investigation of polysaccharide-based hydrogel scaffolds for their therapeutic applications, b ... Full text Cite

Micropatterned surfaces to study hyaluronic acid interactions with cancer cells.

Journal Article Journal of visualized experiments : JoVE · December 2010 Cancer invasion and progression involves a motile cell phenotype, which is under complex regulation by growth factors/cytokines and extracellular matrix (ECM) components within the tumor microenvironment. Hyaluronic acid (HA) is one stromal ECM component t ... Full text Cite

Differences in the microrheology of human embryonic stem cells and human induced pluripotent stem cells.

Journal Article Biophysical journal · December 2010 Embryonic and adult fibroblasts can be returned to pluripotency by the expression of reprogramming genes. Multiple lines of evidence suggest that these human induced pluripotent stem (hiPS) cells and human embryonic stem (hES) cells are behaviorally, karyo ... Full text Cite

Guiding endothelial progenitor cell tube formation using patterned fibronectin surfaces

Journal Article Soft Matter · October 21, 2010 Engineering vascular networks is a key initiative in regenerative medicine. Moreover, control over the formation of organized vascular networks in vitro may facilitate their rapid and functional integration with the host vasculature after implantation. The ... Full text Cite

Engineering blood vessels using stem cells: innovative approaches to treat vascular disorders.

Journal Article Expert review of cardiovascular therapy · October 2010 Vascular disease is the leading cause of mortality in the USA, providing the impetus for new treatments and technologies. Current therapies rely on the implantation of stents or grafts to treat injured blood vessels. However, these therapies may be immunog ... Full text Cite

Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells.

Journal Article Journal of cellular and molecular medicine · October 2010 Endothelial progenitor cells (EPCs) in the circulatory system have been suggested to maintain vascular homeostasis and contribute to adult vascular regeneration and repair. These processes require that EPCs break down the extracellular matrix (ECM), migrat ... Full text Cite

Functional surfaces for high-resolution analysis of cancer cell interactions on exogenous hyaluronic acid.

Journal Article Biomaterials · July 2010 Hyaluronic acid, a nonsulfated, linear glycosaminoglycan, is ubiquitously distributed in the extracellular matrix and is known to facilitate tumor progression by enhancing invasion, growth, and angiogenesis. Native HA has been attached to substrates to cre ... Full text Cite

Functional groups affect physical and biological properties of dextran-based hydrogels.

Journal Article Journal of biomedical materials research. Part A · June 2010 Modification of dextran backbone allows the development of a hydrogel with specific characteristics. To enhance their functionality for tissue-engineered scaffolds, a series of dextran-based macromers was synthesized by incorporating various functional gro ... Full text Cite

Smooth-muscle-like cells derived from human embryonic stem cells support and augment cord-like structures in vitro.

Journal Article Stem cell reviews and reports · June 2010 Engineering vascularized tissue is crucial for its successful implantation, survival, and integration with the host tissue. Vascular smooth muscle cells (v-SMCs) provide physical support to the vasculature and aid in maintaining endothelial viability. In t ... Full text Cite

Adaptation to oxygen deprivation in cultures of human pluripotent stem cells, endothelial progenitor cells, and umbilical vein endothelial cells.

Journal Article American journal of physiology. Cell physiology · June 2010 Hypoxia plays an important role in vascular development through hypoxia-inducible factor-1alpha (HIF-1alpha) accumulation and downstream pathway activation. We sought to explore the in vitro response of cultures of human embryonic stem cells (hESCs), induc ... Full text Cite

Vascular differentiation of human embryonic stem cells in bioactive hydrogel-based scaffolds.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2010 The vascularization of tissue constructs remains a major challenge in regenerative medicine, as the diffusional supply of oxygen can support only 100-200 mum thick layers of viable tissue. The formation of a mature and functional vascular network requires ... Full text Cite

Vascularization of biodegradable dextran hydrogels

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · 2010 Cite

The Integrated Role of Biomaterials and Stem Cells in Vascular Regeneration

Chapter · January 1, 2010 A healthy vascular system is essential for maintaining normal blood supply and circulation in the body, while ischemia can lead to limb amputation or even death. Vascular regeneration engineering holds the promise of permanent, effective treatments for man ... Full text Cite

Preview. Mending the failing heart with a vascularized cardiac patch.

Journal Article Cell stem cell · December 2009 Functional, stem-cell-containing cardiac grafts will require vascularized myocardial constructs to support their survival and integration into the host vasculature. Recently in Tissue Engineering, Part A, Lesman et al. (2009) reported the successful integr ... Full text Cite

Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species.

Journal Article Experimental cell research · December 2009 Exogenous electric fields have been implied in cardiac differentiation of mouse embryonic stem cells and the generation of reactive oxygen species (ROS). In this work, we explored the effects of electrical field stimulation on ROS generation and cardiogene ... Full text Cite

Mapping the Interactions among Biomaterials, Adsorbed Proteins, and Human Embryonic Stem Cells.

Journal Article Advanced materials (Deerfield Beach, Fla.) · July 2009 Full text Cite

Vascular regeneration: engineering the stem cell microenvironment.

Journal Article Regenerative medicine · May 2009 Vascular diseases are a major threat to human health nowadays. While current treatments can cure some vascular diseases, their beneficial effects are only temporary; vascular regeneration holds the promise of permanent, effective treatments for many vascul ... Full text Cite

Stem cells and scaffolds for vascularizing engineered tissue constructs.

Journal Article Advances in biochemical engineering/biotechnology · January 2009 The clinical impact of tissue engineering depends upon our ability to direct cells to form tissues with characteristic structural and mechanical properties from the molecular level up to organized tissue. Induction and creation of functional vascular netwo ... Full text Cite

Vascular engineering using human embryonic stem cells.

Journal Article Biotechnology progress · January 2009 Engineering vascularized tissue constructs remains a major problem in regenerative medicine. The formation of such a microvasculature--like the vasculogenesis in early embryogenesis that it closely resembles--is guided by biochemical and biophysical cues, ... Full text Cite

POLY 327-Biomaterials for vascular differentiation and assembly

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · 2009 Cite

BIOT 148-Functional surfaces for the study of vascular growth and assembly

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · 2009 Cite

BIOT 21-Dextran-based biodegradable hydrogel scaffolds for controllable studies of vasculogenesis

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · 2009 Cite

Engineered microenvironments for human stem cells.

Journal Article Birth defects research. Part C, Embryo today : reviews · December 2008 Regulation of cell differentiation and assembly remains a fundamental question in developmental biology. During development, tissues emerge from coordinated sequences of the renewal, differentiation, and assembly of stem cells. Likewise, regeneration of an ... Full text Cite

Enhancement of in vitro capillary tube formation by substrate nanotopography

Conference Technical Proceedings of the 2008 NSTI Nanotechnology Conference and Trade Show, NSTI-Nanotech, Nanotechnology 2008 · October 1, 2008 Tissue engineering scaffolds often aim to control cell behavior using a variety of signaling modalities including chemistry, mechanical properties, and local microenvironmental factors such as oxygen concentration. However, few efforts have explored the us ... Cite

Enhancement of In Vitro Capillary Tube Formation by Substrate Nanotopography.

Journal Article Advanced materials (Deerfield Beach, Fla.) · January 2008 Full text Cite

A porous photocurable elastomer for cell encapsulation and culture.

Journal Article Biomaterials · November 2007 Encapsulating cells within a polymer matrix creates a three-dimensional (3D) scaffold that may more accurately represent the native microenvironment and cell organization. Here we report a porous scaffold prepared from a photocurable elastomer, poly(glycer ... Full text Cite

The effect of actin disrupting agents on contact guidance of human embryonic stem cells.

Journal Article Biomaterials · October 2007 Mammalian cells respond to their substrates by complex changes in gene expression profiles, morphology, proliferation and migration. We report that substrate nanotopography alters morpohology and proliferation of human embryonic stem cells (hESCs). Fibrone ... Full text Cite

Human embryonic stem cell transplantation to repair the infarcted myocardium.

Journal Article Heart (British Cardiac Society) · October 2007 ObjectiveTo test the hypothesis that human embryonic stem cells (hESCs) can be guided to form new myocardium by transplantation into the normal or infarcted heart, and to assess the influence of hESC-derived cardiomyocytes (hESCMs) on cardiac func ... Full text Cite

Biomimetic approach to cardiac tissue engineering.

Journal Article Philosophical transactions of the Royal Society of London. Series B, Biological sciences · August 2007 Here, we review an approach to tissue engineering of functional myocardium that is biomimetic in nature, as it involves the use of culture systems designed to recapitulate some aspects of the actual in vivo environment. To mimic the capillary network, subp ... Full text Cite

Vascular progenitor cells isolated from human embryonic stem cells give rise to endothelial and smooth muscle like cells and form vascular networks in vivo.

Journal Article Circulation research · August 2007 We report that human embryonic stem cells contain a population of vascular progenitor cells that have the ability to differentiate into endothelial-like and smooth muscle (SM)-like cells. Vascular progenitor cells were isolated from EBs grown in suspension ... Full text Cite

Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · July 2007 Control of self-renewal and differentiation of human ES cells (hESCs) remains a challenge. This is largely due to the use of culture systems that involve poorly defined animal products and do not mimic the normal developmental milieu. Routine protocols inv ... Full text Cite

Micro-bioreactor array for controlling cellular microenvironments.

Journal Article Lab on a chip · June 2007 High throughput experiments can be used to spatially and temporally investigate the many factors that regulate cell differentiation. We have developed a micro-bioreactor array (MBA) that is fabricated using soft lithography and contains twelve independent ... Full text Cite

Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells.

Journal Article Biomaterials · June 2007 We propose a new methodology to enhance the vascular differentiation of human embryonic stem cells (hESCs) by encapsulation in a bioactive hydrogel. hESCs were encapsulated in a dextran-based hydrogel with or without immobilized regulatory factors: a tethe ... Full text Cite

Practical aspects of cardiac tissue engineering with electrical stimulation.

Journal Article Methods in molecular medicine · January 2007 Heart disease is a leading cause of death in western society. Despite the success of heart transplantation, a chronic shortage of donor organs, along with the associated immunological complications of this approach, demands that alternative treatments be f ... Full text Cite

Legal and ethical aspects of human embryonic stem cell research in Europe and Israel

Conference IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL · 2005 Cite

Transfusion-transmitted virus in liver-transplanted children.

Journal Article Transplantation proceedings · September 2001 Full text Cite