Scholars@Duke
Shyni Varghese

Shyni Varghese

Laszlo Ormandy Distinguished Professor of Orthopaedic Surgery
Orthopaedic Surgery

Selected Publications

Specialized pro-resolving mediator Maresin 1 attenuates pain in a mouse model of osteoarthritis.

Journal Article Osteoarthritis Cartilage · November 29, 2024 OBJECTIVE: We test whether the specialized pro-resolving molecule Maresin 1 (MaR1) attenuates nociceptive behaviors in mice with osteoarthritis-like pain. DESIGN: Osteoarthritis (OA)-like pain behavior was induced by intra-articular injection of monosodium ... Full text Link to item Cite

Grafting of cationic molecules to hyaluronic acid improves adsorption and cartilage lubrication.

Journal Article Biomater Sci · September 10, 2024 Synovial fluid lubricates articular joints by forming a hydrated layer between the cartilage surfaces. In degenerative joint diseases like osteoarthritis (OA), the synovial fluid is compromised, which leads to less effective innate lubrication and exacerba ... Full text Link to item Cite

Gene Therapy and Spinal Fusion: Systematic Review and Meta-Analysis of the Available Data.

Journal Article World Neurosurg · June 2024 OBJECTIVE: To analyze the extant literature describing the application of gene therapy to spinal fusion. METHODS: A systematic review of the English-language literature was performed. The search query was designed to include all published studies examining ... Full text Open Access Link to item Cite

Branched poly-l-lysine for cartilage penetrating carriers.

Journal Article Bioeng Transl Med · May 2024 Joint diseases, such as osteoarthritis, often require delivery of drugs to chondrocytes residing within the cartilage. However, intra-articular delivery of drugs to cartilage remains a challenge due to their rapid clearance within the joint. This problem i ... Full text Link to item Cite

Active immunotherapy for C5a-mediated inflammation using adjuvant-free self-assembled peptide nanofibers.

Journal Article Acta Biomater · April 15, 2024 The terminal protein in the complement cascade C5a is a potent inflammatory molecule and chemoattractant that is involved in the pathology of multiple inflammatory diseases including sepsis and arthritis, making it a promising protein to target with immuno ... Full text Link to item Cite

UDP-6-glucose dehydrogenase in hormonally responsive breast cancers.

Journal Article bioRxiv · March 21, 2024 Survival for metastatic breast cancer is low and thus, continued efforts to treat and prevent metastatic progression are critical. Estrogen is shown to promote aggressive phenotypes in multiple cancer models irrespective of estrogen receptor (ER) status. S ... Full text Link to item Cite

Differential roles of normal and lung cancer-associated fibroblasts in microvascular network formation.

Journal Article APL Bioeng · March 2024 Perfusable microvascular networks offer promising three-dimensional in vitro models to study normal and compromised vascular tissues as well as phenomena such as cancer cell metastasis. Engineering of these microvascular networks generally involves the use ... Full text Link to item Cite

Grand Challenges at the Interface of Engineering and Medicine.

Journal Article IEEE Open J Eng Med Biol · 2024 Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication w ... Full text Link to item Cite

Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.

Journal Article Adv Sci (Weinh) · December 2023 Bone injuries such as fractures are one major cause of morbidities worldwide. A considerable number of fractures suffer from delayed healing, and the unresolved acute pain may transition to chronic and maladaptive pain. Current management of pain involves ... Full text Open Access Link to item Cite

Radiation-induced bone loss in mice is ameliorated by inhibition of HIF-2α in skeletal progenitor cells.

Journal Article Sci Transl Med · November 29, 2023 Radiotherapy remains a common treatment modality for cancer despite skeletal complications. However, there are currently no effective treatments for radiation-induced bone loss, and the consequences of radiotherapy on skeletal progenitor cell (SPC) surviva ... Full text Link to item Cite

Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer.

Journal Article Nat Commun · August 11, 2023 Unlike adult mammals, zebrafish regenerate spinal cord tissue and recover locomotor ability after a paralyzing injury. Here, we find that ependymal cells in zebrafish spinal cords produce the neurogenic factor Hb-egfa upon transection injury. Animals with ... Full text Link to item Cite

Progress in the design and synthesis of viscosupplements for articular joint lubrication

Journal Article Current Opinion in Colloid and Interface Science · August 1, 2023 Throughout a lifetime, articular joints experience many loading cycles and are prone to mechanical degradation. To safeguard the cartilage in these joints, the synovial fluid acts as a natural lubricant. However, degenerative joint diseases, like osteoarth ... Full text Cite

Deciphering the Mechanics of Cancer Spheroid Growth in 3D Environments through Microfluidics Driven Mechanical Actuation.

Journal Article Adv Healthc Mater · June 2023 Uncontrolled growth of tumor cells is a key contributor to cancer-associated mortalities. Tumor growth is a biomechanical process whereby the cancer cells displace the surrounding matrix that provides mechanical resistance to the growing cells. The process ... Full text Link to item Cite

Extracellular adenosine signaling in bone health and disease.

Journal Article Current opinion in pharmacology · June 2023 Purinergic signaling is a key molecular pathway in the maintenance of bone health and regeneration. P1 receptor signaling, which is activated by extracellular adenosine, has emerged as a key metabolic pathway that regulates bone tissue formation, function, ... Full text Cite

Mindin (SPON2) Is Essential for Cutaneous Fibrogenesis in a Mouse Model of Systemic Sclerosis.

Journal Article J Invest Dermatol · May 2023 Systemic sclerosis is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as systemic sclerosis has been aided by various animal mod ... Full text Link to item Cite

Self-assembled innervated vasculature-on-a-chip to study nociception.

Journal Article Biofabrication · April 13, 2023 Nociceptor sensory neurons play a key role in eliciting pain. An active crosstalk between nociceptor neurons and the vascular system at the molecular and cellular level is required to sense and respond to noxious stimuli. Besides nociception, interaction b ... Full text Link to item Cite

Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice.

Journal Article Br J Anaesth · February 2023 BACKGROUND: Peripheral surgical trauma can trigger neuroinflammation and ensuing neurological complications, such as delirium. The mechanisms whereby surgery contributes to postoperative neuroinflammation remain unclear and without effective therapies. Her ... Full text Link to item Cite

Microgel-Assisted Delivery of Adenosine to Accelerate Fracture Healing.

Journal Article ACS Biomater Sci Eng · November 14, 2022 Extracellular adenosine plays a key role in promoting bone tissue formation. Local delivery of adenosine could be an effective therapeutic strategy to harness the beneficial effect of extracellular adenosine on bone tissue formation following injury. Herei ... Full text Link to item Cite

Rationally Designed Anisotropic and Auxetic Hydrogel Patches for Adaptation to Dynamic Organs

Journal Article Advanced Functional Materials · October 1, 2022 Current hydrogel or fabric patches for organ repair are generally not designed to conform to the complex mechanics of dynamic organs such as the lung or heart. This study presents a new, biocompatible and bilayered, hydrogel-based patch platform, consistin ... Full text Cite

pH-Sensitive nanocarrier assisted delivery of adenosine to treat osteoporotic bone loss.

Journal Article Biomater Sci · September 13, 2022 Bone tissue undergoes continuous remodeling via osteoclast-mediated bone resorption and osteoblast-mediated bone formation. An imbalance in this process with enhanced osteoclastic activity can lead to excessive bone resorption, resulting in bone thinning. ... Full text Link to item Cite

Loss of ATRX promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin binding.

Journal Article JCI Insight · September 8, 2022 Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here, we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypi ... Full text Link to item Cite

Molecularly Tailored Interface for Long-Term Xenogeneic Cell Transplantation.

Journal Article Adv Funct Mater · January 19, 2022 Encapsulation of therapeutic cells in a semipermeable device can mitigate the need for systemic immune suppression following cell transplantation by providing local immunoprotection while being permeable to nutrients, oxygen, and different cell-secreted bi ... Full text Link to item Cite

An In Vitro Microfluidic Alveolus Model to Study Lung Biomechanics.

Journal Article Front Bioeng Biotechnol · 2022 The gas exchange units of the lung, the alveoli, are mechanically active and undergo cyclic deformation during breathing. The epithelial cells that line the alveoli contribute to lung function by reducing surface tension via surfactant secretion, which is ... Full text Open Access Link to item Cite

Characterization of bending balloon actuators.

Journal Article Front Robot AI · 2022 The emerging field of soft robotics often relies on soft actuators powered by pressurized fluids to obtain a variety of movements. Strategic incorporation of soft actuators can greatly increase the degree of freedom of soft robots thereby bestowing them wi ... Full text Link to item Cite

Self-Healing of Hyaluronic Acid to Improve In Vivo Retention and Function.

Journal Article Adv Healthc Mater · December 2021 Convergent advances in the field of soft matter, macromolecular chemistry, and engineering have led to the development of biomaterials that possess autonomous, adaptive, and self-healing characteristics similar to living systems. These rationally designed ... Full text Link to item Cite

Meniscus cell regional phenotypes: Dedifferentiation and reversal by biomaterial embedding.

Journal Article J Orthop Res · October 2021 Meniscus injuries are common and a major cause of long-term joint degeneration and disability. Current treatment options are limited, so novel regenerative therapies or tissue engineering strategies are urgently needed. The development of new therapies is ... Full text Link to item Cite

Resolution of inflammation in bone regeneration: From understandings to therapeutic applications.

Journal Article Biomaterials · October 2021 Impaired bone healing occurs in 5-10% of cases following injury, leading to a significant economic and clinical impact. While an inflammatory response upon injury is necessary to facilitate healing, its resolution is critical for bone tissue repair as elev ... Full text Link to item Cite

Microengineered Materials with Self‐Healing Features for Soft Robotics

Journal Article Advanced Intelligent Systems · July 2021 Recent advancements in soft robotics have led to the development of compliant robots that can exhibit complex motions driven by living cells, chemical reactions, or electronics. Further innovations are, however, needed to cr ... Full text Cite

Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss.

Journal Article Biomaterials · June 2021 Extracellular adenosine has been shown to play a key role in maintaining bone health and could potentially be used to treat bone loss. However, systemic administration of exogenous adenosine to treat bone disorders remains a challenge due to the ubiquitous ... Full text Link to item Cite

Temporal mechanisms of myogenic specification in human induced pluripotent stem cells.

Journal Article Sci Adv · March 2021 Understanding the mechanisms of myogenesis in human induced pluripotent stem cells (hiPSCs) is a prerequisite to achieving patient-specific therapy for diseases of skeletal muscle. hiPSCs of different origin show distinctive kinetics and ability to differe ... Full text Link to item Cite

Cellular Respiratory Toxicity of Novel Flavor-Solvent Adducts in Electronic Cigarettes

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · 2021 Cite

In Vivo Sequestration of Innate Small Molecules to Promote Bone Healing.

Journal Article Adv Mater · February 2020 Approaches that enable innate repair mechanisms hold great potential for tissue repair. Herein, biomaterial-assisted sequestration of small molecules is described to localize pro-regenerative signaling at the injury site. Specifically, a synthetic biomater ... Full text Link to item Cite

An Engineered Tumor-on-a-Chip Device with Breast Cancer-Immune Cell Interactions for Assessing T-cell Recruitment.

Journal Article Cancer Res · January 15, 2020 Recruitment of immune cells to a tumor is determined by the complex interplay between cellular and noncellular components of the tumor microenvironment. Ex vivo platforms that enable identification of key components that promote immune cell recruitment to ... Full text Link to item Cite

Dysregulation of ectonucleotidase-mediated extracellular adenosine during postmenopausal bone loss.

Journal Article Sci Adv · August 2019 Adenosine and its receptors play a key role in bone homeostasis and regeneration. Extracellular adenosine is generated from CD39 and CD73 activity in the cell membrane, through conversion of adenosine triphosphate to adenosine monophosphate (AMP) and AMP t ... Full text Link to item Cite

Biomaterial-assisted local and systemic delivery of bioactive agents for bone repair.

Journal Article Acta Biomater · July 15, 2019 Although bone tissues possess an intrinsic capacity for repair, there are cases where bone healing is either impaired or insufficient, such as fracture non-union, osteoporosis, osteomyelitis, and cancers. In these cases, treatments like surgical interventi ... Full text Link to item Cite

Three-Dimensional Monolayer Stress Microscopy.

Journal Article Biophys J · July 9, 2019 Many biological processes involve the collective generation and transmission of mechanical stresses across cell monolayers. In these processes, the monolayer undergoes lateral deformation and bending because of the tangential and normal components of the c ... Full text Link to item Cite

Tissue engineered bone mimetics to study bone disorders ex vivo: Role of bioinspired materials.

Journal Article Biomaterials · April 2019 Recent advances in materials development and tissue engineering has resulted in a substantial number of bioinspired materials that recapitulate cardinal features of bone extracellular matrix (ECM) such as dynamic inorganic and organic environment(s), hiera ... Full text Link to item Cite

In vivo RNA editing of point mutations via RNA-guided adenosine deaminases.

Journal Article Nat Methods · March 2019 We present in vivo sequence-specific RNA base editing via adenosine deaminases acting on RNA (ADAR) enzymes with associated ADAR guide RNAs (adRNAs). To achieve this, we systematically engineered adRNAs to harness ADARs, and comprehensively evaluated the s ... Full text Link to item Cite

Ex Vivo Tumor-on-a-Chip Platforms to Study Intercellular Interactions within the Tumor Microenvironment.

Journal Article Adv Healthc Mater · February 2019 The emergence of immunotherapies and recent FDA approval of several of them makes them a promising therapeutic strategy for cancer. While these advancements underscore the potential of engaging the immune system to target tumors, this approach has so far b ... Full text Link to item Cite

Stimuli-Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine.

Journal Article Macromol Biosci · January 2019 Supramolecular hydrogels are a class of self-assembled network structures formed via non-covalent interactions of the hydrogelators. These hydrogels capable of responding to external stimuli are considered to be smart materials due to their ability to unde ... Full text Link to item Cite

Phenylboronic Acid-polymers for Biomedical Applications.

Journal Article Curr Med Chem · 2019 BACKGROUND: Phenylboronic acid-polymers (PBA-polymers) have attracted tremendous attention as potential stimuli-responsive materials with applications in drug-delivery depots, scaffolds for tissue engineering, HIV barriers, and biomolecule-detecting/sensin ... Full text Link to item Cite

Effect of age on biomaterial-mediated in situ bone tissue regeneration.

Journal Article Acta Biomater · September 15, 2018 UNLABELLED: Emerging studies show the potential application of synthetic biomaterials that are intrinsically osteoconductive and osteoinductive as bone grafts to treat critical bone defects. Here, the biomaterial not only assists recruitment of endogenous ... Full text Link to item Cite

Functionally graded multilayer scaffolds for in vivo osteochondral tissue engineering.

Journal Article Acta Biomater · September 15, 2018 UNLABELLED: Osteochondral tissue repair remains a significant challenge in orthopedic surgery. Tissue engineering of osteochondral tissue has transpired as a potential therapeutic solution as it can effectively regenerate bone, cartilage, and the bone-cart ... Full text Link to item Cite

Macroporous Dual-compartment Hydrogels for Minimally Invasive Transplantation of Primary Human Hepatocytes.

Journal Article Transplantation · September 2018 BACKGROUND: Given the shortage of available organs for whole or partial liver transplantation, hepatocyte cell transplantation has long been considered a potential strategy to treat patients suffering from various liver diseases. Some of the earliest appro ... Full text Link to item Cite

In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.

Journal Article Mol Ther · July 5, 2018 Development of efficacious in vivo delivery platforms for CRISPR-Cas9-based epigenome engineering will be critical to enable the ability to target human diseases without permanent modification of the genome. Toward this, we utilized split-Cas9 systems to d ... Full text Link to item Cite

Mineralized Biomaterials Mediated Repair of Bone Defects Through Endogenous Cells.

Journal Article Tissue Eng Part A · July 2018 Synthetic biomaterials that create a dynamic calcium (Ca2+)-, phosphate (PO43-) ion-, and calcium phosphate (CaP)-rich microenvironment, similar to that found in native bone tissue, have been shown to promote osteogenic commitment of stem cells in vitro an ... Full text Link to item Cite

Biomimetic Tissue Engineering for Musculoskeletal Tissues

Chapter · June 22, 2018 Current trends in the application of stem cells in tissue engineering have prompted further investigation and incorporation of developmental biology in the field. A greater understanding of human development, specifically the intricate and complex processe ... Full text Link to item Cite

Direct Conversion of Human Pluripotent Stem Cells to Osteoblasts With a Small Molecule.

Journal Article Curr Protoc Stem Cell Biol · February 28, 2018 Human pluripotent stem cells (hPSCs), which exhibit unlimited self-renewal ability and can differentiate into all cell types in the human body, are a promising cell source for cell-based therapies and regenerative medicine. Small molecules hold great poten ... Full text Link to item Cite

Matrix Topographical Cue-Mediated Myogenic Differentiation of Human Embryonic Stem Cell Derivatives.

Journal Article Polymers (Basel) · November 5, 2017 Biomaterials varying in physical properties, chemical composition and biofunctionalities can be used as powerful tools to regulate skeletal muscle-specific cellular behaviors, including myogenic differentiation of progenitor cells. Biomaterials with define ... Full text Link to item Cite

Skeletal muscle-on-a-chip: an in vitro model to evaluate tissue formation and injury.

Journal Article Lab Chip · October 11, 2017 Engineered skeletal muscle tissues can be used for in vitro studies that require physiologically relevant models of native tissues. Herein, we describe the development of a three-dimensional (3D) skeletal muscle tissue that recapitulates the architectural ... Full text Link to item Cite

In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism.

Journal Article Proc Natl Acad Sci U S A · May 23, 2017 Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engine ... Full text Link to item Cite

Biomineralized matrices as intelligent scaffolds for bone tissue regeneration

Chapter · January 1, 2017 Bone is an example of a biomineralized functional living tissue. The mineralized components of bone tissue endow them with unique mechanical and chemical functions. Specifically, bone tissue is composed of inorganic calcium phosphate (CaP)-rich mineralized ... Full text Cite

Hydrogels as extracellular matrix analogs

Journal Article Gels · September 1, 2016 The extracellular matrix (ECM) is the non-cellular component of tissue that provides physical scaffolding to cells. Emerging studies have shown that beyond structural support, the ECM provides tissue-specific biochemical and biophysical cues that are requi ... Full text Cite

Small molecule-driven direct conversion of human pluripotent stem cells into functional osteoblasts.

Journal Article Sci Adv · August 2016 The abilities of human pluripotent stem cells (hPSCs) to proliferate without phenotypic alteration and to differentiate into tissue-specific progeny make them a promising cell source for regenerative medicine and development of physiologically relevant in ... Full text Link to item Cite

Magnetically-responsive silica-gold nanobowls for targeted delivery and SERS-based sensing.

Journal Article Nanoscale · June 9, 2016 Composite colloidal structures with multi-functional properties have wide applications in targeted delivery of therapeutics and imaging contrast molecules and high-throughput molecular bio-sensing. We have constructed a multifunctional composite magnetic n ... Full text Link to item Cite

Chemotaxis-driven assembly of endothelial barrier in a tumor-on-a-chip platform.

Journal Article Lab Chip · May 21, 2016 The integration of three-dimensional micropatterning with microfluidics provides a unique opportunity to create perfusable tissue constructs in vitro. Herein, we have used this approach to create a tumor-on-a-chip with an endothelial barrier. Specifically, ... Full text Link to item Cite

In vivo comparison of biomineralized scaffold-directed osteogenic differentiation of human embryonic and mesenchymal stem cells.

Journal Article Drug Deliv Transl Res · April 2016 Human pluripotent stem cells such as embryonic stem cells (hESCs) and multipotent stem cells like mesenchymal stem cells (hMSCs) hold great promise as potential cell sources for bone tissue regeneration. Comparing the in vivo osteogenesis of hESCs and hMSC ... Full text Link to item Cite

Progress in orthopedic biomaterials and drug delivery.

Journal Article Drug Deliv Transl Res · April 2016 Full text Link to item Cite

3D cardiac μtissues within a microfluidic device with real-time contractile stress readout.

Journal Article Lab Chip · January 7, 2016 We present the development of three-dimensional (3D) cardiac microtissues within a microfluidic device with the ability to quantify real-time contractile stress measurements in situ. Using a 3D patterning technology that allows for the precise spatial dist ... Full text Link to item Cite

Biomaterials for pluripotent stem cell engineering: From fate determination to vascularization

Journal Article Journal of Materials Chemistry B · January 1, 2016 Recent advancements in materials science and engineering may hold the key to overcoming reproducibility and scalability limitations currently hindering the clinical translation of stem cell therapies. Biomaterial assisted differentiation commitment of stem ... Full text Cite

Poly(ethylene glycol) hydrogels with cell cleavable groups for autonomous cell delivery.

Journal Article Biomaterials · January 2016 Cell-responsive hydrogels hold tremendous potential as cell delivery devices in regenerative medicine. In this study, we developed a hydrogel-based cell delivery vehicle, in which the encapsulated cell cargo control its own release from the vehicle in a pr ... Full text Link to item Cite

Embedded 3D Photopatterning of Hydrogels with Diverse and Complex Architectures for Tissue Engineering and Disease Models.

Journal Article Tissue Eng Part C Methods · November 2015 Techniques that can create three-dimensional (3D) structures to provide architectural support for cells have a significant impact in generating complex and hierarchically organized tissues/organs. In recent times, a number of technologies, including photop ... Full text Link to item Cite

The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis.

Journal Article Nat Commun · October 15, 2015 Fibrosis is a pervasive disease in which the excessive deposition of extracellular matrix (ECM) compromises tissue function. Although the underlying mechanisms are mostly unknown, matrix stiffness is increasingly appreciated as a contributor to fibrosis ra ... Full text Link to item Cite

Synthetic bone mimetic matrix-mediated in situ bone tissue formation through host cell recruitment.

Journal Article Acta Biomater · June 2015 Advances in tissue engineering have offered new opportunities to restore anatomically and functionally compromised tissues. Although traditional tissue engineering approaches that utilize biomaterials and cells to create tissue constructs for implantation ... Full text Link to item Cite

Biomineralized matrices dominate soluble cues to direct osteogenic differentiation of human mesenchymal stem cells through adenosine signaling.

Journal Article Biomacromolecules · March 9, 2015 Stem cell differentiation is determined by a repertoire of signals from its microenvironment, which includes the extracellular matrix (ECM) and soluble cues. The ability of mesenchymal stem cells (MSCs), a common precursor for the skeletal system, to diffe ... Full text Link to item Cite

Extracellular-matrix-based and Arg-Gly-Asp-modified photopolymerizing hydrogels for cartilage tissue engineering.

Journal Article Tissue Eng Part A · February 2015 Articular cartilage damage is a persistent and increasing problem with the aging population. Strategies to achieve complete repair or functional restoration remain a challenge. Photopolymerizing-based hydrogels have long received an attention in the cartil ... Full text Link to item Cite

Biomimetic Material-Assisted Delivery of Human Embryonic Stem Cell Derivatives for Enhanced In Vivo Survival and Engraftment.

Journal Article ACS Biomater Sci Eng · January 12, 2015 The ability of human embryonic stem cells (hESCs) and their derivatives to differentiate and contribute to tissue repair has enormous potential to treat various debilitating diseases. However, improving the in vivo viability and function of the transplante ... Full text Link to item Cite

Adenosine signaling mediates osteogenic differentiation of human embryonic stem cells on mineralized matrices

Journal Article Frontiers in Bioengineering and Biotechnology · January 1, 2015 Human embryonic stem cells (hESCs) are attractive cell sources for tissue engineering and regenerative medicine due to their self-renewal and differentiation ability. Design of biomaterials with an intrinsic ability that promotes hESC differentiation to th ... Full text Cite

3D traction stresses activate protease-dependent invasion of cancer cells.

Journal Article Biophys J · December 2, 2014 Cell invasion and migration that occurs, for example, in cancer metastasis is rooted in the ability of cells to navigate through varying levels of physical constraint exerted by the extracellular matrix. Cancer cells can invade matrices in either a proteas ... Full text Link to item Cite

Mineralized gelatin methacrylate-based matrices induce osteogenic differentiation of human induced pluripotent stem cells.

Journal Article Acta Biomater · December 2014 Human induced pluripotent stem cells (hiPSC) are a promising cell source with pluripotency and self-renewal properties. Design of simple and robust biomaterials with an innate ability to induce lineage-specificity of hiPSC is desirable to realize their app ... Full text Link to item Cite

Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism.

Journal Article Eur Cell Mater · November 25, 2014 Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as ... Full text Link to item Cite

Biomineralized matrix-assisted osteogenic differentiation of human embryonic stem cells

Journal Article Journal of Materials Chemistry B · September 14, 2014 The physical and chemical properties of a matrix play an important role in determining various cellular behaviors, including lineage specificity. We demonstrate that the differentiation commitment of human embryonic stem cells (hESCs), both in vitro and in ... Full text Cite

WNT3A promotes myogenesis of human embryonic stem cells and enhances in vivo engraftment.

Journal Article Sci Rep · August 1, 2014 The ability of human embryonic stem cells (hESCs) to differentiate into skeletal muscle cells is an important criterion in using them as a cell source to ameliorate skeletal muscle impairments. However, differentiation of hESCs into skeletal muscle cells s ... Full text Link to item Cite

Fusarisetins: structure-function studies on a novel class of cell migration inhibitors

Journal Article Organic Chemistry Frontiers · April 1, 2014 Herein, we report the effects of fusarisetin A on cell morphology focusing in particular on actin and microtubules dynamics. We also report the synthesis and structure-function studies of a designed library of synthetic fusarisetins in cell-based assays. ... Full text Cite

Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling.

Journal Article Proc Natl Acad Sci U S A · January 21, 2014 Synthetic matrices emulating the physicochemical properties of tissue-specific ECMs are being developed at a rapid pace to regulate stem cell fate. Biomaterials containing calcium phosphate (CaP) moieties have been shown to support osteogenic differentiati ... Full text Link to item Cite

Smart hydrogels as functional biomimetic systems

Journal Article Biomaterials Science · January 1, 2014 Stimuli-responsive (smart) hydrogels have attracted widespread attention as biomimetic systems due to their ability to respond to subtle changes in external and internal stimuli ranging from physical triggers such as temperature and electric field to chemi ... Full text Cite

Biomaterials directed in vivo osteogenic differentiation of mesenchymal cells derived from human embryonic stem cells.

Journal Article Tissue Eng Part A · August 2013 Spontaneous differentiation of human embryonic stem cells (hESCs) is generally inefficient and leads to a heterogeneous population of differentiated and undifferentiated cells, limiting the potential use of hESCs for cell-based therapy and studies of speci ... Full text Link to item Cite

Effect of scaffold microarchitecture on osteogenic differentiation of human mesenchymal stem cells.

Journal Article Eur Cell Mater · January 18, 2013 Design of macroporous synthetic grafts that can promote infiltration of cells, their differentiation, and synthesis of bone-specific extracellular matrix is a key determinant for in vivo bone tissue regeneration and repair. In this study, we investigated t ... Full text Link to item Cite

Traction stress as a modulator for protease dependent invasion of cancer cells

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

Directed in vitro myogenesis of human embryonic stem cells and their in vivo engraftment.

Journal Article PLoS One · 2013 Development of human embryonic stem cell (hESC)-based therapy requires derivation of in vitro expandable cell populations that can readily differentiate to specified cell types and engraft upon transplantation. Here, we report that hESCs can differentiate ... Full text Link to item Cite

Engineering cell-material interfaces for long-term expansion of human pluripotent stem cells.

Journal Article Biomaterials · January 2013 Cost-effective and scalable synthetic matrices that support long-term expansion of human pluripotent stem cells (hPSCs) have many applications, ranging from drug screening platforms to regenerative medicine. Here, we report the development of a hydrogel-ba ... Full text Link to item Cite

Isolation of collagen from cortical bovine bone for preparation of porous collagen sponges

Conference Conference Proceedings of the Society for Experimental Mechanics Series · January 1, 2013 Fabrication of collagen sponges from type I collagen isolated from cortical bovine femur bone is reported. Collagen was extracted with 0.1 M EDTA by refreshing the solution every 24 h for 9 days. Sodium dodecyl sulfate poly-acrylamide gel electrophoresis ( ... Full text Cite

Cartilage-like mechanical properties of poly (ethylene glycol)-diacrylate hydrogels.

Journal Article Biomaterials · October 2012 Hydrogels prepared from poly-(ethylene glycol) (PEG) have been used in a variety of studies of cartilage tissue engineering. Such hydrogels may also be useful as a tunable mechanical material for cartilage repair. Previous studies have characterized the ch ... Full text Link to item Cite

Mineralized synthetic matrices as an instructive microenvironment for osteogenic differentiation of human mesenchymal stem cells.

Journal Article Macromol Biosci · August 2012 The effect of substrate-mediated signals on osteogenic differentiation of hMSCs is studied using a synthetic bone-like material comprising both organic and inorganic components that supports adhesion, spreading, and proliferation of hMSCs. hMSCs undergo os ... Full text Link to item Cite

Spatial tuning of negative and positive Poisson's ratio in a multi-layer scaffold.

Journal Article Acta Biomater · July 2012 While elastic modulus is tunable in tissue engineering scaffolds, it is substantially more challenging to tune the Poisson's ratio of scaffolds. In certain biological applications, scaffolds with a tunable Poisson's ratio may be more suitable for emulating ... Full text Link to item Cite

A three-dimensional polymer scaffolding material exhibiting a zero Poisson's ratio

Journal Article Soft Matter · May 14, 2012 Poisson's ratio describes the degree to which a material contracts (expands) transversally when axially strained. A material with a zero Poisson's ratio does not transversally deform in response to an axial strain (stretching). In tissue engineering applic ... Full text Cite

Rapid self-healing hydrogels.

Journal Article Proc Natl Acad Sci U S A · March 20, 2012 Synthetic materials that are capable of autonomous healing upon damage are being developed at a rapid pace because of their many potential applications. Despite these advancements, achieving self-healing in permanently cross-linked hydrogels has remained e ... Full text Link to item Cite

Musculoskeletal cell mechanics

Chapter · January 1, 2012 Musculoskeletal mechanics occur over many length scales, from macroscopic muscle extension and weight-bearing bone compression to microscopic muscle bers, down to the cytoskeleton that supports the bone cell structure and facilitates muscle cell contractio ... Full text Cite

Controlling stem cells with biomaterials

Chapter · December 1, 2011 Stem cell engineering has enormous potential to study developmental processes, disease progression, drug screening, and to provide new therapeutics. The interaction of stem cells with their microenvironment plays an important role in determining the stem c ... Full text Cite

Oligo(trimethylene carbonate)-poly(ethylene glycol)-oligo(trimethylene carbonate) triblock-based hydrogels for cartilage tissue engineering.

Journal Article Acta Biomater · September 2011 A triblock co-polymer of oligo(trimethylene carbonate)-block-poly(ethylene glycol) 20000-block-oligo(trimethylene carbonate) diacrylate (TMC20) was used as a photo-polymerizable precursor for the encapsulation of primary articular chondrocytes. The efficac ... Full text Link to item Cite

Engineered microenvironments for self-renewal and musculoskeletal differentiation of stem cells.

Journal Article Regen Med · July 2011 Stem cells hold great promise for therapies aimed at regenerating damaged tissue, drug screening and studying in vitro models of human disease. However, many challenges remain before these applications can become a reality. One such challenge is developing ... Full text Link to item Cite

Influence of physical properties of biomaterials on cellular behavior.

Journal Article Pharm Res · June 2011 PURPOSE: In this study, we evaluated the effect of hydrogel structural properties on proliferation and biosynthesis activity of encapsulated chondrocytes. METHODS: Hydrogels with varying structural and mechanical properties were prepared by photopolymerizi ... Full text Link to item Cite

Engineering the cell-material interface for controlling stem cell adhesion, migration, and differentiation.

Journal Article Biomaterials · May 2011 The effective utilization of stem cells in regenerative medicine critically relies upon our understanding of the intricate interactions between cells and their extracellular environment. While bulk mechanical and chemical properties of the matrix have been ... Full text Link to item Cite

Method for decellularizing skeletal muscle without detergents or proteolytic enzymes.

Journal Article Tissue Eng Part C Methods · April 2011 Decellularized skeletal muscle is a promising model that can be used to study cell-matrix interactions and changes that occur in muscle extracellular matrix (ECM) in myopathies and muscle wasting diseases. The goal of this study is to develop a novel metho ... Full text Link to item Cite

Dynamic Electromechanical Hydrogel Matrices for Stem Cell Culture.

Journal Article Adv Funct Mater · January 7, 2011 Hydrogels have numerous biomedical applications including synthetic matrices for cell culture and tissue engineering. Here we report the development of hydrogel based multifunctional matrices that not only provide three-dimensional structural support to th ... Full text Link to item Cite

Regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in PEG-ECM hydrogels

Journal Article Cell and Tissue Research · January 1, 2011 Bone-marrow-derived mesenchymal stem cells (MSCs) are candidates for regeneration applications in musculoskeletal tissue such as cartilage and bone. Various soluble factors in the form of growth factors and cytokines have been widely studied for directing ... Full text Cite

Synthetic bio-actuators and their applications in biomedicine

Journal Article Smart Structures and Systems · January 1, 2011 The promise of biomimetic smart structures that can function as sensors and actuators in biomedicine is enormous. Technological development in the field of stimuli-responsive shape memory polymers have opened up a new avenue of applications for polymer-bas ... Full text Cite

Osteoarthritic chondrocyte-secreted morphogens induce chondrogenic differentiation of human mesenchymal stem cells.

Journal Article Arthritis Rheum · January 2011 OBJECTIVE: The potential of stem cells to repair compromised cartilage tissue, such as in osteoarthritis (OA), depends strongly on how transplanted cells respond to factors secreted from the residing OA chondrocytes. This study was undertaken to determine ... Full text Link to item Cite

Heparin mimicking polymer promotes myogenic differentiation of muscle progenitor cells.

Journal Article Biomacromolecules · December 13, 2010 Heparin and heparan sulfate mediated basic fibroblast growth factor (bFGF) signaling plays an important role in skeletal muscle homeostasis by maintaining a balance between proliferation and differentiation of muscle progenitor cells. In this study we inve ... Full text Link to item Cite

Long-term human pluripotent stem cell self-renewal on synthetic polymer surfaces.

Journal Article Biomaterials · December 2010 Realization of the full potential of human pluripotent stem cells (hPSCs) in regenerative medicine requires the development of well-defined culture conditions for their long-term growth and directed differentiation. Current practices for maintaining hPSCs ... Full text Link to item Cite

PEG/clay nanocomposite hydrogel: A mechanically robust tissue engineering scaffold

Journal Article Soft Matter · October 21, 2010 Nanocomposite hydrogels with enhanced mechanical properties could have tremendous biomedical applications. Here we describe synthesis and characterizations of biocompatible poly(ethylene glycol) diacrylate (PEGDA)/Laponite nanocomposite (NC) hydrogels that ... Full text Cite

Interconnected macroporous poly(ethylene glycol) cryogels as a cell scaffold for cartilage tissue engineering.

Journal Article Tissue Eng Part A · October 2010 Macroporous networks of poly(ethylene glycol) (PEG) with interconnected pores can be created by cryogelation techniques. In this study, we describe the potential application of such PEG cryogels as scaffolds for cartilage tissue engineering. Three-dimensio ... Full text Link to item Cite

Templated mineralization of synthetic hydrogels for bone-like composite materials: role of matrix hydrophobicity.

Journal Article Biomacromolecules · August 9, 2010 Bone-mimetic mineral-polymer composite materials have several applications ranging from artificial bone grafts to scaffolds for bone tissue engineering; templated mineralization is an effective approach to fabricate such composites. In this study, we synth ... Full text Link to item Cite

Nanotube surface triggers increased chondrocyte extracellular matrix production

Journal Article Materials Science and Engineering C · May 10, 2010 We have altered TiO2 nanotube diameters from 30 to 100 nm by anodization and investigated the in vitro bovine cartilage chondrocyte (BCC) response to the different nanoscale dimensions. The nanotopography of the vertically aligned TiO2 nanotube structures ... Full text Cite

Engineering musculoskeletal tissues with human embryonic germ cell derivatives.

Journal Article Stem Cells · April 2010 The cells derived from differentiating embryoid bodies of human embryonic germ (hEG) cells express a broad spectrum of gene markers and have been induced toward ecto- and endodermal lineages. We describe here in vitro and in vivo differentiation of hEG-der ... Full text Link to item Cite

Poly(ethylene glycol) cryogels as potential cell scaffolds: Effect of polymerization conditions on cryogel microstructure and properties

Journal Article Journal of Materials Chemistry · January 1, 2010 We report the synthesis and characterization of interconnected macroporous network structures of poly(ethylene glycol) (PEG) using cryogelation techniques. Novel monolithic networks containing a gradient of pore size in a layered fashion were created from ... Full text Cite

Functional Biomaterials for Controlling Stem Cell Differentiation

Chapter · January 1, 2010 Differentiation of stem cells has shown to be strongly influenced through several cues provided by reciprocal interactions with the extracellular microenvironment, consisting of soluble bioactive agents and the extracellular matrix.While the dynamic extrac ... Full text Cite

A novel single precursor-based biodegradable hydrogel with enhanced mechanical properties

Journal Article Soft Matter · October 21, 2009 A mechanically tough biodegradable hydrogel is developed from a single precursor comprising poly(ethylene glycol) and oligo(trimethylene carbonate), where both the crosslink density and swelling properties of the polymer network are independently controlle ... Full text Cite

Embryonic germ cells are capable of adipogenic differentiation in vitro and in vivo.

Journal Article Tissue Eng Part A · March 2009 There is an extensive clinical need for soft tissue filler materials, such as adipose tissue, for plastic and reconstructive surgery. Due to limitations with autologous adipose transplantation, engineered adipose tissue provides a potential alternative the ... Full text Link to item Cite

Mesenchymal stem cell differentiation and roles in regenerative medicine.

Journal Article Wiley Interdiscip Rev Syst Biol Med · 2009 Adult stem cells with multi or unipotent differentiation potential are present in almost all tissues of adult organisms. The main function of these stem cells is to support normal repair and rejuvenation of diseased and aging tissues. Mesenchymal stem cell ... Full text Link to item Cite

In vivo commitment and functional tissue regeneration using human embryonic stem cell-derived mesenchymal cells.

Journal Article Proc Natl Acad Sci U S A · December 30, 2008 Development of clinically relevant regenerative medicine therapies using human embryonic stem cells (hESCs) requires production of a simple and readily expandable cell population that can be directed to form functional 3D tissue in an in vivo environment. ... Full text Link to item Cite

Enhanced chondrogenesis of mesenchymal stem cells in collagen mimetic peptide-mediated microenvironment

Journal Article Tissue Engineering - Part A. · November 1, 2008 A new type of synthetic hydrogel scaffold that mimics certain aspects of structure and function of natural extracellular matrix (ECM) has been developed. We previously reported the conjugation of collagen mimetic peptide (CMP) to poly(ethylene oxide) diacr ... Full text Cite

Derivation of chondrogenically-committed cells from human embryonic cells for cartilage tissue regeneration.

Journal Article PLoS One · June 25, 2008 BACKGROUND: Heterogeneous and uncontrolled differentiation of human embryonic stem cells (hESCs) in embryoid bodies (EBs) limits the potential use of hESCs for cell-based therapies. More efficient strategies are needed for the commitment and differentiatio ... Full text Link to item Cite

Enhanced chondrogenic differentiation of embryonic stem cells by coculture with hepatic cells.

Journal Article Stem Cells Dev · June 2008 Enhancing the specific differentiation of pluripotent embryonic stem (ES) cells has been a challenge in the field of tissue engineering. Previously, hepatic cells have been shown to secrete various soluble morphogenic factors to direct mesodermal different ... Full text Link to item Cite

Controlled differentiation of stem cells.

Journal Article Adv Drug Deliv Rev · January 14, 2008 The extracellular microenvironment plays a significant role in controlling cellular behavior. Identification of appropriate biomaterials that support cellular attachment, proliferation and, most importantly in the case of human embryonic stem cells, lineag ... Full text Link to item Cite

Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells.

Journal Article Matrix Biol · January 2008 Bone marrow-derived mesenchymal stem cells (MSCs) have strong potential in regeneration of musculoskeletal tissues including cartilage and bone. The microenvironment, comprising of scaffold and soluble factors, plays a pivotal role in determining the effic ... Full text Link to item Cite

Response of zonal chondrocytes to extracellular matrix-hydrogels.

Journal Article FEBS Lett · September 4, 2007 We investigated the biological response of chondrocytes isolated from different zones of articular cartilage and their cellular behaviors in poly (ethylene glycol)-based (PEG) hydrogels containing exogenous type I collagen, hyaluronic acid (HA), or chondro ... Full text Link to item Cite

Morphogenetic signals from chondrocytes promote chondrogenic and osteogenic differentiation of mesenchymal stem cells.

Journal Article J Cell Physiol · August 2007 Mesenchymal stem cells (MSCs) are potentially useful cells for musculoskeletal tissue engineering. However, controlling MSC differentiation and tissue formation in vivo remains a challenge. There is a significant need for well-defined and efficient protoco ... Full text Link to item Cite

Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration.

Journal Article Nat Mater · May 2007 A biologically active, high-strength tissue adhesive is needed for numerous medical applications in tissue engineering and regenerative medicine. Integration of biomaterials or implants with surrounding native tissue is crucial for both immediate functiona ... Full text Link to item Cite

Glucosamine modulates chondrocyte proliferation, matrix synthesis, and gene expression.

Journal Article Osteoarthritis Cartilage · January 2007 OBJECTIVE: To investigate the effects of glucosamine (GlcN) on chondrocyte proliferation, matrix production, and gene expression for providing insights into the biochemical basis of its reported beneficial effects in osteoarthritis (OA). METHODS: Dose-depe ... Full text Link to item Cite

Cartilage tissue engineering: Directed differentiation of embryonic stem cells in three-dimensional hydrogel culture.

Journal Article Methods Mol Biol · 2007 The clinical goal of tissue engineering is to restore, repair, or replace damaged tissues in the body. Significant advances have been made in recent years using stem cells as a cell source for cartilage tissue engineering and reconstructive surgery applica ... Full text Link to item Cite

Enhanced chondrogenic differentiation of murine embryonic stem cells in hydrogels with glucosamine.

Journal Article Biomaterials · December 2006 Differentiation of embryonic stem (ES) cells generally occurs after formation of three-dimensional cell aggregates, known as embryoid bodies (EBs). We have previously reported that hydrogels provide EBs a supportive environment for in vitro chondrogenic di ... Full text Link to item Cite

Hydrogels for musculoskeletal tissue engineering

Book · December 1, 2006 The advancements in scaffold-supported cell therapy for musculoskeletal tissue engineering have been truly dramatic in the last couple of decades. This article briefly reviews the role of natural and synthetic hydrogels in the above field. The most appeali ... Full text Cite

Chondrogenic differentiation of human embryonic stem cell-derived cells in arginine-glycine-aspartate-modified hydrogels.

Journal Article Tissue Eng · September 2006 Human embryonic stem cells (hESCs) have the potential to self-renew and generate multiple cell types, producing critical building blocks for tissue engineering and regenerative medicine applications. Here, we describe the efficient derivation and chondroge ... Full text Link to item Cite

The role of biomaterials in stem cell differentiation: applications in the musculoskeletal system.

Journal Article Stem Cells Dev · June 2006 The capabilities of stem cells continue to be revealed, leading to excitement regarding potential new therapies. Regenerative medicine is an area in which stem cells hold great promise for overcoming the challenge of limited cell sources for tissue repair. ... Full text Link to item Cite

Chondrogenic differentiation of human embryonic germ cell derived cells in hydrogels.

Journal Article Conf Proc IEEE Eng Med Biol Soc · 2006 Human embryonic germ (hEG) cells have the potential to self-renew over long periods of time and differentiate into various lineages. Cells derived from embryoid bodies of hEG cells express a broad spectrum of gene markers and have been induced towards cell ... Full text Link to item Cite

Metal-ion-mediated healing of gels

Journal Article Journal of Polymer Science, Part A: Polymer Chemistry · January 1, 2006 Metal-ion-mediated healing, a healing phenomenon in lightly cross-linked hydrophilic polymer gels, is described. The gels were synthesized from acryloyl derivatives of amino acids, which contain a hydrophobic alkyl chain and a terminal hydrophilic carboxyl ... Full text Cite

Novel macroscopic self-organization in polymer gels

Journal Article Advanced Materials · October 16, 2001 A different type of self-organization in a hydrogel is described. In this self-organization, a cylindrical piece of gel transforms into a completely hollow spherical or ellipsoidal object in the presence of specific transition metal ions. It is shown that ... Full text Cite

Role of hydrophobicity on structure of polymer-metal complexes

Journal Article Journal of Physical Chemistry B · June 14, 2001 Metal complexation of a series of polymeric gels, with different degrees of ionization, prepared from acrylic acid and acryloyl amino acid monomers (CH2=CHCONH(CH2)nCOOH, where n = 4, 6 and 8), were investigated. The binding of Cu(II) ions to the gels was ... Full text Cite

Designing new thermoreversible gels by molecular tailoring of hydrophilic-hydrophobic interactions

Journal Article Journal of Chemical Physics · February 8, 2000 We have shown that the lattice fluid hydrogen bond (LFHB) model can successfully quantify the first-order volume transition in hydrogels. The model predicts that a critical balance of hydrophilic and hydrophobic interactions is required for a gel to exhibi ... Full text Cite

Effect of Polymer-Metal Complexation on the Phase Transition of Thermoreversible Copolymer Gels

Journal Article Journal of Physical Chemistry B · November 4, 1999 We have investigated the effect of transition metal complexation on the swelling behavior in water of a new terpolymer gel made from N-tert-butylacrylamide (N-t-BAm) as the hydrophobia monomer, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) as the hyd ... Full text Cite

Molecular tailoring of thermoreversible copolymer gels: Some new mechanistic insights

Journal Article Journal of Chemical Physics · December 1, 1998 We earlier reported the role of hydrophobic and hydrogen bonding interactions on the transition temperatures of thermoreversible copolymer gels. We show here that the chemical structure of the hydrophobe and its concentration determine the transition tempe ... Full text Cite

Thermoreversible hydrogel based on radiation induced copolymerisation of poly(N-isopropyl acrylamide) and poly(ethylene oxide) †

Journal Article Polymer · January 1, 1998 Thermoreversible copolymer hydrogel based on poly(ethylene oxide) and poly(N-isopropyl acrylamide) has been prepared by γ-radiation technique. The utility of 13C n.m.r. spectroscopy in elucidating the structure and copolymer composition has been demonstrat ... Full text Cite