Thomas H Barker

Thomas H Barker
  • Ph.D.
  • Professor (Associate) at Georgia Institute of Technology

About

123
Publications
20,884
Reads
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6,679
Citations
Current institution
Georgia Institute of Technology
Current position
  • Professor (Associate)
Additional affiliations
July 2006 - June 2012
Georgia Institute of Technology
Position
  • Professor (Assistant)
July 2012 - present
Georgia Institute of Technology
Position
  • Professor (Associate)
Description
  • We study of the role of ECM in directing cell phenotype, mechanotransduction within the ECM, and engineering fibrin-based polymers for tissue regeneration and morphogenesis.
August 2004 - June 2006
Swiss Federal Institute of Technology in Lausanne
Position
  • Senior Researcher
Description
  • Used molecular engineering to create mutants of FN's cell binding domain to impart integrin specificity. Applied novel factor XIIIa coupling technology to present these motifs with engineered fibrin matrices for enhanced MSC osteogenic differentiation.

Publications

Publications (123)
Preprint
Full-text available
Dysregulation of the cellular mechanisms that coordinate the interpretation and transduction of microenvironmental biophysical signals are a unifying feature of tissue remodeling pathologies such as fibrosis and cancer. While genomic regulation downstream of normal mechanotransduction (i.e. cases where cells sense soft and stiff appropriately) is w...
Article
Full-text available
Investigating the molecular, cellular, and tissue-level changes caused by disease, and the effects of pharmacological treatments across these biological scales, necessitates the use of multiscale computational modeling in combination with experimentation. Many diseases dynamically alter the tissue microenvironment in ways that trigger microvascular...
Article
Full-text available
The extracellular matrix (ECM) is a protein polymer network that physically supports cells within a tissue. It acts as an important physical and biochemical stimulus directing cell behaviors. For fibronectin (Fn), a predominant component of the ECM, these physical and biochemical activities are inextricably linked as physical forces trigger conform...
Article
Background The epididymis is important for sperm maturation and without its proper development, male infertility will result. Biomechanical properties of tissues/organs play key roles during their morphogenesis, including the Wolffian duct. It is hypothesized that structural/bulk stiffness of the capsule and mesenchyme/extracellular matrix that sur...
Article
Fibrosis-associated fibroblasts have been identified across various fibrotic disorders, but not in the context of biomaterials, fibrotic encapsulation, and the foreign body response. In other fibrotic disorders, a fibroblast subpopulation defined by Thy-1 loss is strongly correlated with fibrosis yet we do not know what promotes Thy-1 loss. We have...
Article
Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical...
Article
The term 'fibroblast' often serves as a catch-all for a diverse array of mesenchymal cells, including perivascular cells, stromal progenitor cells and bona fide fibroblasts. Although phenotypically similar, these subpopulations are functionally distinct, maintaining tissue integrity and serving as local progenitor reservoirs. In response to tissue...
Preprint
Full-text available
Investigating the molecular, cellular, and tissue-level changes caused by disease, and the effects of pharmacological treatments across these biological scales, necessitates the use of multiscale computational modeling in combination with experimentation. Many diseases dynamically alter the tissue microenvironment in ways that trigger microvascular...
Article
Full-text available
Introduction Up to 30% of hospitalized COVID-19 patients experience persistent sequelae, including pulmonary fibrosis (PF). Methods We examined COVID-19 survivors with impaired lung function and imaging worrisome for developing PF and found within six months, symptoms, restriction and PF improved in some (Early-Resolving COVID-PF), but persisted i...
Preprint
Full-text available
Rationale: Up to 30% of COVID-19 patients experience persistent sequelae, including dyspnea, restrictive physiology, and early radiographic signs of pulmonary fibrosis (PF). The mechanisms that provoke post-COVID progressive PF are poorly understood, and biomarkers to identify at-risk patients are urgently needed. Methods: We evaluated a cohort of...
Article
Full-text available
Increasingly, the matrisome, a set of proteins that form the core of the extracellular matrix (ECM) or are closely associated with it, has been demonstrated to play a key role in tumor progression. However, in the context of gynecological cancers, the matrisome has not been well characterized. A holistic, yet targeted, exploration of the tumor micr...
Article
Full-text available
Thy-1 is a cell surface glycosylphosphatidylinositol (GPI)-anchored glycoprotein that bears a broad mosaic of biological roles across various cell types. Thy-1 displays strong physiological and pathological implications in development, cancer, immunity, and tissue fibrosis. Quite uniquely, Thy-1 is capable of mediating integrin-related signaling th...
Article
Background Long-term survival of lung transplants lags behind other solid organs due to early onset of a fibrotic form of chronic rejection known as chronic lung allograft dysfunction (CLAD). Preventing CLAD is difficult as multiple immunologic and physiologic insults contribute to its development. Targeting fibroblast activation, which is the fina...
Article
Full-text available
Vascular development is a complex multistep process involving the coordination of cellular functions such as migration, proliferation, and differentiation. How mechanical forces generated by cells and transmission of these physical forces control vascular development is poorly understood. Using an endothelial-specific genetic model in mice, we show...
Article
IntroductionTissue fibrosis is characterized by progressive extracellular matrix (ECM) stiffening and loss of viscoelasticity that ultimately impairs organ functionality. Cells bind to the ECM through integrins, where αv integrin engagement in particular has been correlated with fibroblast activation into contractile myofibroblasts that drive fibro...
Chapter
Aberrant deposition of the extracellular matrix (ECM) causes fibrosis and leads to ECM stiffening. This fibrotic ECM provides biological and biophysical stimulations to alter cell activity and drive progression of fibrosis. As an emerging discipline, mechanobiology aims to access the impact of both these cues on cell behavior and relates the recipr...
Preprint
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with poorly defined pathogenic mechanism and no cure. It is characterized by chronic inflammation, myofibroblast accumulation, and aberrant extracellular matrix (ECM) remodeling. Fibrosis progression is considered to occur due to sustained aberrant fibroblast mechanotransduction: sensing "norma...
Preprint
Full-text available
The extracellular matrix (ECM) is a protein polymer network that physically supports cells within a tissue and also acts as an important biochemical stimulus directing cell behaviors. For fibronectin, a predominant component of the ECM, these physical and biochemical activities are inextricably linked as physical forces trigger conformational chang...
Article
Full-text available
Native platelets are crucial players in wound healing. Key to their role is the ability of their surface receptor GPIIb/IIIa to bind fibrin at injury sites, thereby promoting clotting. When platelet activity is impaired as a result of traumatic injury or certain diseases, uncontrolled bleeding can result. To aid clotting and tissue repair in cases...
Preprint
Full-text available
Tissue fibrosis is characterized by progressive extracellular matrix (ECM) stiffening and loss of viscoelasticity that ultimately results in reduced organ functionality. Cells bind to the ECM through integrins, where αv integrin engagement in particular has been correlated with fibroblast activation into contractile myofibroblasts that drive fibros...
Preprint
Vascular development is a complex multistep process involving the coordination of cellular functions such as migration, proliferation and differentiation. Understanding the underlying mechanisms of these processes is of importance due to involvement of vessel expansion in various pathologies. How mechanical forces generated by cells and transmissio...
Article
Full-text available
Of the many origins of pulmonary myofibroblasts, microvascular pericytes are a known source. Prior literature has established the ability of pericytes to transition into myofibroblasts, but provide limited insight into molecular cues that drive this process during lung injury repair and fibrosis. Fibronectin and RGD-binding integrins have long been...
Preprint
Full-text available
Of the many origins of pulmonary myofibroblasts, microvascular pericytes are a known source. Prior literature has established the ability of pericytes to transition into myofibroblasts, but provide limited insight into molecular cues that drive this process during lung injury repair and fibrosis. Fibronectin and RGD-binding integrins have long been...
Article
The architectural complexity of the lung is crucial to its ability to function as an organ of gas exchange; the branching tree structure of the airways transforms the tracheal cross-section of only a few square centimeters to a blood-gas barrier with a surface area of tens of square meters and a thickness on the order of a micron or less. Connectiv...
Article
Full-text available
Biophysical cues stemming from the extracellular environment are rapidly transduced into discernible chemical messages (mechanotransduction) that direct cellular activities–placing the extracellular matrix (ECM) as a potent regulator of cell behavior. Dynamic reciprocity between the cell and its associated matrix is essential to the maintenance of...
Article
The extracellular matrix (ECM) microenvironment is increasingly implicated in the instruction of pathologically relevant cell behaviors, from aberrant transdifferentation to invasion and beyond. Indeed, pathologic ECMs possess a panoply of alterations that provide deleterious instructions to resident cells. Here we demonstrate the precise manner in...
Article
Fibrosis is characterized by persistent deposition of extracellular matrix (ECM) by fibroblasts. Fibroblast mechanosensing of a stiffened ECM is hypothesized to drive the fibrotic program; however, the spatial distribution of ECM mechanics and their derangements in progressive fibrosis are poorly characterized. Importantly, fibrosis presents with s...
Article
Full-text available
Materials can be engineered to deliver specific biological cues that control stem cell growth and differentiation. However, current materials are still limited for stem cell engineering as stem cells are regulated by a complex biological milieu that requires spatiotemporal control. Here a new approach of using materials that incorporate designed ba...
Article
Hemorrhage or uncontrolled bleeding can arise either due to a medical condition or from a traumatic injury and are typically controlled with the application of a hemostatic agent. Hemostatic agents are currently derived from animal or human products, which carry risks of blood borne infections and immune dysregulation. Therefore, the need exists fo...
Article
Full-text available
Transforming growth factor-beta (TGFβ) signaling through SMAD2/3 is an important driver of pathological fibrosis in multiple organ systems. TGFβ signaling and extracellular matrix (ECM) stiffness form an unvirtuous pathological circuit in which matrix stiffness drives activation of latent TGFβ, and TGFβ signaling then drives cellular stress and ECM...
Article
Excessive bleeding and resulting complications are a major cause of death in both trauma and surgical settings. Recently, there have been a number of investigations into the design of synthetic hemostatic agents with platelet-mimicking activity to effectively treat patients suffering from severe hemorrhage. We developed platelet-like particles from...
Article
Full-text available
Fibroblasts are key participants in wound healing and inflammation, and are capable of driving the progression of tissue repair to fully functional tissue or pathologic scar, or fibrosis, depending on the specific mechanical and biochemical cues with which they are presented. Thus, understanding and modulating the fibroblastic response to implanted...
Article
We investigate microgels synthesized from N-isopropylacrylamide (NIPAM) copolymerized with a large mol% of acrylic acid, finding that when the acid groups are partially ionized at high temperatures, competition between ion-induced swelling and hydrophobic deswelling of poly(NIPAM) chains results in microphase separation. In cross-linked microgels,...
Article
Full-text available
Significance Decoupling stiffness, pore size, and cell infiltration is a critical hurdle in biomaterials design. Here, by adding ultrasoft colloidal hydrogels to polymerizing fibrin, the particles are driven into a percolated three-dimensional tunnel-like structure throughout the fibrin network. The colloidal particles remain embedded, in stark con...
Article
Statement of significance: Innovative strategies for improved retention and viability of mesenchymal stem cells (MSCs) are needed for cellular therapies. Human platelet lysate is a potent serum supplement that improves the expansion of MSCs. Here we characterize our novel PL hydrogel's desirable structural and biologic properties for human MSCs an...
Article
Background: Quantitative and qualitative differences in the hemostatic systems exist between neonates and adults, including the presence of "fetal" fibrinogen, a qualitatively dysfunctional form of fibrinogen that exists until 1 yr of age. The consequences of "fetal" fibrinogen on clot structure in neonates, particularly in the context of surgery-...
Conference Paper
Activated fibroblasts—characterized by various altered behaviors including invasiveness, altered protein secretion profiles, and resistance to apoptosis—contribute to the development and exacerbation of numerous chronic human inflammatory diseases including cancer, rheumatoid arthritis, and interstitial lung disease. Citrullination, a post-translat...
Chapter
The first of its kind, this comprehensive resource integrates cellular mechanobiology with micro-nano techniques to provide unrivalled in-depth coverage of the field, including state-of-the-art methods, recent advances, and biological discoveries. Structured in two parts, the first part offers detailed analysis of innovative micro-nano techniques i...
Article
Full-text available
Progressive fibrosis is characterized by excessive deposition of extracellular matrix (ECM), resulting in gross alterations in tissue mechanics. Changes in tissue mechanics can further augment scar deposition through fibroblast mechanotransduction. In idiopathic pulmonary fibrosis, a fatal form of progressive lung fibrosis, previous work has shown...
Article
Full-text available
Neural stem cells (NSCs) possess great potential for neural tissue repair after traumatic injuries to the central nervous system (CNS). However, poor survival and self-renewal of NSCs after injury severely limits its therapeutic potential. Sulfated chondroitin sulfate glycosaminoglycans (CS-GAGs) linked to CS proteoglycans (CSPGs) in the brain extr...
Article
Full-text available
Fibronectin (Fn) is a promiscuous ligand for numerous cell adhesion receptors, or integrins. The vast majority of Fn-integrin interactions are mediated through Fn's Arg-Gly-Asp (RGD) motif located on the 10th type III repeat. In the case of integrins αIIbβ3 and α5β1, the integrin binds RGD and the synergy site (PHSRN) located on the adjacent 9th ty...
Article
Significance: Cells communicate with the extracellular matrix (ECM) protein fibronectin (Fn) through integrin receptors on the cell surface. Controlling integrin-Fn interactions offers a promising approach to directing cell behavior, such as adhesion, migration, and differentiation, as well as coordinated tissue behaviors such as morphogenesis and...
Article
Full-text available
Protein based polymers provide an exciting and complex landscape for tunable natural biomaterials through modulation of molecular level interactions. Here we demonstrate the ability to modify protein polymer structural and mechanical properties at multiple length scales by molecular 'interference' of fibrin's native polymerization mechanism. We hav...
Article
Full-text available
Fibrin-specific targeting capabilities have been highly sought for over 50 years due to their implications for bio-molecule delivery, diagnostics, and regenerative medicine. Yet only recently has our full knowledge of fibrin's complex polymerization dynamics and biological interactions begun to be fully exploited in pursuit of this goal. This highl...
Article
Here, we present a universal, simple, efficient, and reliable way to add small BioBrick parts to any BioBrick via PCR that is compatible with BioBrick assembly standard 10. As a proof of principle, we have designed a universal primer, rbs_B0034, that contains a ribosomal binding site (RBS; BBa_B0034) and that can be used in PCR to amplify any codin...
Article
Background: During hemostasis, platelets, as the first-responders of vascular injury, are subjected to a dynamic microenvironment. Biochemically, diverse and rapidly changing gradients of soluble proteins and agonists, such as von Willebrand factor, ADP, and thrombin, drive platelet adhesion and activation. Biophysically, the hemodynamic shear forc...
Article
Dysfunctional pulmonary homeostasis and repair, including diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD*), and tumorigenesis, have been increasing steadily over the past decade, a fact that heavily implicates environmental influences. Several investigations have suggested that the lung "precursor cell"--the alveol...
Article
Full-text available
Significance Platelets are cell fragments in the blood that initiate clot formation at the site of bleeding. Although the biological aspects of this process have been well characterized, whether platelets can detect and physiologically respond to the mechanical aspects of its local environment is unclear. Here, we show that platelets sense the stif...
Article
Full-text available
Dysfunctional pulmonary homeostasis and repair, including diseases such as pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), and tumorigenesis have been increasing over the past decade, a fact that heavily implicates environmental influences. Several investigations have suggested that in response to increased transforming growt...
Article
Cancer cell adhesion to the vascular endothelium is a critical step of tumour metastasis. Endothelial surface molecule Thy-1 (CD90) is implicated in the metastatic process through its interactions with integrins and syndecans. However, how Thy-1 supports cell-cell adhesion in a dynamic mechanical environment is not known. Here we show that Thy-1 su...
Article
Full-text available
Efforts to create platelet-like structures for the augmentation of haemostasis have focused solely on recapitulating aspects of platelet adhesion; more complex platelet behaviours such as clot contraction are assumed to be inaccessible to synthetic systems. Here, we report the creation of fully synthetic platelet-like particles (PLPs) that augment...
Article
Myocardial infarction is the leading cause of death worldwide and phase I clinical trials utilizing cardiac progenitor cells (CPCs) have shown promising outcomes. Notch1 signaling plays a critical role in cardiac development and in the survival, cardiogenic lineage commitment, and differentiation of cardiac stem/progenitor cells. In this study, we...
Article
In this paper we describe a combined magnetophoresis (MAP) and dielectrophoresis (DEP) based platform for high throughput characterization of specific biomolecular interactions. The magnetic manipulation enables parallel loading of individual magnetic beads onto a magnetic pad array, while the combination of tightly controlled opposing magnetic and...
Article
The ability to design artificial extracellular matrices as cell-instructive scaffolds has opened the door to technologies capable of studying the fate of cells in vitro and to guiding tissue repair in vivo. One main component of the design of artificial extracellular matrices is the incorporation of biochemical cues to guide cell phenotype and mult...
Article
Many biomaterials constructed today are complex chemical structures that incorporate biologically active components derived from nature, but the field can still be said to be in its infancy. The need for materials that bring sophisticated properties of structure, dynamics, and function to medical and non-medical applications will only grow. Increas...
Article
The creation of fluorescently-labeled viruses is currently limited by the length of imaging observation time (e.g. labeling an envelope protein) and the rescue of viral infectivity (e.g. encoding a GFP protein). Using single molecule sensitive RNA hybridization probes delivered to the cytoplasm of infected cells, we were able to isolate individual,...
Article
The development of tissue engineering scaffolds has focused on mimicking the natural biochemical and biophysical environment of the extracellular matrix (ECM). In this review, we describe a variety of strategies aimed at reproducing and also simplifying the ECM. Despite the progress that has been made, the degree of complexity that needs to be inco...
Article
Fibrinogen is one of the primary components of the coagulation cascade and rapidly forms an insoluble matrix following tissue injury. In addition to its important role in hemostasis, fibrin acts as a scaffold for tissue repair and provides important cues for directing cell phenotype following injury. Because of these properties and the ease of poly...
Article
Elastin-like polypeptides (ELPs) are polypentapeptides that undergo hydrophobic collapse and aggregation above a specific transition temperature, T(t) . ELP diblocks sharing a common "core" block (I60) but varying "outer" blocks (A80, P40) were designed, where T(t,I) < T(t,A) < T(t,P) . The formation of ∼55 nm diameter mixed micelles from these ELP...
Article
The extracellular matrix (ECM) is critically important for many cellular processes including growth, differentiation, survival, and morphogenesis. Cells remodel and reshape the ECM by degrading and reassembling it, playing an active role in sculpting their surrounding environment and directing their own phenotypes. Both mechanical and biochemical m...
Article
Fibrin clot formation has been studied to determine the mechanical properties of fibrin fibers modified by blocking the B-b knob-pocket interaction. Synthetic B-knob peptides AHRPYAAC or AHRPYAAC-Peg have been added to a fibrinogen solution to allow for binding to the b-pockets prior to clot formation. After fibrin clot formation, a combined atomic...
Article
Increased tissue stiffness and epithelial to mesenchymal transitions (EMT) are two seemingly discrete hallmarks of fibrotic diseases. Despite recent findings highlighting the influence of tissue mechanical properties on cell phenotype, it remains unclear what role increased tissue stiffness has in the regulation of previously reported fibronectin-m...
Article
2172 Background Previous studies on clot formation have shown that the mechanical properties of clots have direct effects on hemostasis and thrombosis, and alterations of those clot mechanics are associated with disease(Collet, et al. 2006) (Hvas, et al. 2007). As such, understanding the mechanical properties of clots is vital to understand hemost...
Article
384 Background Whereas surface-immobilized fibrinogen readily causes platelet adhesion and spreading, soluble fibrinogen, on the other hand, does not lead to platelet activation without the presence of other hemostatic/thrombotic signals. This dramatically different response of platelets to fibrinogen may be due to biochemical difference in fibrin...
Article
We tested what to our knowledge is a new computational model for fibrin fiber mechanical behavior. The model is composed of three distinct elements: the folded fibrinogen core as seen in the crystal structure, the unstructured α-C connector, and the partially folded α-C domain. Previous studies have highlighted the importance of all three regions a...
Article
Full-text available
Rationale: Extracellular matrix (ECM) is a dynamic tissue that contributes to organ integrity and function, and its regulation of cell phenotype is a major aspect of cell biology. However, standard in vitro culture approaches are of unclear physiologic relevance because they do not mimic the compositional, architectural, or distensible nature of a...
Article
Cell interactions with their extracellular matrix (ECM) microenvironments play a major role in directing cellular processes that can drive wound healing and tissue regeneration but, if uncontrolled, lead to pathological progression. One such process, epithelial to mesenchymal transition (EMT), if finely controlled could have significant potential i...
Conference Paper
Growing evidence suggests that physical microenvironments and mechanical stresses direct cell fate in developing tissues. However, how these physical properties affect morphogenesis remains unknown. We show here that ECM mechanical properties, i.e. stiffness, reproduced by using hydrogel, guide tissue morphogenesis in the developing lung bud. In pa...
Article
Full-text available
Applied forces and the biophysical nature of the cellular microenvironment play a central role in determining cellular behavior. Specifically, forces due to cell contraction are transmitted into structural ECM proteins and these forces are presumed to activate integrin "switches." The mechanism of such switches is thought to be the partial unfoldin...
Article
The mechanical properties of the extracellular matrix have recently been shown to promote myofibroblast differentiation and lung fibrosis. Mechanisms by which matrix stiffness regulates myofibroblast differentiation are not fully understood. The goal of this study was to determine the intrinsic mechanisms of mechanotransduction in the regulation of...
Article
Fibrin is an attractive material for regenerative medicine applications. It not only forms a polymer but also contains cryptic matrikines that are released upon its activation/degradation and enhance the regenerative process. Despite this advantageous biology associated with fibrin, commercially available systems (e.g. TISSEEL) display limited rege...
Article
Engineered polyethylene glycol-maleimide matrices for regenerative medicine exhibit improved reaction efficiency and a wider range of Young's moduli by utilizing maleimide cross-linking chemistry. This hydrogel chemistry is advantageous for cell delivery due to the mild reaction that occurs rapidly enough for in situ delivery, while easily lending...
Article
Current anticoagulants target coagulation Factors upstream from fibrin assembly and polymerization (i.e. formation of fibrin clot). While effective, this approach requires constant patient monitoring since pharmacokinetics and pharmacodynamics vary from patient to patient. To address these limitations, we developed an alternative anticoagulant that...
Chapter
Biomaterials offer discrete advantages over standard ECM systems, like matrigel, in the context of both fundamental stem cell biology and control of stem cell fate/phenotype. In particular, one can specifically design features into the 3D microenvironment with high levels of control. The fundamental limitation to date is that we currently lack the...
Article
The promise of biomaterials design for regenerative medicine tissue engineering is predicated on the fundamental ability to direct or guide specific and highly coordinated cellular behaviors that culminate in the creation of physiologically functional tissues and organs. To date, our efforts have focused primarily on the grafting and presentation o...
Article
Bridging of long peripheral nerve gaps remains a significant clinical challenge. Electrospun nanofibers have been used to direct and enhance neurite extension in vitro and in vivo. While it is well established that oriented fibers influence neurite outgrowth and Schwann cell migration, the mechanisms by which they influence these cells are still un...
Article
Fibrin is a widely used biological scaffold in tissue engineering and regenerative medicine. While the polymerization dynamics from its soluble precursor fibrinogen has been studied for decades, few attempts have been made to modulate fibrin network structure through the addition of external agents that actively engage this process. We propose the...
Article
Full-text available
The extracellular matrix (ECM) provides important cues for directing cell phenotype. Cells interact with underlying ECM through cell-surface receptors known as integrins, which bind to specific sequences on their ligands. During tissue development, repair, and regeneration of epithelial tissues, cells must interact with an interstitial fibronectin...
Article
Full-text available
Fibrin polymerizes via noncovalent and dynamic association of thrombin-exposed "knobs" with complementary "holes." Synthetic knob peptides have received significant interest as a means for understanding fibrin assembly mechanisms and inhibiting fibrin polymerization. Nevertheless, the inability to crystallize short peptides significantly limits our...
Chapter
By definition, biomaterials and tissue engineering materials aim to replace, restore, and/or regenerate tissue where disease or injury has caused irreparable damage to native tissue. However, mimicking the complexity of the in vivo milieu has proved to be a serious challenge for current biomaterials. For example, one common strategy involves incorp...
Article
Full-text available
We present a microfluidic cell culture array with unique versatility and parallelization for experimental trials requiring perfusion cultures. Specifically, we realize a rectangular chamber array in a PDMS device with three attributes: (i) continuous perfusion; (ii) flow paths that forbid cross-chamber contamination; and (iii) chamber shielding fro...
Conference Paper
Continuous perfusion during cell culture is desirable for greater control of the microenvironment, particularly when controlling for the effects of autocrine or paracrine signaling. Microfluidic devices are well-suited for continuous perfusion because they offer dramatic savings of reagents due to their small volumes. A variety of microfluidic cult...
Article
Engineering extracellular matrices that utilize the body's natural healing capacity enable the progression of regenerative therapies. Fibrin, widely used as a surgical sealant, is one such matrix that may be augmented by the addition of protein factors to promote cell infiltration and differentiation. The thrombin-catalyzed conversion of fibrinogen...
Article
Inflammation in the setting of interstitial lung disease (ILD) occurs in the distal alveolar spaces of the lung, which presents significant challenges for therapeutic delivery. The development of aerosolizable microparticles from non-immunogenic polymers is needed to enable the clinical translation of numerous experimental therapeutics that require...
Article
Full-text available
Directing specific, complex cell behaviors, such as differentiation, in response to biomaterials for regenerative medicine applications is, at present, a mostly unrealized goal. To date, current technological advances have been inspired by the reductionist point of view, focused on developing simple and merely adequate environments that facilitate...
Article
A recent study by Hermosilla et al. [T. Hermosilla, D. Munoz, R. Herrera-Molina, A. Valdivia, N. Munoz, S.U. Nham, P. Schneider, K. Burridge, A.F. Quest, L. Leyton, Direct Thy-1/alphaVbeta3 integrin interaction mediates neuron to astrocyte communication, Biochim Biophys Acta 1783 (2008) 1111–1120] demonstrates that Thy-1 on neurons binds to αvβ3 in...
Article
The extracellular matrix (ECM) exerts powerful control over many cellular phenomena, including stem cell differentiation. As such, design and modulation of ECM analogs to ligate specific integrin is a promising approach to control cellular processes in vitro and in vivo for regenerative medicine strategies. Although fibronectin (FN), a crucial ECM...
Article
Secreted protein acidic and rich in cysteine (SPARC) regulates cell-extracellular matrix interactions that influence cell adhesion and migration. We have demonstrated that SPARC is highly expressed in human gliomas, and it promotes brain tumor invasion in vitro and in vivo. To further our understanding regarding SPARC function in glioma migration,...

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