Matching Items (32)

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Biomaterial Approaches for Stem Cell-Based Myocardial Tissue Engineering

Description

Adult and pluripotent stem cells represent a ready supply of cellular raw materials that can be used to generate the functionally mature cells needed to replace damaged or diseased heart

Adult and pluripotent stem cells represent a ready supply of cellular raw materials that can be used to generate the functionally mature cells needed to replace damaged or diseased heart tissue. However, the use of stem cells for cardiac regenerative therapies is limited by the low efficiency by which stem cells are differentiated in vitro to cardiac lineages as well as the inability to effectively deliver stem cells and their derivatives to regions of damaged myocardium. In this review, we discuss the various biomaterial-based approaches that are being implemented to direct stem cell fate both in vitro and in vivo. First, we discuss the stem cell types available for cardiac repair and the engineering of naturally and synthetically derived biomaterials to direct their in vitro differentiation to the cell types that comprise heart tissue. Next, we describe biomaterial-based approaches that are being implemented to enhance the in vivo integration and differentiation of stem cells delivered to areas of cardiac damage. Finally, we present emerging trends of using stem cell-based biomaterial approaches to deliver pro-survival factors and fully vascularized tissue to the damaged and diseased cardiac tissue.

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Date Created
  • 2015-06-01

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Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment

Description

In this study, to model 3D chemotactic tumor-stroma invasion in vitro, we developed an innovative microfluidic chip allowing side-by-side positioning of 3D hydrogel-based matrices. We were able to (1) create

In this study, to model 3D chemotactic tumor-stroma invasion in vitro, we developed an innovative microfluidic chip allowing side-by-side positioning of 3D hydrogel-based matrices. We were able to (1) create a dual matrix architecture that extended in a continuous manner, thus allowing invasion from one 3D matrix to another, and (2) establish distinct regions of tumor and stroma cell/ECM compositions, with a clearly demarcated tumor invasion front, thus allowing us to quantitatively analyze progression of cancer cells into the stroma at a tissue or single-cell level. We showed significantly enhanced cancer cell invasion in response to a transient gradient of epidermal growth factor (EGF). 3D tracking at the single-cell level displayed increased migration speed and persistence. Subsequently, we analyzed changes in expression of EGF receptors, cell aspect ratio, and protrusive activity. These findings show the unique ability of our model to quantitatively analyze 3D chemotactic invasion, both globally by tracking the progression of the invasion front, and at the single-cell level by examining changes in cellular behavior and morphology using high-resolution imaging. Taken together, we have shown a novel model recapitulating 3D tumor-stroma interactions for studies of real-time cell invasion and morphological changes within a single platform.

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Date Created
  • 2016-09-28

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UTILIZING A NOVEL 3D BREAST TUMOR MODEL TO STUDY COMBINATORIAL DRUG TREATMENT EFFICACY

Description

Stromal cells play an important role in facilitating disease progression of ductal carcinoma. Cancer associated fibroblasts (CAFs) are an important component of the extracellular matrix (ECM) which constitutes the microenvironment

Stromal cells play an important role in facilitating disease progression of ductal carcinoma. Cancer associated fibroblasts (CAFs) are an important component of the extracellular matrix (ECM) which constitutes the microenvironment of breast tumor cells. They are known to participate in chemotherapeutic drug resistance by modulating various biochemical and biophysical factors that contribute to increased matrix stiffness and collagen I density of the tumor-adjacent stroma. To address these issues in terms of patient treatment, anti-cancer drug regimes have been assembled to incorporate both chemotherapeutic as well as anti-fibrotic drugs to both target tumor cells while also diminishing the elastic modulus of the microenvironment by targeting CAFs. The quantitative assessment of these drug regimes on tumor progression is missing in terms of CAFs role alone.

A high density 3D tumor model was utilized to recapitulate the tumor microenvironment of ductal carcinoma in vitro. The tumor model consisted of MDA-MB-231 tumors seeded within micromolded collagen wells, chemically immobilized upon a surface treated PDMS substrate. CAFs were seeded within the greater collagen structure from which the microwells were formed. The combinatorial effect of anti-fibrotic drug (Tranilast) and chemotherapy drug (Doxorubicin) were studied within 3D co culture conditions. Specifically, the combinatorial effects of the drugs on tumor cell viability, proliferation, and invasion were examined dynamically upon coculture with CAFs using the microengineered model.

The results of the study showed that the combinatorial effects of Tranilast and Doxorubicin significantly decreased the proliferative ability of tumor cells, in addition to significantly decreasing the ability of tumor cells to remain viable and invade their surrounding stroma, compared to control conditions.

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Date Created
  • 2019-05

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Structure-function study of N-isopropylacrylamide copolymers with enzyme degradable GAPGLF and GAPGLL side chains

Description

With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such

With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending on the conditions in which polymers are used, they are modified to accommodate a specific need. For instance, polymers used in drug delivery are more efficient if they are biodegradable. This ensures that the delivery system does not remain in the body after releasing the drug. It is therefore crucial that the polymer used in the drug system possess biodegradable properties. Such modification can be done in different ways including the use of peptides to make copolymers that will degrade in the presence of enzymes. In this work, we studied the effect of a polypeptide GAPGLL on the polymer NIPAAm and compare with the previously studied Poly(NIPAAm-co-GAPGLF). Both copolymers Poly(NIPAAm-co-GAPGLL) were first synthesized from Poly(NIPAAm-co-NASI) through nucleophilic substitution by the two peptides. The synthesis of these copolymers was confirmed by 1H NMR spectra and through cloud point measurement, the corresponding LCST was determined. Both copolymers were degraded by collagenase enzyme at 25 ° C and their 1H NMR spectra confirmed this process. Both copolymers were cleaved by collagenase, leading to an increase in solubility which yielded a higher LCST compared to before enzyme degradation. Future studies will focus on evaluating other peptides and also using other techniques such as Differential Scanning Microcalorimetry (DSC) to better observe the LCST behavior. Moreover, enzyme kinetics studies is also crucial to evaluate how fast the enzyme degrades each of the copolymers.

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Created

Date Created
  • 2018-05

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Engineering 3D Breast Tumor Model for Studying Tumor Stromal Interactions

Description

The objective of this research was to create a 3D in vitro model to mimic the native breast tumor microenvironment. Polydimethylsiloxane (PDMS) stamps and micromolding techniques were utilized to develo

The objective of this research was to create a 3D in vitro model to mimic the native breast tumor microenvironment. Polydimethylsiloxane (PDMS) stamps and micromolding techniques were utilized to develop collagen based 3D tumor model. Geometrical design was optimized for the PDMS stamp to compartmentalize the tumor and stromal region of the 3D model. Addition of tumor and stromal cells into the platform further demonstrated the successful fabrication of the 3D model which will be used to investigate the role of stromal components on tumor growth and progression. Atomic force microscopy will also be utilized to access stromal remodeling during active invasion.

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Created

Date Created
  • 2017-05

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Advanced biomaterials and microengineering technologies to recapitulate the stepwise process of cancer metastasis

Description

Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains

Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions.

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Created

Date Created
  • 2017-05

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In Cell Western Blotting for Quantifying Protein Expression in 3D Tumor-Stroma Microfluidic Device

Description

After more than 40 years since the signing of the National Cancer Act in 1970, cancer remains a formidable challenge. Cancer is currently the second most common cause of death

After more than 40 years since the signing of the National Cancer Act in 1970, cancer remains a formidable challenge. Cancer is currently the second most common cause of death in the United States, and worldwide cancer cases are projected to rise 50% between 2012 and 2030 [1-2]. While researchers have dramatically expanded our understanding of the biology of cancer, they have also revealed the staggering complexity and difficulty of developing successful treatments for the disease. More complex assays involving three dimensional cell culture offer the potential to model complex interactions, such as those involving the extracellular matrix (ECM), chemical concentration gradients, and the impact of vascularization of a tissue mass. Modern cancer assays thus promise to be both more accurate and more complex than previous models. One promising newly developed type of assay is microfluidics. Microfluidic devices consist of a silicone polymer stamp bonded to a glass slide. The stamp is patterned to produce a network of channels for cell culture. These devices allow manipulation of liquids on a sub-millimeter level, allowing researchers to produce a tightly controlled 3D microenvironment for cell culture. Our lab previously developed a microfluidic device to measure cancer cell invasion in response to a variety of signals and conditions. The small volume associated with microfluidics offers a number of advantages, but simultaneously make it impractical to use certain traditional cell analysis procedures, such as Western Blotting. As a result, measuring protein expression of cells in the microfluidic device was a continuing challenge. In order to expand the utility of microfluidic devices, it was therefore very enticing to develop a means of measuring protein expression inside the device. One possible solution was identified in the technique of In-Cell-Western blotting (ICW). ICW consists of using infrared-fluorescently stained antibodies to stain a protein of interest. This signal is measured using an infrared laser scanner, producing images that can be analyzed to quantitatively measure protein expression. ICW has been well validated in traditional 2D plate culture conditions, but has not been applied in conjunction with microfluidic devices. This project worked to evaluate In-Cell-Western blotting for use in microfluidic devices as a method of quantifying protein expression in situ.

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Agent

Created

Date Created
  • 2018-05

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Electrically Conductive Hydrogel-Based Topographies for Development of Three Dimensional (3D) Cardiac Tissues

Description

Cardiac tissue engineering is an emerging field that has the potential to regenerate and repair damaged cardiac tissues after myocardial infarction. Numerous studies have introduced hydrogel-based cardiac tissue constructs featuring

Cardiac tissue engineering is an emerging field that has the potential to regenerate and repair damaged cardiac tissues after myocardial infarction. Numerous studies have introduced hydrogel-based cardiac tissue constructs featuring suitable microenvironments for cell growth along with precise surface topographies for directed cell organization. Despite significant progress, previously developed cardiac tissue constructs have suffered from electrically insulated matrices and low cell retention. To address these drawbacks, we fabricated micropatterned hybrid hydrogel constructs (uniaxial microgrooves with 50 µm with) using a photocrosslinkable gelatin methacrylate (GelMA) hydrogel incorporated with gold nanorods (GNRs). The electrical impedance results revealed a lower impedance in the GelMA-GNR constructs versus the pure GelMA constructs. Superior electrical conductivity of GelMA-GNR hydrogels (due to incorporation of GNRs) enabled the hybrid tissue constructs to be externally stimulated using a pulse generator. Furthermore, GelMA-GNR tissue hydrogels were tested to investigate the biological characteristics of cultured cardiomyocytes. The F-actin fiber analysis results (area coverage and alignment indices) revealed higher directed (uniaxial) cytoskeleton organization of cardiac cells cultured on the GelMA-GNR hydrogel constructs in comparison to pure GelMA. Considerable increase in the coverage area of cardiac-specific markers (sarcomeric α-actinin and connexin 43) were observed on the GelMA-GNR hybrid constructs compared to pure GelMA hydrogels. Despite substantial dissimilarities in cell organization, both pure GelMA and hybrid GelMA-GNR hydrogel constructs provided a suitable microenvironment for synchronous beating of cardiomyocytes.

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Date Created
  • 2016-05

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Determining GPNMB Abundance Effects on Breast Cancer-Stroma Interactions

Description

Tumor-stroma interactions significantly influence cancer cell metastasis and disease progression. These interactions partly comprise crosstalk between tumor and stromal fibroblasts, but the key molecular mechanisms within the crosstalk governing cancer

Tumor-stroma interactions significantly influence cancer cell metastasis and disease progression. These interactions partly comprise crosstalk between tumor and stromal fibroblasts, but the key molecular mechanisms within the crosstalk governing cancer invasion are still unclear. Here we develop a 3D in vitro organotypic microfluidic to model tumor-stroma interaction by mimicking the spatial organization of the tumor microenvironment on a chip. We co-culture breast cancer and patient-derived fibroblast cells in 3D tumor and stroma regions respectively and combine functional assessments, including cancer cell migration, with transcriptome profiling to unveil the molecular influence of tumor-stroma crosstalk on invasion. This led to the observation that cancer associated fibroblasts enhanced invasion in 3D by inducing the expression of a novel gene of interest, GPNMB, in breast cancer cells resulting in increased migration speed. Importantly, knockdown of GPNMB blunted the influence of CAFs on enhancing cancer invasion. Overall, these results demonstrate the ability of our model to recapitulate patient specific tumor microenvironment to investigate cellular and molecular consequences of tumor-stroma interactions.

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Date Created
  • 2019-05

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Miniaturized Passive Hydrogel Check Valves for the Treatment of Hydrocephalic Fluid Retention

Description

BioMEMS has the potential to provide many future tools for life sciences, combined with microfabrication technologies and biomaterials. Especially due to the recent corona 19 epidemic, interest in BioMEMS technology

BioMEMS has the potential to provide many future tools for life sciences, combined with microfabrication technologies and biomaterials. Especially due to the recent corona 19 epidemic, interest in BioMEMS technology has increased significantly, and the related research has also grown significantly. The field with the highest demand for BioMEMS devices is in the medical field. In particular, the implantable device field is the largest sector where cutting-edge BioMEMS technology is applied along with nanotechnology, artificial intelligence, genetic engineering, etc. However, implantable devices used for brain diseases are still very limited because unlike other parts of human organs, the brain is still unknow area which cannot be completely replaceable.To date, the most commercially used, almost only, implantable device for the brain is a shunt system for the treatment of hydrocephalus. The current cerebrospinal fluid (CSF) shunt treatment yields high failure rates: ~40% within first 2 years and 98% within 10 years. These failures lead to high hospital admission rates and repeated invasive surgical procedures, along with reduced quality of life. New treatments are needed to improve the disease burden associated with hydrocephalus. In this research, the proposed catheter-free, completely-passive miniaturized valve is designed to alleviate hydrocephalus at the originating site of the disorder and diminish failure mechanisms associated with current treatment methods. The valve is composed of hydrogel diaphragm structure and polymer or glass outer frame which are 100% bio-compatible material. The valve aims to be implanted between the sub-arachnoid space and the superior sagittal sinus to regulate the CSF flow substituting for the obstructed arachnoid granulations.
A cardiac pacemaker is one of the longest and most widely used implantable devices and the wireless technology is the most widely used with it for easy acquisition of vital signs and rapid disease diagnosis without clinical surgery. But the conventional pacemakers with some wireless technology face some essential complications associated with finite battery life, ultra-vein pacing leads, and risk of infection from device pockets and leads. To solve these problems, wireless cardiac pacemaker operating in fully-passive modality is proposed and demonstrates the promising potential by realizing a prototype and functional evaluating.

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Agent

Created

Date Created
  • 2020