Matching Items (5)
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- All Subjects: Tissue Engineering
- Creators: Fumasi, Fallon
- Creators: Smith, Barbara
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 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.
ContributorsMoore, Nathan Allen (Author) / Nikkhah, Mehdi (Thesis director) / Smith, Barbara (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Breast cancer cell invasion is a highly orchestrated process driven by a myriad of complex microenvironmental stimuli. These complexities make it difficult to isolate and assess the effects of specific parameters including matrix stiffness and tumor architecture on disease progression. In this regard, morphologically accurate tumor models are becoming instrumental to perform fundamental studies on cancer cell invasion within well-controlled conditions. In this study, the use of photocrosslinkable hydrogels and a novel, two-step photolithography technique was explored to microengineer a 3D breast tumor model. The microfabrication process presented herein enabled precise localization of the cells and creation of high stiffness constructs adjacent to a low stiffness matrix. To validate the model, breast cancer cell lines (MDA-MB-231, MCF7) and normal mammary epithelial cells (MCF10A) were embedded separately within the tumor model and cellular proliferation, migration and cytoskeletal organization were assessed. Proliferation of metastatic MDA-MB-231 cells was significantly higher than tumorigenic MCF7 and normal mammary MCF10A cells. MDA-MB-231 exhibited highly migratory behavior and invaded the surrounding matrix, whereas MCF7 or MCF10A cells formed clusters that were confined within the micropatterned circular features. F-actin staining revealed unique 3D protrusions in MDA-MB-231 cells as they migrated throughout the surrounding matrix. Alternatively, there were abundance of 3D clusters formed by MCF7 and MCF10A cells. The results revealed that gelatin methacrylate (GelMA) hydrogel, integrated with the two-step photolithography technique, has great promise in creating 3D tumor models with well-defined features and tunable stiffness for detailed studies on cancer cell invasion and drug responsiveness.
ContributorsSam, Feba Susan (Author) / Nikkhah, Mehdi (Thesis advisor) / Ros, Robert (Committee member) / Smith, Barbara (Committee member) / Arizona State University (Publisher)
Created2015
Description
The tendon-bone junction is essential for allowing humans to transfer mechanical loads during activities. When injury does occur to this important area, current surgical techniques improperly bypass important physical and chemical gradients and do not restore proper function. It is essential to create tissue engineered scaffolds that create proper models for the region and induce healing responses for repair. To advance research into these scaffolds, electrospinning fibers and hydrogels made of norbornene functionalized hyaluronic acid (NorHA) were used to promote bone growth by adhering calcium to the material. To further improve calcium adherence, which is indicative of bone regions, a mineralization peptide was allowed to soak through the fibers. NorHA proved to be a suitable material for biomineralization experiments, showing slow calcium adherence within the first hour before accelerating in adherence over 24 hours in both fibers and hydrogels. When the mineralization peptide was implemented calcium adherence on fibers increased nearly eight times within the first 15 minutes of experimentation.
ContributorsCasey, Nathan Robert (Author) / Holloway, Julianne (Thesis director) / Tindell, Raymond (Committee member) / Fumasi, Fallon (Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Tissue engineering is an emerging field focused on the repair, replacement, and regeneration of damaged tissue. Engineered tissue consists of three factors: cells, biomolecular signals, and a scaffold. Cell-free scaffolds present a unique opportunity to develop highly specific microenvironments with tunable properties. Norbornene-functionalized hyaluronic acid (NorHA) hydrogels provide spatial control over biomolecule binding through a photopolymerization process. With this, biomimetic gradients can be produced to model a variety of tissue interfaces. To produce these patterns, a gradient mechanism was developed to function in tandem with a syringe pump. A conversion equation was derived to calculate a panel speed from the volumetric flow rate setting on the pump. Seven speeds were used to produce fluorophore gradients on the surface of NorHA hydrogels to assess changes in the length and slope of the gradient. The results indicated a strong positive linear correlation between the speed of the panel and the length of the gradient as well as a strong negative correlation between the speed of the panel and the slope of the gradient. Additionally, the mechanism was able to successfully produce several other types of gradients including multiregional, dual, and triregional.
ContributorsSogge, Amber (Author) / Holloway, Julianne (Thesis director) / Stabenfeldt, Sarah (Committee member) / Fumasi, Fallon (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Patients with type 2 diabetes mellitus experience a slower healing process and poor osteointegration, making it difficult for them to heal properly after a bone fracture. This study aims to compare the proliferation and differentiation of human mesenchymal stromal cells at different glucose concentrations, as well as with an advanced glycated end-product (AGE) concentration, to mimic a healthy, prediabetic, and diabetic environment in an in vitro model over several experiments. Each experiment was composed of treatment groups in either growth or osteogenic media, with varying levels of glucose concentration or an advanced glycated end-product concentration. The treatment groups were cultured in 24 well plates over 28 days with staining of FITC-maleimide, DAPI, or alkaline phosphatase conducted at varying time points. The plates were imaged, then analyzed in ImageJ and GraphPad Prism. The study supports that at 28 days in culture, the more glucose added to osteogenic media treatment groups, the lower the nuclear count. At 14 days the same is true of growth media treatment groups, though the trend does not persist until 28 days. It does not seem that cell surface area of osteogenic groups, and growth media treatment groups was affected by glucose level. At 14 days, the alkaline phosphatase expression was unaffected by glucose level. However, at the 28 day time point the higher the glucose level of osteogenic treatment groups, the less expression of alkaline phosphatase. The effect of the added AGE concentration on hMSC osteogenesis was inconclusive. Overall, this study enhanced understanding of the role that glucose and AGEs play in the bone healing process for diabetic patients, allowing for future improvements of biomaterials and engineered tissue.
ContributorsMoya, Adriana Allyssa (Author) / Holloway, Julianne (Thesis director) / Fumasi, Fallon (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05