- Browse by Subject
Browsing by Subject "hydrogels"
Now showing 1 - 6 of 6
Results Per Page
ItemComparative study of visible light polymerized gelatin hydrogels for 3D culture of hepatic progenitor cells(Wiley, 2017-03) Greene, Tanja; Lin, Tsai-Yu; Andrisani, Oaurania M.; Lin, Chien-Chi; Department of Biomedical Engineering, School of Engineering and TechnologyPhotopolymerization techniques have been widely used to create hydrogels for biomedical applications. Visible light-based photopolymerizations are commonly initiated by type II (i.e., noncleavage-type) photoinitiator in conjunction with a coinitiator. On the other hand, type I photoinitiators (i.e., cleavage type) are rarely compatible with visible light-based initiation due to their limited molar absorbability in the visible light wavelengths. Here, we report visible light initiated orthogonal photoclick crosslinking to fabricate gelatin-norbornene and poly(ethylene glycol)-tetra-thiol hydrogels using either cleavage-type (i.e., lithium acylphosphinate, LAP) or noncleavage-type photoinitiator (i.e., eosin-Y, EY) without the use of a coinitiator. Regardless of the initiator type, the step-growth gelatin-PEG hybrid hydrogels crosslinked and degraded similarly. While both systems exhibited similar cytocompatibility for hepatic progenitor HepaRG cells, gelation initiated by noncleavage-type initiator EY afforded slightly higher degree of hepatic gene expression. ItemDesigner hydrogels: Shedding light on the physical chemistry of the pancreatic cancer microenvironment(Elsevier, 2018-11) Lin, Chien-Chi; Korc, Murray; Biomedical Engineering, School of Engineering and TechnologyPancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer mortality in the United States, with a 5-year survival of ∼8%. PDAC is characterized by a dense and hypo-vascularized stroma consisting of proliferating cancer cells, cancer-associated fibroblasts, macrophages and immune cells, as well as excess matrices including collagens, fibronectin, and hyaluronic acid. In addition, PDAC has increased interstitial pressures and a hypoxic/acidic tumor microenvironment (TME) that impedes drug delivery and blocks cancer-directed immune mechanisms. In spite of increasing options in targeted therapy, PDAC has mostly remained treatment recalcitrant. Owing to its critical roles on governing PDAC progression and treatment outcome, TME and its interplay with the cancer cells are increasingly studied. In particular, three-dimensional (3D) hydrogels derived from or inspired by components in the TME are progressively developed. When properly designed, these hydrogels (e.g., Matrigel, collagen gel, hyaluronic acid-based, and semi-synthetic hydrogels) can provide pathophysiologically relevant compositions, conditions, and contexts for supporting PDAC cell fate processes. This review summarizes recent efforts in using 3D hydrogels for fundamental studies on cell-matrix or cell-cell interactions in PDAC. ItemHydrogel Models with Stiffness Gradients for Interrogating Pancreatic Cancer Cell Fate(MDPI, 2021-03) Chang, Chun-Yi; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and TechnologyPancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and has seen only modest improvements in patient survival rate over the past few decades. PDAC is highly aggressive and resistant to chemotherapy, owing to the presence of a dense and hypovascularized fibrotic tissue, which is composed of stromal cells and extracellular matrices. Increase deposition and crosslinking of matrices by stromal cells lead to a heterogeneous microenvironment that aids in PDAC development. In the past decade, various hydrogel-based, in vitro tumor models have been developed to mimic and recapitulate aspects of the tumor microenvironment in PDAC. Advances in hydrogel chemistry and engineering should provide a venue for discovering new insights regarding how matrix properties govern PDAC cell growth, migration, invasion, and drug resistance. These engineered hydrogels are ideal for understanding how variation in matrix properties contributes to the progressiveness of cancer cells, including durotaxis, the directional migration of cells in response to a stiffness gradient. This review surveys the various hydrogel-based, in vitro tumor models and the methods to generate gradient stiffness for studying migration and other cancer cell fate processes in PDAC. ItemIn situ formation of silk-gelatin hybrid hydrogels for affinity-based growth factor sequestration and release(RSC, 2016) Bragg, John C.; Kweon, HaeYong; Jo, You-Young; Lee, Kwang Gill; Lin, Chien-Chi; Department of Biomedical Engineering, School of Engineering and TechnologySilk fibroin (SF) and gelatin are natural polymers suitable for biomedical applications, including controlled protein release. SF offers high mechanical strength and slow enzymatic degradability, whereas gelatin contains bioactive motifs that can provide biomimicry to the resulting scaffolds. Owing to their complementary material properties, SF and gelatin are increasingly being used together to afford hybrid scaffolds with adjustable properties. Here, we report the use of in situ crosslinked SF/gelatin hydrogels as a platform for tunable growth factor sequestration and delivery. We demonstrate that the physical assembly of SF into insoluble networks could be accelerated by sonication even in the presence of gelatin. However, the processing conditions from which to prepare SF aqueous solution (e.g., heating duration and number of processing steps) drastically altered the resulting hydrogel physical properties. Furthermore, the stiffness of SF/gelatin hybrid gels displayed temperature dependency. Specifically, incorporation of gelatin increased gel stiffness at 25 °C but decreases hydrogel mechanical stability at 37 °C. The thermostability of SF/gelatin gels can be restored by using a low concentration of genipin, a naturally derived chemical crosslinker. We also incorporate heparin-conjugated gelatin (GH) into the hydrogels to create a hybrid matrix capable of sequestering growth factors, such as basic fibroblast growth factor (bFGF). Both sonicated SF (SSF) and hybrid SSF-GH gels exhibit moderate bFGF sequestration, but only SSF-GH gels afford slow release of bFGF. On the other hand, genipin-stabilized network exhibited the highest retention and sustained release of bFGF, suggesting the suitability of this particular formulation as a scaffold for tissue engineering applications. ItemOrthogonal enzymatic reactions for rapid crosslinking and dynamic tuning of PEG–peptide hydrogels(RSC, 2017-11) Arkenberg, Matthew R.; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and TechnologyStiffening of the extracellular matrix is a hallmark in cancer progression, embryonic development, and wound healing. To mimic this dynamic process, our work explored orthogonal enzymatic reactions capable of modulating the properties of poly(ethylene glycol) (PEG)–peptide hydrogels. A hepta-mutant bacterial transpeptidase sortase A (SrtA7M) was used to ligate two PEG–peptide macromers (i.e., PEG-YLPRTG and NH2-GGGG-PEG) into a primary hydrogel network. The hydrogels were dynamically stiffened using mushroom tyrosinase (MT), which oxidized tyrosine residues into di-tyrosine and led to increased matrix stiffness. After confirming the expression and enhanced catalytic activity of SrtA7M, we investigated the cytocompatibility of the enzymatic reaction with a mouse insulinoma cell line, MIN6. In addition, we altered peptide substrate concentrations and evaluated their influence on primary hydrogel network properties and MT-triggered stiffening. Using a pancreatic cancer cell line, COLO-357, the effect of MT-triggered stiffening on spheroid formation was investigated. We found that cell spheroids formed in hydrogels that were exposed to MT were significantly smaller than spheroids formed without MT incubation, suggesting that matrix stiffening played a crucial role in the sizes of cancer cell spheroids. Through utilizing highly specific and orthogonal enzymatic reactions, this hydrogel platform permits rapid and mild in situ cell encapsulation, as well as dynamic control of matrix stiffness for investigating the role of matrix stiffening on cell fate processes. ItemVisible light cured thiol-vinyl hydrogels with tunable degradation for 3D cell culture(Elsevier B.V., 2014-01) Hao, Yiting; Shih, Han; Muňoz, Zachary; Kemp, Arika; Lin, Chien-Chi; Department of Biomedical Engineering, School of Engineering and TechnologyWe report here a synthetically simple yet highly tunable and diverse visible light mediated thiol- vinyl gelation system for fabricating cell-instructive hydrogels. Gelation was achieved via a mixed-mode step-and-chain-growth photopolymerization using functionalized 4-arm poly(ethylene glycol) as backbone macromer, eosin-Y as photosensitizer, and di-thiol containing molecule as dual purpose co-initiator/cross-linker. N-vinylpyrrolidone (NVP) was used to accelerate gelation kinetics and to adjust the stiffness of the hydrogels. Visible light (wavelength: 400–700nm) was used to initiate rapid gelation (gel points: ~20 seconds) that reached completion within a few minutes. The major differences between current thiol-vinyl gelation and prior visible light mediated photopolymerization are that: (1) the co-initiator triethanolamine (TEOA) used in the previous systems was replaced with multifunctional thiols and (2) mixed-mode polymerized gels contain less network heterogeneity. The gelation kinetics and gel properties at the same PEG macromer concentration could be tuned by changing the identity of vinyl groups and di-thiol cross-linkers, as well as concentration of cross-linker and NVP. Specifically, acrylate-modified PEG afforded the fastest gelation rate, followed by acrylamide and methacrylate-functionalized PEG. Increasing NVP concentration also accelerated gelation and led to a higher network cross- linking density. Further, increasing di-thiol peptide concentration in the gel formulation increased hydrogel swelling and decreased gel stiffness. Due to the formation of thiol-ether-ester bonds following thiol-acrylate reaction, the gels degraded hydrolytically following a pseudo first order degradation kinetics. Degradation rate was controlled by adjusting thiol or NVP content in the polymer precursor solution. The cytocompatibility and utility of this hydrogel system were evaluated using in situ encapsulation of human mesenchymal stem cells (hMSC). Encapsulated hMSCs remained alive (>90%) throughout the duration of the study and the cells were differentiated down osteogenic lineage with varying degrees by controlling the rate and mode of gel degradation.