Browsing by Subject "Hydrogel"

Now showing 1 - 5 of 5
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    Combinational treatment approach for traumatic spinal cord injury
    (2016-03-02) Walker, Melissa J.; Xu, Xiao-Ming
    Spinal cord injury (SCI) is devastating and debilitating, and currently no effective treatments exist. Approximately, 12,000 new cases of SCI occur annually in the United States alone. The central nervous system has very low repair capability after injury, due to the toxic environment in the injured tissue. After spinal cord trauma, ruptured blood vessels cause neighboring cells and tissues to be deprived of oxygen and nutrients, and result in the accumulation of carbon dioxide and waste. New blood vessels form spontaneously after SCI, but then retract as the injured tissue forms a cavity. Thus, the newly formed vasculature likely retracts because it lacks a structural support matrix to extend across the lesion. Currently, in the field of spinal cord injury, combinational treatment approaches appear to hold the greatest therapeutic potential. Therefore, the aim of these studies was to transplant a novel, non-immunogenic, bioengineered hydrogel, into the injured spinal cord to serve as both a structural scaffold (for blood vessels, axons, and astrocytic processes), as well as a functional matrix with a time-controlled release of growth factors (Vascular endothelial growth factor, VEGF; Glial cell line-derived neurotrophic factor, GDNF). The benefit of this hydrogel is that it remains liquid at cooler temperatures, gels to conform to the space surrounding it at body temperature, and was designed to have a similar tensile strength as spinal cord tissue. This is advantageous due to the non-uniformity of lesion cavities following contusive spinal cord injury. Hydrogel alone and combinational treatment groups significantly improved several measures of functional recovery and showed modest histological improvements, yet did not provoke any increased sensitivity to a thermal stimulus. Collectively, these findings suggest that with further investigation, hydrogel along with a combination of growth factors might be a useful therapeutic approach for repairing the injured spinal cord.
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    Dynamic Control of Hydrogel Properties via Enzymatic Reactions
    (2019-05) Moore, Dustin M.; Lin, Chien-Chi; Xie, Dong; Li, Jiliang
    Dynamic changes to the extracellular matrix (ECM) impact many cell fate pro- cesses. The ECM can experience changes in sti ness as well as changes in composi- tion in response to injury, development, and diseases. To better understand the role that these dynamic processes have on the cells residing within the environment, re- searchers have turned towards 4-dimensional (4D) hydrogel designs. These 4D hydro- gels re-capitulate not only 3-dimensional (3D) matrix architectures, but also temporal changes in the physicochemical properties. The goal of this thesis was to design a unify chemistry (i.e., Sortase A (SrtA)-mediated transpeptidation) for dynamic tun- ing hydrogel sti ness and the presence of bioactive ligands. The rst objective was to establish a tunable and cytocompatible enzymatic scheme for softening cell-laden hydrogels. Brie y, the e ects of SrtA-mediated matrix cleavage were investigated us- ing poly(ethylene glycol) (PEG)-peptide hydrogels crosslinked by SrtA-sensitive and insensitive peptides. Initially, the e ects of various parameters with respect to cat- alytic reactions of SrtA were characterized rheologically, including enzyme and sub- strate concentrations, macromer content, peptide composition, and treatment time. Gel moduli pre- and post-enzyme treatment were measured to verify SrtA-mediated hydrogel softening. The cytocompatibility of SrtA-mediated gel softening system was investigated using human mesenchymal stem cell (hMSC). Upon treatment with SrtA and an oligoglycine substrate, encapsulated hMSCs exhibited extensive spreading in comparison to those within statically sti matrices. The second objective was to es- tablish a reversible ligand exchange system utilizing SrtA-mediated transpeptidation. SrtA-sensitive pendant ligands were immobilized within PEG hydrogels, which were treated with SrtA and an oligoglycine substrate to a ord tunable removal of the pen- dant ligand. Through measurement of the liberated pendant peptide concentration, it was found that higher concentrations of SrtA or extending treatment times led to higher ligand removal e ciency. Finally, the e ect of peptide ligand removal on cell behaviors were evaluated using NIH 3T3 broblasts. Fibroblasts were culture both on and within hydrogels containing SrtA-cleavable cell adhesion peptide. After treatment, both conditions led to a decrease in broblast spreading in comparison to non-treated gels. Overall, the utility of SrtA as versatile agent for controlling the mechanical properties and the presence of biologically active components within a hydrogel system was demonstrated. These systems could be further explored with natural-based materials to better mimic the physiological environment experienced by cells.
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    Immunotherapy with Injectable Hydrogels to Treat Obstructive Nephropathy
    (Wiley, 2014-07) Soranno, Danielle E.; Lu, Hoang D.; Weber, Heather M.; Rai, Reena; Burdick, Jason A.; Pediatrics, School of Medicine
    Hydrogels are gaining attention as injectable vehicles for delivery of therapeutics for a range of applications. We describe self-assembling and injectable Dock-and-Lock hydrogels for local delivery of interleukin-10 (IL-10) to abate the progression of inflammation and fibrosis that leads to chronic kidney disease. As monitored with a fluorescent tag, hydrogels degraded within a few days in vitro and matched IL-10 release profiles; however, hydrogels remained in the kidney for up to 30 days in vivo. A unilateral ureteral obstruction (UUO) mouse model was used to investigate in vivo outcomes after hydrogel injection and IL-10 delivery. Eight groups were investigated (7, 21, 35 days, n = 4): healthy, sham, healthy injected with mouse serum albumin (MSA), healthy + hydrogel, UUO, UUO + IL-10, UUO + hydrogel, UUO + hydrogel/IL-10. 15 μL of IL-10, hydrogel, or hydrogel/IL-10 was injected under the renal capsule 3 days after the UUO. Immunohistochemistry (IHC) was performed on paraffin sections to identify macrophages and apoptotic cells and trichrome staining was used to evaluate fibrosis. There were no significant differences in inflammatory markers between all control groups. With hydrogel delivery, macrophage infiltration and apoptosis were significantly reduced at days 21 and 35 compared to untreated animals. By day 35, IL-10 delivery via hydrogel reduced macrophage infiltration and apoptosis more than IL-10 injection alone. Fibrosis was decreased by day 35 in all treatment groups. This work supports the use of hydrogel delivery of IL-10 to treat chronic kidney disease.
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    Integrative Click Chemistry for Tuning Physicochemical Properties of Cancer Cell-Laden Hydrogels
    (2020-05) Johnson, Hunter C.; Lin, Chien-Chi; Naumann, Christoph; Na, Sungsoo
    The pancreas is a vital organ that secretes key metabolic hormones and digestive enzymes. In pancreatic ductal adenocarcinoma (PDAC), one of the leading causes of cancer-related death in the world, limited advances in diagnosis or therapies have been made over decades. Key features of PDAC progression include an elevated matrix sti ness and an increased deposition of extracellular matrices (ECM), such as hyaluronic acid (HA). Understanding how cells interact with components in the tumor microenvironment (TME) as PDAC progresses can assist in developing diagnostic tools and therapeutic treatment options. In recent years, hydrogels have proven to be an excellent platform for studying cell-cell and cell-matrix interactions. Utilizing chemically modi ed and naturally derived materials, hydrogel networks can be formed to encompass not only the components, but also the physicochemical properties of the dynamic TME. In this work, a dynamic hydrogel system that integrates multiple click chemistries was developed for tuning matrix physicochemical properties in a manner similar to the temporally increased matrix sti ness and depositions of HA. Subsequently, these dynamic hydrogels were used to investigate how matrix sti ening and increased HA presentation might a ect survival of PDAC cells and their response to chemotherapeutics.
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    Modular and adaptable tumor niche prepared from visible light-initiated thiol-norbornene photopolymerization
    (American Chemical Society, 2016-12-12) Shih, Han; Greene, Tanja; Korc, Murray; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and Technology
    Photopolymerized biomimetic hydrogels with adaptable properties have been widely used for cell and tissue engineering applications. As a widely adopted gel crosslinking method, photopolymerization provides experimenters on-demand and spatial-temporal controls in gelation kinetics. Long wavelength ultraviolet (UV) light initiated photopolymerization is among the most popular methods in the fabrication of cell-laden hydrogels owing to its rapid and relatively mild gelation conditions. The use of UV light, however, still causes concerns regarding its potential negative impacts on cells. Alternatively, visible light based photopolymerization can be used to crosslink cell-laden hydrogels. The majority of visible light based gelation schemes involve photoinitiator, co-initiator, and co-monomer. This multi-component initiation system creates added challenges for optimizing hydrogel formulations. Here, we report a co-initiator/co-monomer-free visible light initiated thiol-norbornene photopolymerization scheme to prepare modular biomimetic hydrogels suitable for in situ cell encapsulation. Eosin-Y was used as the sole initiator to initiate modular gelation between synthetic macromers (e.g., thiolated poly(vinyl alcohol) or poly(ethylene glycol)) and functionalized extracellular matrices (ECM), including norbornene-functionalized gelatin (GelNB) and/or thiolated hyaluronic acid (THA). These components are modularly crosslinked to afford bio-inert (i.e., purely synthetic), bioactive (i.e., using gelatin), and biomimetic (i.e., using gelatin and hyaluronic acid) hydrogels. The stiffness of the hydrogels can be easily tuned without affecting the contents of the bioactive components. Furthermore, the use of naturally-derived biomacromolecules (e.g., gelatin and HA) renders these hydrogels susceptible to enzyme-mediated degradation. In addition to demonstrating efficient and tunable visible light mediated gelation, we also utilized this biomimetic modular gelation system to formulate artificial tumor niche and to study the effects of cell density and gel modulus on the formation of pancreatic ductal adenocarcinoma (PDAC) spheroids.,