Browsing by Subject "Hydrogel"

Now showing 1 - 6 of 6
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    3D Printed Functional Materials and Devices and Applications in AI-powered 3D Printing on Moving Freeform Surfaces
    (2020-08) Zhu, Zhijie
    The capability of 3D printing a diverse palette of functional inks will enable the mass democratization of manufactured patient-specific wearable devices and smart biomedical implants for applications such as health monitoring and regenerative biomedicines. These personalized wearables could be fabricated via in situ printing --- direct printing of 3D constructs on the target surfaces --- at ease of the conventional fabricate-then-transfer procedure. This new 3D printing technology requires functional (e.g., conductive and viscoelastic) inks and devices (e.g., wearable and implantable sensors) that are compatible with in situ printing, as well as the assistance of artificial intelligence (AI) to sense, adapt, and predict the state of the printing environment, such as a moving hand and a dynamically morphing organ. To advance this in situ printing technology, this thesis work is focused on (1) the development of functional materials and devices for 3D printing, and (2) the AI-assisted 3D printing system. To extend the palette of 3D printable materials and devices, on-skin printable silver conductive inks, hydrogel-based deformable sensors, and transparent electrocorticography sensors were developed. As with the AI for in situ 3D printing, solutions for four types of scenarios were studied (with complexity from low to high): (1) printing on static, planar substrates without AI intervention, with a demonstration of fully printed electrocorticography sensors for implantation in mice; (2) printing on static, non-planar parts with open-loop AI, with a demonstration of printing viscoelastic dampers on hard drives to eliminate specific modes of vibration; (3) printing on moving targets with closed-loop and predictive AI, with demonstrations of printing wearable electronics on a human hand and depositing cell-laden bio-inks on live mice; (4) printing on deformable targets with closed-loop and predictive AI, with demonstrations of printing a hydrogel sensor on a breathing lung and multi-material printing on a phantom face. We anticipate that this convergence of AI, 3D printing, functional materials, and personalized biomedical devices will lead to a compelling future for on-the-scene autonomous medical care and smart manufacturing.
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    Design of Silica-Collagen Nanocomposite for Corneal Replacement
    (2015-09) DiVito, Michael
    The cornea is the most commonly transplanted tissue in the United States. Globally, corneal diseases are the second leading cause of blindness. Due to strict FDA regulations, lack of eye banking facilities, and other factors which limit the supply of donor tissue, designing an artificial cornea made of readily available materials is of great interest. The synthetic constructs that are currently clinically available in the United States have had moderate success, but biocompatibility issues such as stromal melting and epithelial defects are still common. When considering a potential material for corneal replacement, it must meet the design criteria of the normal functioning cornea. The relevant design criteria can be broken down into three main groups: optical behavior, biomechanical properties, and biocompatibility. The presented work proposes silica-collagen nanocomposites as a viable candidate material to meet these design criteria. A bottom-up approach starting from the molecular level is utilized to modify the surface chemistry and physical properties of collagen fibrils. In doing so, methodologies are presented which allow for fine-tuning of optical, biomechanical, and biodegradation behavior. The first part of this work validates the theory that light scattering of collagen hydrogels is heavily dependent on the change in the material’s index of refraction over length scales comparable to the wavelength of incident light. This work shows that light scattering of collagen hydrogels can be minimized by a rapid neutralization technique, and by the addition of nanocrystalline cellulose. Additionally, collagen hydrogels with embedded magnetic nanowires can be polarized to form an aligned fibril microstructure and show an increase in light transmission. The second part of this thesis characterizes the mechanical and optical behavior, as well as the biocompatibility of silica-collagen nanocomposites. This work shows that a copolymerization method can be used to make implants which have improved biomechanical properties (when compared to pure collagen hydrogels) and can be re-epithelialized in an ex vivo rabbit model. Additionally, an improved two-step process for silica deposition onto collagen fibrils is presented. This new method shows that poly-L-lysine can be used to induce a uniform silica shell around collagen fibrils in the absence of large silica aggregates. This new method increases mechanical stiffness and enzymatic degradation resistance without producing any additional light scattering in the material. Silica-collagen nanocomposites show great potential in the context of corneal replacement. The methods developed and results presented here can be useful for improving any collagen-based corneal replacement, as well as in other applications such as drug delivery and silica nanoparticle templating.
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    Self-assembly of fibronectin mimetic peptide-amphiphile nanofibers.
    (2010-06) Rexeisen, Emilie Lynn
    Many therapeutic strategies incorporate peptides into their designs to mimic the natural protein ligands found in vivo. A few examples are the short peptide sequences RGD and PHSRN that mimic the primary and synergy-binding domains of the extracellular matrix protein, fibronectin, which is recognized by the cell surface receptor, α5β1 integrin. Even though scaffold modification with biomimetic peptides remains one of the most promising approaches for tissue engineering, the use of these peptides in therapeutic tissue-engineered products and drug delivery systems available on the commercial market is limited because the peptides are not easily able to mimic the natural protein. The design of a peptide that can effectively target the α5β1 integrin would greatly increase biomimetic scaffold therapeutic potential. A novel peptide containing both the RGD primary binding domain and PHSRN synergy-binding domain for fibronectin joined with the appropriate linker should bind α5β1 integrin more efficiently and lead to greater cell adhesion over RGD alone. Several fibronectin mimetic peptides were designed and coupled to dialkyl hydrocarbon tails to make peptide-amphiphiles. The peptides contained different linkers connecting the two binding domains and different spacers separating the hydrophobic tails from the hydrophilic headgroups. The peptide-amphiphiles were deposited on mica substrates using the Langmuir-Blodgett technique. Langmuir isotherms indicated that the peptide-amphiphiles that contained higher numbers of serine residues formed a more tightly packed monolayer, but the increased number of serines also made transferring the amphiphiles to the mica substrate more difficult. Atomic force microscopy (AFM) images of the bilayers showed that the headgroups might be bent, forming small divots in the surface. These divots may help expose the PHSRN synergy-binding domain. Parallel studies undertaken by fellow group members showed that human umbilical vein endothelial cells and α5β1 integrins immobilized on an AFM tip preferred binding to a fibronectin mimetic peptide that contained both hydrophilic and hydrophobic residues in the linker and a medium length spacer. Most cells require a three-dimensional scaffold in order to thrive. To incorporate the fibronectin mimetic peptide into a three-dimensional structure, a single hydrocarbon tail was attached to form a peptideamphiphile. Single-tailed peptide-amphiphiles have been shown to form nanofibers in solution and gel after screening of the electrostatic charges in the headgroup. These gels show promise as scaffolds for tissue engineering. A fibronectin mimetic peptide-amphiphile containing a linker with alternating hydrophobic and hydrophilic residues was designed to form nanofibers in solution. The critical micelle concentration of the peptide-amphiphile was determined to be 38 μM, and all subsequent experiments were performed above this concentration. Circular dichroism (CD) spectroscopy indicated that the peptide headgroup of the peptide-amphiphile forms an α+β secondary structure; whereas, the free peptide forms a random secondary structure. Cryogenic-transmission electron microscopy (cryo-TEM) and small angle neutron scattering showed that the peptide-amphiphile self-assembled into nanofibers. The cryo-TEM images showed single nanofibers with a diameter of 10 nm and lengths on the order of microns. Images of higher peptideamphiphile concentrations showed evidence of bundling between individual nanofibers, which could give rise to gelation behavior at higher concentrations. The peptide-amphiphile formed a gel at concentrations above 6 mM. A 10 mM sample was analyzed with oscillating plate rheometry and was found to have an elastic modulus within the range of living tissue, showing potential as a possible scaffold for tissue engineering.
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    Structure and Phase Behavior of Aqueous Methylcellulose
    (2015-09) McAllister, John
    Methylcellulose is a chemically modified polysaccharide that is partially substituted by methoxyl groups. When the average substitution per monomer is intermediate, MC is water soluble, and these materials see use in a wide variety of commercial products. Aqueous solutions of MC undergo gelation and phase separation upon heating. Using dynamic mechanical spectroscopy, frequency-independent loss tangents were used to identify the gel point (Tgel) in MC solutions well over the chain overlap concentration (c 10c). Transmittance of 633 nm laser light through the solutions revealed that MC solutions cloud upon gelling, with a relative transmittance of 86% closely associated with the gel point. The gelation temperature of MC solutions was found to decrease with increasing MC concentration and the results for all molecular weights superposed. The fibrillar structure of aqueous MC gels was probed using a combination of small-angle neutron scattering (SANS), ultra-small-angle neutron scattering (USANS), and cryogenic transmission electron microscopy (cryo-TEM). The effect of molecular weight (Mw) and concentration on the gel structure was explored. The fibrillar morphology was consistently observed at elevated temperatures ( 70 C), independent of concentration and Mw. Moreover, the fibril dimensions extracted from SANS by fitting to a scattering function for semiflexible cylinders with disperse radii revealed that the fibril diameter of ca. 141 nm is constant for a concentration range of 0.01% to 3.79% and for all Mw investigated (150-530 kg/mol). Comparison of the measured SANS curves with predicted scattering traces revealed that at 70 C the fibrils contain an average volume fraction of 40% polymer. The linear and nonlinear viscoelastic response of MC gels can be described by a filament-based mechanical model. In particular, large-amplitude oscillatory shear experiments show that aqueous MC materials transition from shear thinning to shear thickening behavior at the gelation temperature. The critical stress at which MC gels depart from the linear viscoelastic regime and begin to stiffen is well predicted from the filament model over a concentration range of 0.18-2.0 wt%. These predictions are based on fibril densities and persistence lengths obtained experimentally from neutron scattering, combined with cross-link spacings inferred from the gel modulus via the same model. Mw, z-average radius of gyration (Rg), and second virial coefficient A2 have been determined between 15 and 52 C for dilute aqueous solutions of methylcellulose (MC) with three different molecular weights and constant degree of substitution (DS) of 1.8 using static light scattering. These measurements, conducted within 1 hour of heating the homogeneous solutions from 5 C, reveal that the theta temperature for MC in water is T = 48 2 C, with A2 < 0 for T > T, indicative of lower critical solution temperature (LCST) behavior. However, after annealing a solution for 2 days at 40 C evidence of high molecular weight aggregates appears through massive increases in the apparent Mw and Rg, a process that continues to evolve for at least 12 days. Cryogenic transmission electron microscopy images obtained from a solution aged for three weeks at 40 C reveal the presence of micron size fibrils, which is analogous to the fibrils that form upon gelation of aqueous MC solutions at higher concentrations and elevated temperatures. Growth of fibrils from a solution characterized by a positive A2 indicates that semiflexible MC dissolved in water is metastable at T < T, even though the solvent quality is apparently good. The minimum temperature required for MC solutions to aggregate is estimated to be 30 C, based on the rate independent gel-to-solution transition determined by small amplitude oscillatory shear measurements conducted while cooling 0.5 and 5.0 wt% solutions. These results cannot be explained based solely on separation into two isotropic phases upon heating using classical Flory-Huggins solution theory. It is speculated that the underlying equilibrium phase behavior of aqueous MC solutions involves a nematic order parameter.
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    Thermoresponsive hydrogels from ABC triblock terpolymers
    (2014-03) Zhou, Can
    Two-compartment hydrogels, which are three-dimensional networks with two distinguishable hydrophobic domains, have been prepared from aqueous self-assembly of poly(ethylene-alt-propylene)-b-poly(ethylene oxide)-b-poly(N-isopropylacrylamide) (PEP-b-PEO-b-PNIPAm, PON) triblock terpolymers. The PON terpolymers were synthesized using a combination of anionic and reversible addition-fragmentation chain transfer (RAFT) polymerization. They self-assembled into well-defined micelles with hydrophobic PEP cores surrounded by hydrophilic PEO-PNIPAm coronae at low temperatures and these micelles associated to form larger aggregated structures upon heating above the lower critical solution temperature (LCST) of PNIPAm in dilute aqueous solutions (0.5 and 0.05 wt%). At higher polymer concentrations (1-5 wt%), micellar aggregation manifests itself as gelation on heating due to the non-covalent association of PNIPAm blocks. The separation of micellization and gelation leads to the formation of a two-compartment network with a very high fraction of bridging conformations for the PEO midblocks. Therefore, gelation can be achieved at a much lower concentration, with a much higher modulus at a given polymer concentration and a much sharper sol-gel transition, as compared to poly(N-isopropylacrylamide)-b-poly(ethylene oxide)-b-poly(N-isopropylacrylamide) (NON) copolymer hydrogels, in which both looping and bridging conformations are possible. The formation of a micellar network with two discrete PEP and PNIPAm hydrophobic domains in PON hydrogels is verified by cryogenic scanning electron microscopy (cryo-SEM) and cryogenic transmission electron microscopy (cryo-TEM) experiments and is further confirmed by small-angle neutron scattering (SANS) measurements of two PON triblocks with a normal PNIPAm and a deuterated PNIPAm block. This study confirms the assumption that the formation of two-compartment networks in PON terpolymer hydrogels results in better gelation properties compared with NON copolymer hydrogels. In addition to temperature, it is desirable to have other stimuli such as pH to control the polymer self-assembly. Therefore, poly(ethylene-alt-propylene)-b-poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-acrylic acid) (PO(N/A)) triblock terpolymers in which the PNIPAm block contains a small fraction of AA monomers were prepared to achieve the dual pH- and temperature-sensitive micellar aggregation and gelation in aqueous solutions.Finally, the self-assembly of PON triblock terpolymers in the ionic liquid 1-ethyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)amide ([EMI][TFSA]) shows well-defined sol-gel transitions upon cooling with a lower gelation concentration and a higher modulus when compared with NON copolymers, which further confirms that ABC triblock terpolymers can be beneficial for gel formation in comparison to ABA triblock copolymers. Overall, we demonstrated that the rational design of two immiscible, hydrophobic endblocks in ABC triblocks is crucial for the preparation of compartmentized hydrogels with improved gelation properties. These studies will help guide the design and development of new systems with enhanced performance.
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    Toward the Construction of a Vascularized, Hydrogel-Based Lymph Node Model for In Vitro and In Vivo Therapeutic Applications
    (2021-04) Harff, Caleb
    Clinical trials for drugs and vaccines often suffer from the use of culture or animal models that do not accurately recreate the microenvironment of human tissues, including the lymph nodes. Furthermore, insufficient immune function resulting from genetic deficits, cancer or auto-immune disease, and the loss of lymph nodes due to surgical resection or radiation therapy may benefit from the implantation of therapeutic immune cells. These needs could be served through the development of a biocompatible, vascularized, 3D hydrogel scaffold that supports leukocytes and recreates lymph node function by providing a biomimetic microenvironment. While other lymph node models exist, their complexity and function are limited in that they incorporate few of the bioactive molecules from the lymph node microenvironment and do not contain vasculature. Preliminary viability studies were performed to determine the optimal choice of hydrogel type and density for the 3D culture of peripheral blood mononuclear cells (PBMCs). Fibrin hydrogels were found to better maintain PBMC viability over three days compared to gelatin methacrylate hydrogels. The inclusion of ECM from decellularized porcine lymph nodes into fibrin hydrogels was met with technical challenges with regard to solubilization and peripheral blood cell (PBC) viability assessment, indicating that additional steps or different approaches were required. However, successful decellularization was demonstrated by the sufficient removal of DNA content as determined by DNA quantification and histological staining. Cytokine and growth factor analysis showed significant depletion of many of the analytes but retention of IFNα2, IL-3, IL-9, IL-13, IL-17A, and VEGF. To construct a perfusable model, pin molds were used to create channels that would undergo eventual endothelialization and angiogenesis. Few of these channels maintained structural integrity. While continued experimentation is required to implement all of the features desired for the construction of a biomimetic and functional human lymph node model, these results indicate that it is feasible to improve upon previous designs by incorporating decellularized ECM and introducing vascularization in fibrin hydrogels.