Browsing by Author "Palmese, Luisa L."
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Item Polyethylene glycol hybrid hydrogels and microgels for multi-therapeutic delivery(University of Delaware, 2024) Palmese, Luisa L.Hydrogels, which are aqueously swollen hydrophilic polymer networks, are widely investigated in the field of bioengineering. Their ability to sequester and release therapeutic molecules as well as recapitulate physiological environments makes them ideal for use as in a host of biomedical applications such as drug delivery, tissue scaffolds and wound dressings. Hydrogels can be fabricated via a variety of physical and chemical crosslinking methods. In particular, the use of click-reactions, which occur spontaneously in biologically relevant conditions, can be exploited to easily generate mechanically robust hydrogels that are highly biocompatible. Additionally, these hydrogels can be easily engineered via the same chemistries to include a variety of molecules and cell instructive domains. One way in which these functionalities are added is through the incorporation of nano and micron-sized domains resulting in hybrid hydrogels. ☐ Herein, the fabrication and evaluation of poly(ethylene glycol) (PEG) hydrogels containing chemically crosslinked maleimide-functionalized liposomes and maleimide-functionalized low molecular weight heparin via thiol-Michael type addition for use as hydrogels capable of delivering both a small molecule, rapamycin (RAP), and a protein, basic fibroblast growth factor (FGF-2) in a temporally resolved manner for ultimate application as a perivascular scaffold is reported. Both components were released and remained bioactive as determined by in-vitro evaluation on target cells, human adventitial aortic fibroblasts (AoAFs). ☐ While successful in generating a hybrid hydrogel capable of delivering two therapeutic molecules we sought to investigate methods by which we could increase the temporal resolution of release. As such, translation of this bulk hydrogel platform into microgels, hydrogel particles ranging from 0.1-100µm, was evaluated to increase modularity, tunability, and injectability. Via flow focusing microfluidics, a method to produce uniform spherical PEG microgels with and without chemically crosslinked liposomes (lipo-microgels) was established. Microgels and lipo-microgels were characterized via super-resolution confocal microscopy and atomic force microscopy (AFM). The encapsulation and release of model macromolecular cargo (FITC-Dextran 5kDa) from both microgels and lipo-microgels showed sustained release over 3 weeks. Additionally, the loading and release of model protein cargo (equine myoglobin) confirmed retention of protein secondary structure and composition. ☐ To demonstrate the ability of these microgels to load and release different types of biologically relevant payloads, microgels loaded with either doxorubicin (DOX) or interleukin-2 (IL-2) were generated, and their release profiles evaluated. In both cases release was sustained over two weeks and was determined as diffusion-controlled via modeling. To broaden the mechanisms through which loaded molecules can be released from the microgels for greater control over temporal delivery, cysteine containing matrix metalloprotease (MMP) degradable peptides (MDPs) were synthesized and incorporated into the microgel matrix as bifunctional crosslinkers. MPDs for slow (CGGPQIAGQGGC; referred to as GPQ) and fast (CGGVPLSLYSGGC; referred to as VPLS) degradation were successfully incorporated into microgels and their subsequent degradation in response to MMP-1 was evaluated. Degradation of both GPQ and VPLS microgels in response to MMP-1 was observed over one week with VPLS microgels degrading within 48 hours and onset of GPQ microgel degradation occurring by day five. Future work will be aimed at characterizing the release of therapeutically relevant cargoes from these microgels as well as investigating mixed microgel populations for multiple cargo release.Item Sequence-Encoded Differences in Phase Separation Enable Formation of Resilin-like Polypeptide-Based Microstructured Hydrogels(Biomacromolecules, 2023-08-14) Patkar, Sai S.; Garcia, Cristobal Garcia; Palmese, Luisa L.; Kiick, Kristi L.Microstructured hydrogels are promising platforms to mimic structural and compositional heterogeneities of the native extracellular matrix (ECM). The current state-of-the-art soft matter patterning techniques for generating ECM mimics can be limited owing to their reliance on specialized equipment and multiple time- and energy-intensive steps. Here, a photocross-linking methodology that traps various morphologies of phase-separated multicomponent formulations of compositionally distinct resilin-like polypeptides (RLPs) is reported. Turbidimetry and quantitative 1H NMR spectroscopy were utilized to investigate the sequence-dependent liquid–liquid phase separation of multicomponent solutions of RLPs. Differences between the intermolecular interactions of two different photocross-linkable RLPs and a phase-separating templating RLP were exploited for producing microstructured hydrogels with tunable control over pore diameters (ranging from 1.5 to 150 μm) and shear storage moduli (ranging from 0.2 to 5 kPa). The culture of human mesenchymal stem cells demonstrated high viability and attachment on microstructured hydrogels, suggesting their potential for developing customizable platforms for regenerative medicine applications.