A. James Clark School of Engineering

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The collections in this community comprise faculty research works, as well as graduate theses and dissertations.

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Subject: search.filters.subject.mesenchymal stem cells

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    Mesenchymal Stem Cell Culture within Perfusion Bioreactors Incorporating 3D-Printed Scaffolds Enables Improved Extracellular Vesicle Yield with Preserved Bioactivity
    (Wiley, 2023-03-17) Kronstadt, Stephanie M.; Patel, Divya B.; Born, Louis J.; Levy, Daniel; Lerman, Max J.; Mahadik, Bhushan; McLoughlin, Shannon T.; Fasuyi, Arafat; Fowlkes, Lauren; Van Heyningen, Lauren Hoorens; Aranda, Amaya; Abadchi, Sanaz Nourmohammadi; Chang, Kai-Hua; Hsu, Angela Ting Wei; Bengali, Sameer; Harmon, John W.; Fisher, John P.; Jay, Steven M.
    Extracellular vesicles (EVs) are implicated as promising therapeutics and drug delivery vehicles in various diseases. However, successful clinical translation will depend on the development of scalable biomanufacturing approaches, especially due to the documented low levels of intrinsic EV-associated cargo that may necessitate repeated doses to achieve clinical benefit in certain applications. Thus, here the effects of a 3D-printed scaffold-perfusion bioreactor system are assessed on the production and bioactivity of EVs secreted from bone marrow-derived mesenchymal stem cells (MSCs), a cell type widely implicated in generating EVs with therapeutic potential. The results indicate that perfusion bioreactor culture induces an ≈40-80-fold increase (depending on measurement method) in MSC EV production compared to conventional cell culture. Additionally, MSC EVs generated using the perfusion bioreactor system significantly improve wound healing in a diabetic mouse model, with increased CD31+ staining in wound bed tissue compared to animals treated with flask cell culture-generated MSC EVs. Overall, this study establishes a promising solution to a major EV translational bottleneck, with the capacity for tunability for specific applications and general improvement alongside advancements in 3D-printing technologies.
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    Mechanical, Structural and Biological Properties of Biopolymer-Based Hydrogels
    (2012) Hyland, Laura; Yu, Yihua B.; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The aim of this dissertation was to begin to understand how biopolymer interactions affect mechanical and structural properties of biomaterials, and how those properties affect stem cell behavior. Polysaccharide, oligopeptide and oligopeptide-polysaccharide composite materials were made and then characterized using a range of techniques. It was found that chondroitin addition to chitosan-alginate networks improved both tensile and compressive strength. Increasing polysaccharide concentration also improved mechanical properties. Also, polysaccharide incorporation into peptide hydrogels increased biomaterial resistance to strain break. Structural analysis supported mechanical data, showing that incorporation of the peptides dramatically changed the morphology of the polysaccharide networks. Biopolymer chirality was also explored in this work. By incorporating polysaccharides and oligosaccharides into both L- and D-forms of peptide hydrogels, we observed differences in mechanical properties not seen in L- and D-oligopeptide hydrogels alone. Greater interactions between L-oligopeptides and D-saccharides lead to stronger materials with distinctively different structural characteristics from hydrogels made from D-oligopeptides and D-saccharides. This phenomenon, known as chiral selectivity, has previously only been seen at the molecular level. Here, we showed that chiral selectivity is another unique property of biopolymers that can be exploited to tune mechanical and structural properties of materials. Chiral selectivity was also observed in terms of stem cell behavior in this work. However another property, hydrogel charge, was used to diminish the effects of chiral selectivity in order to enhance the biocompatibility of D-oligopeptide hydrogels. It was found that negative charges significantly improved human mesenchymal stem cell attachment and proliferation in D-oligopeptide gels but had little effect on their interactions with L-oligopeptide gels. These results suggest that it is possible to use charge and other properties of biopolymers to engineer biomaterials whose chirality is distinct from that of natural biomaterials but whose performance is close to that of natural biomaterials. These oligopeptide-based biomaterials also offer new tools to investigate biohomochirality, an important and unresolved question in biology.