Dissertation
Magnetically actuated alginate scaffolds: effects on macrophage function and regenerative outcomes
Doctor of Philosophy (Ph.D.), Drexel University
Jul 2020
DOI:
https://doi.org/10.17918/00000294
Abstract
Artificial tissue presents a novel therapeutic approach for restoring function in severely damaged tissues. Macrophages have a central role in the vascularization and engraftment of implanted artificial tissue constructs. Our laboratory engineered magnetically responsive alginate scaffolds capable of delivering dynamic mechanical cues to scaffold associated cells in response to remote magnetic stimulation. In the current study, we investigated the ability of magnetically actuated scaffolds to modulate macrophage function in vitro and in vivo. We report that magnetically actuated scaffolds enhance the phenotype of classically activated (M1) macrophages, as shown by the increased expression of the M1 cell-surface marker CD86 and increased secretion of multiple M1 cytokines. Likewise, cyclic stretch applied directly to M1 macrophages using a commercial tension generating cell culture system increased the expression of CD86 and secretion of numerous M1 cytokines, corroborating the impact of cyclic strain on macrophage function. When scaffolds were implanted subcutaneously into mice and treated with magnetic stimulation days 5-8 post-implantation, there was increased infiltration of host macrophages and an increase in macrophage expression of CD86. Analysis of downstream regenerative outcomes revealed a subtle but encouraging trend towards an increase in scaffold vascularization and a decrease in fibrous capsule formation. These results advance our understanding of how remote-controlled mechanical cues, namely cyclic strain, impact macrophage function, and demonstrate the feasibility of using mechanically active materials to modulate the macrophage response in vivo.
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Details
- Title
- Magnetically actuated alginate scaffolds
- Creators
- Lindsay Allyson Steele
- Contributors
- Boris Polyak (Advisor)Christian Sell (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 173 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991014695537904721