Enhancing drug delivery from electrospun fiber scaffolds for neural tissue engineering

D'Amato, Anthony R.
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Gilbert, Ryan
Palermo, Edmund
Hahn, Mariah
Thompson, Deanna M.
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Biomedical engineering
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Attribution-NonCommercial-NoDerivs 3.0 United States
This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
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The final aim in this study details the creation of an entirely new polymer that is made out of E2. With the help of Dr. Palermo’s lab, I synthesized a new, slowly-degrading E2 and polyethylene glycol (PEG) copolymer (PPEAP) and fabricated materials directly from this new copolymer. PPEAP materials were neurotrophic and neuroprotective for dorsal root ganglion (DRG) and dissociated cortical neurons in culture, respectively. We also demonstrate that electrospun PPEAP fibers direct neurite extension in vitro with DRG, demonstrating PPEAP fiber contact guidance capabilities. These results prove that PPEAP materials are bioactive, and have beneficial cellular effects in vitro. Further, drug release kinetic studies predict that PPEAP materials can release E2 with zero-order kinetics for years. This time-scale of drug release is significantly longer than any traditional drug-releasing biomaterial scaffolds found in the literature. PPEAP, and the materials derived from it, hold great potential for SCI treatment as they provide sustained delivery of E2, which promotes beneficial phenotypic changes in all CNS cells.
Spinal cord injury (SCI) is a complex obstacle to overcome as it causes multiple cell types in the spinal cord to undergo detrimental phenotypic changes at varying time points post-injury. To achieve full functional recovery following SCI, it is necessary to promote regenerative phenotypes in each individual cell type, at the appropriate time point post-injury. Biomaterials are commonly researched to facilitate functional recovery following SCI, but require complex engineering design to adequately address the complex pathophysiology of the injury environment.
Electrospun fibers are a commonly researched biomaterial to treat SCI due to their physical characteristics. The diameter and orientation of electrospun fibers can be modified during the electrospinning process to create fibrous scaffolds that promote guided tissue regeneration, which is necessary to repopulate the necrotic SCI lesion with healthy tissue. Electrospun fibers themselves, however, cannot adequately address the myriad obstacles that prevent recovery after SCI. Therefore, electrospun fiber scaffolds are often modified by incorporating drugs to further facilitate recovery. The aim of this thesis is to improve the regenerative potential of electrospun fibers for neural engineering applications by better understanding and improving their drug-delivery capabilities.
First, I studied ways to detect and quantify the amount of organic solvents that are retained in electrospun fibers after the electrospinning process. This study revealed that electrospun poly(L-lactic acid) (PLLA) fibers retain the solvents chloroform and 1,1,1,3,3,3-hexafluoroisopropanol (HFP) in large amounts for as long as four weeks after fabrication. I then performed a second study to determine how this solvent retention can affect drug delivery from electrospun PLLA fibers. I found that slow removal of solvent over the course of 28 days by maintaining fibers in laboratory conditions (20-25 °C and atmospheric pressure) followed by heating the fibrous scaffolds in a cell culture incubator at 37 °C prolonged the release duration of the drug 6-aminonicotinamide by nearly a factor of five (from 9 days to 44 days). This fiber treatment regimen also increased the amount of drug that the fibers release by nearly a factor of two. This finding is important, as prolonged drug-release is typically desired to treat SCI, since recovery can take months to years. However, I aimed to further optimize drug delivering electrospun fibers for SCI applications by creating a scaffold to deliver 17β-estradiol (E2). E2 holds great potential to improve outcomes after SCI as it induces beneficial changes in all CNS cells after injury.
December 2018
School of Engineering
Dept. of Biomedical Engineering
Rensselaer Polytechnic Institute, Troy, NY
Rensselaer Theses and Dissertations Online Collection
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