Understanding the effects of retinal scaffold mechanical properties on surgical handling and cellular response
Year: 2020
Type: dissertation
Abstract: Retinal degenerative diseases result in photoreceptor cell death, leading to irreversible vision loss. Emerging treatment strategies involve replacing lost photoreceptors using supportive scaffolds to ensure cells survive the implantation process. While many aspects of the scaffolds, including material chemistry and microstructural cues have been studied, a full set of design constraints has yet to be established. For example, while known to be important in other tissues and systems, the influence of mechanical properties on cellular fate and surgical handling has not been quantified. In this study, photocrosslinked poly(ethylene glycol) dimethacrylate (PEGDMA) was used as a model polymer to study the effects of scaffold modulus (stiffness) on surgical handling, independent of material chemistry. By evaluating scaffold handling characteristics using both in vitro and ex vivo trials, we observed a lower shear modulus limit of 35 kPa. In other words, scaffolds below this modulus were too fragile for effective transplantation. An upper mechanical property limit was not readily apparent. Furthermore, scaffolds composed of dilutions of a lower molecular weight PEGDMA performed less favorably than those composed of two different molecular weight PEGDMA, even at similar moduli. Additionally, we designed and fabricated a custom scaffold holder for these samples such that they may be easily seeded with retinal cells and cultured in vitro. Here, key design parameters included ease of use and non-cytotoxic effects on cells. This custom scaffold holder facilitated culture of cells on a scaffold, enabling additional studies with extended timeframes and end-of life analysis for full device characterization. Taken together, these results delineate the relationship between mechanical properties and retinal scaffold performance. Ultimately, this important groundwork enables better understanding of how scaffold characteristics affect the efficiency and efficacy of scaffold-assisted cell therapies for retinal degenerative diseases.
DOI: 10.17077/etd.005382
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4233649082