Date of Award
5-1-2024
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
College/School/Department
Department of Nanoscale Science and Engineering
Dissertation/Thesis Chair
Yubing Xie
Committee Members
Susan T Sharfstein, Melinda Larsen, Andre J Melendez, Xulang Zhang
Keywords
Alginate, Mechanical testing, Mesenchymal stem cells, Microstrands, Salivary glands, Tissue Regeneration
Subject Categories
Nanoscience and Nanotechnology
Abstract
Fibrosis is a pathological wound healing process, driven by excessive accumulation of extracellular matrix (ECM) following tissue remodeling. Fibrosis occurs in diseased or damaged salivary glands caused by several conditions, such as Sjogren’s syndrome or radiation for head and neck cancers. Having better insight into the cellular and molecular progression of fibrosis will allow us to model new therapeutic approaches as fibrosis prevents salivary gland tissue regeneration and function. Pharmacological, tissue engineering and cell-based regeneration strategies have been widely explored to restore lost salivary gland function. Among cell-based therapies, exploitation of mesenchymal stromal/stem cells (MSC) for salivary gland regeneration has been actively pursued due to their anti-fibrotic and anti-inflammatory properties. However, the therapeutic potential of MSC-based therapies relies on successful migration and engraftment of cells to the diseased or injured site of the tissue or organ. Despite their immunomodulatory properties, MSCs need a delivery vehicle, which can support their growth and allow them to maintain their functional characteristics (phenotype) during transplantation. FDA-approved, biocompatible alginate hydrogels in the form of microstrands have great potential to deliver MSCs at the site of injured tissue due to their ECM mimicking properties, ease of chemical modulations, ease of handling for implantation. Microstrands of diameters ≤200 µm do not limit diffusion of oxygen, nutrients, cytokines, or growth factors unlike bulk hydrogels. In this work, we address the unmet limitations of current fabrication methodologies of cell-laden microstrands using vacuum-driven devices. Two types of devices were designed, developed and optimized to fabricate alginate hydrogel microstrands of desired diameter with high repeatability and reproducibility. We also demonstrated that cell-laden alginate microstrands of different cell types, fabricated using these devices, were able to maintain high cell viability, high-density growth, and homeostatic marker expression. We also determined how factors, such as supplemental calcium ions and high cell-seeding density, affect the mechanical properties of alginate hydrogel microstrands with time. Further, we explored the feasibility of fabricating small-volume alginate hydrogel microstrands (as low as 25 µL) and using these cell-laden microstrands as cell delivery vehicles for in vivo MSC implantation experiments. Overall, in this work, we have developed devices to fabricate injectable cell-laden alginate hydrogel microstrands for cell delivery and in vivo tissue regeneration, including MSC delivery to fibrotic salivary glands.
Recommended Citation
Kollampally, Sujith Chander Reddy, "Design And Fabrication Of Injectable Alginate Hydrogel Microstrands For Mesenchymal Stem Cell Delivery In Salivary Gland Tissue Regeneration" (2024). Legacy Theses & Dissertations (2009 - 2024). 3336.
https://scholarsarchive.library.albany.edu/legacy-etd/3336
