Characterization of diffusivity and mechanical properties of polyethylene glycol hydrogel conformal coatings over time for application in beta cell replacement therapy for type 1 diabetes.
Noa H deHaseth, Grisell C Gonzalez, Aaron A Stock, Ana L Claure, Gabriela Orlando, Alice A Tomei, Noel M Ziebarth
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引用次数: 0
Abstract
Purpose: Type 1 diabetes (T1D) is an autoimmune disorder that causes selected destruction of insulin-secreting pancreatic beta cells leading to insulin deficiency, hyperglycemia, and long-term complications. T1D has no cure and is primarily self-managed with blood sugar monitoring and exogenous insulin injections, which do not enable proper metabolic control and decreases patient's and caregivers' quality of life. Beta cell replacement through islet transplantation could cure T1D if current limitations such as the need for chronic systemic immunosuppression to prevent rejection and recurrence of autoimmunity are addressed. A potential new treatment addressing these limitations is based on transplantation of donor islets encapsulated in hydrogels with suitable and stable permselectivity and mechanical properties. Specifically, these hydrogel coatings must be (1) permeable to nutrients, insulin and glucose, necessary for coated cell viability and functionality, but impermeable to antibodies, to enable immune isolation, and (2) resistant to degradation, over time.
Methods: This study uses Fluorescence Recovery after Photobleaching (FRAP) and Atomic Force Microscopy (AFM) to determine the diffusion coefficient and Young's modulus of elasticity of individual model beads and primary and pseudoislets conformally coated with polyethylene glycol (PEG) over an extended period of time to evaluate the stability and viability of this novel therapeutic method for beta cell replacement without immunosuppression in T1D.
Results: The conformal hydrogel coatings remained functional and did not deteriorate over the 100-day time period, showing a promising stability to enable long-term immunoisolation of encapsulated islets.
Conclusions: This report demonstrated a novel measurement technique capable of assessing the mechanical and transport properties of individually coated samples, giving a more precise characterization of inherent variabilities within a sample population. Moreover, the approach is adaptable to other therapeutic cell clusters and organoids, supporting broader applications in cell transplantation therapies and offering a robust method for batch release validation in clinical applications.
期刊介绍：
The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas:
Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example.
Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions.
Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress.
Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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