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Purpose <p>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 (<i>1</i>) permeable to nutrients, insulin and glucose, necessary for coated cell viability and functionality, but impermeable to antibodies, to enable immune isolation, and (<i>2</i>) resistant to degradation, over time.</p> Methods <p>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&#xa0;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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月16日

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  • Noa H. deHaseth,
  • Grisell C. Gonzalez,
  • Aaron A. Stock,
  • Ana L. Claure,
  • Gabriela Orlando,
  • Alice A. Tomei,
  • Noel M. Ziebarth

摘要

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.