Functionalized, Nanoscale Coatings for Islet Encapsulation

  • Stabler, Cherie, (PI)

Project: Research project

Description

Grant: RFA- DK-08-001
Title: Functionalized, Nanoscale Coatings for Islet Encapsulation
PI: Cherie Stabler
Project Summary
While clinical islet transplantation (CIT) has shown promise for the treatment of Type 1
diabetes, it is dampened by the impaired function and loss of islets following
implantation. This loss is attributed to strong inflammatory and immunological response
to the transplant, primarily due to cell surface inflammatory proteins and antigens. In this
proposal, we seek to minimize detrimental host responses that lead to islet engraftment
failure by encapsulating the islets in novel nanoscale biomaterial layers. By developing
stable capsules on the order of 1000-fold smaller than standard practices via controlled
covalent linking of individual polymers layers on the islet surface, void volumes are
dramatically reduced and nutritional transport and glucose sensing is unaffected.
Nanoscale layers not only serve as a means to immunocamouflage the implant, but also
have tremendous potential to optimize the composition, structure, thickness, and
function of these layers on the nanometer level. Once fabricated, these nanoscale
layers serve as ideal platforms for the tethering of functional agents, proteins or markers
capable of dynamically interacting at the implant-host interface. Therefore, the inert
biomaterial layer can be converted to a bioactive surface capable of actively altering the
localized implant environment. In this proposal, we seek to tether active
immunomodulatory proteins/enzymes, anti-inflammatory agents, and/or engraftment-
enhancing nanoparticles to the nanolayer surface. The design of effective strategies to
build tailored nano-layers on the islet surface capable of expressing active pro-
engraftment agents could significantly improve transplant efficacy and long-term stability.
The public health implications of this research are that this approach may provide a
means to dramatically improve current clinical islet transplantation results, by reducing or
completely eliminating the need for immunosuppressive therapy and improving long-
term implant function.
StatusFinished
Effective start/end date9/30/088/31/13

Funding

  • National Institutes of Health: $2,295,000.00
  • National Institutes of Health: $79,560.00
  • National Institutes of Health: $81,107.00
  • National Institutes of Health: $2,295.00

Fingerprint

Islets of Langerhans Transplantation
Transplants
Biocompatible Materials
Surface Antigens
Immunosuppressive Agents
Nanoparticles
Capsules
Polymers
Membrane Proteins
Proteins
Anti-Inflammatory Agents
Public Health
Glucose
Enzymes
Therapeutics
Research

ASJC

  • Medicine(all)