Microencapsulated islet-like microtissues with toroid geometry for enhanced cellular viability.

Microencapsulated islet-like microtissues with toroid geometry for enhanced cellular viability.

Chen, Yang;Nguyen, Dang T;Kokil, Ganesh R;Xuan Wong, Yun;Dang, Tram T;
Acta biomaterialia 2019
227
chen2019microencapsulatedacta

Abstract

Transplantation of immuno-isolated islets is a promising strategy to restore insulin-secreting function in patients with Type 1 diabetes. However, the clinical translation of this treatment approach remains elusive due to the loss of islet viability resulting from hypoxia at the avascular transplantation site. To address this challenge, we designed non-spherical islet-like microtissues and investigated the effect of their geometries on cellular viability. Insulin-secreting microtissues with different shapes were fabricated by assembly of monodispersed rat insulinoma beta cells on micromolded nonadhesive hydrogels. Our study quantitatively demonstrated that toroid microtissues exhibited enhanced cellular viability and metabolic activity compared to rod and spheroid microtissues with the same volume. At a similar level of cellular viability, toroid geometry facilitated efficient packing of more cells into each microtissue than rod and spheroid geometries. In addition, toroid microtissues maintained the characteristic glucose-responsive insulin secretion of rat-derived beta cells. Furthermore, toroid microtissues preserved their geometry and structural integrity following their microencapsulation in immuno-isolatory alginate hydrogel. Our study suggests that adopting toroid geometry in designing therapeutic microtissues potentially reduces mass loss of cellular grafts and thereby may improve the performance of transplanted islets towards a clinically viable cure for Type 1 diabetes. Statement of Significance Transplantation of therapeutic cells is a promising strategy for the treatment of a wide range of hormone or protein-deficiency diseases. However, the clinical application of this approach is hindered by the loss of cell viability and function at the avascular transplantation site. To address this challenge, we fabricated hydrogel-encapsulated islet-like microtissues with non-spheroidal geometry and optimal surface-to-volume ratio. This study demonstrated that the viability of therapeutic cells can be significantly increased solely by redesigning the microtissue configuration without requiring any additional biochemical or operational accessories. This study suggests that the adoption of toroid geometry provides a possible avenue to improve the long-term survival of transplanted therapeutic cells and expedite the translation of cell-based therapy towards clinical application.

Citation

ID: 11814
Ref Key: chen2019microencapsulatedacta
Use this key to autocite in SciMatic or Thesis Manager

References

Blockchain Verification

Account:
NFT Contract Address:
0x95644003c57E6F55A65596E3D9Eac6813e3566dA
Article ID:
11814
Unique Identifier:
S1742-7061(19)30565-3
Network:
Scimatic Chain (ID: 481)
Loading...
Blockchain Readiness Checklist
Authors
Abstract
Journal Name
Year
Title
5/5
Creates 1,000,000 NFT tokens for this article
Token Features:
  • ERC-1155 Standard NFT
  • 1 Million Supply per Article
  • Transferable via MetaMask
  • Permanent Blockchain Record
Blockchain QR Code
Scan with Saymatik Web3.0 Wallet

Saymatik Web3.0 Wallet