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Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation.

Qingsheng Liu1, Alan Chiu1, Long-Hai Wang1

  • 1Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, 14853, USA.

Nature Communications
|November 22, 2019
PubMed
Summary

Zwitterionic modifications of alginates, specifically sulfobetaine (SB) and carboxybetaine (CB) alginates, effectively reduce cellular overgrowth around implanted microcapsules. This innovation shows promise for improving cell encapsulation therapies, including islet transplantation for type 1 diabetes.

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Immunology

Background:

  • Foreign body reaction (FBR) and cellular overgrowth (CO) are common challenges with implanted biomaterials, potentially leading to device failure.
  • CO and fibrosis around cell encapsulation constructs impede nutrient and oxygen transfer, compromising cell function and transplant outcomes.
  • Developing materials that mitigate FBR and CO is crucial for advancing biomedical applications.

Purpose of the Study:

  • To develop and evaluate zwitterionic modifications of alginates to mitigate foreign body reaction and cellular overgrowth.
  • To assess the efficacy of these modified alginates in improving cell encapsulation and transplant outcomes in preclinical models.

Main Methods:

  • Synthesized sulfobetaine (SB) and carboxybetaine (CB) modified alginates.
  • Implanted modified alginate microcapsules in mice, dogs, and pigs to evaluate foreign body reaction and cellular overgrowth.
  • Utilized a chemically-induced diabetic mouse model for islet encapsulation studies with SB-alginates.

Main Results:

  • Zwitterionic alginate modifications (SB-alginates and CB-alginates) reproducibly mitigated cellular overgrowth around implanted microcapsules across multiple species.
  • SB-alginate encapsulation of islets demonstrated improved outcomes in a diabetic mouse model.
  • The modified alginates maintained structural integrity and biocompatibility.

Conclusions:

  • Zwitterionic modification of alginates is a viable strategy to reduce foreign body reaction and cellular overgrowth for implanted biomaterials.
  • These modified alginates hold significant potential for enhancing the success of cell encapsulation therapies, particularly for type 1 diabetes and other hormone-deficiency disorders.