Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation

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.