Abstract
Foreign body reaction (FBR) to implanted biomaterials and medical devices is common and can compromise the function of implants or cause complications. For example, in cell encapsulation, cellular overgrowth (CO) and fibrosis around the cellular constructs can reduce the mass transfer of oxygen, nutrients and metabolic wastes, undermining cell function and leading to transplant failure. Therefore, materials that mitigate FBR or CO will have broad applications in biomedicine. Here we report a group of zwitterionic, sulfobetaine (SB) and carboxybetaine (CB) modifications of alginates that reproducibly mitigate the CO of implanted alginate microcapsules in mice, dogs and pigs. Using the modified alginates (SB-alginates), we also demonstrate improved outcome of islet encapsulation in a chemically-induced diabetic mouse model. These zwitterion-modified alginates may contribute to the development of cell encapsulation therapies for type 1 diabetes and other hormone-deficient diseases.
Highlights
Foreign body reaction (FBR) to implanted biomaterials and medical devices is common and can compromise the function of implants or cause complications
We studied the impact of the alginate microcapsules on tolllike receptors (TLRs) signaling
After confirming that the zwitterionically modified alginates SB-SLG20 mitigated FBR in C57BL/6J mice and large animals, we explored its therapeutic potential as a cell encapsulation medium for treatment of Type 1 diabetes (T1D)
Summary
Foreign body reaction (FBR) to implanted biomaterials and medical devices is common and can compromise the function of implants or cause complications. We report a group of zwitterionic, sulfobetaine (SB) and carboxybetaine (CB) modifications of alginates that reproducibly mitigate the CO of implanted alginate microcapsules in mice, dogs and pigs. Zwitterionic poly(carboxybetaine methacrylate) (PCBMA) hydrogels have been shown to resist the formation of fibrotic capsule for at least 3 months after subcutaneous implantation in mice[26] Based on these previous studies, we rationalized that chemically modifying alginate with zwitterionic groups might lead to a different class of CO-mitigating alginate derivatives. Compared with the previously published high throughput approach, the zwitterionic modification represents a much simpler and less expensive strategy for the design and development of super-biocompatible alginates We believe that these zwitterionically modified-alginates and our approach may contribute to a cell encapsulation therapy for T1D and potentially other hormone-deficient diseases in the future
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