Characterization of chelator‐mediated recovery of pancreatic islets from barium‐stabilized alginate microcapsules

Abstract

Introduction Islet recovery from within alginate‐based microcapsules is necessary for certain analytical assays like flow cytometry; however, this technology has not been widely characterized. In this study, we explore the ability of EDTA, EGTA, and sodium citrate to induce reverse alginate polymerization via chelation and assess the toxicity of each chelator on pancreatic islets. Methods EDTA, EGTA, and sodium citrate were used to dissolve single‐layered Ba2+ alginate encapsulated islets and the rate of capsule breakdown calculated from analysis of imaging data. The effect of chelator exposure on islet viability and recovery was assessed using flow cytometry, while glucose‐stimulated insulin release (GSIR) assay was used to measure effects on islet function. Results EGTA demonstrated the most rapid microcapsule dissolving rate followed by EDTA and sodium citrate. Islet recovery was significantly better when encapsulated islets were treated with EDTA than EGTA and Na+ citrate. A decrease in viability and increase in apoptotic cells were observed when encapsulated islets were treated with Na+ citrate compared to islets treated with EDTA and EGTA. Islets treated with EDTA and EGTA demonstrated comparable stimulation index values to non‐treated control. Conversely, islets treated with Na+ citrate exhibited significantly decreased SI values compared to control. All chelator groups showed significantly lower insulin secretion than non‐treated islets. Conclusion Islet recovery from alginate microcapsule is possible using common chelators like Na+ citrate, EDTA, and EGTA. Chelation of encapsulated islets using EDTA demonstrated the most efficient dissolving capabilities with the least toxicity toward islet recovery and health.

Interpenetrating Network of Alginate–Human Adipose Extracellular Matrix Hydrogel for Islet Cells Encapsulation

“…However, Ca‐ALG microcapsules are susceptible to chelating agents such as lactate, citrate, and other ions such as those of sodium (Na + ) and magnesium (Mg 2+ ). [ 36,37 ] In physiological conditions, the ion replacement process destabilizes the cross‐bridge formed between the guluronic (G) blocks of adjoining ALG polymers, resulting in the inevitable swelling and rupturing of the gel. In the case of the Ca 2+ ‐cross‐linked AEC microcapsules, significant degradation as indicated by the weight loss was evident after 9 days of incubation in 1 × PBS (Figure S1, Supporting Information).…”

Tissue Regeneration with Hydrogel Encapsulation: A Review of Developments in Plants and Animals

“…The release of encapsulated cells may also be facilitated by utilizing reversible crosslinking methods, which may allow for relatively simple liquefaction of crosslinked hydrogels. For instance, alginates are crosslinked using ionic crosslinking strategies, which are reversible by using calcium chelators such as sodium citrate [37]. Similarly, thermally crosslinked gelatin, and other related hydrogels, can be liquefied by simply varying the external temperature to the liquefaction temperature [38].…”

Core–shell microcapsules: biofabrication and potential applications in tissue engineering and regenerative medicine

“…This was the basis of the first cell microencapsulation procedure, performed by Lim and Sun, 37 who encapsulated pancreatic islets in a core-shell capsule with a liquefied core of alginate. This process involves the use of chelating agents, such as EDTA or sodium citrate, 91,92 which sequester the divalent cations responsible for the ionic crosslinks in the alginate hydrogels. Gelatin can also be used in the formation of liquefied core capsules due to its mechanism of thermal gelation.…”