Biocompatible and nondegradable microcapsules using an ethylamine-bridged EGCG dimer for successful therapeutic cell transplantation

Conventional alginate microcapsules are widely used for encapsulating therapeutic cells to reduce the host immune response. However, the exchange of monovalent cations with divalent cations for crosslinking can lead to a sol-gel phase transition, resulting in gradual degradation and swelling of the microcapsules in the body. To address this limitation, we present a biocompatible and nondegradable epigallocatechin-3-gallate (EGCG)-based microencapsulation with ethylamine-bridged EGCG dimers (EGCG(d)), denoted as ‘Epi-Capsules’. These Epi-Capsules showed increased physical properties and Ca2+ chelating resistance compared to conventional alginate microcapsules. Horseradish peroxidase (HRP) treatment is very effective in increasing the stability of Epi-Capsule((+)HRP) due to the crosslinking between EGCG(d) molecules. Interestingly, the Epi-Capsules(oxi) using a pre-oxidized EGCG(d) can support long-term survival (>90 days) of xenotransplanted insulin-secreting islets in diabetic mice in vivo, which is attributed to its structural stability and reactive oxygen species (ROS) scavenging for lower fibrotic activity. Collectively, this EGCG-based microencapsulation can create Ca2+ chelating-resistance and anti-oxidant activity, which could be a promising strategy for cell therapies for diabetes and other diseases. Herein, a non-degradable microcapsule with pre-oxidized EGCG(d) is developed for the cell's functionality. This Epi-Capsule(oxi) shows Ca2+ chelating resistance, increased structural stability, and H2O2 scavenging ability compared to alginate microcapsules. [Display omitted] •EGCG-based microencapsulation for successful cell transplantation•Ca2+ chelating-resistant Epi-Capsule(oxi) for improving degradation•H2O2 scavenging effect of Epi-Capsule(oxi)•Enhanced structural stability of Epi-Capsule(oxi)•Long-term effect of Epi-Capsule(oxi) with lower degradation after implantation