Pancreatic islet surface bioengineering with a heparin-incorporated starPEG nanofilm

- We have successfully fabricated an orthogonal functionalizable copolymeric (Hep-PEG);
- Hep-PEG-coated islets have significantly improved pro-angiogenic, anti-inflammatory ability;
- Hep-PEG-coated islets exhibit better survival, revascularisation with uncompromised islet insulin secretory function.

Cell surface engineering could protect implanted cells from host immune rejections while modify the cellular landscape for better post-transplantation graft function and survival. Islet transplantation is considered the most promising therapeutic option with the potential to cure diabetes. Current approach to improve clinical efficacy of pancreatic islet transplantation is alginate encapsulation. However, disappointing outcomes have been reported in clinical trials due to larger islet size resulted by encapsulation and alginate-elicited host immune responses. We have developed an ultrathin nanofilm of starPEG with incorporated heparin (Hep-PEG) that binds covalently to the amine groups of islet surface membrane via its N-hydroxysuccinimide groups. The Hep-PEG nanocoating elicited minimal alteration on islet volume in culture. Hep-PEG-coated islets exhibited robust islet viability accompanied by uncompromised islet insulin secretory function. Instant blood-mediated inflammatory reaction was also reduced by Hep-PEG islet coating, accompanied by enhanced intra-islet revascularization. In addition, despite its semi-permeability, Hep-PEG islet coating promoted the survival of islets exposed to pro-inflammatory cytokines. Considering that inflammation and hypoxia are primary causes of immediate cell loss for cell therapy, the Hep-PEG nanofilm represents a viable approach for cell surface engineering which would improve the clinical outcome of cell therapies.

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