About this Abstract |
Meeting |
MS&T24: Materials Science & Technology
|
Symposium
|
Next Generation Biomaterials
|
Presentation Title |
Enhancing Immunomodulation by Novel Glycoconjugate-Based Organ Engineering to Prevent Transplant Rejection |
Author(s) |
Md Mohosin Rana, Peyman Malek Mohammadi Nouri, Haiming D. Luo, Lyann Sim, Jiao-Jing Wang, Zheng Jenny Zhang, Stephen G. Withers, Jayachandran N. Kizhakkedathu |
On-Site Speaker (Planned) |
Md Mohosin Rana |
Abstract Scope |
Organ transplantation is a curative treatment for organ failure but grapples with challenges including tissue damage and rejection. Protecting the transplant’s endothelium and glycocalyx is crucial for success. To address this, we have developed a cell-surface engineering (CSE) approach for endothelial cell surfaces by attaching different custom-designed glycoconjugates. Linear polyglycerol (LPG) served as the base, incorporating clickable alkyne groups and a gtTGase-reactive Q-tag (LPG-Q). Sialyl lactose functionalization replicated the glycocalyx, producing LPG-Q-Sia3Lac conjugates with different molecular weights (14, 27, and 41 kDa) and sugar densities (8%, 16%, and 22% oligosaccharides per LPG). Assessments demonstrated that LPG14k-Q-Sia3Lac8% and LPG27k-Q-Sia3Lac8% protect endothelial cells from immune-mediated toxicity. In rat kidney graft models, 0.5 mM LPG14k-Q-Sia3Lac8% with Tacrolimus or 1.5 mM LPG14k-Q-Sia3Lac8% alone significantly achieved 100% survival and improved kidney function post-transplantation. Minimal immune cell infiltration and damage observed in histological analysis underscored the potential of this strategy in rejection prevention. |