A “Bridge‐Building” Glycan Scaffold Mimicking Microbial Invasion for In Situ Endothelialization

Abstract

The globally high prevalence of peripheral artery diseases poses a pressing need for biomaterials grafts to rebuild vasculature. When implanted, they should promote endothelial cells (ECs) adhesion both profoundly and selectively—but the latter expectation remains unfulfilled. Here, this work is inspired by fungi that invade blood vessels via the “bridge” of galectins that, secreted by ECs, can simultaneously bind carbohydrates on fungal surface and integrin receptors on ECs. A glucomannan decanoate (GMDE) substrate mimicking fungal carbohydrates that highly and preferentially supports ECs adhesion while rejecting several other cell types is designed. Electrospun GMDE scaffolds efficiently sequester endogenous galectin‐1—which bridges ECs to the scaffolds as it functions in fungal invasions—and promote blood perfusion in a murine limb ischemic model. Meanwhile, the application of GMDE requires no exogenous pro‐angiogenic agents and causes no organ toxicity or adverse inflammation in mice, highlighting its high safety of potential translation. This glycan material, uniquely mimicking a microbial action and harnessing a secreted protein as a “bridge,” represents an effective, safe, and different strategy for ischemic vascular therapy.

Advances for the treatment of lower extremity arterial disease associated with diabetes mellitus

“…Lee et al (2020) prepared a microchannel network hydrogel with gelatin solution and poly (N-isopropyl acrylamide) (PNIPAM) fibers. The in vivo results proved that (Mu et al, 2021). (C,D) are reprinted with permission from ref.…”

“…Many researchers have begun to focus on scaffold-based tissue engineering strategies to restore blood perfusion in ischemic limbs. Recently, Mu et al (2021) anchoring hydrogel scaffold and evaluated the therapeutic effect on ischemic hind limbs of mice. The in vivo results showed the scaffold could significantly promote the restoration of blood perfusion (Figures 11C,D).…”

“…In addition to hydrogels, there are still many other types of biomaterials that have been studied to treat LEAD, such as scaffold ( Li et al, 2018 ; Carrabba et al, 2020 ; Leclerc et al, 2021 ; Mu et al, 2021 ), nanoparticle (NP) ( Matsumoto et al, 2020 ; Park et al, 2020 ; Liu et al, 2017 ; Albrecht-Schgoer et al, 2017 ) and spheroid ( Park et al, 2014 ; Choi et al, 2021 ; Lee et al, 2021 ).…”

A Toll-like Receptor-Activating, Self-Adjuvant Glycan Nanocarrier

“…Considering that molecular weight directly affects reaction efficiency and solubility, GM with different molecular weights (GM-100k: ∼100 kDa, GM-8k: ∼8 kDa) were used as starting materials. TFAA-catalyzed acetylation of GM-100k was conducted as previously reported by our group ( Mu et al, 2021 ). The average molecular weight of acGM-100k with a DS of 1.8 was 68,414 Da ( Supplementary Table S1 ), indicating that GM was probably cleaved during acetylation.…”

“…acGM-100k was synthesized according to our previous work starting from high molecular weight GM (about 100 kDa) ( Feng et al, 2019 ; Mu et al, 2021 ). acGM-8k was synthesized starting from low molecular weight GM (about 8 kDa).…”