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

• Published in: Advanced materials (Weinheim) Vol. 33; no. 42; pp. e2103490 - n/a
• Main Authors: Mu, Ruoyu, Zhang, Yuhan, Yan, Lingli, Liao, Zhencheng, Yang, Yushun, Su, Huanxing, Dong, Lei, Wang, Chunming
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-10-2021
• Subjects: Adhesion; angiogenesis; Animals; Biocompatibility; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biocompatible Materials - therapeutic use; Biomedical materials; Blood vessels; Blood Vessels - physiology; Carbohydrates; cell adhesion; Cell Adhesion - drug effects; Cell Line; Disease Models, Animal; Endothelial cells; Fungi; Galectin 1 - metabolism; Glycan; Human Umbilical Vein Endothelial Cells; Humans; Ischemia - drug therapy; Male; Mannans - chemistry; Mannans - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microorganisms; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - metabolism; natural biomaterials; Scaffolds; Substrates; Surgical implants; Toxicity; carbohydrates; blood vessels; natural biomaterials; angiogenesis; cell adhesion
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202103490

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.
A glycan substrate (GMDE) can preferentially support endothelial cells (ECs) adhesion by binding galectin‐1, a carbohydrate‐binding protein highly secreted by ECs, which in turn connects the substrate with the integrin receptors of the ECs. Implantation of GMDE promotes blood vessel formation in a murine ischemic model, suggesting its potential for future vascular therapy.