Engineering pro-angiogenic biomaterials via chemoselective extracellular vesicle immobilization

Yunhui Xing; Saigopalakrishna S Yerneni; Weitao Wang; Rebecca E Taylor; Phil G Campbell; Xi Ren

doi:10.1016/j.biomaterials.2021.121357

Engineering pro-angiogenic biomaterials via chemoselective extracellular vesicle immobilization

Biomaterials. 2022 Feb:281:121357. doi: 10.1016/j.biomaterials.2021.121357. Epub 2021 Dec 31.

Authors

Yunhui Xing¹, Saigopalakrishna S Yerneni¹, Weitao Wang², Rebecca E Taylor³, Phil G Campbell⁴, Xi Ren⁵

Affiliations

¹ Department of Biomedical Engineering, Carnegie Mellon University, 5000, Forbes Avenue, Pittsburgh, PA, United States.
² Department of Mechanical Engineering, Carnegie Mellon University, 5000, Forbes Avenue, Pittsburgh, PA, United States.
³ Department of Biomedical Engineering, Carnegie Mellon University, 5000, Forbes Avenue, Pittsburgh, PA, United States; Department of Mechanical Engineering, Carnegie Mellon University, 5000, Forbes Avenue, Pittsburgh, PA, United States; Department of Electrical and Computer Engineering, Carnegie Mellon University, 5000, Forbes Avenue, Pittsburgh, PA, United States.
⁴ Department of Biomedical Engineering, Carnegie Mellon University, 5000, Forbes Avenue, Pittsburgh, PA, United States. Electronic address: pcampbel@cs.cmu.edu.
⁵ Department of Biomedical Engineering, Carnegie Mellon University, 5000, Forbes Avenue, Pittsburgh, PA, United States; Department of Mechanical Engineering, Carnegie Mellon University, 5000, Forbes Avenue, Pittsburgh, PA, United States. Electronic address: xiren@cmu.edu.

PMID: 34999538
DOI: 10.1016/j.biomaterials.2021.121357

Abstract

Nanoscale extracellular vesicles (EVs) represent a unique cellular derivative that reflect the therapeutic potential of mesenchymal stem cells (MSCs) toward tissue engineering and injury repair without the logistical and safety concerns of utilizing living cells. However, upon systemic administration in vivo,EVs undergo rapid clearance and typically lack controlled targeted delivery, thus reducing their effectiveness in therapeutic regenerative therapies. Here, we describe a strategy that enables long-term in vivo spatial EV retention by chemoselective immobilization of metabolically incoporated azido ligand-bearing EVs (azido-EVs) within a dibenzocyclooctyne-modified collagen hydrogel. MSC-derived azido-EVs exhibit comparable morphological and functional properties as their non-labeled EV counterparts and, when immobilized within collagen hydrogel implants via click chemistry, they elicited more robust host cell infiltration, angiogenic and immunoregulatory responses including vascular ingrowth and macrophage recruitment compared to ten times the higher dose required by non-immobilized EVs. We envision this technology will enable a wide range of applications to spatially promote vascularization and host integration relevant to tissue engineering and regenerative medicine applications.

Keywords: Angiogenesis; Click chemistry; Extracellular matrix; Extracellular vesicle; Metabolic glycan labeling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biocompatible Materials
Extracellular Vesicles*
Hydrogels
Mesenchymal Stem Cells*
Regenerative Medicine

Substances

Biocompatible Materials
Hydrogels