Affiliations 

  • 1 Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, USA
  • 2 Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
  • 3 Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Department of Thoracic Surgery, The University of Tokyo, Tokyo, 113-8655, Japan
  • 4 Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA
  • 5 Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Kepala Batas, Penang, Malaysia
  • 6 Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Department of Surgery, Changzheng Hospital, Shanghai, 200041, China
  • 7 Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, 02114, USA. Electronic address: hott@mgh.harvard.edu
Biomaterials, 2018 11;182:127-134.
PMID: 30118980 DOI: 10.1016/j.biomaterials.2018.08.012

Abstract

Decellularized native extracellular matrix (ECM) biomaterials are widely used in tissue engineering and have reached clinical application as biomesh implants. To enhance their regenerative properties and postimplantation performance, ECM biomaterials could be functionalized via immobilization of bioactive molecules. To facilitate ECM functionalization, we developed a metabolic glycan labeling approach using physiologic pathways to covalently incorporate click-reactive azide ligands into the native ECM of a wide variety of rodent tissues and organs in vivo, and into the ECM of isolated rodent and porcine lungs cultured ex vivo. The incorporated azides within the ECM were preserved after decellularization and served as chemoselective ligands for subsequent bioconjugation via click chemistry. As proof of principle, we generated alkyne-modified heparin, immobilized it onto azide-incorporated acellular lungs, and demonstrated its bioactivity by Antithrombin III immobilization and Factor Xa inhibition. The herein reported metabolic glycan labeling approach represents a novel platform technology for manufacturing click-reactive native ECM biomaterials, thereby enabling efficient and chemoselective functionalization of these materials to facilitate tissue regeneration and repair.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.