Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues

Martin T Spang; Ryan Middleton; Miranda Diaz; Jervaughn Hunter; Joshua Mesfin; Alison Banka; Holly Sullivan; Raymond Wang; Tori S Lazerson; Saumya Bhatia; James Corbitt; Gavin D'Elia; Gerardo Sandoval-Gomez; Rebecca Kandell; Maria A Vratsanos; Karthikeyan Gnanasekaran; Takayuki Kato; Sachiyo Igata; Colin Luo; Kent G Osborn; Nathan C Gianneschi; Omolola Eniola-Adefeso; Pedro Cabrales; Ester J Kwon; Francisco Contijoch; Ryan R Reeves; Anthony N DeMaria; Karen L Christman

doi:10.1038/s41551-022-00964-5

Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues

Nat Biomed Eng. 2023 Feb;7(2):94-109. doi: 10.1038/s41551-022-00964-5. Epub 2022 Dec 29.

Authors

Martin T Spang^{1

2}, Ryan Middleton^{1

2}, Miranda Diaz^{1

2}, Jervaughn Hunter^{1

2}, Joshua Mesfin^{1

2}, Alison Banka³, Holly Sullivan^{1

2}, Raymond Wang^{1

2}, Tori S Lazerson^{1

2}, Saumya Bhatia^{1

2}, James Corbitt^{1

2}, Gavin D'Elia^{1

2}, Gerardo Sandoval-Gomez^{1

2}, Rebecca Kandell^{1

2}, Maria A Vratsanos⁴, Karthikeyan Gnanasekaran⁵, Takayuki Kato^{1

2}, Sachiyo Igata⁶, Colin Luo^{1

2}, Kent G Osborn⁷, Nathan C Gianneschi^{4

5

8}, Omolola Eniola-Adefeso^{3

9}, Pedro Cabrales¹, Ester J Kwon^{1

2}, Francisco Contijoch^{1

10}, Ryan R Reeves⁶, Anthony N DeMaria⁶, Karen L Christman^{11

12}

Affiliations

¹ Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
² Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
³ Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA.
⁵ Department of Chemistry, International Institute for Nanotechnology, Chemistry of Life Processes Institute, Simpson Querrey Institute, Northwestern University, Evanston, IL, USA.
⁶ Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
⁷ Animal Care Program, University of California San Diego, La Jolla, CA, USA.
⁸ Department of Biomedical Engineering and Department of Pharmacology, Northwestern University, Evanston, IL, USA.
⁹ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
¹⁰ Department of Radiology, University of California San Diego, La Jolla, CA, USA.
¹¹ Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. christman@eng.ucsd.edu.
¹² Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA. christman@eng.ucsd.edu.

Abstract

Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d. In rats and pigs with induced acute myocardial infarction followed by intracoronary infusion of the biomaterial, we observed substantially reduced left ventricular volumes and improved wall-motion scores, as well as differential expression of genes associated with tissue repair and inflammation. Delivering pro-healing extracellular matrix by intravascular infusion post injury may provide translational advantages for the healing of inflamed tissues 'from the inside out'.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Biocompatible Materials*
Extracellular Matrix / metabolism
Hydrogels
Myocardial Infarction* / therapy
Myocardium / metabolism
Rats
Swine

Substances

Biocompatible Materials
Hydrogels

Abstract

Publication types

MeSH terms

Substances

Grants and funding