Microfluidic encapsulation of photosynthetic cyanobacteria in hydrogel microparticles augments oxygen delivery to rescue ischemic myocardium

Lyndsay Mariah Stapleton; Justin Michael Farry; Yuanjia Zhu; Haley Joan Lucian; Hanjay Wang; Michael John Paulsen; Kailey Pearl Totherow; Gillie Agmon Roth; Kara Kimberly Brower; Polly Morrell Fordyce; Eric Andrew Appel; Yi-Ping Joseph Woo

doi:10.1016/j.jbiosc.2023.03.001

Microfluidic encapsulation of photosynthetic cyanobacteria in hydrogel microparticles augments oxygen delivery to rescue ischemic myocardium

J Biosci Bioeng. 2023 Jun;135(6):493-499. doi: 10.1016/j.jbiosc.2023.03.001. Epub 2023 Mar 23.

Affiliations

¹ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA.
² Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA.
³ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94110, USA.
⁵ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Materials Science & Engineering, Stanford University, Stanford, CA 94305, USA.
⁶ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA. Electronic address: joswoo@stanford.edu.

PMID: 36966053
DOI: 10.1016/j.jbiosc.2023.03.001

Abstract

Cardiovascular disease, primarily caused by coronary artery disease, is the leading cause of death in the United States. While standard clinical interventions have improved patient outcomes, mortality rates associated with eventual heart failure still represent a clinical challenge. Macrorevascularization techniques inadequately address the microvascular perfusion deficits that persist beyond primary and secondary interventions. In this work, we investigate a photosynthetic oxygen delivery system that rescues the myocardium following acute ischemia. Using a simple microfluidic system, we encapsulated Synechococcus elongatus into alginate hydrogel microparticles (HMPs), which photosynthetically deliver oxygen to ischemic tissue in the absence of blood flow. We demonstrate that HMPs improve the viability of S. elongatus during the injection process and allow for simple oxygen diffusion. Adult male Wistar rats (n = 45) underwent sham surgery, acute ischemia reperfusion surgery, or a chronic ischemia reperfusion surgery, followed by injection of phosphate buffered saline (PBS), S. elongatus suspended in PBS, HMPs, or S. elongatus encapsulated in HMPs. Treatment with S. elongatus-HMPs mitigated cellular apoptosis and improved left ventricular function. Thus, delivery of S. elongatus encapsulated in HMPs improves clinical translation by utilizing a minimally invasive delivery platform that improves S. elongatus viability and enhances the therapeutic benefit of a novel photosynthetic system for the treatment of myocardial ischemia.

Keywords: Hydrogel; Ischemia reperfusion; Microfluidics; Microparticles; Oxygen delivery.

MeSH terms

Animals
Cyanobacteria*
Hydrogels*
Male
Microfluidics
Myocardium
Oxygen
Rats
Rats, Wistar

Substances

Hydrogels
Oxygen