3D Printed Stem-Cell-Laden, Microchanneled Hydrogel Patch for the Enhanced Release of Cell-Secreting Factors and Treatment of Myocardial Infarctions

Molly R. Melhem, Jooyeon Park, Luke Knapp, Larissa Reinkensmeyer, Caroline Cvetkovic, Jordan Flewellyn, Min Kyung Lee, Tor Wolf Jensen, Rashid Bashir, Hyunjoon Kong, Lawrence B. Schook

Research output: Contribution to journalArticle

Abstract

Over the past several years, biomaterials loaded with mesenchymal stem cells (MSCs) have increasingly been used to reduce the myocardial fate of postinfarction collagen deposition and scar tissue formation. Despite successful gains, therapeutic efficacy has remained limited because of restricted transport of cell-secreting factors at the site of implantation. We hypothesized that an MSC-laden hydrogel patch with multiple microchannels would retain transplanted cells on target tissue and support transport of cell-secreting factors into tissue. By doing so, the gel patch will improve the therapeutic potential of the cells and minimize the degradation of myocardial tissue postinfarction. To examine this hypothesis, a stereolithographic apparatus (SLA) was used to introduce microchannels of controlled diameters (e.g., 500 and 1000 μm) during in situ cross-linking reaction of poly(ethylene glycol)dimethacrylate solution suspended with cells. Placement of the MSC-laden, microchanneled gel patch on the occluded left coronary artery in a murine model showed significant improvement in the ejection fraction, fractional shortening, and stroke volume, compared with gel patches without MSCs and MSC-laden gel patches without microchannels. In particular, the microchannels significantly reduced the number of cells required to recover cardiac function, while minimizing cardiac remodeling. In sum, the microchanneled gel patch would provide a means to prevent abnormal fibrosis resulting from acute ischemic injury.

Original languageEnglish (US)
Pages (from-to)1980-1987
Number of pages8
JournalACS Biomaterials Science and Engineering
Volume3
Issue number9
DOIs
StatePublished - Sep 11 2017

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Stem cells
Status Epilepticus
Gels
Microchannels
Tissue
Library Catalogs
Chlorhexidine
Hydrogels
Collagen
Biomaterials
Polyethylene glycols
Degradation
4-Aminobutyrate Transaminase
Anthralin
Psychologic Desensitization

Keywords

  • biotransport
  • cardiac remodeling
  • fibrosis
  • hydrogel
  • ischemia
  • mesenchymal stem cells
  • stereolithographic apparatus

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

Cite this

3D Printed Stem-Cell-Laden, Microchanneled Hydrogel Patch for the Enhanced Release of Cell-Secreting Factors and Treatment of Myocardial Infarctions. / Melhem, Molly R.; Park, Jooyeon; Knapp, Luke; Reinkensmeyer, Larissa; Cvetkovic, Caroline; Flewellyn, Jordan; Lee, Min Kyung; Jensen, Tor Wolf; Bashir, Rashid; Kong, Hyunjoon; Schook, Lawrence B.

In: ACS Biomaterials Science and Engineering, Vol. 3, No. 9, 11.09.2017, p. 1980-1987.

Research output: Contribution to journalArticle

Melhem, Molly R.; Park, Jooyeon; Knapp, Luke; Reinkensmeyer, Larissa; Cvetkovic, Caroline; Flewellyn, Jordan; Lee, Min Kyung; Jensen, Tor Wolf; Bashir, Rashid; Kong, Hyunjoon; Schook, Lawrence B. / 3D Printed Stem-Cell-Laden, Microchanneled Hydrogel Patch for the Enhanced Release of Cell-Secreting Factors and Treatment of Myocardial Infarctions.

In: ACS Biomaterials Science and Engineering, Vol. 3, No. 9, 11.09.2017, p. 1980-1987.

Research output: Contribution to journalArticle

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abstract = "Over the past several years, biomaterials loaded with mesenchymal stem cells (MSCs) have increasingly been used to reduce the myocardial fate of postinfarction collagen deposition and scar tissue formation. Despite successful gains, therapeutic efficacy has remained limited because of restricted transport of cell-secreting factors at the site of implantation. We hypothesized that an MSC-laden hydrogel patch with multiple microchannels would retain transplanted cells on target tissue and support transport of cell-secreting factors into tissue. By doing so, the gel patch will improve the therapeutic potential of the cells and minimize the degradation of myocardial tissue postinfarction. To examine this hypothesis, a stereolithographic apparatus (SLA) was used to introduce microchannels of controlled diameters (e.g., 500 and 1000 μm) during in situ cross-linking reaction of poly(ethylene glycol)dimethacrylate solution suspended with cells. Placement of the MSC-laden, microchanneled gel patch on the occluded left coronary artery in a murine model showed significant improvement in the ejection fraction, fractional shortening, and stroke volume, compared with gel patches without MSCs and MSC-laden gel patches without microchannels. In particular, the microchannels significantly reduced the number of cells required to recover cardiac function, while minimizing cardiac remodeling. In sum, the microchanneled gel patch would provide a means to prevent abnormal fibrosis resulting from acute ischemic injury.",
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