title: Discrete microstructural cues for the attenuation of fibrosis following myocardial infarction.
abstract: Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. We have developed a therapeutic materials strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructures to mechanically alter the microenvironment. Polymeric microstructures were fabricated using photolithographic techniques and studied in a three-dimensional culture model of the fibrotic environment and by direct injection into the infarct zone of adult rats. Here, we show dose-dependent down-regulation of expression of genes associated with the mechanical fibrotic response in the presence of microstructures. Injection of this microstructured material into the infarct zone decreased levels of collagen and TGF-β, increased elastin deposition and vascularization in the infarcted region, and improved functional outcomes after six weeks. Our results demonstrate the efficacy of these discrete anti-fibrotic microstructures and suggest a potential therapeutic materials approach for combatting pathologic fibrosis.
authors.affiliation: UC Berkeley - UCSF Graduate Group in Bioengineering, 1700 4th Street, QB3 Byers Hall, Room 203, San Francisco, CA 94158, USA; UCSF Medical Scientist Training Program, 1700 4th Street, QB3 Byers Hall, Room 203, San Francisco, CA 94158, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Pinney
authors.affiliation: UCSF Department of Medicine, Cardiovascular Research Institute and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Box 1354, 513 Parnassus Ave, MS Room 1136, San Francisco, CA 94143, USA.
authors.forename: Kim T
authors.initials: KT
authors.lastname: Du
authors.affiliation: UC Berkeley - UCSF Graduate Group in Bioengineering, 1700 4th Street, QB3 Byers Hall, Room 203, San Francisco, CA 94158, USA; Beth Israel Deaconess Medical Center, Department of Surgery, Center for Life Science Surgery/BIDMC, 11th Floor, 3 Blackfan Circle, Boston, MA 02115, USA.
authors.forename: Perla
authors.initials: P
authors.lastname: Ayala
authors.affiliation: UCSF Department of Medicine, Cardiovascular Research Institute and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Box 1354, 513 Parnassus Ave, MS Room 1136, San Francisco, CA 94143, USA.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Fang
authors.affiliation: UCSF Department of Medicine, Cardiovascular Research Institute and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Box 1354, 513 Parnassus Ave, MS Room 1136, San Francisco, CA 94143, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sievers
authors.affiliation: UCSF Bioengineering and Therapeutic Sciences, 1700 4th Street, Byers Hall Room 203, San Francisco, CA 94158, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Chew
authors.affiliation: UCSF School of Medicine, 513 Parnassus Ave, MS Room 1136, San Francisco, CA 94143, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Delrosario
authors.affiliation: UC Berkeley - UCSF Graduate Group in Bioengineering, 1700 4th Street, QB3 Byers Hall, Room 203, San Francisco, CA 94158, USA; UCSF Department of Medicine, Cardiovascular Research Institute and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Box 1354, 513 Parnassus Ave, MS Room 1136, San Francisco, CA 94143, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: UC Berkeley - UCSF Graduate Group in Bioengineering, 1700 4th Street, QB3 Byers Hall, Room 203, San Francisco, CA 94158, USA; UCSF Bioengineering and Therapeutic Sciences, 1700 4th Street, Byers Hall Room 203, San Francisco, CA 94158, USA. Electronic address: tejal.desai@ucsf.edu.
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Desai
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000627:therapeutic use*; D003094:Collagen / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005355:Fibrosis; D008689:Methacrylates / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D055616:Microtechnology; D009203:Myocardial Infarction / Q000473:pathology* / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D008689:Methacrylates; C421283:poly(ethylene glycol)-dimethacrylate; D011092:Polyethylene Glycols; D003094:Collagen
keywords: Cardiac tissue engineering; Collagen; ECM; Fibrosis; Photolithography; Polyethylene glycol dimethacrylate