title: Bioreactor for modulation of cardiac microtissue phenotype by combined static stretch and electrical stimulation.
abstract: We describe here a bioreactor capable of applying electrical field stimulation in conjunction with static strain and on-line force of contraction measurements. It consisted of a polydimethylsiloxane (PDMS) tissue chamber and a pneumatically driven stretch platform. The chamber contained eight tissue microwells (8.05 mm in length and 2.5 mm in width) with a pair of posts (2.78 mm in height and 0.8 mm in diameter) in each well to serve as fixation points and for measurements of contraction force. Carbon rods, stimulating electrodes, were placed into the PDMS chamber such that one pair stimulated four microwells. For feasibility studies, neonatal rat cardiomyocytes were seeded in collagen gels into the microwells. Following 3 days of gel compaction, electrical field stimulation at 3-4 V cm(-1) and 1 Hz, mechanical stimulation of 5% static strain or electromechanical stimulation (field stimulation at 3-4 V cm(-1), 1 Hz and 5% static strain) were applied for 3 days. Cardiac microtissues subjected to electromechanical stimulation exhibited elevated amplitude of contraction and improved sarcomere structure as evidenced by sarcomeric α-actinin, actin and troponin T staining compared to microtissues subjected to electrical or mechanical stimulation alone or non-stimulated controls. The expression of atrial natriuretic factor and brain natriuretic peptide was also elevated in the electromechanically stimulated group.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Miklas
authors.forename: Sara S
authors.initials: SS
authors.lastname: Nunes
authors.forename: Aarash
authors.initials: A
authors.lastname: Sofla
authors.forename: Lewis A
authors.initials: LA
authors.lastname: Reis
authors.forename: Aric
authors.initials: A
authors.lastname: Pahnke
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.forename: Carol
authors.initials: C
authors.lastname: Laschinger
authors.forename: Milica
authors.initials: M
authors.lastname: Radisic
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods
chemical_list: D009124:Muscle Proteins; D048049:Extracellular Signal-Regulated MAP Kinases