Esophageal reconstruction with ECM and muscle tissue in a dog model.
An in vivo study was conducted to determine if an extracellular matrix (ECM) scaffold co-localized with autologous muscle tissue could achieve constructive remodeling of esophageal tissue without stricture. ECM derived from the porcine urinary bladder was processed, decellularized, configured into a tube shape, and terminally sterilized for use as a bioscaffold for esophageal reconstruction in a dog model. Twenty-two dogs were divided into four groups, three groups of five and one group of seven. Groups 1 and 2 were repaired with either ECM alone or muscle tissue alone, respectively. Groups 3 and 4 were repaired with ECM plus either a partial (30%) covering with muscle tissue or a complete (100%) covering with muscle tissue, respectively. Animals in groups 1 and 2 were sacrificed within approximately 3 weeks because of the formation of intractable esophageal stricture. Four of five dogs in group 3 and six of seven dogs in group 4 were survived for 26 days to 230 days and showed constructive remodeling of esophageal tissue with the formation of well organized esophageal tissue layers, minimal stricture, esophageal motility, and a normal clinical outcome. Mechanical testing of a subset of the remodeled esophageal tissue from animals in groups 3 and 4 showed progressive remodeling from a relatively stiff, non-compliant ECM tube structure toward a tissue with near normal biomechanical properties. We conclude that ECM bioscaffolds plus autologous muscle tissue, but not ECM scaffolds or muscle tissue alone, can facilitate the in situ reconstitution of structurally and functionally acceptable esophageal tissue.
Badylak
Stephen F
SF
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA. badylaks@upmc.edu
Vorp
David A
DA
Spievack
Alan R
AR
Simmons-Byrd
Abby
A
Hanke
Joseph
J
Freytes
Donald O
DO
Thapa
Anil
A
Gilbert
Thomas W
TW
Nieponice
Alejandro
A
D000818:Animals; D001696:Biomechanical Phenomena; D004285:Dogs; D004940:Esophageal Stenosis / Q000209:etiology / Q000517:prevention & control*; D016629:Esophagectomy / Q000009:adverse effects*; D004947:Esophagus / Q000503:physiopathology / Q000601:surgery*; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D023421:Models, Animal; D009130:Muscle, Smooth / Q000502:physiology* / Q000601:surgery; D019651:Plastic Surgery Procedures / Q000379:methods; D020127:Recovery of Function; D023822:Tissue Engineering / Q000379:methods