title: Trans-apical versus surgical implantation of autologous ovine tissue-engineered heart valves.
abstract: OBJECTIVE
  Living tissue-engineered heart valves (TEHVs) based on rapidly degrading scaffolds and autologous cells might overcome the limitations of today's valve substitutes. Following minimally invasive trans-apical implantation into an ovine model, TEHVs showed adequate in-vivo functionality, but a thickening of the leaflets was observed. In order to evaluate the impact of the substantial tissue deformations of TEHVs associated with the crimping procedure during minimally invasive delivery, trans-apical and conventional implantation technologies were compared in an ovine model.
  
  
  METHODS
  Trileaflet heart valves (n=11) based on PGA/P4HB-scaffolds, integrated into self-expandable stents, were engineered from autologous ovine vascular-derived cells. After in-vitro culture, the TEHVs were either implanted surgically (n=5), replacing the native pulmonary valve, or delivered trans-apically (n=6) into the orthotopic pulmonary valve position. In-vivo functionality was assessed by echocardiography and by angiography for up to eight weeks. The tissue compositions of the explanted TEHVs and corresponding control valves were analyzed.
  
  
  RESULTS
  TEHV implantations were successful in all cases. Independent of the implantation method, the explants demonstrated a comparable layered tissue formation with thickening and deposited fibrous layers. Active remodeling of these layers was evident in the explants, as indicated by vascularization of the walls, invasion of the host cells, and the formation of a luminal endothelial layer on the TEHV leaflets.
  
  
  CONCLUSIONS
  This direct comparison of trans-apical and conventional surgical implantation techniques showed that crimping had no adverse effect on the integrity or functional outcome of TEHVs. This suggests that a thickening of TEHVs in vivo is neither caused by nor enhanced by the crimping procedure, but represents a functional tissue remodeling process.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
authors.forename: Petra E
authors.initials: PE
authors.lastname: Dijkman
authors.forename: Anita
authors.initials: A
authors.lastname: Driessen-Mol
authors.forename: Linda M
authors.initials: LM
authors.lastname: de Heer
authors.forename: Jolanda
authors.initials: J
authors.lastname: Kluin
authors.forename: Lex A
authors.initials: LA
authors.lastname: van Herwerden
authors.forename: Berhard
authors.initials: B
authors.lastname: Odermatt
authors.forename: Frank P T
authors.initials: FP
authors.lastname: Baaijens
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation; D019060:Minimally Invasive Surgical Procedures; D011664:Pulmonary Valve / Q000473:pathology; D012756:Sheep; D023822:Tissue Engineering