BACKGROUND AND AIM OF THE STUDY: 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. CONCLUSION: 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.
BACKGROUND AND AIM OF THE STUDY: 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. CONCLUSION: 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: Petra E Dijkman; Emanuela S Fioretta; Laura Frese; Francesco S Pasqualini; Simon P Hoerstrup Journal: Transfus Med Hemother Date: 2016-07-26 Impact factor: 3.747
Authors: Emanuela S Fioretta; Sarah E Motta; Valentina Lintas; Sandra Loerakker; Kevin K Parker; Frank P T Baaijens; Volkmar Falk; Simon P Hoerstrup; Maximilian Y Emmert Journal: Nat Rev Cardiol Date: 2020-09-09 Impact factor: 32.419
Authors: Iyore A James; Tai Yi; Shuhei Tara; Cameron A Best; Alexander J Stuber; Kejal V Shah; Blair F Austin; Tadahisa Sugiura; Yong-Ung Lee; Joy Lincoln; Aaron J Trask; Toshiharu Shinoka; Christopher K Breuer Journal: Tissue Eng Part C Methods Date: 2015-05-29 Impact factor: 3.056
Authors: Zeeshan Syedain; Jay Reimer; Jillian Schmidt; Matthew Lahti; James Berry; Richard Bianco; Robert T Tranquillo Journal: Biomaterials Date: 2015-09-11 Impact factor: 12.479
Authors: Emanuela S Fioretta; Valentina Lintas; Anna Mallone; Sarah E Motta; Lisa von Boehmer; Petra E Dijkman; Nikola Cesarovic; Etem Caliskan; Héctor Rodriguez Cetina Biefer; Miriam Lipiski; Mareike Sauer; Matilde Putti; Henk M Janssen; Serge H Söntjens; Anthal I P M Smits; Carlijn V C Bouten; Maximilian Y Emmert; Simon P Hoerstrup Journal: JACC Basic Transl Sci Date: 2019-12-11