Table 7:

Manufacturing processes for flexible leaflet polymeric heart valves.

Year	Author(s)	Material and process	Results	References
Dip molding, dip coating, dip casting
1959	Kolff et al., Cleveland	PU dissolved in tetrahydrofuran (THF) and poured into an open mold	In vivo – dog implant (mitral, aortic and tricuspid), high mortality due to clotting on surface	[241]
1959	Braunwald & Morrow, Boston	Dacron fabric placed between two-piece male/female mold and filled with liquid PU	In vivo – human implant (mitral), 60 hours and 4 months	[196], [237]
1977	Reul & Ghista, HIA	Leaflet molds dipped into Avcothane-51 PU solution	In vitro – 350+ million cycles in vitro (aortic)	[163]
1980	Russell et al., Boston	Valved conduit – conduit formed first by dipping in Avcothane-51 solution, then leaflet mold inserted into conduit and filled with solution	In vitro – 58+ million cycles In vivo – calf implant 135 days (aortic)	[231]
1982	Wisman et al., Penn State	PU dissolved in N-N-dimethyl acetamide (DMAc), leaflet mold dipped in solution	In vivo – calf, sheep and goat implant (mitral and tricuspid), survival up to 960 days	[204]
1987	Herold et al., HIA	PU dissolved in THF or DMAc, leaflet molds made by electro-erosion and dipped in PU solution	In vitro – 93 million cycles In vivo – calf implant up to 267 days (trileaflet prosthetic in mitral position)	[214]
1991	Jansen et al., HIA	Leaflet molds and valve stent dipped together into PU solution, after dipping the mold is tumbled in space for even thickness distribution	In vitro – 648 million cycles In vivo – 5 of 7 calves >150 days, outperformed bioprosthetic (trileaflet prosthetic in mitral position)	[212], [242]
1994	Leat & Fisher, Leeds	PU dissolved in dimethyl formamide (DMF), leaflet mold dipped in solution	In vitro – 160+ million cycles	[211]
1995	Wheatley et al., Glasgow	Leaflet molds made by electrical discharge machining (EDM) and dipped in Elast-Eon™ PU-silicone copolymer solution	In vitro – 800 million cycles In vivo – 6-month survival in sheep (trileaflet prosthetic in mitral position)	[35]–[38], [173] [240], [243], [244]
2001	Fisher et al., Leeds	Leaflet mold dipped in Tecothane™ 80A PU solution	In vitro – 362 million cycles (trileaflet)	[39], [245]
2003	Daebritz et al., Munich	Droplets of dissolved ADIAMat PCU deposited onto leaflet mold, thickness intentionally varied to reduce stress at commissures	In vitro – 600/1000 million cycles (aortic/mitral) In vivo – good survival to 5 months in calves, outperformed bioprosthetic	[42], [43], [197] [213]
2005	Yoganathan et al., Georgia Tech	Leaflet mold dipped in Elast-Eon™ solution	In vitro – low flow regions corresponding with thrombus formation in vivo. Thicker leaflets correspond to greater leakage.	[246], [247]
2006	Metzner et al., Kiel & Aachen	Dip-coating in PU to form valved stent for percutaneous, catheter-based delivery	In vivo – good survival in sheep (8 of 9, pulmonary) to 4 weeks	[248], [249]
2009	Seifalian et al., UCL	POSS-PCU dissolved in DMAc, leaflet molds dipped in solution, design later adapted for percutaneous delivery, dipping process automated to improve reproducibility	In vitro – lower leakage vs. commercial TAVI bioprosthetics	[46], [ 188] [47], [185]
2016	Zilla et al., SAT	Dip molding or spray molding of dissolved SAT polymer onto leaflet mold	In vitro – 600 million cycles In vivo – 8 weeks in sheep	[250], [251]
Injection/compression/cavity molding
1958, 1966	Roe et al., San Francisco	Silastic silicone, heated to 177 °C in a compression molding die for 1 hour, removed from die and heat cured at 204 °C for 4 hours In a later iteration, SE-555 silicone heated to 132 °F in the molding die at 100 MPa	In vitro – 786 million In vivo – 18 clinical human implants, 4 post-operative survivors from 79-100 months (aortic)	[200]–[202], [239]
1965	Braunwald & Morrow, Boston	Plain PTFE fabric and PTFE fabric coated with PTFE dispersion	In vivo – 23 clinical human implants, 15 died or required reoperation due to severe regurgitation (aortic)	[252]
1973	Mohri, U. of Washington	Silastic silicone injected into a compression molding die, pressurized to 41 MPa for 5 minutes, air and overflow evacuated, then pressure increased to 62 MPa for 1 minute, vulcanization in oven at 148.9 °C for 50 minutes, then valve removed from die and cured at 148.9 °C for 2.5 hours	In vitro – durability equivalent to 18-25.5 years	[253]
1980	Chetta & Lloyd, Notre Dame	Two-piece male/female mold filled with RTV-615, a room temperature vulcanizing silicone rubber	In vitro – functioned for 280 million cycles until work hardening of silicone rubber prevented leaflet opening	[222]
1989	Kolff & Yu, Utah	Silastic silicone, stent and leaflet molded at same time on a cylindrical mold	N/A	[254]
2004	Jiang et al., Ontario	Polyvinyl alcohol cryogel (PVA-C), cavity mold injected with hot PVA-water solution, then sealed, clamped and immersed in water bath with controlled freeze/thaw cycles.	N/A	[205]
2009	Mohammadi et al., Ontario	Polyvinyl alcohol-bacterial cellulose (PVA-BC) composite, cavity molding process similar to Jiang et al.	N/A	[176], [190], [191]
2013	Bluestein et al., Stony Brook	Raw xSIBS compressed under vacuum in a mold at 260 °C with 1 ton of force for 30 minutes. Mold fabricated by EDM.	In vitro – 400+ million cycles, hydrodynamics comparable to bioprostheses	[45], [165], [215]
2014	Stasiak et al., Cambridge, UK	Injection molding of SIS30 block copolymer to introduce bidirectional, anisotropic cylinder orientatio	In vitro – 3+ million cycles	[218]
2015	De Gaetano et al., Cambridge, UK	Compression molding of styrene block copolymers to introduce anisotropy and microstructural orientation	In vitro – EOA and regurgitation comparable to mechanical and bioprosthetic valves	[255], [256]
Film fabrication
1960	McGoon, Mayo Clinic	PTFE cloth impregnated with PU	In vivo – 98 implantations	[181]
1974	Gerring et al., Oxford	Terylene (PET) fabric coated with Silastic by press curing, then cut and bonded to sewing ring Also, films of Biomer (PU) cast from solution onto glass plate, then cut and bonded to sewing ring	In vivo – survival up to 30+/21+ months for Silastic/Biomer implants in calves (pulmonary)	[182]
1977	Imamura et al., Mayo Clinic	Gore-Tex® (ePTFE) assembled in multilayer laminate to reduce porosity and improve strength, sutured to support frame with additional ePTFE layers for reinforcement	In vivo – survivability 12/28 dogs up to 15 months (tricuspid)	[216], [257]
1989	Kolff & Yu, Utah	Pellethane® polyurethane, vacuum formed or solution cast	In vivo – 5/5 sheep up to 15 months	[254]
1990	Nistal et al., Spain	Gore-Tex® ePTFE (no report of fabrication process)	In vivo – survival up to 42 weeks in sheep (tricuspid)	[224]
1995	Leat & Fisher, Leeds	Solvent casting of flat PU films, cut and bonded to valve frame, then thermally formed into alpharabola geometry on a mold	In vitro – 100 million cycles	[161], [211]
2005	Koh et al., Osaka	Gore-Tex® (ePTFE) membrane cut and sutured to either bovine pericardium or Gore-Tex® vascular grafts. Radiopaque markers sutured to center of leaflet free edges to imitate the nodulus of Arantius	In vivo – 47 human implants (pulmonary), no significant obstruction after 1 month – 7 years	[225]
2009	Ando & Takahashi, Tokyo	Gore-Tex® (ePTFE) membrane manually cut, folded, and sutured to create three pockets that comprise the valve, then sutured within a Dacron conduit to make a valved conduit	In vivo – 139 human implants (pulmonary), good survivability and competence at 10 years	[40]
2010	Wang et al., Innovia	SIBS dissolved in toluene and cast around a Dacron mesh to produce a flat sheet with uniform thickness, leaflet cut and sewn onto a molded SIBS stent using polyester sutures	In vivo – poor survivability (1/4) of sheep aortic implant, valve failure due to material damage and calcification	[165], [169], [258]
2014	Prawel et al., Colorado State	Leaflets formed with a cylindrical sheet of hyaluronanlinear low-density polyethylene interpenetrating networks (HA/LLDPE IPN)	In vitro – EOA higher than bioprostheses, comparable regurgitation	[235]
2014	Zhang et al., Shanghai	Films of Gore-Tex® (ePTFE) dip-coated in phosphorylcholine, then trimmed and sutured to stent	In vivo – good survivability in sheep (9 of 9) to 4 weeks (pulmonary)	[41]
2017	Basir et al., Netherlands	Valve made from textile of woven ultra-high-molecular-weight polyethylene (UHMWPE) fibers and affixed to stent	In vivo – 17/18 sheep survived to 6 months (pulmonary)	[259]
2019	Guo et al., Shenyang	Anisotropic PET fabric impregnated with PEGDA hydrogel, trimmed and sutured to nitinol stent	In vitro – Large EOA and low regurgitation	[236]