Novel transcatheter aortic heart valves exhibiting excellent hemodynamic performance and low-fouling property

doi:10.1016/j.jmst.2018.09.026

Abstract

Abstract:

Transcatheter aortic heart valves (TAHVs) have been widely used for aortic valve replacements, with less trauma and lower clinical risk compared with traditional surgical heart valve replacements. In the present study, composites of poly(ethylene glycol) diacrylate (PEGDA) hydrogels and anisotropic high-shrinkage polyethylene terephthalate/polyamide6 (PET-PA6) fabric (PEGDA/PET-PA6) were fabricated as artificial heart valve leaflets. Dynamic mechanical analyses (DMA) indicated that PEGDA/PET-PA6 composites possessed anisotropic mechanical properties (i.e., storage moduli ～23.30 ± 1.36 MPa parallel to the aligned fabric fibers and ～9.68 ± 0.90 MPa perpendicular to the aligned fibers at 1 Hz) that were comparable to aortic valve leaflets. The PEGDA/PET-PA6 composites with smooth surfaces were highly hydrophilic (contact angle ～41.6° ± 3.8°) and had low-fouling properties without platelet adhesion, suggesting a low risk of thrombogenicity when they interacted with blood. Furthermore, transcatheter aortic heart valves were fabricated using nitinol self-expanding frames and PEGDA/PET-PA6 composites as artificial leaflets, which presented excellent hemodynamic performance with a large orifice area (1.75 cm²) and low regurgitation (3.41%), thus meeting the requirements of ISO 5840-3 standard. Therefore, PEGDA/PET-PA6 composites had suitable mechanical properties, good biocompatibility, and low-fouling properties, indicating that they might be used for TAHVs in the future.

Key words: Transcatheter aortic heart valve, Textile fabric, Poly(ethylene glycol) diacrylate, Anti-fouling

F. Guo, K. Jiao, Y. Bai, J. Guo, Q. Chen, R. Yang, X. Zhang. Novel transcatheter aortic heart valves exhibiting excellent hemodynamic performance and low-fouling property[J]. J. Mater. Sci. Technol., 2019, 35(1): 207-215.

Figures/Tables 8

Fig. 1. The PEGDA/PET-PA6 valve was fabricated in four steps: (a) fabrication of artificial heart valve leaflet using PET-PA6 fabric, (b) assembly of transcatheter heart valve, (c) soaking in PEGDA hydrogel solution, and (d) crosslinking by exposure to UV light.

Fig. 2. (a-c) SEM micrographs of fiber arrangement (a, b) and cross section (c) of the PET-PA6 fabric samples. (d-f) Homogeneous infiltration of PEGDA hydrogels into fabrics for PEGDA/PET-PA6 composites (d, e) and cross section of the composite (f).

Fig. 3. (a) 1H NMR spectrum to characterize the acrylate percentage of 3.4?kDa PEGDA that was prepared in the experiment. (b) XRD pattern and (c) DSC curve of PET-PA6 fabric. (d) FTIR measurements of PET-PA6, PEGDA/PET-PA6, and PEGDA hydrogel.

Fig. 4. Stress-strain curves of (a, b) PET-PA6 and (c, d) PEGDA/PET-PA6 samples in two orthogonal directions: (a, c) parallel to the fiber alignment direction (“para”) and (b, d) perpendicular to the fiber alignment direction (“perp”) in DMA tests at a frequency from 1 to 5?Hz. (e) Calculated storage modulus E’ of the PET-PA6 and PEGDA/PET-PA6 samples in two orthogonal directions in the DMA tests at a frequency from 1 to 5?Hz. (f) tanδ values of different samples at 1 and 2?Hz in the DMA tests. *p?<? 0.05, #p?<? 0.001, significant differences among groups.

Table 1 Effective orifice area (EOA) and regurgitant fraction (RF) of the PET-PA6 valve and PEGDA/PET-PA6 valve at different mean arterial pressures.

Samples	MAP (mmHg)	EOA (cm²)	RF (%)
PET-PA6 valve	26	1.58?±?0.02	9.48?±?0.99
	40	1.58?±?0.01	12.44?±?0.86
	60	1.61?±?0.01	16.58?±?0.88
	80	1.56?±?0.01	20.81?±?1.14
	100	1.69?±?0.03	26.18?±?0.91
PEGDA/PET-PA6 valve	100	1.75?±?0.01	3.41?±?0.52

Fig. 5. Pressure and flow rate waveforms of PEGDA/PET-PA6 prototypes from three cycles of opening and closing, (a) aortic pressure (AO), ventricular pressure (VE), and fluid flow rate and (b) systolic pressure gradient over time. Valve morphology is shown at different time points, (c) early diastole, (d) end of diastole, and (e) systolic peak.

Fig. 6. (a, b) Photographs of water droplet contact state when in contact with (a) PET-PA6 fabric and (b) PEGDA/PET-PA6 composite. (c) Water contact angles of PET-PA6 fabric and PEGDA/PET-PA6 composite samples, indicating significant differences in wettability.

Fig. 7. SEM images of (a) platelets adhered on PET-PA6 fabric and (b) the enlargement of platelets from the yellow dashed box in (a). (c, d) SEM images of surfaces of PEGDA/PET-PA6 composites after platelet-rich plasma culture for 2?h.

References

[1]	A. Cribier, H. Eltchaninoff, A. Bash, N. Borenstein, C. Tron, F. Bauer, G.Derumeaux, F. Anselme, F. Laborde, M.B. Leon, Circulation106 (2002)3006-3008.
[2]	W. Sun, C. Martin, T. Pham, Annu. Rev. Biomed. Eng. 16(2014) 53-76.
[3]	D. Fernández, J. Cevallos, S. Brugaletta, V. Martín-Yuste, X. Freixa, R. Andrea, C.Falces, A. Regueiro-Cueva, M. Masotti, M. Sabaté, Expert Rev. Med. Devices 10(2014) 185-199.
[4]	G. Lutter, R. Ardehali, J. Cremer, P. Bonhoeffer, Ann. Thorac. Surg. 78(2004)2199-2206.
[5]	S.K. Kodali, M.R. Williams, C.R. Smith, L.G. Svensson, J.G. Webb, R.R. Makkar,G.P. Fontana, T.M. Dewey, V.H. Thourani, A.D. Pichard, M. Fischbein, W.Y.Szeto, S. Lim, K.L. Greason, P.S. Teirstein, S.C. Malaisrie, P.S. Douglas, R.T. Hahn,B. Whisenant, A. Zajarias, D. Wang, J.J. Akin, W.N. Anderson, M.B. Leon, N.Engl. J.Med. 366(2012) 1686-1695.
[6]	D. Dvir, T. Bourguignon, C.M. Otto, R.T. Hahn, R. Rosenhek, J.G. Webb, H.Treede, M. Enriquez-Sarano, T. Feldman, H.C. Wijeysundera, Y. Topilsky, M.Aupart, M. Reardon, M. Burkhard, W. Szeto, R. Kornowski, J. Gammie, A.P.Yoganathan, Y. Arbel, M. Borger, M. Simonato, M. Reisman, R.R. Makkar, A.Abizaid, J. McCabe, G. Dahle, G. Aldea, J. Leipsic, P. Pibarot, N. Moat, M.J. Mack,A.P. Kappetein, M.B. Leon, Circulation23 (2018) 388-399.
[7]	P. Zilla, J. Brink, P. Human, D. Bezuidenhout, Biomaterials 29 (2008)385-406.
[8]	D. Mylotte, A. Andalib, P. Thériault-Lauzier, M. Dorfmeister, M. Girgis, W.Alharbi, M. Chetrit, C. Galatas, S. Mamane, I. Sebag, J. Buithieu, L. Bilodeau, B.De Varennes, K. Lachapelle, R. Lange, G. Martucci, R. Virmani, N. Piazza, Eur.Heart J. 36(2015) 1306-1327.
[9]	D. Bezuidenhout, D.F. Williams, P. Zilla, Biomaterials 36 (2015) 6-25.
[10]	A. Metzner, K. Iino, U. Steinseifer, A. Uebing, W. de Buhr, J.Cremer, G. Lutter, J.Thorac. Cardiovasc. Surg. 139(2010) 748-752.
[11]	T. Attmann, U. Steinseifer, J. Cremer, G. Lutter, Eur. J. Cardio-thorac.Surg. 30(2006) 379.
[12]	B. Zhang, X. Chen, T. Xu, Z. Zhang, X. Li, L. Han, Z. Xu,PLoS One 9 (2014),e100065.
[13]	S. Dimitrievska, A. Petit, C.J. Doillon, L. Epure, A. Ajji, L. Yahia, M.N. Bureau,Macromol. Biosci. 11(2011) 13-21.
[14]	F. Khoffi, F. Heim, N. Chakfe, J.T. Lee, J. Biomed. Mater.Res. Part B Appl.Biomater. 103B(2015) 1488-1497.
[15]	R. Zegdi, P. Bruneval, D. Blanchard, J.N. Fabiani, Eur. J. Cardio-thorac.Surg. 40(2011) 257-259.
[16]	A.E. Munnelly, L. Cochrane, J. Leong, N.R. Vyavahare, Biomaterials 33 (2012)1-8.
[17]	A. Yousefi, A. Vaesken, A. Amri, L.P. Dasi, F. Heim, Ann. Biomed. Eng. 45(2017)476-486.
[18]	J.S. Soares, K.R. Feaver, W. Zhang, D. Kamensky, A. Aggarwal, M.S. Sacks,Cardiovasc. Eng. Technol. 7(2016) 309-351.
[19]	E.A. Phelps, N.O. Enemchukwu, V.F. Fiore, J.C. Sy, N. Murthy, T.A. Sulchek, T.H.Barker, A.J. García, Adv. Mater. 24(2012) 64-70.
[20]	J. Witten, K. Ribbeck, Nanoscale 9 (2017)8080-8095.
[22]	O. Chaudhuri, L. Gu, D. Klumpers, M. Darnell, S.A. Bencherif, J.C. Weaver, N.Huebsch, H.P. Lee, E. Lippens, G.N. Duda, D.J. Mooney, Nat. Mater. 15(2016)326-334.
[22]	J.A. Burdick, W.L. Murphy, Nat. Commun. 3(2012) 1-8.
[23]	A.S. Mao, J.W. Shin, S. Utech, H. Wang, O. Uzun, W. Li, M. Cooper, Y. Hu, L.Zhang, D.A. Weitz, D.J. Mooney, Nat. Mater. 16(2017) 236-243.
[24]	J.A. Benton, B.D. Fairbanks, K.S. Anseth, Biomaterials 30 (2009) 6593-6603.
[25]	J. Zhu, Biomaterials 31 (2010) 4639-4656.
[26]	H. Tseng, D.S. Puperi, E.J. Kim, S. Ayoub, J.V. Shah, M.L. Cuchiara, J.L. West, K.J.Grande-Allen, Tissue Eng. Part A 20 (2014) 2634-2645.
[27]	M. Eslami, N.E. Vrana, P. Zorlutuna, S. Sant, S. Jung, N. Masoumi, R.A.Khavari-Nejad, G.Javadi, A. Khademhosseini, J. Biomater. Appl. 29(2014)399-410.
[28]	H. Mohammadi, Proc. Inst. Mech. Eng.Part H J. Eng. Med. 225(2011) 718-722.
[29]	Q. Li, Y. Bai, T. Jin, S. Wang, W. Cui, I. Stanciulescu, R. Yang, H. Nie, L. Wang, X.Zhang, ACS Appl. Mater. Interfaces 9 (2017) 16524-16535.
[30]	H. Hristov, M. Nedyalkova, S. Madurga, V. Simeonov, J. Mater. Sci.Technol. 33(2017) 535-540.
[31]	K.S. Cho, Berlin, 2016, pp. 283-290.
[32]	K.O. Lim, D.R. Boughner, Cardiovasc. Res. 10(1976) 459-465.
[33]	International Organization for Standardization (ISO), CardiovascularImplants-cardiac Valve Prostheses-heart Valve Substitutes Implanted byTranscatheter Techniques, British Standards Institution, London, 2013, pp.16-18.
[34]	R.A. Nishimura, C.M. Otto, R.O. Bonow, B.A. Carabello, J.P. Erwin, L.A. Fleisher,H. Jneid, M.J. Mack, C.J.McLeod, P.T. O’Gara, V.H. Rigolin, T.M. Sundt, A.Thompson, Circulation 135 (2017), e1159-e1195.
[35]	J. Jiang, C. Ai, Z. Zhan, P. Zhang, F. Wan, J. Chen, W. Hao, Y. Wang, J. Yao, Z.Shao, T. Chen, L. Zhou, S. Chen, Artif. Organs 40 (2016) 385-393.
[36]	A. Abdal-Hay, H.R. Pant, J.K. Lim, Eur. Polym. J. 49(2013) 1314-1321.
[37]	H. Van Damme, M. Deprez, E. Creemers, R. Limet, Acta Chir. Belg. 105(2005)249-255.
[38]	R. Guidoin, R. Zegdi, J. Lin, J. Mao, O. Rochette-Drouin, D. How, X. Guan, P.Bruneval, L. Wang, L. Germain, Z. Zhang, Morphologie100 (2016) 234-244.
[39]	A. Vaesken, A. Pelle, G. Pavon-Djavid, J. Rancic, N. Chakfe, F. Heim, Biomed.Eng. Biomed. Technol. 28 (March) (2017) 476-486.
[40]	J. Yang, J. Wang, J. Mater. Sci.Technol. 20(2004) 769-771.
[41]	M. Shayan, Y. Chun, Acta Biomater. 21(2015) 20-34.
[42]	R.B. Hinton, K.E. Yutzey, Annu. Rev. Physiol. 73(2011) 29-46.
[43]	K.J. Grande, R.P. Cochran, P.G. Reinhall, K.S. Kunzelma, Ann. Biomed. Eng. 26(1998) 534-545.
[44]	P.A. Lemos, F. Saia, J. Mariani, C. Marrozzini, A.E. Filho, L.J. Kajita, C. Ciuca, N.Taglieri, B. Bordoni, C. Moretti, T. Palmerini, M.D.A.Dracoulakis, F.B. Jatene, R.Kalil-Filho, A.Marzocchi, Int. J. Cardiol. 157(2012) 288-289.
[45]	A.P. Yoganathan, Z. He, S. Casey Jones, Annu. Rev. Biomed. Eng. 6(2004)331-362.
[46]	R.T. Hahn, P. Pibarot, W.J. Stewart, N.J. Weissman, D. Gopalakrishnan, M.G.Keane, S. Anwaruddin, Z. Wang, M. Bilsker, B.R. Lindman, H.C. Herrmann, S.K.Kodali, R. Makkar, V.H. Thourani, L.G. Svensson, J.J. Akin, W.N. Anderson, M.B.Leon, P.S. Douglas, J. Am. Coll.Cardiol. 61(2013) 2514-2521.
[47]	F. Heim, B.S. Gupta, Text. Res. J. 79(2009) 1001-1013.
[48]	O. Rossvoll, S. Samstad, H.G. Torp, D.T. Linker, T. Skj?rpe, B.A.J.Angelsen, L.Hatle, J.Am. Soc. Echocardiogr. 4(1991) 367-378.
[49]	Y. Wang, J. Mater. Sci.Technol. 32(2016) 801-809.
[50]	K. Bazaka, M.V. Jacob, R.J. Crawford, E.P. Ivanova, Acta Biomater. 7(2011)2015-2028.
[51]	P. Dong, W. Hao, Y. Xia, G. Da, T. Wang, J. Mater. Sci.Technol. 26(2010)1027-1031.
[52]	I.H. Jaffer, J.C. Fredenburgh, J. Hirsh, J.I. Weitz,J. Thromb. Haemost. 13(2015),S72-S81.
[53]	P.M.Eric A Rose, C GElijns, ALln J Moskowitz, Daniel F Heitjan, Lynne, WStevenson, Walter Dembitsky, James W Long, D Ascheim, Anita, R Tierney,Ronald G Levitan, John T Watson, N.Engl. J. Med. 345(2001) 1435-1443.
[54]	P. Lundberg, A. Bruin, J.W. Klijnstra, A.M. Nystr?m, M. Johansson, M. Malkoch,A. Hult, ACS Mater. Interfaces 2 (2010) 903-912.
[55]	A.S. Hoffman, Acta Biomater. 40(2016) 1-5.
[56]	M.B. Gorbet, M.V. Sefton, Biomater. Silver Jubil. Compend. 25(2004)5681-5703.