Design of Tissue-Engineered Leaflet Shape for the Ovine Pulmonary Valve Single Leaflet Replacement Surgery

Author(s):  
Rong Fan ◽  
Christopher M. Hobson ◽  
Ahmed Bayoumi ◽  
John E. Mayer ◽  
William R. Wagner ◽  
...  

Pulmonary valve (PV) replacement surgery is a treatment option for patients with a congenitally defective pulmonary outflow track. A tissue engineered pulmonary valve (TEPV) is a potential approach to serve as a replacement pediatric heart valve that has the potential for somatic growth. The single leaflet replacement surgical model can assist in assessing candidate biomaterials responses to in-vivo function. However, an empirically determined unloaded leaflet shape may result in abnormal valve function due to incomplete coaptation of leaflets and asymmetric stress distributions. Thus, to determine the final deformed shape of an engineered scaffold replacement PV leaflet under transvalvular pressure the following key factors must be determined: the scaffold anisotropic mechanical properties, optimal thickness, and the exact initial leaflet shape. We have used electrospun poly (ester urethane) ureas (ES-PEUU) scaffolds since they exhibit mechanical properties very similar to the native PV [1]. In this work we present a design framework of the optimal leaflet shape determination utilizing a single sheet of ES-PEUU for single leaflet replacement surgery via finite element (FE) simulation. The mechanical properties of ES-PEUU scaffold for leaflet replacement were obtained from biaxial in-plane tension and three-point bending flexural deformation experiments. Generalized Fung-type hyperelastic constitutive model [2] was implemented into a commercial FE software package to simulate the mechanical behavior of ES-PEUU scaffolds. By perturbing the initial shape of leaflet and simulating its quasi-static deformation under PV diastolic loading, the optimal shape of unloaded leaflet can be determined by comparing the deformed shape of leaflet obtained from FE simulation of TEPV with the one from microCT scan of a native ovine PV.

Author(s):  
Rong Fan ◽  
Michael S. Sacks ◽  
Ahmed Bayoumi ◽  
John E. Mayer ◽  
Christopher M. Hobson ◽  
...  

Pulmonary valve (PV) replacement surgery is a treatment option for patients with a congenitally defective pulmonary outflow track. While a tissue engineered approach offers many potential advantages, develop of such a valve involves a complex process of optimization. As an intermediate step, we have used a single leaflet replacement surgical model to further our understanding of the in-vivo remodeling process. A critical step is to determine the deformed shape of the replacement PV leaflet under transvalvular pressure. Key factors in this process are: the scaffold anisotropic mechanical properties, optimal thickness, and the exact initial leaflet shape. We have used electrospun poly (ester urethane) ureas (ES-PEUU) scaffolds since they exhibit mechanical properties very similar to the native PV. In this work we present a design framework of the optimal leaflet shape determination utilizing a single sheet of ES-PEUU for single leaflet replacement surgery via finite element (FE) simulation. The mechanical properties of ES-PEUU scaffold for leaflet replacement were obtained from biaxial in-plane tension experiments. Generalized Fung-type hyperelastic constitutive model [1] was implemented into a commercial FE software package to simulate the deformation of ES-PEUU scaffolds under pressure. By perturbing the initial shape of leaflet and simulating its quasi-static deformation under PV diastolic loading, the optimal shape of unloaded leaflet was determined by comparing the deformed shape of leaflet obtained from FE simulation of TEPV with the one from microCT scan of a native ovine PV. In-vitro test of PV after single leaflet replacement was also conducted to validate the developed method.


2009 ◽  
Vol 131 (10) ◽  
Author(s):  
Brendon M. Baker ◽  
Nandan L. Nerurkar ◽  
Jason A. Burdick ◽  
Dawn M. Elliott ◽  
Robert L. Mauck

Aligned nanofibrous scaffolds hold tremendous potential for the engineering of dense connective tissues. These biomimetic micropatterns direct organized cell-mediated matrix deposition and can be tuned to possess nonlinear and anisotropic mechanical properties. For these scaffolds to function in vivo, however, they must either recapitulate the full dynamic mechanical range of the native tissue upon implantation or must foster cell infiltration and matrix deposition so as to enable construct maturation to meet these criteria. In our recent studies, we noted that cell infiltration into dense aligned structures is limited but could be expedited via the inclusion of a distinct rapidly eroding sacrificial component. In the present study, we sought to further the fabrication of dynamic nanofibrous constructs by combining multiple-fiber populations, each with distinct mechanical characteristics, into a single composite nanofibrous scaffold. Toward this goal, we developed a novel method for the generation of aligned electrospun composites containing rapidly eroding (PEO), moderately degradable (PLGA and PCL/PLGA), and slowly degrading (PCL) fiber populations. We evaluated the mechanical properties of these composites upon formation and with degradation in a physiologic environment. Furthermore, we employed a hyperelastic constrained-mixture model to capture the nonlinear and time-dependent properties of these scaffolds when formed as single-fiber populations or in multipolymer composites. After validating this model, we demonstrated that by carefully selecting fiber populations with differing mechanical properties and altering the relative fraction of each, a wide range of mechanical properties (and degradation characteristics) can be achieved. This advance allows for the rational design of nanofibrous scaffolds to match native tissue properties and will significantly enhance our ability to fabricate replacements for load-bearing tissues of the musculoskeletal system.


2011 ◽  
Vol 5 (2) ◽  
Author(s):  
Rong Fan ◽  
Christopher Hobson ◽  
Ahmed Bayoumi ◽  
John Mayer ◽  
William Wagner ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Minliang Liu ◽  
Liang Liang ◽  
Fatiesa Sulejmani ◽  
Xiaoying Lou ◽  
Glen Iannucci ◽  
...  

Abstract Accurate identification of in vivo nonlinear, anisotropic mechanical properties of the aortic wall of individual patients remains to be one of the critical challenges in the field of cardiovascular biomechanics. Since only the physiologically loaded states of the aorta are given from in vivo clinical images, inverse approaches, which take into account of the unloaded configuration, are needed for in vivo material parameter identification. Existing inverse methods are computationally expensive, which take days to weeks to complete for a single patient, inhibiting fast feedback for clinicians. Moreover, the current inverse methods have only been evaluated using synthetic data. In this study, we improved our recently developed multi-resolution direct search (MRDS) approach and the computation time cost was reduced to 1~2 hours. Using the improved MRDS approach, we estimated in vivo aortic tissue elastic properties of two ascending thoracic aortic aneurysm (ATAA) patients from pre-operative gated CT scans. For comparison, corresponding surgically-resected aortic wall tissue samples were obtained and subjected to planar biaxial tests. Relatively close matches were achieved for the in vivo-identified and ex vivo-fitted stress-stretch responses. It is hoped that further development of this inverse approach can enable an accurate identification of the in vivo material parameters from in vivo image data.


2010 ◽  
Vol 36 (5) ◽  
pp. 789-801 ◽  
Author(s):  
Jean-Luc Gennisson ◽  
Thomas Deffieux ◽  
Emilie Macé ◽  
Gabriel Montaldo ◽  
Mathias Fink ◽  
...  

Author(s):  
David E. Schmidt ◽  
Michael S. Sacks

Tissue engineered pulmonary valves (TEPV) represent a conceptually appealing alternative to current non-viable prosthetic valves and valved conduits for the repair of congenital or acquired lesions in pediatric patients. In addition to the identification of clinically feasible cell sources, engineered soft tissues such as the TEPV require scaffolds with anisotropic mechanical properties that undergo large deformations (not possible with current PGA/PLLA non-wovens) coupled with controllable biodegradative and cell-adhesive characteristics. Electrospun PEUU (ES-PEUU) scaffolds have been produced with tensile biaxial mechanical properties remarkably similar to the native pulmonary valve (Fig. 1-a), including the ability to undergo large physiologic strains and exhibit pronounced mechanical anisotropy. Moreover, a novel cell micro-integration technique has been developed that allows for successful cell integration directly into the scaffolds at the time of fabrication, eliminating cellular penetration problems. These encouraging results suggest that ES-PEUU scaffolds micro-integrated with the appropriate cells and can serve as successful TEPV scaffolds. In the present study, we conducted a finite element based analysis of TEPV leaflets (Fig. 1-b) under quasi-static transvalvular pressure to demonstrate the impact of ES-PEUU mechanical anisotropy on scaffold strain distributions.


Author(s):  
Chad E. Eckert ◽  
Danielle Gottlieb ◽  
Robert F. Padera ◽  
Frederick J. Schoen ◽  
John E. Mayer ◽  
...  

Current clinical options for congential pulmonary valve disease are limited and associated with several complications, including lack of somatic growth in replacements. Often, surgical intervention also requires the reconstruction of the right ventricular outflow tract. Tissue engineered pulmonary valved conduits have received much attention as a potential therapy, offering prospective long-term functional improvements and accommodating somatic growth [1]. Though in vitro work has been performed, little is known concerning the physical properties and quality of the tissue produced in vivo, owing to small specimen sample sizes and a lack of detailed mechanical analyses. This work focuses on elucidating in vivo time-course changes in the mechanical quality of tissue engineered pulmonary valve conduit.


Radiology ◽  
2014 ◽  
Vol 273 (3) ◽  
pp. 726-735 ◽  
Author(s):  
Eric C. Qin ◽  
Lauriane Jugé ◽  
Simon A. Lambert ◽  
Valérie Paradis ◽  
Ralph Sinkus ◽  
...  

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