scholarly journals Biodegradable Poly-ε-Caprolactone Scaffolds with ECFCs and iMSCs for Tissue-Engineered Heart Valves

2022 ◽  
Vol 23 (1) ◽  
pp. 527
Author(s):  
Georg Lutter ◽  
Thomas Puehler ◽  
Lukas Cyganek ◽  
Jette Seiler ◽  
Anita Rogler ◽  
...  

Clinically used heart valve prostheses, despite their progress, are still associated with limitations. Biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds, as a matrix, were seeded with human endothelial colony-forming cells (ECFCs) and human induced-pluripotent stem cells-derived MSCs (iMSCs) for the generation of tissue-engineered heart valves. Cell adhesion, proliferation, and distribution, as well as the effects of coating PCL nanofibers, were analyzed by fluorescence microscopy and SEM. Mechanical properties of seeded PCL scaffolds were investigated under uniaxial loading. iPSCs were used to differentiate into iMSCs via mesoderm. The obtained iMSCs exhibited a comparable phenotype and surface marker expression to adult human MSCs and were capable of multilineage differentiation. EFCFs and MSCs showed good adhesion and distribution on PCL fibers, forming a closed cell cover. Coating of the fibers resulted in an increased cell number only at an early time point; from day 7 of colonization, there was no difference between cell numbers on coated and uncoated PCL fibers. The mechanical properties of PCL scaffolds under uniaxial loading were compared with native porcine pulmonary valve leaflets. The Young’s modulus and mean elongation at Fmax of unseeded PCL scaffolds were comparable to those of native leaflets (p = ns.). Colonization of PCL scaffolds with human ECFCs or iMSCs did not alter these properties (p = ns.). However, the native heart valves exhibited a maximum tensile stress at a force of 1.2 ± 0.5 N, whereas it was lower in the unseeded PCL scaffolds (0.6 ± 0.0 N, p < 0.05). A closed cell layer on PCL tissues did not change the values of Fmax (ECFCs: 0.6 ± 0.1 N; iMSCs: 0.7 ± 0.1 N). Here, a successful two-phase protocol, based on the timed use of differentiation factors for efficient differentiation of human iPSCs into iMSCs, was developed. Furthermore, we demonstrated the successful colonization of a biodegradable PCL nanofiber matrix with human ECFCs and iMSCs suitable for the generation of tissue-engineered heart valves. A closed cell cover was already evident after 14 days for ECFCs and 21 days for MSCs. The PCL tissue did not show major mechanical differences compared to native heart valves, which was not altered by short-term surface colonization with human cells in the absence of an extracellular matrix.

Author(s):  
Zeeshan H. Syedain ◽  
Robert T. Tranquillo

Tissue engineering provides a means to create fully functional tissue-equivalents that can grow, repair and remodel in vivo. Our laboratory’s approach to fabricating artery- and heart valve-equivalents utilizes cell-seeded fibrin gels. However, even after 4–5 weeks of static incubation, the mechanical properties of these constructs are below those of native tissue. Previous studies in our laboratory have shown a significant role of mechanical stretching in improving properties of collagen-based tissue constructs (Isenberg and Tranquillo, 2003). We examined the effects of cyclic distention (CD) of cell-seeded fibrin-based tubular constructs (TC) and valve-equivalents (VE) after five weeks of culture. We used human dermal fibroblasts and porcine valve interstitial cells as the cell sources. Circumferential strain amplitudes from 2.5% to 15% were applied to evaluate the effects of CD on remodeling of the TC. We further hypothesized that during long-term conditioning, cells adapt to CD of constant strain amplitude, diminishing the remodeling into tissue. We tested this hypothesis by applying step-wise incremental CD (ICD) from 5%–15% strain amplitude and compared this group to a set of samples subject to CD of constant strain amplitude in this range. Based on the outcome of the cyclic distension study with tubular constructs, we applied CD to VE in a novel bioreactor.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Mark Vander Roest ◽  
Camryn Johnson ◽  
H. Scott Baldwin ◽  
W. David Merryman

Objectives: Specialized endocardial cells are responsible for the development of heart valves in utero . During a highly regulated morphogenetic process, these endocardial cells undergo endothelial-to-mesenchymal transformation (EMT) to become valve interstitial cells (VICs) and reorganize the extracellular matrix to form the structure of the valves. Potentially, induced pluripotent stem cells (iPSCs) may be coaxed into endocardial cells, then to VICs, to yield a suitable cell source for tissue engineered heart valves. Unfortunately, no method to generate iPSC derived endocardial cells exists. Current biochemical strategies utilize static culture, which does not represent the dynamic mechanical environment of the developing heart, which is known to affect differentiation and function of endocardial cells. Methods and Results: Human iPSCs were differentiated and purified to endothelial progenitors (CD34+), seeded onto collagen IV coated plates, and grown to confluency. Using a FlexCell system and a custom-built fluid shear device (A,B) , mechanical strain and shear stress were administered to the maturing cells independently, which were then assayed via qPCR for changes to endocardial and EMT markers. Bidirectional shear stress (C) was found to downregulate endothelial markers CD31, VE-cadherin and VEGFR2, as well as endocardial specific gene Nfatc1, yet increased expression of EMT markers BMP2 and Snai2. Conversely, unidirectional shear (D) increased Nfatc1 while causing lower expression of BMP2 and Snai2 than bidirectional shear. Cyclic strain decreased both endocardial and EMT markers (E) . Conclusions: These data suggest that unidirectional shear stress maintains an endocardial phenotype, while bidirectional shear stress induces EMT, promoting an interstitial cell phenotype. These stimuli may be utilized to maintain and expand patient-specific endocardial and valve interstitial cells for the creation of tissue engineered heart valves.


Author(s):  
Jeroen Kortsmit ◽  
Niels J. B. Driessen ◽  
Marcel C. M. Rutten ◽  
Frank P. T. Baaijens

Contemporary tissue engineered heart valves seem to have sufficient mechanical strength for implantation [1]. Nevertheless, mechanical properties, tissue structure and architecture still need to be improved. Recent studies indicate enhancement of mechanical properties by applying cyclic diastolic pressure loads to the developing tissue in a bioreactor system [2]. However, current bioreactors operate with a preset transvalvular pressure applied to the tissue. Mechanical properties of the engineered construct may vary during culturing and consequently, the pressure-induced deformations are unknown. To systematically study the effects of mechanical straining on tissue development and to design an optimal conditioning protocol, real-time measurement and control of local tissue strains are desired.


Author(s):  
Jeroen Kortsmit ◽  
Niels J. B. Driessen ◽  
Marcel C. M. Rutten ◽  
Frank P. T. Baaijens

Despite recent progress, mechanical properties of tissue engineered heart valves still lack mechanical strength compared to native aortic valves [1]. Although cyclic tissue straining in bioreactor systems is known to enhance tissue formation [2], specific optimal loading protocols have not yet been defined. To get a better insight in the effects of mechanical loading on tissue development, mechanical behavior of tissue constructs should be monitored and controlled during culture. However, currently used methods for mechanical characterization (e.g. tensile tests, indentation tests) are destructive and can therefore only be performed at the end stage of tissue culture. An experimental-numerical approach was previously proposed by which leaflet deformation was assessed during culture in a bioreactor system, real-time and non-invasively [3]. Further development of this approach now enables a non-invasive and non-destructive assessment of mechanical properties of engineered heart valve leaflets.


2013 ◽  
Vol 873 ◽  
pp. 627-634 ◽  
Author(s):  
Bin En Nie ◽  
Shi Dong Hu ◽  
Jian Liang Zhou

Tissue engineered heart valve (TEHV) is a valve replacement of scaffold materials on which live cells grow. Theoretically, TEHV has good tissue compatibility, self-repair potential and life-long durability, which serves as the optimal replacement for a heart valve. As a result of the specific position and function of a specific heart valve, significantly high requirements of mechanical and biological properties are necessary for optimal function. A substantial number of studies suggested that the TEHV available at present has insufficient mechanical properties and lacks relevant anti-calcification function, both of which prevent the successful application of TEHV into clinical practice. A desirable valvular scaffold, which mimics the three-dimensional ultrastructures of extracellular matrix (ECM) in the heart valve, should possess the ECM bioactivity, favorable tissue compatibility and suitable mechanical properties. However, no such valve scaffold is currently available. Hence, clinical efforts should be made to remodel the scaffold materials, allowing for utilizing its functionalization. Here, we reviewed the scaffold materials previously used in TEHV, e.g. decellularized scaffold, polymer-based scaffold, nanoscaffold and nanocomposite scaffold and scaffold material modification.


2010 ◽  
Vol 58 (S 01) ◽  
Author(s):  
PM Dohmen ◽  
A Lembcke ◽  
S Holinski ◽  
JP Braun ◽  
W Konertz

2021 ◽  
Vol 5 (2) ◽  
pp. 48
Author(s):  
Yuxuan Wang ◽  
Yuke Zhong ◽  
Qifeng Shi ◽  
Sen Guo

Thermoplastic starch/butyl glycol ester copolymer/polylactic acid (TPS/PBSA/PLA) biodegradable composites were prepared by melt-mixing. The structure, microstructure, mechanical properties and heat resistance of the TPS/PBSA/PLA composites were studied by Fourier-transform infrared spectrometry (FTIR), scanning electron microscopy (SEM), tensile test and thermogravimetry tests, respectively. The results showed that PBSA or PLA could bind to TPS by hydrogen bonding. SEM analysis showed that the composite represents an excellent dispersion and satisfied two-phase compatibility when the PLA, TPS and PBSA blended by a mass ration of 10, 30, and 60. The mechanical properties and the heat resistance of TPS/PBSA/PLA composite were improved by adding PLA with content less than 10%, according to the testing results.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mahmoud Haghighi ◽  
Hossein Golestanian ◽  
Farshid Aghadavoudi

Abstract In this paper, the effects of filler content and the use of hybrid nanofillers on agglomeration and nanocomposite mechanical properties such as elastic moduli, ultimate strength and elongation to failure are investigated experimentally. In addition, thermoset epoxy-based two-phase and hybrid nanocomposites are simulated using multiscale modeling techniques. First, molecular dynamics simulation is carried out at nanoscale considering the interphase. Next, finite element method and micromechanical modeling are used for micro and macro scale modeling of nanocomposites. Nanocomposite samples containing carbon nanotubes, graphene nanoplatelets, and hybrid nanofillers with different filler contents are prepared and are tested. Also, field emission scanning electron microscopy is used to take micrographs from samples’ fracture surfaces. The results indicate that in two-phase nanocomposites, elastic modulus and ultimate strength increase while nanocomposite elongation to failure decreases with reinforcement weight fraction. In addition, nanofiller agglomeration occurred at high nanofiller contents especially higher than 0.75 wt% in the two-phase nanocomposites. Nanofiller agglomeration was observed to be much lower in the hybrid nanocomposite samples. Therefore, using hybrid nanofillers delays/prevents agglomeration and improves mechanical properties of nanocomposite at the same total filler content.


Metals ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 80 ◽  
Author(s):  
Mykola Chausov ◽  
Janette Brezinová ◽  
Andrii Pylypenko ◽  
Pavlo Maruschak ◽  
Liudmyla Titova ◽  
...  

A simple technological method is proposed and tested experimentally, which allows for the improvement of mechanical properties in sheet two-phase high-strength titanium alloys VT23 and VT23M on the finished product (rolled metal), due to impact-oscillatory loading. Under impact-oscillatory loading and dynamic non-equilibrium processes (DNP) are realized in titanium alloys, leading to the self-organization of the structure. As a result, the mechanical properties of titanium alloys vary significantly with subsequent loading after the realization of DNP. In this study, the test modes are found, which can be used in the production conditions.


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