Optimization of Engineered Ovine Pulmonary Heart Valve Leaflet Tissue Shape for Single Leaflet Replacement

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.

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.


2016 ◽  
Vol 720 ◽  
pp. 130-140
Author(s):  
Berrak Bulut ◽  
Ziya Engin Erkmen ◽  
Eyup Sabri Kayali

Hydroxyapatite (HA) is a very popular bioceramic for orthopedic and dental applications. Although HA has excellent biocompatibility, its inferior mechanical properties make it unsuitable for load-bearing implant applications. Therefore, HA should be strengthened by a secondary phase for robust mechanical properties. The aim of this study was to compare the properties of HA-Al2O3 (HAC) and HA-ZrO2 (HZC) composites with the addition of 5 and 10 wt% commercial inert glass (CIG); independently. The mixture powders were pressed and then, the pellets were sintered between 1000-1300 °C for 4 hours. Microstructural characterizations were carried out using SEM + EDS and XRD, while hardness and compression tests were done to measure mechanical properties. In order to investigate the biocompatibility behavior of the samples in vitro and in vivo tests were performed. The mechanical properties of HAC composites increased with rising CIG content and increasing sintering temperature. For HZC composites, increasing CIG content caused an elevation in hardness and a decrease in compressive strength values at 1300 °C. The composites having the best physical and mechanical properties also showed improved bioactive properties at in vitro test. In this study, the ideal composite was selected as HZC5 sintered at 1200 °C depending on the microstructure, mechanical and biocompatibility properties.


1996 ◽  
Vol 24 (3) ◽  
pp. 325-331
Author(s):  
Iain F. H. Purchase

The title of this paper is challenging, because the question of how in vitro methods and results contribute to human health risk assessment is rarely considered. The process of risk assessment usually begins with hazard assessment, which provides a description of the inherent toxicological properties of the chemical. The next step is to assess the relevance of this to humans, i.e. the human hazard assessment. Finally, information on exposure is examined, and risk can then be assessed. In vitro methods have a limited, but important, role to play in risk assessment. The results can be used for classification and labelling; these are methods of controlling exposure, analogous to risk assessment, but without considering exposure. The Ames Salmonella test is the only in vitro method which is incorporated into regulations and used widely. Data from this test can, at best, lead to classification of a chemical with regard to genotoxicity, but cannot be used for classification and labelling on their own. Several in vitro test systems which assess the topical irritancy and corrosivity of chemicals have been reasonably well validated, and the results from these tests can be used for classification. The future development of in vitro methods is likely to be slow, as it depends on the development of new concepts and ideas. The in vivo methods which currently have reasonably developed in vitro alternatives will be the easiest to replace. The remaining in vivo methods, which provide toxicological information from repeated chronic dosing, with varied endpoints and by mechanisms which are not understood, will be more difficult to replace.


1995 ◽  
Vol 23 (1) ◽  
pp. 61-73
Author(s):  
Coenraad Hendriksen ◽  
Johan van der Gun

In the quality control of vaccine batches, the potency testing of inactivated vaccines is one of the areas requiring very large numbers of animals, which usually suffer significant distress as a result of the experimental procedures employed. This article deals with the potency testing of diphtheria and tetanus toxoids, two vaccines which are used extensively throughout the world. The relevance of the potency test prescribed by the European Pharmacopoeia monographs is questioned. The validity of the potency test as a model for the human response, the ability of the test to be standardised, and the relevance of the test in relation to the quality of the product are discussed. It is concluded that the potency test has only limited predictive value for the antitoxin responses to be expected in recipients of these toxoids. An alternative approach for estimating the potency of toxoid batches is discussed, in which a distinction is made between estimation of the immunogenic potency of the first few batches obtained from a seed lot and monitoring the consistency of the quality of subsequent batches. The use of animals is limited to the first few batches. Monitoring the consistency of the quality of subsequent batches is based on in vitro test methods. Factors which hamper the introduction and acceptance of the alternative approach are considered. Finally, proposals are made for replacement, reduction and/or refinement (the Three Rs) in the use of animals in the routine potency testing of toxoids.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erfan Dashtimoghadam ◽  
Farahnaz Fahimipour ◽  
Andrew N. Keith ◽  
Foad Vashahi ◽  
Pavel Popryadukhin ◽  
...  

AbstractCurrent materials used in biomedical devices do not match tissue’s mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.


Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1797
Author(s):  
Manuel Toledano ◽  
Marta Vallecillo-Rivas ◽  
María T. Osorio ◽  
Esther Muñoz-Soto ◽  
Manuel Toledano-Osorio ◽  
...  

Barrier membranes are employed in guided bone regeneration (GBR) to facilitate bone in-growth. A bioactive and biomimetic Zn-doped membrane with the ability to participate in bone healing and regeneration is necessary. The aim of the present study is to state the effect of doping the membranes for GBR with zinc compounds in the improvement of bone regeneration. A literature search was conducted using electronic databases, such as PubMed, MEDLINE, DIMDI, Embase, Scopus and Web of Science. A narrative exploratory review was undertaken, focusing on the antibacterial effects, physicochemical and biological properties of Zn-loaded membranes. Bioactivity, bone formation and cytotoxicity were analyzed. Microstructure and mechanical properties of these membranes were also determined. Zn-doped membranes have inhibited in vivo and in vitro bacterial colonization. Zn-alloy and Zn-doped membranes attained good biocompatibility and were found to be non-toxic to cells. The Zn-doped matrices showed feasible mechanical properties, such as flexibility, strength, complex modulus and tan delta. Zn incorporation in polymeric membranes provided the highest regenerative efficiency for bone healing in experimental animals, potentiating osteogenesis, angiogenesis, biological activity and a balanced remodeling. Zn-loaded membranes doped with SiO2 nanoparticles have performed as bioactive modulators provoking an M2 macrophage increase and are a potential biomaterial for promoting bone repair. Zn-doped membranes have promoted pro-healing phenotypes.


Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 360
Author(s):  
Xiaojian Zhang ◽  
Kaili Dai ◽  
Chenyu Liu ◽  
Haofeng Hu ◽  
Fulin Luo ◽  
...  

Biomimetic microspheres containing alginate/carboxymethylcellulose/gelatin and coated with 0%, 1%, 3%, and 6% berberine (BACG, BACG-1B, BACG-3B, BACG-6B) were prepared by the oil-in-water emulsion method combined with spray drying. Through a series of physicochemical parameters and determination of hemostatic properties in vitro and in vivo, the results indicated that BACG and BACG-Bs were effective in inducing platelet adhesion/aggregation and promoting the hemostatic potential due to their biomimetic structure and rough surface. In addition, BACG-6B with high berberine proportion presented better hemostatic performance compared with the commercial hemostatic agent compound microporous polysaccharide hemostatic powder (CMPHP). BACG-6B also showed strong antibacterial activity in the in vitro test. The hemolysis test and cytotoxicity evaluation further revealed that the novel composite biomaterials have good hemocompatibility and biocompatibility. Thus, BACG-6B provides a new strategy for developing a due-functional (hemostat/antibacterial) biomedical material, which may have broad and promising applications in the future.


Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 778 ◽  
Author(s):  
Ruben Daum ◽  
Dmitri Visser ◽  
Constanze Wild ◽  
Larysa Kutuzova ◽  
Maria Schneider ◽  
...  

Appropriate mechanical properties and fast endothelialization of synthetic grafts are key to ensure long-term functionality of implants. We used a newly developed biostable polyurethane elastomer (TPCU) to engineer electrospun vascular scaffolds with promising mechanical properties (E-modulus: 4.8 ± 0.6 MPa, burst pressure: 3326 ± 78 mmHg), which were biofunctionalized with fibronectin (FN) and decorin (DCN). Neither uncoated nor biofunctionalized TPCU scaffolds induced major adverse immune responses except for minor signs of polymorph nuclear cell activation. The in vivo endothelial progenitor cell homing potential of the biofunctionalized scaffolds was simulated in vitro by attracting endothelial colony-forming cells (ECFCs). Although DCN coating did attract ECFCs in combination with FN (FN + DCN), DCN-coated TPCU scaffolds showed a cell-repellent effect in the absence of FN. In a tissue-engineering approach, the electrospun and biofunctionalized tubular grafts were cultured with primary-isolated vascular endothelial cells in a custom-made bioreactor under dynamic conditions with the aim to engineer an advanced therapy medicinal product. Both FN and FN + DCN functionalization supported the formation of a confluent and functional endothelial layer.


2022 ◽  
Vol 12 (2) ◽  
pp. 411-416
Author(s):  
Liang Tang ◽  
Si-Yu Zhao ◽  
Ya-Dong Yang ◽  
Geng Yang ◽  
Wen-Yuan Zhang ◽  
...  

To investigate the degradation, mechanical properties, and histocompatibility of weft-knitted silk mesh-like grafts, we carried out the In Vitro and In Vivo silk grafts degradation assay. The In Vitro degradation experiment was performed by immersing the silk grafts in simulated body fluid for 1 year, and the results showed that the degradation rate of the silk mesh-like grafts was very slow, and there were few changes in the mechanical properties and quality of the silk mesh-like graft. In Vivo degradation assay was taken by implantation of the silk mesh-like grafts into the subcutaneous muscles of rabbits. At 3, 6, and 12 months postoperation, the rate of mass loss was 19.36%, 31.84%, and 58.77%, respectively, and the maximum load was 63.85%, 34.63%, and 10.76%, respectively of that prior to degradation. The results showed that the degradation rate of the silk graft and the loss of mechanical properties In Vivo were faster than the results obtained in the In Vitro experiments. In addition, there were no significant differences in secretion of serum IL-6 and TNF-α between the experimental and normal rabbits (P >0.05), suggesting no obvious inflammatory reaction. The findings suggest that the weft-knitted silk mesh-like grafts have good mechanical properties, histocompatibility, and In Vivo degradation rate, and therefore represent a candidate material for artificial ligament


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