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Biocomposites reinforced with soft coral collagen fibers: towards bio-inspired cardiovascular tissue therapies


Shir Wertheimer(1), Mirit Sharabi(2), Rami Haj-Ali(1)

Affiliations: (1)Tel Aviv University,  (2) Ariel University


Contact:

Shir Wertheimer – shirwerth@gmail.com


Abstract:

Cardiovascular Diseases (CVDs) are the leading cause of death worldwide.  Two common CVDs, aortic stenosis (AS) and coronary artery disease (CAD), are characterized by narrowing that restricts the normal blood flow through the valve and the arteries, respectively. In severe cases of CAD, surgical interventions are conducted to implant autologous vessels. Synthetic grafts often fail in the case of small-diameter (<6mm) blood vessels (SDBV). The treatment in severe AS cases includes an AV prosthesis, either mechanical heart valve or a bioprosthetic valve, each with its assets and drawbacks. Therefore, there is a real need for engineered SDBV and an ideal prosthetic AV that will mimic the mechanical properties and the microstructure of the native tissues. 

This study introduces a new class of biocomposite material systems consisting of unique and long (cm-scale) collagen fibers derived from soft corals embedded within a hydrogel matrix, for cardiovascular applications. Tubular constructs consisting of both circumferentially and longitudinally oriented collagen fibers and alginate matrix were fabricated and mechanically tested with a new inflation testing setup. The biocomposite tubes demonstrated compliance of 4.88±0.99 %/100 mmHg for a physiologic pressure range of 80-120 mmHg, similar to native coronary arteries. In addition, a numerical finite element (FE) simulation model is proposed to simulate the hyperelastic mechanical response of the biocomposite construct.  A good prediction is demonstrated when compared with the measured pressure-strain response [1]. Furthermore, a parametric model of the AV is used to design and optimize a biohybrid construct for AV cusps biomimicking, by tailoring the mechanical response according to the native tissue. 

In-vitro biocompatibility tests and cell growth on the collagen fibers were also conducted using fibroblast cells. The experiment lasted for 32 days and showed cell-configurations aligned with the collagen fiber orientation [2]. The proposed novel biocomposite graft demonstrated both mechanical and biological compatibility and can be the basis for future SDBV grafts and AV prostheses.


Representative Results:






Paper Publication

[1] Wertheimer, S., Sharabi, M., Shelah, O., Lesman, A., & Haj-Ali, R. (2021). Bio-composites reinforced with unique coral collagen fibers: Towards biomimetic-based small diameter vascular grafts. Journal of the Mechanical Behavior of Biomedical Materials, 119, 104526.


[2] Shelah, O., Wertheimer, S., Haj-Ali, R., & Lesman, A. (2021). Coral-derived collagen fibers for engineering aligned tissues. Tissue Engineering Part A, 27(3-4), 187-200.


[3] Sharabi, M., Wertheimer, S., Wade, K. R., Galbusera, F., Benayahu, D., Wilke, H. J., & Haj-Ali, R. (2019). Towards intervertebral disc engineering: Bio-mimetics of form and function of the annulus fibrosus lamellae. Journal of the Mechanical Behavior of Biomedical Materials, 94, 298-307.


Education

02/2019-Present:  Ph.D. student in Mechanical Engineering  

School of Mechanical Engineering, Engineering Faculty, Tel Aviv University 

Dissertation title: “Bio-Composites based on soft coral collagen: towards cardiovascular replacements". 

Supervisor: Professor Rami Haj-Ali

10/2016-01/2019:  M.Sc. in Mechanical Engineering (Magna Cum Laude) 

School of Mechanical Engineering, Engineering Faculty, Tel Aviv University 

Thesis title: “Bio-Composites based on soft coral collagen: towards engineered blood vessels" ; Supervisor: Professor Rami Haj-Ali 

10/2012-08/2016:  B.Sc. in Bio-Medical Engineering (Magna Cum Laude)

Bio-Medical Engineering Department, Engineering Faculty, Tel Aviv University


Research Experience

Analysis of biocomposite materials using finite element method.Development of in-house experimental setup, conducting mechanical experiments of composites using DIC technique.Preparing biocomposite materials, and scanning using SEM microscopy.

Conducting laboratory research involving cell culture techniques and utilizing confocal microscopy. 

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