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Updated: Nov 27, 2025
Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
Decellularized tissue-engineered heart valves calcification: what do animal and clinical studies tell us?
Adel F Badria1,2, Petros G Koutsoukos3, Dimosthenis Mavrilas4
1Department of Fiber and Polymer Technology, Division of Coating Technology, KTH Royal Institute of Technology, Stockholm, Sweden. badria@kth.se.
Insights
Decellularized tissue-engineered heart valves (dTEHV) show potential to prevent calcification. Proper tissue source selection, decellularization techniques, and implantation methods are key to their anti-calcification performance.
Area of Science:
- Biomaterials Science
- Cardiovascular Engineering
- Regenerative Medicine
Background:
- Cardiovascular diseases are a leading cause of death globally, with heart valve failure due to calcification being a significant challenge.
- Current heart valve replacements (mechanical and biological) have long-term drawbacks, including thrombosis and calcification-induced stenosis/regurgitation.
- Decellularized tissue-engineered heart valves (dTEHV) offer promising alternatives due to superior biomechanics and biocompatibility.
Purpose of the Study:
- To investigate whether decellularized heart valves calcify.
- To identify factors influencing calcification in dTEHV.
- To compare calcification mechanisms in dTEHV with native and bioprosthetic valves.
Main Methods:
- Retrospective review of published animal and clinical studies on decellularized heart valves.
- Categorization of studies based on the effect of decellularization on calcification.
- Exclusion of in vitro and in silico studies due to the complexity of in vivo calcification.
Main Results:
- Proper selection of tissue sources, decellularization techniques, and implantation methods can lead to significant anti-calcification potential in dTEHV.
- Optimized processes can prevent calcification even without in vitro cell seeding or additional scaffold treatments.
- Key factors include minimizing immunogenic residues, ensuring complete removal of cellular debris and agents, and avoiding surgical suturing.
Conclusions:
- Decellularized heart valves can be engineered to possess excellent anti-calcification properties.
- Careful consideration of tissue source, decellularization process, and surgical implantation is crucial for preventing valve calcification.
- dTEHV represent a viable regenerative solution for heart valve disease, mitigating calcification issues seen in traditional prostheses.
Abstract:
Cardiovascular diseases are the first cause of death worldwide. Among different heart malfunctions, heart valve failure due to calcification is still a challenging problem. While drug-dependent treatment for the early stage calcification could slow down its progression, heart valve replacement is inevitable in the late stages. Currently, heart valve replacements involve mainly two types of substitutes: mechanical and biological heart valves. Despite their significant advantages in restoring the cardiac function, both types of valves suffered from serious drawbacks in the long term. On the one hand, the mechanical one showed non-physiological hemodynamics and the need for the chronic anticoagulation therapy. On the other hand, the biological one showed stenosis and/or regurgitation due to calcification. Nowadays, new promising heart valve substitutes have emerged, known as decellularized tissue-engineered heart valves (dTEHV). Decellularized tissues of different types have been widely tested in bioprosthetic and tissue-engineered valves because of their superior biomechanics, biocompatibility, and biomimetic material composition. Such advantages allow successful cell attachment, growth and function leading finally to a living regenerative valvular tissue in vivo. Yet, there are no comprehensive studies that are covering the performance of dTEHV scaffolds in terms of their efficiency for the calcification problem. In this review article, we sought to answer the question of whether decellularized heart valves calcify or not. Also, which factors make them calcify and which ones lower and/or prevent their calcification. In addition, the review discussed the possible mechanisms for dTEHV calcification in comparison to the calcification in the native and bioprosthetic heart valves. For this purpose, we did a retrospective study for all the published work of decellularized heart valves. Only animal and clinical studies were included in this review. Those animal and clinical studies were further subcategorized into 4 categories for each depending on the effect of decellularization on calcification. Due to the complex nature of calcification in heart valves, other in vitro and in silico studies were not included. Finally, we compared the different results and summed up all the solid findings of whether decellularized heart valves calcify or not. Based on our review, the selection of the proper heart valve tissue sources (no immunological provoking residues), decellularization technique (no damaged exposed residues of the decellularized tissues, no remnants of dead cells, no remnants of decellularizing agents) and implantation techniques (avoiding suturing during the surgical implantation) could provide a perfect anticalcification potential even without in vitro cell seeding or additional scaffold treatment.
