Age-dependent changes in geometry, tissue composition and mechanical properties of fetal to adult cryopreserved human heart valves

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Biomechanical studies on transverse olecranon and patellar fractures : a systematic review with the development of a new scoring method

Introduction: Several methods of transverse patellar and olecranon fixation have been described. This article compares biomechanical studies of various fixation methods using a newly developed scoring method. Source of data: The databases PubMed, Web of Science, Science Direct, Google Scholar and Google were searched for relevant studies. Areas of agreement: Fixation hardware failure remains a problem. Various materials and fixation techniques have been tested to provide an improved fixation of transverse olecranon and patellar fractures. Areas of controversy: The difference in biomechanical testing setup between the studies makes it hard to compare different fixation techniques. Growing points: The newly developed grading method was proved to be unbiased and reliable; however, extra specifications need to be added at some criteria when adopting the scoring method. Areas timely for developing research: Non-metallic constructs may provide an improvement to the currently used metallic tension band wiring technique; however, clinical research is required

Nondestructive mechanical characterization of developing biological tissues using inflation testing

One of the hallmarks of biological soft tissues is their capacity to grow and remodel in response to changes in their environment. Although it is well-accepted that these processes occur at least partly to maintain a mechanical homeostasis, it remains unclear which mechanical constituent(s) determine(s) mechanical homeostasis. In the current study a nondestructive mechanical test and a two-step inverse analysis method were developed and validated to nondestructively estimate the mechanical properties of biological tissue during tissue culture. Nondestructive mechanical testing was achieved by performing an inflation test on tissues that were cultured inside a bioreactor, while the tissue displacement and thickness were nondestructively measured using ultrasound. The material parameters were estimated by an inverse finite element scheme, which was preceded by an analytical estimation step to rapidly obtain an initial estimate that already approximated the final solution. The efficiency and accuracy of the two-step inverse method was demonstrated on virtual experiments of several material types with known parameters. PDMS samples were used to demonstrate the method's feasibility, where it was shown that the proposed method yielded similar results to tensile testing. Finally, the method was applied to estimate the material properties of tissue-engineered constructs. Via this method, the evolution of mechanical properties during tissue growth and remodeling can now be monitored in a well-controlled system. The outcomes can be used to determine various mechanical constituents and to assess their contribution to mechanical homeostasis

Scaffold Geometry-Imposed Anisotropic Mechanical Loading Guides the Evolution of the Mechanical State of Engineered Cardiovascular Tissues in vitro.

Cardiovascular tissue engineering is a promising approach to develop grafts that, in contrast to current replacement grafts, have the capacity to grow and remodel like native tissues. This approach largely depends on cell-driven tissue growth and remodeling, which are highly complex processes that are difficult to control inside the scaffolds used for tissue engineering. For several tissue engineering approaches, adverse tissue growth and remodeling outcomes were reported, such as aneurysm formation in vascular grafts, and leaflet retraction in heart valve grafts. It is increasingly recognized that the outcome of tissue growth and remodeling, either physiological or pathological, depends at least partly on the establishment of a homeostatic mechanical state, where one or more mechanical quantities in a tissue are maintained in equilibrium. To design long-term functioning tissue engineering strategies, understanding how scaffold parameters such as geometry affect the mechanical state of a construct, and how this state guides tissue growth and remodeling, is therefore crucial. Here, we studied how anisotropic versus isotropic mechanical loading-as imposed by initial scaffold geometry-influences tissue growth, remodeling, and the evolution of the mechanical state and geometry of tissue-engineered cardiovascular constructs in vitro. Using a custom-built bioreactor platform and nondestructive mechanical testing, we monitored the mechanical and geometric changes of elliptical and circular, vascular cell-seeded, polycaprolactone-bisurea scaffolds during 14 days of dynamic loading. The elliptical and circular scaffold geometries were designed using finite element analysis, to induce anisotropic and isotropic dynamic loading, respectively, with similar maximum stretch when cultured in the bioreactor platform. We found that the initial scaffold geometry-induced (an)isotropic loading of the engineered constructs differentially dictated the evolution of their mechanical state and geometry over time, as well as their final structural organization. These findings demonstrate that controlling the initial mechanical state of tissue-engineered constructs via scaffold geometry can be used to influence tissue growth and remodeling and determine tissue outcomes

A bioreactor to identify the driving mechanical stimuli of tissue growth and remodeling

Tissue growth and remodeling are essential processes that should ensure long-term functionality of tissue-engineered (TE) constructs. Even though it is widely recognized that these processes strongly depend on mechanical stimuli, the underlying mechanisms of mechanically induced growth and remodeling are only partially understood. It is generally accepted that cells sense mechanical changes and respond by altering their surroundings, by means of extracellular matrix growth and remodeling, in an attempt to return to a certain preferred mechanical homeostatic state. However, the exact mechanical cues that trigger cells to synthesize and remodel their environment remain unclear. To identify the driving mechanical stimuli of these processes, it is critical to be able to temporarily follow the mechanical state of developing tissues under physiological loading conditions. Therefore, a novel "versatile tissue growth and remodeling" (Vertigro) bioreactor was developed that is capable of tissue culture and mechanical stimulation for a prolonged time period, while simultaneously performing mechanical testing. The Vertigro's unique two-chamber design allows easy, sterile handling of circular 3D TE constructs in a dedicated culture chamber, while a separate pressure chamber facilitates a pressure-driven dynamic loading regime during culture. As a proof-of-concept, temporal changes in the mechanical state of cultured tissues were quantified using nondestructive mechanical testing by means of a classical bulge test, in which the tissue displacement was tracked using ultrasound imaging. To demonstrate the successful development of the bioreactor system, compositional, structural, and geometrical changes were qualitatively and quantitatively assessed using a series of standard analysis techniques. With this bioreactor and associated mechanical analysis technique, a powerful toolbox has been developed to quantitatively study and identify the driving mechanical stimuli of engineered tissue growth and remodeling

Age-dependent changes of stress and strain in the human heart valve and their relation with collagen remodeling

In order to create tissue-engineered heart valves with long-term functionality, it is essential to fully understand collagen remodeling during neo-tissue formation. Collagen remodeling is thought to maintain mechanical tissue homeostasis. Yet, the driving factor of collagen remodeling remains unidentified. In this study, we determined the collagen architecture and the geometric and mechanical properties of human native semilunar heart valves of fetal to adult age using confocal microscopy, micro-indentation and inverse finite element analysis. The outcomes were used to predict age-dependent changes in stress and stretch in the heart valves via finite element modeling. The results indicated that the circumferential stresses are different between the aortic and pulmonary valve, and, moreover, that the stress increases considerably over time in the aortic valve. Strikingly, relatively small differences were found in stretch with time and between the aortic and pulmonary valve, particularly in the circumferential direction, which is the main determinant of the collagen fiber stretch. Therefore, we suggest that collagen remodeling in the human heart valve maintains a stretch-driven homeostasis. Next to these novel insights, the unique human data set created in this study provides valuable input for the development of numerical models of collagen remodeling and optimization of tissue engineering. Statement of significance Annually, over 280,000 heart valve replacements are performed worldwide. Tissue engineering has the potential to provide valvular disease patients with living valve substitutes that can last a lifetime. Valve functionality is mainly determined by the collagen architecture. Hence, understanding collagen remodeling is crucial for creating tissue-engineered valves with long-term functionality. In this study, we determined the structural and material properties of human native heart valves of fetal to adult age to gain insight into the mechanical stimuli responsible for collagen remodeling. The age-dependent evolutionary changes in mechanical state of the native valve suggest that collagen remodeling in heart valves is a stretch-driven process

Age-dependent changes in geometry, tissue composition and mechanical properties of fetal to adult cryopreserved human heart valves

There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation-but more pronounced in aortic valves-the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age