One of the fundamental aspects of tissue engineering (TE) is the population of three-dimensional (3D) scaffolds with appropriate cells that recapitulate the physiological situation. This is particularly valid for heart valve engineering as this tissue contains different cell types arranged in distinct regions. Therefore, a technique was developed that utilises a 44 filament PCL yarn to create “living threads” based on thin biodegradable PCL fibers of different diameters (23 -243 um), as a first step to provide specific spatial organisation of cells in a tissue engineered valve. These versatile fibers can be used to produce scaffolds of 3D shapes identical to the cup-like structure of a normal human valve while preserving the particular orientation of both the cells and the fibers (see Figure 1. a-d). We aimed to assess their ability to bind to stem cells and to measure the mechanical strength of the fibres.

Within the field of biomedicine, alginate applications are numerous, from wound healing and cell transplantation to delivery of bioactive molecules. Recently, alginate based biomaterials are entering into clinical trials for the treatment of myocardial infarction. Due to its non-thrombogenic nature, this polymer is very promising for cardiac applications, including scaffold for heart valve tissue engineering. One essential property of alginates in this respect is the possibility to form virtually any shapes (films, fibers, beads) in a variety of sizes. Alginate solutions can form gels under mild conditions in the presence of calcium, by displacement of sodium ions and resulting attraction of the alginate molecules. Our aim is, therefore, to fabricate three-dimensional (3D) alginate scaffolds mimicking precisely the anatomical shape of human aortic valves, as a substrate for valve tissue engineering and repair.

The first task of tissue engineer trying to make a scaffold of a heart valve is to adopt some model of a heart valve to establish target geometries and properties that should be recreated in the artificial scaffold. The natural way to do so is to conduct literature research and find the current scientific consensus on the topic. Here the problems start, each researcher seems to have an individual opinion about the optimal geometry of valve. What makes the situation more complicated is that each researcher has carefully chosen arguments to explain why that particular design is better than others. Hence, the consensus is not there yet; we decided to contribute to this discussion. The analysis of available reports enables to “cook out” 2 distinguishable and to some extent contrary hypothesis. 1st the optimal architecture of artificial valve is an architecture of native one (Professor Sir Magdi Yacoub). 2nd there is not such a thing as optimal architecture of a heart valve, and never will be. The consensus of both strategies is in our opinion the establishing the most “beautiful HV” but according to objective physical parameters. What additionally supports this logic is that the scaffold, under physiological condition, will adjust to the patient by changing the geometries. To confirm our observation and conclusion we contacted prominent clinicians and tissue engineers with question: What is an optimal design of aortic heart valve? In this report we are presenting their responses and comments.

Reverse addition-fragmentation atom transfer (RAFT) living polymerization is a very versatile and efficient method of preparing copolymers with narrowly defined size distributions and architectures that can readily be performed in sub-milliliter quantities yielding biocompatible materials with excellent yields and low PDI values, and a linear molecular weight response curve extending to above 180,000 g·mol-1. In this poster, we present a conception of automated, miniaturized workflow involving a controlled/living polymerization reaction, which would be amenable to a wide range of monomers, and would be suitable for biomaterials. The method requires minimal equipment input, and can be readily applied to a large number of samples in parallel. To examine the feasibility of this approach, the copolymerization of methyl methacrylate (MMA) and methacrylic acid was chosen as it is a well characterized and known system. Using inkjet printing, the resulting micropolymerization could be transformed into polymer arrays for cell screening.

Knitting is a versatile technology which offers a large portfolio of products and solutions that are of interest in heart valve (HV) tissue engineering (TE). One of the main advantages of knitting is its ability to construct complex shapes and structures by precisely assembling the yarns in the desired position. Recently multiple examples of applications of knitted fabrics in HVTE were reported. One of the most frequently cited strategies was developed in Mela’s group. In that case, the fibrin constituting the leaflets of valves is enforced using a warp-knitted tubular mesh, made out of polyethylene terephthalate (PET). This approach is potentially adaptable for the intelligent scaffold development, which will require replacing non-degradable yarns with bioresorbable yarns. Also, the structure of scaffold should be altered to resemble closely the original valve's shape. Our group developed a model, which reproduces the anisotropic structure characteristic for the heart valve, in particular, the 3-layered architecture of the leaflets. The biodegradable yarns used can provide oriented growth of cells in a lengthwise direction and consequently enable the deposition of extracellular matrix (ECM) proteins in an oriented manner.

Commonly used mechanical or animal derived are being replaced by tissue engineered (TE) heart valves (HV), due to their disadvantages such as thrombogenicity and poor durability. A tissue engineered valve, ideally mimics the function of a native valve by responding to growth and physical forces. It is also believed to have a longer life span, close to that of a native valve. In this exposition, a new method of preparing heart valve scaffold composites developed with the use of textile engineering is introduced. Knitting technology that provides freedom of design and form in scaffold preparation, also, mechanical stability and elasticity of obtained material, is combined with non-woven technology, allowing to construct nanomaterial with a high density of fibers. Non-woven seals the pores of knitted fabric to prevent leakage, allowing its full functionality. Both textile materials are prepared using bioresorbable polycaprolactone (PCL) to enhance their functionality as a heart valve scaffold composite. An additional task of this report is to describe an example of interaction between tissue and textile engineers. To enable that communication the textile engineers had to gain a basic understanding of structural and mechanical aspects of the heart valve, and tissue engineers needed to acquire the knowledge of tools and capacities that are essential in knitting technology.