PolyKARD prints polymeric tissue for hearts

Materials World magazine
4 Mar 2020

Elastic photourethane resins have been created in a step torwards making pericardial implants that mimic real human tissue. Idha Valeur reports.

Elastic photourethane resins have been successfully synthesised and printed by a collaborative team project established less than a year ago. On 4 February 2020, the research group announced that the material could eventually lead to several products, including patches for congenital heart defects or heart valves.

The project, called PolyKARD, aims to produce biomimetic tissue for implants, similar to the human pericardium using polymer-based materials. PolyKARD is led and coordinated by AdjuCor GmbH and the project partners include the Fraunhofer Institute for Applied Polymer Research (IAP), Natural and Medical Sciences Institute (NMI), Young Optics Europe GmbH and pro3dure medical GmbH, all based in Germany.

‘Currently, we are identifying candidates for the core material, with a focus on mechanical strength and flexibility, dominant characteristics of the native pericardium,’ said AdjuCor GmbH CEO and Co-Founder, Dr Stephen Wildhirt.

IAP Researcher, Wolfdietrich Meyer, who leads the development of two material classes for the project, told Materials World the team at Fraunhofer IAP is developing photo-resins, which consist of smaller molecules with low viscosity. These can be transformed by light into a material that is solid, elastic and tear-resistant. ‘These resins can be used in high-resolution digital light processing (DLP) or standard triangle language (STL) printing. On the other hand, we synthesise high molecular weight polymers, which can be dissolved in solvents and can be processed into nonwovens by electrospinning.’

Following material development on a polyurethane basis, Meyer said the team synthesised all the polyurethane prepolymers by non-isocyanate urethane (NIU) chemistry, with the intention of improving biocompatibility since toxic isocyanates or toxic tin catalysts could be avoided completely.

‘In order to mimic the special mechanical properties of the pericardium in a polymer material, we need a mechanically sophisticated polymer that is also biocompatible,’ he said. ‘The urethane bond in polyurethane is similar to the peptide bond in natural biopolymers e.g. proteins, and we believe this circumstance leads cells to accept the polyurethanes more readily than natural materials. Another strategy is to use a protein, i.e. collagen, as a building block for polymer synthesis.’

Addressing the pericardium

According to IAP, there are about 23 million people who live with cardiac insufficiency, with only 3,000 transplants performed annually on a worldwide basis. Artificial implants could help patients currently waiting for a donor heart.

Being able to manufacture implants that are fully compatible and bespoke to the patient has become essential practice in medicine, but creating implants able to replace elastic tissue is complicated due to the multitude of requirements that need to be met.

Currently, to replace human heart valves or reconstruct blood vessels, the pericardium of pigs or cows are commonly used. However, this process is costly and cannot ensure mechanical stability for the long term. PolyKARD’s main objective is to create biomimetic tissue that has the same characteristics as the natural pericardium.

Meyer said the argument for using polymers as implants is its biocompatibility, biostability against hydrolysis and oxidation, and mechanical properties. For this specific project, the elasticity and the polymer being resistant to tearing is the main worry.

Wildhirt explained that this development is important as isolating biological pericardium can currently only be accomplished by decellularisation and fixation protocols that are costly and alters both the mechanical and biochemical properties of extracted pericardium.

‘These unintended modifications provoke several pathological reactions in-vivo such as calcification and shrinkage, resulting in mechanical failure of the modified material,’ he said. ‘In heart valves for example, leaflet calcification requires replacement of the prosthesis in a second, surgical, intervention. A synthetically manufactured biomimetic pericardium could overcome these limitations capable to reduce the complication rate and their associated costs.’

Materials testing

The aforementioned polymers the team recently synthesised underwent testing at NMI’s facility. IAP said in a statement that the spinning process makes the structures porous and able to grow together with the patient’s natural tissue. ‘The carrier substrates produced are characterised in terms of their mechanical and biological properties,’ the statement read.

‘Characterisation of the polyurethane monomers and prepolymers has been carried out by rheometry, ATR-FTIR, H-NMR, C-NMR, DSC,’ Wildhirt said. ‘The cured polymers have been mechanically characterised. Development of a suitable protocol to determine functionality of the biological polymer is in progress and will most likely be based on Raman spectroscopy.’

Meyer expressed that it is encouraging to see photo-resins being cured into flexible, mechanically stable and relatively tear-resistant materials. He said it is equally exciting that the first geometric structure of the pericardial sack could be fabricated by DPL printing, where the thickness of the wall will be ‘significantly less than 1mm, even 200 micrometres. The preliminary tests have already shown the biocompatibility of printed resins. This shows us that we are on the right track’.

Moving forward, the team will need to carry out further mechanical and stability characterisation of the polyurethane candidate, which will be conducted in the next few months. ‘A novel 3D printer will be constructed and commissioned that is capable to print the PolyKARD material under GMP conditions,’ Wildhirt said. ‘First 3D-printed prototypes will be generated. After complete characterisation, and assurance of biological compatibility and safety, in-vivo studies will be carried out.’