New Biomaterials in Heart Valve Tissue Engineering

Abstract

AbstractIn situ tissue engineering may lead to a clinically and economically attractive new generation of heart valve replacement therapies, overcoming the limitations of currently used prostheses. Development of novel scaffolds is required for the proposed in situ tissue engineering. These scaffolds must be able to carry a full mechanical load immediately after implantation, and should subsequently provide all biological cues for the recruitment and attachment of specific circulating cells, and should also induce the growth of new tissue. The properties of the scaffold materials should be optimized with respect to mechanical properties and biodegradability characteristics. Synthetic biomaterials are tunable, which enables the creation of tailor made scaffolds suitable for in situ tissue engineering of heart valves. Two different approaches towards scaffold materials have been investigated, based on a biodegradable polyester (PCL or PLLCL), and either a quadruple hydrogen-bonding ureidopyrimidinone (UPy) unit or a bis-urea (BU) moiety. Both were investigated in vivo regarding biocompatibility and degradation kinetics. Thirty rats received the UPy and BU polyester based, disk-shaped implants subcutaneously. To investigate the effects of the implants over time, samples were explanted on day 2, 5, 10, 21 and 84. Disks with surrounding tissue were fixed in 10% neutral buffered formalin. After fixation, explants were dehydrated in graded alcohols and longitudinal sections were embedded in paraffin and stained. From each explant the foreign body response was quantified per high power field. Both the UPy and the BU-based materials proved biocompatible. In the acute phase all investigated biomaterials showed an infiltration of neutrophil granulocytes and mononuclear cells. In the chronic phase encapsulation by fibroblasts took place in all cases. Degradation rates were investigated by gel permeation chromatography (GPC) after 21 and 84 days. Little degradation was observed for the PCL-based polymers over the course of the experiment. The PLLCL-based polymers with a BU moiety, however, showed little at 21 days, but marked degradation at 84 days. Which of the explored materials is best suitable for in situ tissue engineering of heart valves will depend on further experiments, investigating how much time is needed for cell recruitment, adhesion, differentiation and tissue growth. This research forms part of the Project P1.01 iValve of the research program of the BioMedical Materials institute, co-funded by the Dutch Ministry of Economic Affairs, Agriculture and Innovation. The financial contribution of the Nederlandse Hartstichting is gratefully acknowledged.