Background: Currently used replacements to treat heart valve disease are associated with
drawbacks that limit their function in the long term. These drawbacks have been linked to the
inability of such substitutes to remodel in response to the surrounding environment, due to the
absence of viable cells in their composition. In situ tissue engineering of heart valves provides a
promise to resolve these limitations. One of the potential endogenous cell sources to endothelialise
and populate tissue engineering scaffolds is endothelial progenitor cells (EPCs), which have been
shown to participate in repair mechanisms. Thus, the aim of this work was to biofunctionalise
polycaprolactone (PCL) nanofibrous scaffolds to enhance the adhesion and proliferation of a subset
of EPCs that differentiate to blood outgrowth endothelial cells (BOECs). Approach: (i) BOECs and
human valve endothelial cells (hVECs) were compared in terms of phenotype and function; (ii) the
biocompatibility of BOECs (and hVECs) with PCL was determined; (iii) PCL was biofunctionalised
using the BOEC-specific peptide (TPS), through a covalent crosslinking approach and functionality of
the material was determined under static conditions as well as dynamic-flow conditions of the aortic
valve, (iv) the ability of the biofunctionalised PCL to capture EPCs/BOECs directly from blood
mononuclear cells was tested. Conclusion: BOECs characteristics and their compatibility with PCL
make them a potential cell source for the endothelialisation of PCL tissue engineering scaffolds.
Biofunctionalisation of PCL using TPS peptide enhanced BOECs capture, without inducing cytotoxicity
or inflammatory responses. BOECs cultured on the material were able to align and secret endothelial
mediators. Under dynamic conditions, BOECs were able to adhere, proliferate and infiltrate through
the modified scaffolds. The modified scaffold was able to recruit endothelial cells from blood
mononuclear cells under static conditions. These findings are promising, and should be confirmed
under flow conditions in a bioreactor and in animal models.