Tissue engineering is a new approach, whereby techniques are being developed to transplant
autologous cells onto biodegradable scaffolds to ultimately form new functional tissue
in vitro and in vivo. Our laboratory has focused on the tissue engineering of heart
valves, and we have fabricated a trileaflet heart valve scaffold from a biodegradable
polymer, a polyhydroxyalkanoate. In this experiment we evaluated the suitability of
this scaffold material as well as in vitro conditioning to create viable tissue for
tissue engineering of a trileaflet heart valve.
We constructed a biodegradable and biocompatible trileaflet heart valve scaffold from
a porous polyhydroxyalkanoate (Meatabolix Inc, Cambridge, MA). The scaffold consisted
of a cylindrical stent (1 x 15 x 20 mm inner diameter) and leaflets (0.3 mm thick),
which were attached to the stent by thermal processing techniques. The porous heart
valve scaffold (pore size 100 to 240 microm) was seeded with vascular cells grown
and expanded from an ovine carotid artery and placed into a pulsatile flow bioreactor
for 1, 4, and 8 days. Analysis of the engineered tissue included biochemical examination,
enviromental scanning electron microscopy, and histology.
It was possible to create a trileaflet heart valve scaffold from polyhydroxyalkanoate,
which opened and closed synchronously in a pulsatile flow bioreactor. The cells grew
into the pores and formed a confluent layer after incubation and pulsatile flow exposure.
The cells were mostly viable and formed connective tissue between the inside and the
outside of the porous heart valve scaffold. Additionally, we demonstrated cell proliferation
(DNA assay) and the capacity to generate collagen as measured by hydroxyproline assay
and movat-stained glycosaminoglycans under in vitro pulsatile flow conditions.
Polyhydroxyalkanoates can be used to fabricate a porous, biodegradable heart valve
scaffold. The cells appear to be viable and extracellular matrix formation was induced
after pulsatile flow exposure.