Biomedical Engineering Reference
In-Depth Information
with particular interest in the pores. It is possible the cells are trying to migrate into
the material through extending fi liopdia into the pores or the pores provide a more
attractive anchoring site than the fl at surfaces of the membrane.
Taken together, these results suggest that the osteoblasts are reacting to the nano-
pores by anchoring themselves faster and more strongly to the membranes that
have pores. The pores themselves are at a scale comparable to cellular extensions,
and the in growth of extensions into the membrane pores suggest that osseointegra-
tion could be enhanced by creating nanopores on prosthetic implant surfaces.
3
Cardiac Tissue Engineering on Microfabricated Membranes
One of the major challenges in engineering tissues is mimicking the complex cel-
lular organizations and functions of the native tissues of the human body. Tissue
structure and function are very highly interrelated in most cases. The cellular and
macromolecular organization of the tissue often brings about mechanical and bio-
logical functionality. For example, it is the circumferential arrangement of smooth
muscle fi ber layers that allows for change in the caliber of the lumen of blood ves-
sels (Fawcett
1986
); the wickerwork pattern of collagen fi bers in the skin give it
mechanical strength (Alberts et al.
1994
); and the end-to-end connections and paral-
lel arrangement of myocytes allow the ventricle to contract as a unit and eject blood
(Sommer
1995
). Without proper cellular organization, an artifi cial tissue does not
function adequately.
In order to recapitulate cardiac myocyte structure and function in vitro, microtex-
tured silicone substrates were designed to induce the natural end-to-end, parallel
arrangement of myocytes. The substrates were designed to have rows of micropegs
(5 mm high), parallel groves (5 mm wide) or a combination pattern where the pegs
were spaced within the grooves. These cardiac tissue-tailored substrates were pro-
duced through a series of photolithography and microfabrication techniques. Neonatal
rat ventricular myocytes (NRVM) were plated on these substrates and compared to
those on nontextured substrates. NRVM displayed an increase in myofi brillar height
and decrease in cell area that did not affect the stoichiometry of the myofi brillar pro-
teins. The microtopography did elicit microenvironmental remodeling of proteins that
mechanically attach the cell to its surroundings. Cells on nontextured surfaces ended
in long non-striated cables while those on pegged substrates ended in sarcomeric stria-
tions at the vertical face of the pegs. Expression of focal adhesion proteins, such as
vinculin and paxillin, were decreased on combination surfaces as compared to nontex-
tured substrates (Motlagh et al.
2003b
). Through the use of the microgrooved surface
topography, it was possible to orient the cardiac myocytes in vitro. The addition of
microgrooves increased the end-to-end cell-cell contact and the expression of both
N-cadherin (mechanical) and connexin43 (electrical) junctions reminiscent of appear-
ance in the intact neonatal heart (Fig.
3
) (Motlagh et al.
2003a
) .
