Biomedical Engineering Reference
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Fig. 1 Spontaneous in situ autologization of decellularized tissues in various animal models.
Akhyari et al. [ 64 ],
Baraki et al. [ 40 ],
Ota et al. [ 39 ],
Dohmen et al. [ 42 ],
Dohmen et al. [ 44 ],
Elkins et al. [ 43 ],
da Costa et al. [ 65 ],
Leyh et al. [ 45 ],
Lichtenberg et al. [ 41 ],
Erdbrügger et al. [ 38 ]. The division of the time axis is not equidistant
layers. Regardless of the animal model (xenogeneic, allogeneic), the method of
decellularization, and the type of valve replacement (aortic or pulmonary valve), the
results are extremely homogeneous. Figure 1 shows the degree of cell-population
settlement as a function of time. The element which all experiments have in common
is that decellularized tissues were implanted in an orthotopic position (with the
exception of [ 39 ]). An early-stage endothelialization is mainly observed after
3 months. In some experiments, it was possible to observe the invasion of interstitial
cells and the production of procollagen [ 38 , 40 - 43 ]. After 6 months, a confluent
endothelium and a colonization of the deeper layers of tissue was observed in most
cases [ 39 , 44 , 45 ]. An exception to these findings is the study of Baraki et al. [ 40 ],
where, even after 9 months, no confluent endothelium was determined. In these
experiments, however, aortic valves were implanted. The average pressure in the
aorta is about 100 mmHg [ 46 ] and in the pulmonary artery it is about 14 mmHg [ 47 ].
It is conceivable that the increased blood flow in the aorta impedes or delays a
cellular settlement. Furthermore, increased mechanical stress at the coaptation sites
of the valve leaflets results in a very thin thrombotic layer that prevents the adhesion
of cells. The ingrowth of interstitial cells, such as myofibroblasts and smooth muscle
cells, neovascularization, and synthesis of procollagen between months 3 and 11 are
evidence for tissue remodelling of the adventitial side and the subsequent recon-
struction of deeper layers of tissue.
There are only few clinical spontaneous in situ autologization data available.
The reasons for this are the lack of in vivo imaging systems and the low number
of explanted heart valve substitutes based on decellularized tissue. In 2006,
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