Biomedical Engineering Reference
In-Depth Information
that the multilaminated structure was completely degraded and replaced by host-
derived tissue, mostly organized collagen, within 3 months after surgery (Badylak
et al. 2002). A study of Achilles tendon repair using an acellular matrix derived from
SIS showed that, at 60 days, the acellular graft was degraded completely and was
replaced by an organized connective tissue similar to that of normal tendon (Gilbert
et al. 2007). Similar results were obtained following the use of an acellular matrix
derived from the urinary bladder to repair the thoracic wall, where site-appropriate
stroma was observed at the site of the degraded implant (Gilbert et al. 2008). In this
study, bony defects in the thoracic wall were reported to have been replaced with
new calcified bone (Gilbert et al. 2008).
Epithelial cells have been seeded frequently in acellular matrices. Although
these autologous cells (e.g., urothelial cells in studies of the urological system) had
been shown capable of spontaneous regeneration (El-Kassaby et al. 2003; Dorin
et al. 2008), it was observed that spontaneous epithelialization was occasionally
limited in scale.
In a particularly revealing study of bladder regeneration using unseeded matri-
ces, the investigators estimated the maximum migration distance of urothelial cells
from the anastomotic sites at 0.5 cm. The estimate suggested a limitation on the size
of defect to be repaired by unseeded matrices (Dorin et al. 2008). These results were
substantiated by comparing studies conducted with short and long urethral defects.
Although short urethral defects could be regenerated using acellular matrices, long
defects could only be regenerated if these matrices had been seeded with epithelial
cells prior to implantation (Orabi et al. 2012). In these studies, muscle cells were
occasionally also seeded in acellular matrices in order to regenerate a smooth mus-
cle layer allowing storage of urine; these cells complemented urothelial cells that
normally provide a barrier function which prevents leakage of urine (Horst et al.
2012). Support of the notion that epithelial cell regeneration is limited by distance
of migration was reported in a study of an acellular matrix used to regenerate the
bladder. It was observed that only the peripheral regions of grafts were repopulated
with cells; toward the center, grafts were devoid of cells (Brown et al. 2002a).
To overcome the problem of limitation in the scale of spontaneous epithelializa-
tion investigators have resorted to cell seeding of their scaffolds. Since the acellular
matrices derived from bladder submucosa consisted of dense collagen fibers, they
deliberately opened pores in acellular matrices by combined chemical oxidation
and decellularization processes in order to seed them with epithelial cells (Liu et al.
2009). Improved regeneration of urethral tissues was reported with the cell-seeded
grafts compared to unseeded grafts in two studies (De Filippo et al. 2002; Liu et al.
2009).
Imperfections in function of regenerated organs were noted by several inves-
tigators who used decellularized matrices. These have included abnormally high
stiffness of a regenerated bladder (Brown et al. 2002a) and lack of restoration of
physiologic voiding of the bladder (Horst et al. 2012).
In conclusion, the experimental evidence from several studies of decellularized
matrices shows that an appropriate scaffold implant suffices to induce at least par-
tial regeneration and is replaced by site-specific stroma. Epithelial cells that are
