Biomedical Engineering Reference
In-Depth Information
were reported since then with organs as diverse as the urethra (Chen et al. 1999),
large defects in the abdominal wall (Badylak et al. 2002), the bladder (Atala et al.
2006), Achilles tendon (Gilbert et al. 2007), the lung (Ott et al. 2010), the larynx
(Birchall et al. 2012), and other organs.
Several accomplishments using DCM are discussed below in terms of the five
empirical rules for induced regeneration presented above. The primary objective
of the discussion is to find out whether or not the empirical rules that describe the
collagen scaffold regeneration paradigm apply to diverse organs other than skin
and peripheral nerves. The methodology used to prepare decellularized matrices is
quite different from that used to synthesize the collagen scaffolds used in studies
of the regeneration paradigm. However, there is sufficient information in the DCM
literature to compare and contrast the predictions of the paradigm with findings in
the DCM field.
Rule 1 of the regeneration paradigm (see above) distinguishes between tissues
that regenerate spontaneously and those that do not. Although it is well known that
the adult stroma does not regenerate spontaneously, epithelial cells show quite a
different response to injury. We have previously discussed the use of keratinocytes
seeded into the dermis regeneration template (DRT) as well as spontaneous epi-
thelialization of newly synthesized stroma from the edges of small skin wounds
(Chap. 5). Likewise, the spontaneous response of epithelial cells to injury is best ap-
preciated with matrices that have not been seeded prior to implantation. For exam-
ple, following implantation of a matrix based on the small intestinal submucosa, a
naturally acellular matrix material (Voytik-Harbin et al. 1997), a continuous layer of
transitional epithelium was eventually observed on the luminal surface of the graft
(Badylak et al. 1998). In a clinical study of urethral repair using unseeded conduits
based on an acellular bladder submucosa matrix, the biopsy specimens showed the
typical urethral stratified epithelium, undoubtedly resulting from epithelial tissue
regeneration (El-Kassaby et al. 2003). A study of urethral replacement using matri-
ces derived from bladder submucosa documented ingrowth of urothelial cells from
the anastomotic sites (Dorin et al. 2008). An epithelial cell layer spontaneously
formed in cell-free scaffolds that had been implanted to reconstruct long urethral
defects (Orabi et al. 2012). We conclude that data from studies with decellularized
matrices are in agreement with empirical Rule 1.
Rule 2 selects the minimal reactants that are required for regeneration: an ap-
propriate scaffold and, optionally, autologous exogenously seeded epithelial cells.
Investigators who have used decellularized matrices have been mostly successful in
inducing replacement of the acellular matrix by host tissue, specifically host stroma.
For example, in a study of bladder wall regeneration using an implant based on the
small intestinal submucosa (SIS), it was observed that, by the end of 4 weeks after
surgery, the graft had been replaced by the new host-derived neovascularized matrix
that resembled normal bladder with a continuous layer of transitional epithelium
on the luminal surface and no evidence of the originally implanted acellular matrix
(Badylak et al. 1998; Record et al. 2001). In a study of a body wall repair using a
SIS, the acellular matrix was processed to form a multilaminated graft (eight sheets
of SIS were mechanically apposed and joined by vacuum pressing). It was observed
