Biomedical Engineering Reference
In-Depth Information
native to the implantation site spontaneously migrate and proliferate over the im-
plant surface providing new epithelia over relatively short distances (cm). When
the scale of epithelial cell migration is much larger a scaffold is occasionally seeded
with autologous epithelial cells which proliferate and migrate spontaneously form-
ing epithelial tissues. This conclusion follows directly from Rule 2.
Rule 3 recognizes the essential modification of the wound healing process
(contraction blockade) that must be realized prior to regeneration. Contraction is
extensively reported in the literature when it affects the geometry of an organ in a
particularly striking manner, e.g., constriction of a hollow organ leading to closure
of the lumen; however, there is lack of quantitative data on contraction of wounds
in this field (Chap. 4). For example, it is known that urethral stricture is caused
typically by trauma, resulting in scar tissue formation in or around the urethra (Liu
et al. 2009). Stricture can block the flow of urine and can cause a high incidence
of associated complications such as acute urinary retention, painful voiding symp-
toms, recurrent urinary tract infections, bladder or urethral stones, hydronephrosis,
and renal failure (Liu et al. 2009). In a study of repair of esophageal defects, no
stricture was observed when the acellular matrix was used for reconstruction in par-
tial-circumference (< 50 %) esophageal defects; however, when full-circumferential
replacement of the esophagus was attempted, the matrix healed with unacceptable
stricture (Badylak et al. 2000). In a later study, the problem of stricture was pre-
vented using endoscopic placement of an acellular matrix (Nieponice et al. 2009).
In a study of bladder repair using an acellular matrix, an average graft shrinkage
of 48 % was observed; this was interpreted as a fibroproliferative change (fibrosis)
that may have affected the compliance of new bladder tissue (Brown et al. 2002a).
In studies with decellularized matrices, the antagonistic relation between wound
contraction and quality of regeneration (Chap. 8) appears to have been reported
indirectly in qualitative terms (e.g., urethral stricture; blocking of esophageal con-
traction). Direct quantitative data on modification of wound contraction or changes
in morphology of contractile cells in the presence of implanted DCM are lacking.
We conclude that there is insufficient information by which to judge whether Rule
3 applies to uses of decellularized matrices or not.
Rule 4 identifies three structural features of a collagen scaffold that are required
for regenerative activity: Pore structure, degradation rate, and scaffold surface
chemistry.
We consider first the effect of pore size. The acellular tissues that are produced
by the typical decellularization process are much more densely structured than the
original collagen scaffold. The lack of a highly interconnected macro- or micropo-
rous structure was considered a limitation by investigators who seeded these acellu-
lar matrices with cells prior to implantation (Liu et al. 2009). For example, in prepa-
ration for a clinical study of urethral regeneration the objective of the investigators
was to (a) decellularize bladder submucosal tissue derived from an animal source in
order to eliminate the antigenic epitopes, and (b) recellularize the matrix with hu-
man bladder cells prior to implantation in the human. The investigators treated the
acellular matrix with chemical reagents that not only removed the cells but also gen-
erated pores that facilitated penetration of cells inside the matrix (Liu et al. 2009).
