Biomedical Engineering Reference
In-Depth Information
in the range between 1 and 850 μm (Yannas et al. 1989). The primary objective of
this study was to search for evidence describing the effect of scaffold pore size on
the healing outcome, in the context of a wider search directed toward character-
izing the distinguishing features of DRT. Pore size was adjusted by appropriate
choice of the freezing temperature during the freeze-drying process, while the other
structural features of the collagen scaffolds remained unchanged during process-
ing of scaffolds (Dagalakis et al. 1980). It was shown that maximum contraction
inhibition, amounting to a delay for onset of contraction of about Δt = 19.5 ± 3 days,
occurred in the pore size range 20-125 μm (Yannas et al. 1989). Outside this range,
the delay in onset of contraction dropped down to levels of Δt = 2−9 days. The qual-
ity of regeneration, assessed by detailed histological views in the dermoepidermal
region and in the dermis itself, was high when using KC-seeded DRT with pore
size in the selected range. A detailed study of dermis and epidermis regeneration
following grafting with the KC-seeded DRT was presented earlier in this volume
(Chap. 5, Murphy et al. 1990). The quality of regeneration observed with the guinea
pig model by grafting the KC-seeded DRT was later confirmed in the swine model
(Compton et al. 1990). We conclude that grafting the guinea pig model as well as
the swine model with KC-seeded DRT, where the pore size of the scaffold was
adjusted inside the selected range, led to regeneration of nearly physiological epi-
dermis and dermis, and coincided with maximum values of contraction inhibition
(guinea pig data). The molecular mechanism by which pore size affects contraction
will be discussed in a later chapter.
Multiple disruptive changes in the myofibroblast population were observed in
the presence of KC-seeded DRT studied in the same guinea pig model as described
previously (Yannas 1981; Yannas et al. 1982, 1989; Orgill 1983), in which blocking
of skin wound contraction and incidence of regeneration were observed to occur.
In wounds that had not been grafted, myofibroblasts formed a fraction greater than
50 % of dermal fibroblasts by 14 days, and their axes were regularly aligned in par-
allel with the overlying epidermal layer. By contrast, a fibroblast fraction less than
10 % exhibited features of myofibroblasts in the site grafted with KC-seeded DRT
at 14 days, with their long axes randomly aligned (Murphy et al. 1990). Further
evidence of a substantial decrease in density of myofibroblasts was also evident in
longitudinal sections of a guinea pig skin wound that had been grafted with DRT,
compared with the ungrafted control (Fig.
8.12
, Troxel 1994). In the same longitu-
dinal views, it is also clear that the long axes of myofibroblasts, highly oriented in
the plane of the epidermis in the ungrafted control, have lost their axial and even
planar orientation in the DRT-grafted wounds (Troxel and Yannas 1991). The pho-
tographic evidence further shows that myofibroblasts had lost contact with other
cells that stained in a similar manner and were consequently disassembled in the
presence of DRT (Fig.
8.12
, Troxel 1994). In summary, the immunohistochemi-
cal evidence is consistent with a decrease in the number of myofibroblasts, loss
of their state of tight assembly, and loss of axial orientation of their long axes in
the presence of DRT. The combined changes in the myofibroblast population sug-
gest a serious decline in the macroscopic contraction force and are consistent with
the observed blocking of macroscopic contraction in the presence of DRT (Yannas
1981; Yannas et al. 1981, 1982, 1989; Orgill et al. 1983).
