Biomedical Engineering Reference
In-Depth Information
levels of the ligand density. Ligand density is accordingly expected to be minimal
at large values of pore size.
In a homologous series of scaffolds where scaffold members possess increas-
ingly larger pore size, one should therefore expect that contraction blocking
activity should go through a maximum, as observed in the range 20-120 µm
(Yannas
et al
., 1989;
Fig. 14.2b
). Finally, the requirement for an optimal degrada-
tion rate in studies of induced skin regeneration (Yannas
et al
., 1989) as well as
studies of peripheral nerve regeneration (Harley
et al
., 2004) is explained in terms
of the need for the presence of an insoluble scaffold over the entire period
(approximately 3 weeks) during which contraction remains active during wound
healing. Degradation that occurs too early apparently prevents scaffolds from
binding contractile cells, thereby blocking contraction, during the entire contrac-
tile period, while persistent scaffold insolubility beyond termination of the
contraction process interferes sterically with the synthesis of new tissue. The
requirement for a critical scaffold duration period is thereby explained (Yannas,
2001).
14.10 Future trends
Regeneration was first observed about 25 years ago (Yannas
et al
., 1981, 1982a,b).
Since then the tempo of publication of studies in this field has steadily increased.
Clinical use of the earliest biologically active scaffold (DRT; Integra
TM
) has also
increased steadily, especially in recent years.
Several important questions demand answers. Detailed studies of the mechanis-
tic aspects of the activity of regeneration templates, especially transcriptional
screening studies of DRT and analysis of concentration changes in wounds treated
with DRT, are currently under way and will undoubtedly become more common
as the biological properties of templates become better understood. As the clinical
use of templates becomes more widespread in skin as well as other organs where
there is solid evidence of induced regeneration (peripheral nerves, conjunctiva),
questions will be raised about the speed with which regeneration takes place, since
this affects a patient's duration of stay in the hospital setting. Other questions relate
to the speed with which angiogenesis takes place in the presence of scaffolds. It has
been shown, both in animal models and in clinical studies, that angiogenesis
proceeds spontaneously from the host's wound tissues into an active scaffold
(Murphy
et al
., 1990; Compton
et al
., 1998). However, the kinetics of angiogen-
esis are likely to be related inversely to the incidence of infection, especially in a
clinical setting. This presumptive relationship needs to be studied by working with
appropriate modifications in scaffold structure that accelerate angiogenesis.
A greater issue is the development of templates or other means of inducing
regeneration in organs other than those in which it has been accomplished. One
aspect of organ regeneration that has been inadequately studied so far (Yannas,
2005c; Yannas
et al
., 2007a) is the relation between early fetal regeneration and
