Biomedical Engineering Reference
In-Depth Information
Kanitakis, 2002). Each layer has a unique architecture which imparts specific
attributes to overall organ function, including general system homeostasis, protec-
tion against environmental insult, thermoregulation and the biomechanical stability
required for a wide variety of body motion. As a result of this functional impor-
tance, wounding initiates a cascade of events with the sole purpose of rapidly
regaining integrity.
Wound healing describes a specific and complex biological process initiated by
a loss of integrity and is characterized by five overlapping stages: (1) hemostasis,
(2) inflammation, (3) cellular migration and proliferation, (4) matrix protein
synthesis and wound contraction and (5) tissue remodeling (Monaco and Law-
rence, 2003). Regaining hemostatic control is primarily accomplished through
platelet activation and aggregation followed by fibrin deposition (Lind, 1995).
Platelet activation releases a variety of soluble peptides, including platelet-derived
growth factor (PDGF), insulin-like growth factor (IGF), epidermal growth factor
(EGF), transforming growth factor-
) and vascular endothelial growth
factor (VEGF), all of which direct biological responses to a wound. In addition to
growth factors, the wound healing process is regulated by cytokines and chemokines
which are first released by polymorphonuclear cells during the inflammatory
phase and subsequently by fibroblasts, endothelial cells and keratinocytes as ECM
deposition and remodeling occur (Gillitzer and Goebeler, 2001;Werner and Grose,
2003). The coordinated efforts of growth factors, cytokines and chemokines adjust
the biochemical and cellular environment of the wound, thereby achieving resolu-
tion. Unfortunately, unless the wound depth is less than a critical level (Dunkin
et
al
., 2007), the characteristic adult reparative wound healing process results in scar
formation with eventual scar tissue contraction. While the ability to heal cutaneous
wounds by this reparative process is essential for survival, scar tissue has neither
the structural, nor the physiological, attributes of the tissue it has replaced and
therefore represents a comparatively dysfunctional tissue relative to native tissue.
Epidermal and superficial dermal wounds typically heal within a couple of
weeks without hypertrophic scarring and contracture (Chapman, 2007). However,
when the size, depth, or biochemical environment is such that the wound is
precluded from healing naturally, medical intervention is necessary. Such wounds
requiring delayed closure are associated with increased morbidity and mortality
owing to tissue dehydration, reduced thermal regulation and are at increased risk
of infection and elevated pain levels (Brown and Barot, 1986). Burns, trauma and
chronic ulcerations resulting from co-morbidities such as diabetes are the principal
causes of the over 35 million cases per year of significant skin loss ultimately
requiring medical treatment (Clark
et al.
, 2007). With nearly 1.2 million hospital
visits annually for burns (Sánchez
et al
., 2007) and over four million individuals
suffering from chronic wounds resulting from diabetes, venous stasis, or pressure-
induced necrosis, it is easy to understand why the overall health care costs for
treatment of skin injuries in the USA alone are in excess of $10 billion (Clark
et al.
,
2007). But despite the large incidence and the associated costs of treatment,
β
(TGF-
β
