Biomedical Engineering Reference
In-Depth Information
that differ from the description of an anatomically well-defined defect presented
here. In one of these studies of the central nervous system, information on axonal
growth has been obtained using an animal model injured by midthoracic dorsal spi-
nal cord hemisection (Duffy et al. 2009; Deng et al. 2013). Hemisection models of
nerve injury appear to provide an experimental volume that allows studies of wound
healing or of axonal regeneration rather than studies of whole organ regeneration.
Another major requirement for a standardized experimental defect is inclusion
of the tissue exudate that forms spontaneously inside the wound. The initial events
in the inflammatory response following injury are flow of blood and extravascular
tissue fluid inside the wound, together with migration of cells from adjoining tis-
sues. This fluid is often collectively referred to as “wound fluid”; it will be referred
to here as “exudate”. The exudate that fills deep wounds, both in skin and nerve,
contains a large number of soluble regulators of cell function that orchestrate the
inflammatory response. Substantial information is known about the composition of
exudate in skin wounds, showing that this fluid is endowed richly with soluble regu-
lators (Regan and Barbul 1991; Breuing et al. 1992; Kroeze et al. 2012). An analysis
of required reactants for inducing regeneration in skin and peripheral nerves, de-
scribed in detail in Chap. 7, suggests strongly that the exudate provides indispens-
able endogenous reactants that contribute to induction of regeneration.
Uncontrolled escape of exudate from a defect, or even a significant alteration
in concentration of its soluble regulators, has significantly modified the outcome
both of a spontaneous and an induced healing process. For example, the rate of
epithelialization in dehydrated skin wounds, in which the soluble regulators were
presumably unable to exist in a sufficiently diffusible state due to lack of aqueous
solvent, was significantly inhibited and the time for wound closure was increased
compared with wounds that were maintained simply moist by use of an occlusive
dressing (Winter 1972). The importance of a moderate amount of moisture in skin
wound healing has been confirmed in later studies while dehydrated wounds or
wounds with excessive fluid have been considered much less favorable for optimal
healing (Bishop et al. 2003; Lachenbruch and VanGilder 2012).
A little more is known about the role of wound exudate in peripheral nerve re-
generation. Following transection of the sciatic nerve in the rat, a cylindrical tissue
about 1 mm in diameter, fluid exudate leaves the stumps at a rate estimated at about
1 ml/h (Longo et al. 1983a, b; Williams and Varon 1985). The exudate comprises
primarily of plasma that has leaked out of blood vessels, as a result of the increase in
vascular permeability associated with trauma, as well as resulting from components
synthesized by the injured neuron (Fu and Gordon 1997). Axotomized neurons
synthesize cytokines, including platelet-derived growth factor (PDGF) and acidic
fibroblast growth factor (FGF1), which contribute to the inflammatory response
of the transected nerve. These cytokines synthesize neurotrophic factors, including
nerve growth factor (NGF; Lundborg et al. 1982b; Longo et al. 1983a, b; Fu and
Gordon 1997). These cytokines also upregulate migration of nonneuronal cells and
enhance angiogenesis (Fu and Gordon 1997). In an example from peripheral nerve
wound healing, a transected nerve that was allowed to lose a significant mass of
exudate before the two stumps were sutured directly together had a markedly di-
