Biomedical Engineering Reference
In-Depth Information
1988; Williams 1987). These studies emphasized observations during the first 4
weeks following tubulation repair and typically did not exceed 8 weeks. They led to
understanding the early cellular events following tubulation and, more importantly,
provided a powerful experimental paradigm that others have since used to study the
cell and molecular biology of nerve regeneration (Fu and Gordon 1997).
Silicone tubes have been widely used as bridges for gaps in the PNS in both
experimental protocols and clinical studies. The first detailed study of the early cel-
lular events that led to regeneration across a gap (Williams et al. 1983) as well as
the first long-term study of morphological and conductivity properties of a PNS re-
generate (Fields and Ellisman 1986a, b; Fields et al. 1989) were conducted with the
aid of silicone tubes. The results of clinical studies in PNS regeneration of silicone
tubes have been reported in unusual depth (Lundborg et al. 1991, 1994).
Regenerates produced across a 10-mm gap bridged by silicone tubes have typi-
cally displayed axons that were smaller in diameter and had thinner myelin sheaths
compared with normal controls. After 40 weeks, the values of electrical conductiv-
ity (64 % normal) and amplitude (9 % normal) remained significantly lower than
normal controls (Fields and Ellisman 1986a, b; Fields et al. 1989). Nerve degenera-
tion inside silicone tubes has been observed in longer studies (Le Beau et al. 1988;
Merle et al. 1989).
Below we discuss the effect of various fillings for silicone tubes, including solu-
tions used as internal controls by investigators; gels and insoluble substrates.
ΔL
values are used extensively from Table
6.1
.
Solutions used as
internal controls
by investigators typically led to Δ
L
values that
were not significantly different from zero. A possible exception was the observa-
tion of a very modest upregulation of regeneration,
ΔL
≥ 1.5, when the silicone tube
was filled with PBS compared with implanting an unfilled silicone tube (Williams
et al. 1987). In another study,
ΔL
was a low 1.2 when the activity of a silicone tube
prefilled with saline was compared with an initially unfilled silicone tube (Chang
et al. 1990; Chang and Yannas 1992). Twofold dilution of PBS solution used as tube
contents, did not affect regenerative activity; it led to a
ΔL
value of − 0.2 (Williams
et al. 1987). A cytochrome C solution led to a value of 0.7, also insignificantly dif-
ferent from zero (Hollowell et al. 1990).
Gels
based on macromolecular substances generally displayed little, if any, re-
generative activity. Values of
ΔL
were not significantly different from zero when
silicone tubes were prefilled with gels at the following concentrations: a laminin
gel at 0.5 mg/ml, a fibronectin gel at 0.5 mg/ml or a fibronectin/laminin gel at a
concentration of 0.5 mg/ml for each macromolecular solute (Bailey et al. 1993); a
laminin gel at 4 mg/ml (Labrador et al. 1998); a collagen gel at 1.28 mg/ml as well
as at 2.56 mg/ml (Labrador et al. 1998); a collagen gel at 3 mg/ml (Itoh et al. 1999);
a hyaluronate gel at 5 mg/ml in the mouse sciatic nerve (Labrador et al. 1998); and
a plasma fibrin matrix, prepared by injecting CaCl
2
into the tube before clotting
(Labrador et al. 1998). Axons did not elongate beyond 6-7 mm along a 15-mm gap
bridged by a silicone tube filled with a collagen gel, at 2.4 mg/ml, or a laminin-
containing gel, at approximately 7 mg/ml laminin (Madison et al. 1988). In contrast
to the above, a solution comprising a fibronectin/laminin gel at 0.5 mg/ml for each
