Biomedical Engineering Reference
In-Depth Information
of water, increasing as the ethylene content of ethylene vinyl alcohol decreases. The presence of
water results in plasticization of the polymer, with
T
g
decreasing in more humid environments [5].
When mixed with polar physiological fl uids, such as blood, the dimethyl sulfoxide in the Enteryx
solution disperses, resulting in the hydrophobic copolymer becoming a solidifi ed spongy mass. Enteryx
can be injected through a 23-25 gauge needle due to its low viscosity before contact with physiological
fl uids, and the biocompatibility of its constituents is reported to be good [6]. The polymer becomes
encapsulated in fi brous tissue after 3-6 months and has been shown to be durable for at least 3 years
following implantation [6-8]. To enable visualization of the polymer under fl uoroscopy, micronized
tantalum powder (30% w/v) is added to the polymer/solvent mixture as a contrast agent.
20.3
BIOMATERIALS USED FOR GASTROINTESTINAL FISTULA REPAIR
20.3.1 G
ASTROINTESTINAL
F
ISTULAS
Fistulas are a common complication of Crohn's disease, a chronic infl ammatory disorder affect-
ing any part of the gastrointestinal tract. Crohn's fi stulas are most commonly present as a perianal
manifestation in 14-38% of patients suffering from Crohn's disease in referral populations [9]. The
pathogenesis of perianal fi stulas remains unknown, but it is believed either they may begin as deep
penetrating ulcers in the anus or rectum that extend over time due to feces being forced into the
ulcer with the pressure of defecation [10], or they may arise due to an infection or abscess of the anal
glands that exist at the base of the anal crypts [11-13]. Either way, fi stulas are thought to form when
there is no rapid compensatory fi brogenic response to fi ll up the defect [14]. Furthermore, fi stulas
might be perpetuated due to bacterial colonization by a variety of normal commensals of the lower
gastrointestinal tract [15]. Although the options for treating fi stulas in Crohn's disease continue
to evolve, fi stulas rarely heal. Medical therapies with proven effi cacy for the treatment of Crohn's
perianal fi stulas include antibiotics, mercaptopurine and azathioprine, ciclosporin, tacrolimus, and
infl iximab [16]. Antibiotics are the most commonly used agents for Crohn's perianal fi stulas, with
clinical improvement usually seen after 6-8 weeks of metronidazole therapy, but fi stulas frequently
reoccur once metronidazole is discontinued [16]. The most successful treatment of perianal Crohn's
disease is usually achieved when medical therapy is used in conjunction with surgery, but surgery
carries the risk of causing incontinence [16].
20.3.2 F
ISTULA
R
EPAIR
U
SING
B
IOMATERIALS
20.3.2.1 Fibrin Glue
During the last decade, fi brin glue (also called fi brin sealant or fi brin tissue adhesive) has been
proposed as an alternative to the cutting seton and mucosal advancement fl ap repair of complex
fi stulas. Due to its ease of application via injection, this procedure is considered safe and painless
and without signifi cant morbidity. Fibrin glue simulates physiological clot formation and was fi rst
used as a hemostatic agent at the beginning of the last century. Its use for surgical procedures pro-
gressed when a method was developed to combine highly concentrated fi brinogen with factor XIII
fi brin-stabilizing factor) and inhibitors of fi bronolysis, such as aprotonin. Commercially available
concentrated fi brinogen preparations became available during the 1970s, but the risk of viral trans-
mission in pooled fi brinogen concentrates led to license revocation. Autologous human fi brinogen
was used as an alternative, and despite subsequent development of viral elimination procedures and
the relicensing of fi brin glue, autologous fi brin is still used for the closure of fi stulas and in other
surgical procedures [17].
Fabrication of fi brin glue is based on chemical reactions that occur during the physiological
coagulation cascade. It is produced by mixing a fi brinogen solution containing factor XIII, fi bronec-
tin, and aprotonin with thrombin and calcium ions (Figure 20.2). Thrombin mediates the cleavage
of fi brin monomers from fi brinogen, which spontaneously aggregate and form weak clot. Thrombin
