Advances in Collagen-based Tissue Engineering - Natural Polymers, Biopolymers, Biomaterials, and Their Composites, Blends, and IPNs - page 209

materials such as synthetic or collagenous tissues as well as collagen covered vicryl
mesh have been employed for dural repair.
A commercially available substitute for dural repair is DuraGen ® (Integra Life-
Sciences Corporation, US) (Narotam et al., 1999). DuraGen ® is made by acid pre-
cipitation, freeze drying, and thermal/chemical cross-linking of collagen in combina-
tion with chondroitin 6-sulfate. Another one, Promogran (Jonson &Jonson Medical)
is designed for wound healing (Vin et al., 2002). Promogran is freeze dried composite
of oxidized regenerated cellulose (45%) and collagen (55%). Recently, TissuDura ®
with equine collagen as dura mater has been developed (Parlato et al., 2011). Unfortu-
nately, the great differences exist between natural (ECM) and manufactured synthetic
implants. It is important to realize that up to now no ideal dural implant is available .
Muscle fascia remains the most accepted autologous implant in general use.
Over 20 years ago the author of this review in collaboration with surgeons ob-
tained collagen substitute of dura mater (Pietrucha, 1991). Collagen type I was derived
from purified bovine Achilles tendons by pepsin digestion and acetic acid treatment to
prepare dispersion. Whereas native collagen tissue possesses significant strength, this
is lost when collagen products are made from collagen solution. These reconstituted
products may therefore require treatment with cross-linking agent, so as to increase the
strength for particular applications. Cross-linking agents (physical or mostly chemical
treatments) are used to stabilize biological products. Cross-linking procedure can de-
crease biodegradation rate and immunogenicity. However, most cross-linking agents
(i.e., aldehyde family) used to stabilize biological molecules produce toxic byproducts
which are detrimental to the wound healing process. That is why reaction cross-linking
of collagen and preparation hydrogels was carried out by irradiation with electron
beam. However, even extensively radiation cross-linked collagen hydrogels have poor
physical strength for the preparation of dural substitute. For that reason collagen, hy-
drogels were reinforced with poly(ethylene terephthalate) (PET) mesh. The key fea-
tures which had to be achieved were: (a) an elastic hydrogel of defined stable structure,
(b) optimized range of network pore sizes, (c) covalent bonding to the synthetic fiber
net, and (d) freedom from harmful chemical residues.
All the key features were achieved by the use of high energy radiation under op-
timized and strictly controlled conditions. The radiation process produced a sterilized
implant which could be stored for at least a year. It could be implanted without any
additional treatment. The implant material underwent with good success three stages
of evaluation: biochemical in vitro , pre-clinical on animals and clinical . This collagen
composite material has been used in neurosurgery, plastic, and reconstructive surgery
to replace, complete or strengthen the cerebral and spinal cord dura mater as well as
other soft tissues. Satisfactory results have been also obtained in short-term and long-
term (8 years) studies with dural substitute on over 100 patients in several independent
clinics. The prostheses had been implanted in patients with posttraumatic CFC-leak-
age and with intracranial neoplasms as well as in the surgical treatment of meningo-
encephalocele, meningomyelocele, and various dystrophic defects on central nervous
system of children ( Figures 1 -4) (Pietrucha, 2010a; Pietrucha and Polis, 2009; Pietru-
cha et al., 2000; Polis et al., 1993). Moreover, the biomaterial was used for closure of
abdominal wall defect in new-born (Figure 5) (Chilarski and Pietrucha, 1996).