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384 Part 3: Meat, Poultry and Seafoodscomplete dermis have been removed by surgical excision (Meena
et al. 1999). Wisser and Steffes (2003) described the success-
ful wound management of a 19-year-old patient with 63% of
the body surface burnt covered with Integra©R, consists of a
modified bovine collagen matrix and a silastic membrane facing
toward the body surface. After 1 year of surgical development,
a common feature of wound areas treated with Integra showed
the good sliding characteristics of the skin on its support and
the lack of scar lines. Taguchi et al. (2004) developed a novel
tissue adhesive, consisting of type I collagen from pig skin and
cross-linking by citric acid derivative. This adhesive is biode-
graded under the skin of mice within 7 days after subcutaneous
injection. Synthetic materials in the form of dressings are used
primarily for treatment of superficial wounds to prevent mois-
ture and heat loss from the skin as well as to prevent bacterial
infiltration from the environment (Meena et al. 1999). Anti-
szko et al. (1996) developed collagen membranes as carriers of
antiseptics. Microdressings prepared with collagen membranes
containing povidone-iodine or chlorhexidine glycerin solution
and packed into envelopes made of laminated aluminum foil
were stable for 8 weeks concerning their antibacterial activ-
ity. After implantation beneath mouse skin, the dressings did
not cause inflammation. Such dressings may be useful in a treat-
ment of ulcers, superficial burns, and chronic granulated wounds
(Antiszko et al. 1996).
Advantages of collagen for biomedical application include
(Meena et al. 1999) (i) abundant sources of highly purified (med-
ical grade) collagen, (ii) the ability to be reconstituted into high
strength forms useful in surgery, (iii) the wealth of research liter-
ature on the characterization of collagen, (iv) improved process-
ing techniques, (v) introduction of several commercial collagen
products, and (vi) recent advances in the use of collagen as a
delivery system.Pharmaceutical ApplicationsBovine collagen was approved by the Food and Drug Adminis-
tration in 1982, and since that time, it has remained as a primary
filler of choice for soft-tissue augmentation of dermal defects
(Matarasso 2006). The advent of human-derived collagen from
fibroblast cultures further increased the popularity of injectable
products. Cultured autologous collagen and several other for-
mulations of collagen have been undergoing clinical trials or
are available outside the United States (Matarasso 2006). These
advances in collagen technology may deliver products that are
more persistent in duration and comfortable to administer than
materials that are presently in use. It is widely known that the di-
gestion of collagen proteins or hydrolysates in vivo will generate
peptides that may be useful for organic biosynthetic processes
(Cuneo et al. 2010). Thus, the consumption of collagen-rich ́
foods might be beneficial for bone health. Several functional
properties of enzymatic collagen hydrolysates have been in-
vestigated in osteoarthritis and suggest a beneficial stimulating
effect with an increased synthesis of extracellular matrix macro-
molecules produced by chondrocytes (Bello and Oesser 2006,
Cuneo et al. 2010). Wu et al. (2004) postulated that oral admin- ́
istered collagen peptide may provide beneficial effects on bonemetabolism in rat, especially in the calcium-deficient condition,
without obvious undesirable effects. In a randomized, double-
blind, placebo-controlled trial with osteoporotic women, Adam
et al. (1996) investigated the use of a diet rich in collagen hy-
drolysate (10 g/day) and observed that calcitonin associated with
this type of diet had a greater effect in inhibiting bone collagen
breakdown than calcitonin alone, as determined by a decrease
in urinary levels of pyridinoline cross-links. Bello and Oesser
(2006) postulated that collagen hydrolysate ingestion stimulates
a statistically significant increase in synthesis of extracellular
matrix macromolecules by chondrocytes compared with un-
treated controls. These findings suggest mechanisms that might
help patients affected by joint disorders such as osteoarthritis.
A growing body of evidence provides a rationale for the use
of collagen hydrolysate for patients with osteoarthritis (Bello
and Oesser 2006). The cell biological properties of collagen,
gelatin, and collagen hydrolysate (<15,000 Da) were studied
using murine keratinocytes (Li et al. 2005). Keratinocyte culture
experiments demonstrated that only collagen had significant ef-
fects on cell attachment and proliferation, but the results of cells
cultured on gelatin and collagen hydrolysate showed that the
rates of adhesion and proliferation were similar to those of cells
cultured on plastic as a control. It is concluded that collagen has
better physiological effects than those of gelatin and collagen
hydrolysate as skin-care cosmetic materials (Li et al. 2005).
In addition, collagen has served as an excellent carrier for
drug delivery systems. Collagen can be extracted into an aque-
ous solution and molded into various forms of delivery systems.
The main applications of collagen as drug delivery systems are
collagen shield in ophthalmology, sponges for burns/wounds,
minipellets and tablets for protein delivery, gel formulation in
combination with liposomes for sustained drug delivery, con-
trolling material for transdermal delivery, and nanoparticles for
gene delivery (Lee et al. 2001). Atelocollagen, which is pro-
duced by elimination of the telopeptide moieties using pepsin,
has demonstrated its potential as a drug carrier, especially for
gene delivery (Kohmura et al. 1999, Ochiya et al. 1999, Lee
et al. 2001). Ho et al. (1997) demonstrated that gel formulation
prepared by gelling the vehicle mixture of citric acid solution,
ethanol, and propylene glycol with 1% (w/w) of telopeptide-poor
collagen (atelocollagen) sample was suitable for transdermal de-
livery. Takaoka et al. (1991) reported that bovine skin collagens
prepared by use of conventional methods (acid-solubilized col-
lagen, or collagen-digested once with pepsin) were also assessed
as carriers for bone morphogenetic protein (BMP) in mice, but
were found to be inferior in terms of consistency of bone forma-
tion and amount of induced bone mass. The results suggest that
telopeptide-depleted collagen (atelocollagen) permitted a grad-
ual release of purified BMP for induction of bone, with minimal
immunogenic interference. Consequently, this collagen carrier
represents an important development for future clinical applica-
tion of BMP (Takaoka et al. 1991). Ochiya et al. (1999) described
a new gene transfer method that allows prolonged release and
expression of plasmid DNA in vivo in normal adult animals
through the use of atelocollagen, a biocompatible polymer, as
the carrier. Plasmid DNA was carried in the atelocollagen, re-
sulting in a minipellet of cylindrical shape (0.6 mm in diameter