Biomedical Engineering Reference
In-Depth Information
carboxymethylcellulose [49]. It is biocompatible and relatively easy to handle and apply. It readily
adheres to tissues, turning into a hydrophilic gel after 24-48 h and provides a protective barrier over
traumatized surfaces in the abdomen for up to 7 days during which time it is slowly reabsorbed from
the abdominal cavity before being excreted from the body in 28 days [50].
Hyaluronic acid (also called hyaluronan or hyaluronate) is a glycosaminoglycan found abundantly
in epithelial, connective, and neural tissues, where it is a chief component of the extracellular matrix.
Because of its ubiquitous presence in the extracellular matrix of tissues and its biocompatibility,
hyaluronic acid is an attractive biomaterial for biomedical applications. However, due to its poor
biomechanical properties, it usually requires chemical modifi cation, such as grafting onto natural
or synthetic polymers, to produce mechanically robust materials. Fabrication of Seprafi lm involves
blending hyaluronic acid and carboxymethylcellulose, both of which are polyanionic polymers and
contain carboxylic acid groups, followed by chemical modifi cation with 1-(3-dimethylaminopropyl)-
3-ethylcarbodiimide
hydrochloride (carbodiimide) [51]. The carbodiimide modifi es the negatively
charged carboxylic acid groups and leaves a proportion of these groups cationic by the formation of
N
-acylurea. This creates an anionic-cationic cross-linked network that reduces the rate of
in vivo
degradation and absorption of both hyaluronic acid and carboxymethylcellulose polymers. This
effect enables membranes prepared from this composite polymer to remain at the tissue surface
longer to function as a barrier to separate the traumatized tissue surfaces [52].
However, the use of membranes and fi lms such as Seprafi lm is limited to surfaces easily acces-
sible during surgery, and therefore alternative barrier approaches are being sought to prevent adhe-
sion. One example is the use of an auto-cross-linked hyaluronic acid-derivative gel, which has been
found to be effective in reducing adhesions after hemostasis [53,54]. Auto-cross-linked hyaluronic
acid polymers, such as those produced by Fidia Advanced Biopolymers, Italy, are fabricated by
an auto-cross-linking esterifi cation reaction between the carboxyl groups and hydroxyl groups
belonging to the same molecule and different molecules of hyaluronic acid, forming a mixture
of lactones and intermolecular ester bonds [55]. By adjusting the reaction conditions, the level of
cross-linking can be controlled. Because no additional bridging molecules are present between the
cross-linked hyaluronic acid chains, only natural products are released during degradation of the
hydrogel.
Further modifi cations to hyaluronic acid-based hydrogel barrier-type materials have included
the incorporation of agents that inhibit cellular proliferation at the traumatized surface. Liu et al.
recently reported on the
in vivo
effi cacy of cross-linked hyaluronic acid fi lms loaded with mitomy-
cin C, an antitumour antibiotic that alkylates and cross-links DNA [56]. The use of an acrylamide
derivative of mitomycin C enabled the incorporation of this agent into the fi lms by conjugate addition
chemistry [57].
20.5.2.2 Nanofi brous Sheets
Despite the reported success of these materials, there still remains a need to develop improved and
inexpensive products that are effective in various surgical applications.
One example is the use of nanofi brous scaffolds, which are being considered for a number of
different tissue engineering applications. They appear to offer a physical environment that more
closely resembles that of native extracellular matrix, favoring cellular adhesion, proliferation, and
differentiation compared with other human-made materials [58]. Zong and colleagues tested a novel
nanostructured barrier fabricated by electrospinning poly(lactic-
co
-glycolic acid) copolymers designed
to prevent postsurgery-induced abdominal adhesions [59]. The starting material is biocompatible and
biodegradable and has previously been used in many FDA-approved implant devices, such as suture
fi bers. Electrospinning is a process that uses an electrostatic fi eld to control the formation and the
deposition of polymer fi bers that can be submicron in diameter. The polymer solution at the tip of a
nozzle is subjected to a large electric potential (typically 15-30 kV) and is separated by a distance from
an oppositely charged target to create a static electric fi eld. As the electric fi eld potential increases,
