Biomedical Engineering Reference
In-Depth Information
drug incorporated. When modified with a polymeric carrier or encapsulated into a particulate carrier,
drug can be targeted to a tissue or an organ according to the tissue-specific affinity of the carrier itself
[27-30]
as well as the phagocytic cells based on the susceptibility of the carrier to cellular uptake
[31,32]
. Once the combination of a drug and a carrier matrix is performed, the molecular compat-
ibility between the drug and the carrier matrix, in other words, their affinity to associate with each
other becomes an influential factor for sustaining the release of the drug from the matrix. If the com-
patibility is poor, the drug molecules will not be dispersed homogeneously in the matrix phase, cre-
ating microscopic phase separation, and subsequently a burst effect (i.e., rapid initial release of the
drug). On the other hand, good compatibility between the drug and the matrix will lead to a long-
term sustained release with zero-order, first-order, or diffusion-controlled release kinetics. Various
biodegradable or nonbiodegradable polymeric materials have been developed recently for medical,
pharmaceutical, drug delivery, and tissue engineering applications
[33]
. The objective of controlled
release technology involves sustaining the release of drug, the prolongation of drug life-span
in vivo
,
increasing the rate of drug absorption, and enhancing the drug targeting properties.
14.5
CONTROLLED RELEASE SYSTEMS FOR BONE REGENERATION
Several preclinical studies have revealed that BMP administrated in the solution forms does not
always induce the expected efficiency in bone regeneration. High physiological doses of BMP are
often required to achieve bone formation
[34]
. To tackle this problem, various biodegradable carriers,
including collagen, lactide-glycolide copolymers, β-TCP, and ethylene glycol-lactic acid copolymers
have been employed as carrier matrices that would accommodate and release BMP
[35-38]
. An oste-
ogenic product composed of BMP-7 and collagen has been commercialized
[39]
. Thus, the combina-
tion of BMP with the release materials is highly needed to achieve the
in-vivo
BMP-induced bone
formation. However, only little
in-vivo
investigations have been conducted on the ability of BMP
associated with carrier systems to promote bone regeneration.
Our previous research has involved preparation of a hydrogel from gelatin having different bio-
degradability. These systems succeeded in augmenting the biological effects of bFGF, TGF-β1, and
HGF
[40-42]
. Gelatin was selected as the carrier materials for growth factor release because it is
commercially available with various physicochemical properties and has been extensively used in
industrial, pharmaceutical, and medical applications. The biological safety of gelatin has been also
proved through the long clinical use
[43]
. Another unique advantage of gelatin is its electrical nature
which allows the growth factor with an electrical charge to physically immobilize into the gelatin-
based hydrogel
[44]
. When the hydrogel is enzymatically degraded to generate water-soluble gelatin
fragments, the growth factor immobilized can be released from the hydrogel
[45]
.
Figure 14.3
shows
a schematic illustration of the mechanism of growth factors release from the carrier matrix based on
the degradation of the matrix. The
in-vivo
degradability of gelatin hydrogels depends on their water
content which can be modified by changing the preparation conditions. It should be noted that gelatin
hydrogels can be formulated into different shapes, such as disks, tubes, sheets, or microspheres.
Recently, Tabata's group have prepared a biodegradable hydrogel from gelatin with an isoelec-
tric point (IEP) of 9.0 for the controlled release of BMP-2 based on hydrogel biodegradation. In this
study, ectopic bone formation by the BMP release system was investigated and compared with the
in-vivo
profile of the BMP release. Hydrogels with different water contents were prepared through
glutaraldehyde cross-linking of gelatin with IEP of 9.0 under various reaction conditions. Following
