BIOMATERIALS AND MANUFACTURING METHODS FOR SCAFFOLD IN REGENERATIVE MEDICINE - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 31

the fabrication process. The release mechanisms are largely divided
into categories: (i) diffusion-controlled, (ii) degradation-controlled,
and(iii)solvent-controlledreleasemechanismthroughtheselection
of biomaterials. The mechanism of biodegradable scaffolds materi-
als was degradation controlled, whereas that of the nondegradable
one was diffusion and/or solvent controlled. The desired release
patternsuchasconstant,pulsatile,andtime-programmedbehaviors
along the specific site and the type of injury can be achieved by the
appropriate combination of these mechanisms. Also, the cytokine
releasesystemmightbedesignedinavariationwithgeometriesand
configurations such as scaffold, tube, nose, microsphere, injectable
forms, fiber, etc. 1 , 10 One of the serious problems during the fabrica-
tion of a cytokine-loaded scaffold is the denaturation and deactiva-
tion of cytokines, resulting in the loss of biological activity. Hence,
an optimized method must be developed for a stabilized cytokine
release scaffold.
Another available emerging technology is the tethering to the
surface, that is, immobilization of protein on the surface of the
scaffold matrix. Immobilization of insulin and transferrin to the
poly(methylmetacrylate) films stimulates the growth of fibroblast
cell compared to the same concentrations of soluble or physically
adsorbed proteins. For the enhancement of cytokine activity, a PEO
chain was applied as a short spacer between the surface of the
scaffold and the cytokine. Tethered EGF, immobilized to the scaf-
fold through the PEO chain, showed more improved DNA syn-
thesis or cell rounding compared to the physically adsorbed EGF
surface. 35
Conjugation of cytokine with an inert carrier prolongs the
short half-life of protein molecules. Inert carriers are albumin,
gelatin, dextran, and PEG. PEGylation—that means PEG-conjugated
cytokine—ismostwidelyusedfortherelease.Itappearstodecrease
the rate of cytokine degradation, attenuate the immunological
response, and reduce clearance by the kidneys. 1 , 35 Also, the PEGy-
lated cytokine can be impregnated into scaffold materials by phys-
ical entrapment for sustained release. This conjugation method
can be applied to the delivery of proteins and peptides. Immo-
bilized arginin-glycine-aspartic acid (RGD) and tyrosin-leucine-
glycine-serine-arginine (YIGSR), which are typical ECM proteins,