Biomedical Engineering Reference
In-Depth Information
In drug delivery-related studies, silk scaffolds/matrices have been widely used. Horseradish peroxi-
dase (HRP) enzyme gradients were immobilized on silk 3D scaffolds to prepare new functional scaf-
folds including regional patterning of the gradients to control cell and tissue outcomes [91]. Recently,
adenosine release via silk-based implants to the brain of rats have been successfully used for refractory
epilepsy treatments [92,93]. Silk-based implants to release adenosine demonstrated therapeutic ability,
including the sustained release of adenosine over a period of 2 weeks, with diffusion from the silk, slow
degradation of the matrix, biocompatibility, and the delivery of predetermined doses of adenosine [92].
Nerve growth factor (NGF)-loaded silk fibroin nerve conduits have guided the sprouting of axons and
to physically protect the axonal cone for peripheral nerve repair [94]. NGF release from the differently
prepared silk fibroin nerve conduits was prolonged over 3 weeks, while the total amount of NGF released
depended on the procedures used in the preparation of the nerve conduits, such as air-drying or freeze-
drying [94]. Silk fibroin scaffolds containing insulin-like growth factor I (IGF-I) were also prepared for
controlled IGF-I release in the context of cartilage repair [95].
7.4.5 Regenerated Silk Fibroin Hydrogels
Silk hydrogels can be formed from regenerated fibroin solution by sol-gel transition in the presence
of acid, ions, or other additives [96-101]. In addition, temperature, silk fibroin concentration, and pH
significantly impact the gelation process. Gelation time decreases with an increase in silk fibroin con-
centration, temperature, concentration of additives such as Ca
2+
, glycerol, and poly(ethylene oxide), or a
decrease in pH [98,99]. During the gelation process, silk undergoes a structural transition from random
coil to β-sheet due to enhanced hydrophobic interactions and hydrogen bond formation [98-100,102,103].
For composites, regenerated silk fibroin can also be blended with other biopolymers such as chitosan
and gelatin to form hydrogels [96,104,105] and scaffolds [106]. In addition, genetically engineered silk
fibroin-like polymers have been used for hydrogels [107-110]. Silk fibroin hydrogels have been studied for
controlled release/delivery of bioactive agents such as plasmid DNA, viruses, and growth factors [17,98].
Silk fibroin hydrogels have been explored for guided tissue repair. The repair of confined, critical-sized
cancellous bone defects in a rabbit model using silk fibroin hydrogels was reported [111]. These hydro-
gels were prepared by adding 1 M citric acid to a 2% (w/v) regenerated silk fibroin aqueous solution until
passing the isoelectric point (3.8), and subsequently used for
in vitro
cytotoxicity and cytocompatibility
evaluations with a human osteoblast-like cell line (MG63). The silk fibroin hydrogels showed cytocom-
patibility comparable to poly(d,l-lactide-glycolide), based on cell proliferation, differentiation, and the
release of the inflammation-related cytokine IL-6. These silk fibroin hydrogels supported the healing
of critical-sized cancellous bone defects
in vivo
in 12 weeks with no obvious inflammatory reactions.
Similarly, with further processing, such as freeze-drying, microporous silk fibroin sponges were formed
from hydrogels and used for cell culture and tissue engineering [87-89,99]. Microporous silk fibroin
sponges were combined with rabbit chondrocytes for cartilage tissue engineering [87-89], and the cells
proliferated and maintained differentiated phenotype better than in collagen gels used as controls. The
mechanical properties of the regenerated cartilage tissue demonstrated culture time-dependent changes
that correspond to the temporal and spatial deposition of cartilage-like ECMs [88,89]. These results sug-
gest the potential of hydrogel-derived silk fibroin sponges as 3D porous scaffolds for chondrocyte-based
cartilage regeneration.
7.4.6 Silk Microspheres
Silk spheres were explored for drug delivery applications and in tissue regeneration. These silk micro-
spheres were processed using spray-drying; however, the sizes of the microspheres were above 100 μm,
which is suboptimal for drug delivery [112]. Lipid vesicle templating can also be used to efficiently load
bioactive molecules for local controlled release [113]. The lipid was subsequently removed by metha-
nol or NaCl, resulting in silk microspheres with β-sheet structure and ~2 μm in diameter [113]. Silk
