Biomedical Engineering Reference
In-Depth Information
are natural L-amino acids, the RADA16-I has been shown not to elicit noticeable
immune response, nor infl ammatory reactions in animals (Zhang et al.
2005
; Davis
et al.
2005
; Ellis-Behnke et al.
2006
a,
b
), the degraded products can be reused by
the body, they may also be useful as a bio-reabsorbable scaffold for neural repair
and neuroengineering to alleviate and to treat a number of neuro-trauma and neuro-
degeneration diseases.
In a recent work led by Richard Lee, mouse embryonic stem cells were sus-
pended in RADA16-II peptide scaffold solutions and injected in the myocardium of
10-weeks-old mice (Davis et al.
2005
). In that study it has been demonstrated that
self-assembling peptides can be injected into the myocardium to create 3-D microen-
vironment. After 7, 14 and 28 days these microenvironments recruit both endoge-
nous endothelial and smooth muscle cells, and exogenously injected cells survive in
the microenvironments: self-assembling peptides can thus create injectable microen-
vironments that promote vascularization.
In addition Lee's group also developed an appealing drug delivery strategy by
using a biotinylated version of RADA-II to demonstrate a slow release of Insulin-
like growth factor 1 (IGF-1) in infarctuated rat myocardia (Davis et al.
2006
) . The
biotin sandwich strategy allowed binding of IGF-1 and did not prevent self-assembly
of the peptides into nanofi bers within the myocardium. In conjunction with cardio-
myocytes transplantation the strategy showed that cell therapy with IGF-1 delivery
by biotinylated nanofi bers signifi cantly improved systolic function after experimental
myocardial infarction.
Ellis-Behnke and colleagues showed that self-assembling peptide material is a
promising scaffold for neural regeneration medicine (Ellis-Behnke et al.
2006
a,
b
). In vivo application to brain wounds was carried out using postnatal day-2
Syrian hamster pups. The optic tract within the superior colliculus (SC) was
completely severed with a deep knife wound, extending at least 1 mm below the
surface. At surgery, ten animals were treated by injection into the wound with
10-30 ml of 1% RADA16-I in 99% water (w/v). Control animals with the same
brain lesion included 3 with isotonic saline injection (10 ml), and numerous
additional cases, including 10 in which the dye Congo red was added into the
peptide scaffold, and 27 earlier animals with knife cuts and no injection surviving
6-9 days. Animals were sacrifi ced at 1, 3, 6, 30 and 60 days for brain examina-
tions. Histological specimen examinations revealed that only in the peptide scaf-
fold-injected animals, but not in untreated animals, the brain tissue appears to
have reconnected itself together in all survival times. Additionally, axons labeled
from their retinal origin with a tracer molecule were found to have grown beyond
the tissue bridge, reinnervating the SC caudal to the lesion. Most importantly,
functional tests proved a signifi cant restoration of visual function in all peptide
scaffold-treated animals.
Ellis-Behnke and colleagues during the brain surgery experiments found that the
peptide nanofi ber scaffold hydrogel could also stop bleeding in less than 15 s (Ellis-
Behnke et al. 2007). This is unlikely to be the conventional blood clogging mecha-
nism because it takes place so rapidly. The molecular mechanism of speedy stopping
bleeding still remains to be uncovered. It is plausible that the nanofi bers self-assembled
