Biomedical Engineering Reference
In-Depth Information
nanomachines will work on cells and move into tissues, organs, and finally the
whole organism can be restored to good health.
6.6.1 Nanomachines for Delivery in Cells
To date, nanomaterials are in use as cell delivery vehicles either to facilitate
the presentation of microenvironmental cues to aid in the process of tissue
regeneration
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or to physically deliver
molecules that repair cells or kill harmful cells such as cancer cells.
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98,101-103,106,304-310
A cell delivery vehicle can be engineered such that it is pro-
vided with proteins or genes that serve as cues that allow cascade of biochemical
events to occur such as the release of cytokines and growth factors or apoptosis.
The release of cytokine or growth factor can lead to the production of antibodies
that can sequester damaging unnatural materials such as cancer proteins, virus,
bacteria, or toxins. It can also lead to healing of cells in a wound at physiologi-
cal levels for a sustained period of time.
Various biomaterials have been used for delivery in cells including viruses.
Although viruses are highly efficient for transfection, they are recognized as for-
eign materials causing an inherent risk of immunogenicity and pathogenicity.
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This prompted the development of nonviral alternatives including nanoparticu-
late DNA-polycation complexes and other polymers that facilitate the entry
of DNA into the cell and its release therein that results in higher transfection
efficiencies than the DNA alone.
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The polycations are typically polymers
such as PEI and chitosan, but functionalized CNTs have also been employed
recently.
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A gene-activated matrix which consists of a matrix carrier that holds DNA
until endogenous wound-healing cells arrive that invade the matrix.
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The
recruited host cells serve as bioreactors in order for the DNA to produce the
proteins needed for tissue regeneration. Gene delivery vectors within the same
matrix could transfect cells with appropriate growth factor so that these can
be produced in a sustained manner. Schillinger et al. transfected chondrocytes
cultured in clotted fibrin glue.
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The optimized glue is based on the fibrino-
gen component of TISSUCOL, a fibrin glue that is widely used in clinics, co-
lyophilized with copolymer-protected PEI-DNA vectors (COPROGs) was used
to mediate growth factor gene delivery to admixed primary keratinocytes and
primary chondrocytes before clotting. The chondrocyte colonized COPROG
clots showed endocytotic vector uptake. Bone morphogenetic protein (BMP-2)
gene transfection in situ and subsequent expression in chondrocytes grown in
COPROG clots showed in vitro upregulation of alkaline phosphatase expression
and increased ECM formation. COPROG-fibrinogen chondrocytes delivered
to rabbit osteochondral defects led to reporter gene expression for 2weeks.
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The gene-activated matrix concept for cell repair has yielded some promis-
ing results and it is being further improved and refined.
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Various combina-
tions of matrix materials and gene vectors have been studied.
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