Biomedical Engineering Reference
In-Depth Information
presence of physiological conditions. Other stimuli including light (Ogura et al. 2009),
antibodies (Wiegel et al. 1987), proteins (Xie et al. 2007) and micelle (Ding et al. 2007) used in
nanotechonlogy could be explored as the trigger for dynamic DNA based macro-materials.
Along this line, DNA interstrand crosslinking from radical precursor independent of O2
(Greenberg 2005) may be of interest.
5.2 Refinement of the current designs
For DNA only system, multiple designs of the DNA building blocks can be incorporated for
graded (with respect to time or location) control of the material properties. By combining
physical and chemical crosslinking, gels with DNA backbones may achieve properties not
seen in either system. Refinement of the DNA crosslinked hydrogel includes multi-step
control by introducing multiple DNA crosslinker in a single system allowing multiple-step
in increasing or decreasing crosslinking density. It also includes adding responsiveness to
multiple cues by inclusion of DNA crosslinkers that are sensitive to stimuli including pH,
temperature, and exogenous DNA strands. Responsiveness of these materials to different
stimuli may be combined for the benefits of versatility and wider range of applications and
control.
5.3 Force generation
It is possible to induce volume change of DNA based macromaterials
as a way of generating
forces in all three categories of DNA gel system (i.e., DNA-only, DNA as backbone, and
DNA as crosslinker) (e.g., (Amiya & Tanaka 1987, Horkay & Basser 2004, Jiang et al. 2010c,
Um et al. 2006b)) if the materials are implanted at injury site (e.g., spinal cord injury). This
has been implicated to be useful in a myriad of applications including 'towed' (stretched)
axonal regeneration (Bray 1984) in neural tissue engineering.
5.4 Dynamic porous scaffold
The porosity of the DNA-only gel system may be adjusted with DNA content and design for
specific applications such as drug delivery or tissue engineering. For the DNA crosslinked
macromaterials, the porosity and pore structure can be altered with the choice of
crosslinking density, monomer concentration and monomer nature. For example, in
constructing Acrydite-DNA crosslinked polymers (Jiang et al. 2008b, Lin et al. 2004b), the
reactive end of the Acrydite-modified oligonucleotides contains vinyl group, thus besides
polyacrylamide, poly-hydroxyethyl methacrylate (pHEMA), poly-hydroxy-propyl-
methacrylamide(pHPMA), polymethyl methacrylate (pMMA), and copolymers (e.g. pHEMA-
co-MMA and pHEMA-co-AEMA) are also candidates for DNA crosslinking (
Table 3
). These
polymers are among the most studied non-biodegradable polymers for tissue engineering
applications, including spinal cord injury research (Duconseille et al. 1998, Flynn et al. 2003,
Lesny et al. 2002, Novikova et al. 2003) owing in part to their inhere biocompatibility (Ratner
& Bryant 2004) and suitable pore size and porosity They have been engineered to carry
neuro-trophic factors and present communicating porous structures (e.g., (Bakshi et al.
2004)), and to facilitate necrosis reduction, vasculature formation and axonal outgrowth
across the graft-tissue interface (Dalton et al. 2002, Lesny et al. 2002, Yu & Shoichet 2005).
5.5 Controlled delivery
Previous work indicates that biomaterials based scaffold can provide enhanced gene
delivery efficiency (De Laporte & Shea 2007). In the DNA crosslinked gel network,
