Biomedical Engineering Reference
In-Depth Information
using other more sophisticated shape memory polymers as discussed earlier
in minimally invasive tissue engineering approaches.
Multifunctional Polymers
Another approach that has been employed for in situ hydrogel formation in-
volves the mixing of two oligomer solutions having functional groups such
that they form viscoelastic hydrogels upon reaction between the functional
groups, similar to fibrin glue formation (Wang and Elisseeff, 2005, personal
communication) [174, 307, 308]. To this end, Schiff base reaction of amine and
aldehyde groups has been extensively explored in the past.
Balakrishnan et al. developed gelatin-based hydrogels in situ by mixing ox-
idized alginate and gelatin [307]. The hydrogels formed using this approach
were nontoxic to the encapsulated mouse fibroblasts. In our laboratory, Wang
and coworkers have used a similar approach for in situ integration of hydrogel
implants (that can be immobilized onto the defect site) with the native tissue,
which will be discussed in detail in Sect. 8 (Wang and Elisseeff, 2005, personal
communication). The in situ gelation ability of two liquid reactants containing
the functional groups, aldehyde functionalized CS and poly(vinyl alcohol-
co-vinylamine), have been used for sealing corneal incisions by Reyes and
coworkers [98]. Hyaluronic acid functionalized with various active groups such
as amine and aldehyde groups can undergo in situ hydrogel formation when
mixed with multifunctional monomers [174]. These materials are biocompat-
ible, and in the presence of appropriate growth factors, these hydrogels can be
used for bone or cartilage tissue engineering. Prestwich and coworkers used
similar in situ gelation techniques to create HA and CS-based hydrogel films
using poly(ethyleneglycol)-dialdehydes for wound healing applications [308].
These authors also applied in situ gelation of HA hydrogels for incorporat-
ing drugs that can be released in a controlled manner [263]. Sperinde and
Griffith utilized enzyme-mediated crosslinking of peptide-modified PEG pre-
cursors to achieve in situ gelation. Such in situ formation of hydrogels can be
used for tissue engineering and drug delivery applications without any toxic-
ity concerns [99, 100]. This reaction enjoys the ability of transglutaminase to
form amide linkage between the
-carboxamide group of glutamine residues
and primary amines such as the one in lysine. These covalent bonds between
specific functional groups are strong and permanent unlike physical crosslinks.
Hydrogels for Stem Cell Differentiation
It is only in the last decade or so that the therapeutic value associated with
donor/patient differentiated cells is being exploited to create functional re-
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