Biomedical Engineering Reference
In-Depth Information
colleagues [19, 21]. Reaction of multiarm PEG-vinylsulfone with bovine serum
albumin or fibrinogen produces biohybrid materials [25]. Proteins may be
specifically engineered to contain enzymatically degradable sites, adhesion sites
and free cysteines to react with PEG by a Michael-type addition [42]. The
enzyme adenylate kinase was engineered to have two free cysteines that were
used to crosslink four arm PEG-maleimide. Incubation of the hydrogels with
ATP resulted in a 20% contraction of the hydrogels [43].
Mixed mode thiol-acrylate hybrid hydrogels have been formed by reaction of
PEG-DA with peptides containing two cysteines. The chain growth nature of the
mixed mode reaction may be exploited to eliminate the need for multi-arm PEG
[44]. Because the free radicals are generated photochemically, this allows
patterning that is not possible with the typical step growth reactions. Click
chemistry may also used to produce hydrogels from PEG-tetraazide and an
acetylene-modified peptide [45]. Biologically active polysaccharides such as
hyaluronan may be modified with thiols and used to crosslink PEG-diacrylate
[46]. Alternatively, acrylated hyaluronan may be reacted with enzymatically
degradable peptides by Michael-type addition and subsequently photo-
polymerized [47]. Other strategies to produce hybrid hydrogels have been
recently reviewed [48].
3. Swelling Properties of PEG Hydrogels
Regardless of the physical/chemical route to hydrogel formation, the use of
reaction conditions that are well-tolerated by living cells is highly desirable.
While this requirement initially limited progress in the field, the list of cell-
compatible reactions continues to increase, as illustrated by the numerous
crosslinking schemes listed above. However, one principle that does not change
with the introduction of new crosslinking schemes is that the swelling and
degradation of hydrogels are determined by the balance between the number of
crosslinks in the hydrogel and the affinity of water for the constituent polymers.
Mechanical and degradation properties of hydrogel scaffolds ultimately
determine their clinical relevance and are thus of paramount importance in the
design of hybrid biomaterials.
A starting point for understanding the mechanical properties of biohybrid
hydrogels is the classic gel swelling model of Flory and Rehner. Building on
earlier work in the field of statistical mechanics, Flory and Rehner calculated the
probabilities for a polymer chain to adopt a particular end-to-end distance in the
presence of solvent and crosslinks [49, 50]. They imagined the assembly of the
swollen network from 'network chains' of uniform length. The network chains
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