platform that allows fine adjustment of many of these parameters as well as
incorporation of the essential features required for tissue engineering and drug
delivery applications.
The Deming laboratory has developed hydrogels based on amphiphilic block
copolypeptides possessing many features that make them attractive as candidates
for medical applications [92]. Foremost, through combination of chemical synthesis
and structural characterization, a detailed understanding of structure–property
relationships in these materials has been established, allowing a high level of
control over gel strength, gel porosity, gel functionality, and media stability;
many which can be adjusted independent of each other [26]. Second, these
physically associated gels are readily injectable through a 30G needle for facile
application and filling of wound cavities [92]. Finally, the hydrogels can be
prepared to be minimally toxic to cells in culture [111]. Hydrogel formation was
first discovered in a series of diblock copolypeptides containing a charged, water
solubilizing domain [poly(L-lysine·HBr], K; or poly(L-glutamate Na salt), E] and a
α-helical hydrophobic domain [poly(L-leucine), L], i.e., K x L y or E x L y (Fig. 6)
[92]. Hydrogel formation is the result of self-assembly of these polymeric
amphiphiles by direct dissolution in water, and the resultant gels possess a network
structure composed of nanoscale to microscale porosity and significant material
rigidity, despite being composed of >95% water. In order to determine the role
played by each copolypeptide domain, a comprehensive study was performed using
an array of samples where both overall chain segment length and hydrophilic to
hydrophobic composition were systematically varied. It was found that chain length
modification of both positively charged polyelectrolyte and hydrophobic segments
had significant effects on properties [92]. It is worth noting that analogous samples
prepared with negatively charged polyelectrolyte domains, i.e., poly(L-glutamate),
were found to behave similarly, which opens the possibility for preparation of both
cationic and anionic hydrogels.
Compositional studies with different copolypeptides revealed many trends
relating molecular parameters to hydrogel properties. First, as oligoleucine
composition was increased, the gel strength was found to increase dramatically.
Furthermore, only hydrophobic segments with α-helical conformations were found
to form strong gels, as evidenced by the inability of a K 160 (rac-L) 40 sample, where
the racemic residues yield a disordered conformation, to form strong hydrogels. It
was found that longer polyelectrolyte segments increase interchain repulsions such
that the packing of the hydrophobic helices, which prefer formation of flat 2D
sheets [88], must distort to minimize the overall energy of the system. The most
efficient way to do this, while maintaining favorable helix packing, is to twist the
sheets into fibrillar tapes, where tape width is determined by the degree of twist
[112]. In this model, the helices are still able to pack perpendicular to the fibril axis,
but with a slight twist between planes of parallel packed helices (Fig. 6). TEM
imaging of the nanostructure in K 180 L 30 does, in fact, reveal a more fibrillar,
tape-like nanostructure constituting the hydrogel network (Fig. 6). Overall,
copolypeptide gel strength can be adjusted by many molecular parameters such
as overall chain length, hydrophilic to hydrophobic composition, and block
28
T.J. Deming
incorporation of the essential features required for tissue engineering and drug
delivery applications.
The Deming laboratory has developed hydrogels based on amphiphilic block
copolypeptides possessing many features that make them attractive as candidates
for medical applications [92]. Foremost, through combination of chemical synthesis
and structural characterization, a detailed understanding of structure–property
relationships in these materials has been established, allowing a high level of
control over gel strength, gel porosity, gel functionality, and media stability;
many which can be adjusted independent of each other [26]. Second, these
physically associated gels are readily injectable through a 30G needle for facile
application and filling of wound cavities [92]. Finally, the hydrogels can be
prepared to be minimally toxic to cells in culture [111]. Hydrogel formation was
first discovered in a series of diblock copolypeptides containing a charged, water
solubilizing domain [poly(L-lysine·HBr], K; or poly(L-glutamate Na salt), E] and a
α-helical hydrophobic domain [poly(L-leucine), L], i.e., K x L y or E x L y (Fig. 6)
[92]. Hydrogel formation is the result of self-assembly of these polymeric
amphiphiles by direct dissolution in water, and the resultant gels possess a network
structure composed of nanoscale to microscale porosity and significant material
rigidity, despite being composed of >95% water. In order to determine the role
played by each copolypeptide domain, a comprehensive study was performed using
an array of samples where both overall chain segment length and hydrophilic to
hydrophobic composition were systematically varied. It was found that chain length
modification of both positively charged polyelectrolyte and hydrophobic segments
had significant effects on properties [92]. It is worth noting that analogous samples
prepared with negatively charged polyelectrolyte domains, i.e., poly(L-glutamate),
were found to behave similarly, which opens the possibility for preparation of both
cationic and anionic hydrogels.
Compositional studies with different copolypeptides revealed many trends
relating molecular parameters to hydrogel properties. First, as oligoleucine
composition was increased, the gel strength was found to increase dramatically.
Furthermore, only hydrophobic segments with α-helical conformations were found
to form strong gels, as evidenced by the inability of a K 160 (rac-L) 40 sample, where
the racemic residues yield a disordered conformation, to form strong hydrogels. It
was found that longer polyelectrolyte segments increase interchain repulsions such
that the packing of the hydrophobic helices, which prefer formation of flat 2D
sheets [88], must distort to minimize the overall energy of the system. The most
efficient way to do this, while maintaining favorable helix packing, is to twist the
sheets into fibrillar tapes, where tape width is determined by the degree of twist
[112]. In this model, the helices are still able to pack perpendicular to the fibril axis,
but with a slight twist between planes of parallel packed helices (Fig. 6). TEM
imaging of the nanostructure in K 180 L 30 does, in fact, reveal a more fibrillar,
tape-like nanostructure constituting the hydrogel network (Fig. 6). Overall,
copolypeptide gel strength can be adjusted by many molecular parameters such
as overall chain length, hydrophilic to hydrophobic composition, and block
28
T.J. Deming