Pentablock copolypeptides of the composition K 60 L 20 K z L 20 K 60 , where z was
varied from 10 to 200, were synthesized by stepwise linear block copolymerization
using (PMe 3 ) 4 Co initiator in THF, followed by removal of protecting groups and
purification. Deming’s laboratory found that K 60 L 20 K 10 L 20 K 60 formed clusters of
micelle-like aggregates with diameters ranging from 50 to 200 nm, which differed
greatly from the fibrillar structures seen with diblock and triblock samples. On the
other hand, the K 60 L 20 K z L 20 K 60 copolypeptides, when z > 60, self-assembled in
water to form fibrillar hydrogel assemblies. Furthermore, adjustment of the central
K segment length allowed tuning of assembly morphology and hydrogel properties;
it was observed that G
0 increased and minimum gelation concentration decreased
as the pentablock central K segments were lengthened. The ability to control
intramolecular versus intermolecular assembly of the two hydrophobic L segments
in these pentablock sequences gave substantial enhancement of hydrogel properties
compared to the corresponding diblock and triblock architectures [72]. The ability
to tune intrachain interactions in these materials via molecular design is also a key
advance in biomimetic assembly.
Inorganic–organic biocompatible composites have tremendous potential for
therapeutic and diagnostic materials applications. Block copolypeptide hydrogels
are promising templates for formation of porous composites, where the porous gel
scaffold can serve as a template for mineral growth. In 2009, Mallapragada and
coworkers reported the use of K 170 L 30 hydrogels as templates for assembly of
calcium phosphate nanocomposites [118]. The porous nature of the hydrogels,
and their ability to form gels at low concentrations, allowed composites to be
formed that contained up to 50% inorganic material, approaching the inorganic
content of bone. Furthermore, detailed characterization of the composites revealed
the mineral phase to be carbonated hydroxyapatite, with elongated plate-like
morphology of nanoscale dimensions, similar to natural bone. In a similar study,
Li’s group studied the ability of a series of K x L y hydrogels (170 < x < 440;
10 < y < 30) to direct silica morphology by sol–gel condensation of tetramethylorthosilicate in the presence of the hydrogels [119]. They found that both the
polypeptide lengths, as well as nature of anionic counterions used, had significant
effects on resulting silica morphology, where either plates or rods of silica could be
formed.
Initial quantitative measurements of polypeptide cytotoxicity involved cell
culture within three dimensional hydrogel substrates in cell culturing medium
[111]. Although polylysine is known to be cytotoxic when free in solution [120],
use of higher concentrations of polypeptide above gelation concentrations revealed
that both cationic and anionic functionalized gels were promising substrates for
short-term cell culture. It is likely that the hydrogel network prevents bulk diffusion
of gel-bound lysine chains, thus limiting the amount of polylysine that can interact
with the cells. Although the cells remained viable, in neither gel was cell
attachment or proliferation observed. The cells, in the presence of either of the
hydrogel matrices, retain their spherical shape after 4 h and up to 24 h. Although it
appears that cell binding epitopes need to be incorporated into these hydrogels, their
peptidic backbone provides many advantages for use of these materials as scaffolds.
Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via. . .
31
varied from 10 to 200, were synthesized by stepwise linear block copolymerization
using (PMe 3 ) 4 Co initiator in THF, followed by removal of protecting groups and
purification. Deming’s laboratory found that K 60 L 20 K 10 L 20 K 60 formed clusters of
micelle-like aggregates with diameters ranging from 50 to 200 nm, which differed
greatly from the fibrillar structures seen with diblock and triblock samples. On the
other hand, the K 60 L 20 K z L 20 K 60 copolypeptides, when z > 60, self-assembled in
water to form fibrillar hydrogel assemblies. Furthermore, adjustment of the central
K segment length allowed tuning of assembly morphology and hydrogel properties;
it was observed that G
0 increased and minimum gelation concentration decreased
as the pentablock central K segments were lengthened. The ability to control
intramolecular versus intermolecular assembly of the two hydrophobic L segments
in these pentablock sequences gave substantial enhancement of hydrogel properties
compared to the corresponding diblock and triblock architectures [72]. The ability
to tune intrachain interactions in these materials via molecular design is also a key
advance in biomimetic assembly.
Inorganic–organic biocompatible composites have tremendous potential for
therapeutic and diagnostic materials applications. Block copolypeptide hydrogels
are promising templates for formation of porous composites, where the porous gel
scaffold can serve as a template for mineral growth. In 2009, Mallapragada and
coworkers reported the use of K 170 L 30 hydrogels as templates for assembly of
calcium phosphate nanocomposites [118]. The porous nature of the hydrogels,
and their ability to form gels at low concentrations, allowed composites to be
formed that contained up to 50% inorganic material, approaching the inorganic
content of bone. Furthermore, detailed characterization of the composites revealed
the mineral phase to be carbonated hydroxyapatite, with elongated plate-like
morphology of nanoscale dimensions, similar to natural bone. In a similar study,
Li’s group studied the ability of a series of K x L y hydrogels (170 < x < 440;
10 < y < 30) to direct silica morphology by sol–gel condensation of tetramethylorthosilicate in the presence of the hydrogels [119]. They found that both the
polypeptide lengths, as well as nature of anionic counterions used, had significant
effects on resulting silica morphology, where either plates or rods of silica could be
formed.
Initial quantitative measurements of polypeptide cytotoxicity involved cell
culture within three dimensional hydrogel substrates in cell culturing medium
[111]. Although polylysine is known to be cytotoxic when free in solution [120],
use of higher concentrations of polypeptide above gelation concentrations revealed
that both cationic and anionic functionalized gels were promising substrates for
short-term cell culture. It is likely that the hydrogel network prevents bulk diffusion
of gel-bound lysine chains, thus limiting the amount of polylysine that can interact
with the cells. Although the cells remained viable, in neither gel was cell
attachment or proliferation observed. The cells, in the presence of either of the
hydrogel matrices, retain their spherical shape after 4 h and up to 24 h. Although it
appears that cell binding epitopes need to be incorporated into these hydrogels, their
peptidic backbone provides many advantages for use of these materials as scaffolds.
Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via. . .
31