Results and Discussion
Stable and well-characterized series of curves are generated from our
equation, demonstrating the deswelling of the biopolymer (i.e., type I
collagen) gel matrix with a temperature increase. Under a fixed
crosslinking condition, the gel elasticity-associated coefficientα appears to be a major factor in determining the deswelling
behavior (Fig. 2). The gel shrinkage becomes more sensitive to the
normalized temperature change at T/Θ < 0.95, as
decreasing α value on the order of magnitude range of α ≤
109. When α exceeds
~109, the volume change curves are no
longer an injective function in the given range of normalized
temperature. For the subsequent analyses, we assume α = 1.0 ×
107 as an optimal elastic condition.
Next, we find that the doping ratio of thermoresponsive pNIPAM chains
(A = -6.4 and Θ = 315 K 13) in the type
I collagen gel matrix is another critical parameter to tune the overall
temperature range of the volume phase transition. Fig. 3 demonstrates
that the phase transition temperature is tunable in a wide range
(~50 degrees) from room temperature
(Troom ~22 °C), by varying the
mixing ratio of pNIPAM (rpolym ) from 0.3 to 0.5.
[Note that the curves for only four values of rpolymhas been plotted in different colors in the Fig. 3. The transition
temperature tuning can be achieved in a fully continuous manner in this
range.]
In a fixed doping ratio (rpolym ) of the
thermosensitive component pNIPAM, it is found that the crosslinking
degree of the network (represented by the degree of polymerization
between crosslinks, Nx ) is the parameter which
controls the temperature sensitivity of the gel matrix. For each
transition curve at different rpolym value in
Fig. 3, a higher gel volume change occurs for less crosslinked networks
(i.e., larger Nx ; displayed as a series of curves
with decreasing saturation), when compared in a given temperature
domain. The condition of rpolym = 0.35 andNx = 1 has selected as an optimized
physicochemical parameter set under the consideration of (1) the onset
of the phase transition at a temperature slightly higher than the body
temperature (Tbody ~37 °C) and
(2) the transition temperature range spanning a few degrees aboveTbody , which corresponds to unharmful
hyperthermia for human tissues in short time scales14.
Under the selected parameter values, the effect of collagen molecular
structure on the transition temperature range of the gel matrix has been
investigated (Fig. 4). Because the information on the conformation of
type I collagen is reflected in the Flory-Huggins interaction parameter
between biopolymer and water, χbio , we plot for
the four different values of χbio that are
chemically plausible in acellular in vitro situations. In Fig. 4,
the curve for gel matrix made of intact collagen type I
(χbio = 0.161 15), which is a
composite of a main helical rod and extrahelical peptides at both
terminals, is presented with the parameter set chosen in Fig. 3 (blue
solid line). If the gel comprises the pronase-digested collagen type I
(χbio = 0.107 15), which has no
extrahelical structures to be closer to a rod particle, the phase
transition range decreases about by 8 degrees (blue dashed line). When
the input value of χbio is for gelatin
(χbio = 0.48 for coil state16and χbio = 0.49 for coexistence of coil and
helical states16,17), the resulting plots (cyan solid
and dashed lines, respectively in Fig. 4) illustrate that the transition
temperature ranges appear to be above the temperature threshold for
denaturation from type I collagen to gelatin (~65 °C18), which partially validates the effectiveness of
our model in a biophysical basis.
For bioengineering applications, the representative examples of the
optimized matrix design are suggested for type I collagen and gelatin
gels with different doping ratios of pNIPAM (Fig. 5). Assuming the
volume ratio of the total polymers in a swollen hydrogel is about 0.1
(with Vi/VNIPA = 20), thenrpolym = 0.35 for collagen type I andrpolym = 0.48 for gelatin are found to be
suitable for inducing gel deswelling through local heating in the viable
temperature range for tissues in vivo and in vitro . In
these conditions, the gel matrices are fully swelled atTbody and completes deswelling at slightly
augmented temperatures (i.e., ~8 degrees aboveTbody ) and vice versa . For instance, this
property can be utilized for controlled release of drugs in human body
or as miniaturized tissue-resembling actuators in organ-on-a-chip
platforms for cell cultures10.