Fabrication of crosslinker free hydrogels with diverse properties: An interplay of multiscale physical forces within polymer matrix

Abstract

Physical/chemical crosslinking and surface-modifications of hydrogels have been extensively endorsed to enhance their biomaterial functionalities. The latter approaches involve using toxic crosslinkers or chemical modifications of the biopolymers, limiting the clinical translation of hydrogels beyond short-term promising results. The current study aims to tailor the polymer's structure to obtain customized applications using the same FDA-approved ingredients. PEGs of different molecular weights have been used to tune the van der Waal's forces, NaCl has been used to alter the electrostatic interactions of the charged polymers, and glycerol has been used to tweak the H-bonding. Same crosslinker-free sodium alginate/gelatin hydrogel formulation unfolds multiple properties: controlled-release, self-healing, mesh size, storage modulus, degradation rate. The hydrogels, lacking in one aspect, displayed superior performance in another. This study, including experiments and molecular simulations, illustrates that developing new materials may not always be necessary, as the same polymeric matrix can generate immense variations in different aspects.

Keywords: Materials science; Polymers.

Graphical abstract

Figure 1

Hydrogel preparation procedure Schematic representation of hydrogel preparation with sequential addition of the ingredients. See also STAR Methods section fabrication of hydrogel.

Figure 2

Size of the gelatin polymer P1K (PEG 1000), P2K (PEG 2000), P4K (PEG 4000), Gly (Glycerol). (A) Hydrodynamic radius with the addition of each individual ingredient. Data are represented as mean ± SD of n = 3 samples. (B) Radius of gyration with the addition of each individual ingredient. Data are represented as mean ± SD of n = 3 samples.

Figure 3

Two-dimensional (2D) plot of NSD vs. NGS The colored circles depict the six clusters and the blue tick-marks are the representative points. The results are obtained from n = 3 replicates and normalized with respect to the highest value. The data are statistically significant (p value <0.05). See also Tables S1 and S2.

Figure 4

Release fraction from cumulative release (A) Three-dimensional (3D) plot of NRF, NSD and NGS; (B) Cumulative release profiles; (C) Swelling degree curves; (D) Hydrodynamic radius; (E) Radius of Gyration; (F) Schematic representation of drug release; (G) Hydrogen bond mechanism for Exp 7. Data are represented as mean ± SD of n = 3 samples (B–E). The data are statistically significant (p value <0.05). See also Figure S1.

Figure 5

Percentage recovery from self-healing (A) 3D plot of NPR, NSD, and NGS; (B) FTIR-ATR spectra for 3000-4000 cm⁻¹; (C) Total number of H-bonds obtained from MD simulation. Data are represented as mean ± SD of n = 3 samples; (D) 2D plot of NPR vs. NSD showing the same clustered points obtained previously; (E) Schematic representation of self-healing. The data are statistically significant (p value <0.05). See also Figure S2A.

Figure 6

Mesh size of the hydrogels (A) 3D plot of NMS, NSD, and NGS; (B) 2D plot of NMS vs. NSD showing the same clustered points obtained initially; (C) Swelling degree curves. Data are represented as mean ± SD of n = 3 samples; (D) Schematic representation of mesh size and its impact on drug release. The data are statistically significant (p value <0.05). See also Table S3.

Figure 7

Storage modulus of the hydrogels (A) 3D plot of NSM, NSD, and NGS; (B) 2D plot of NSM vs. NSD; (C) schematic representation of rigid hydrogel and flexible hydrogel with the addition of plasticizers. The data are statistically significant (p value <0.05). See also Table S3 and Figures S2B and S2C.

Figure 8

Degradation rate of the hydrogels (A) 3D plot of NDR, NSD, and NGS; (B) 2D plot of NDR vs. NSD; (C) schematic representation of degradation of hydrogel. The data are statistically significant (p value <0.05). See also Figure S3 and Table S4.