A Highly Stretchable, Tough, Fast Self-Healing Hydrogel Based on Peptide⁻Metal Ion Coordination

Abstract

Metal coordination bonds are widely used as the dynamic cross-linkers to construct self-healing hydrogels. However, it remains challenging to independently improve the toughness of metal coordinated hydrogels without affecting the stretchability and self-healing properties, as all these features are directly correlated with the dynamic properties of the same metal coordination bonds. In this work, using histidine-Zn²⁺ binding as an example, we show that the coordination number (the number of binding sites in each cross-linking ligand) is an important parameter for the mechanical strength of the hydrogels. By increasing the coordination number of the binding site, the mechanical strength of the hydrogels can be greatly improved without sacrificing the stretchability and self-healing properties. By adjusting the peptide and Zn²⁺ concentrations, the hydrogels can achieve a set of demanding mechanical features, including the Young's modulus of 7-123 kPa, fracture strain of 434-781%, toughness of 630-1350 kJ m^-3, and self-healing time of ~1 h. We anticipate the engineered hydrogels can find broad applications in a variety of biomedical fields. Moreover, the concept of improving the mechanical strength of metal coordinated hydrogels by tuning the coordination number may inspire the design of other dynamically cross-linked hydrogels with further improved mechanical performance.

Keywords: hydrogel; metal ion coordination; self-healing; stretch-ability.

Figure 1

Illustrative scheme and rheological mechanical properties of the self-healing hydrogels based on the coordination interactions between peptides and Zn²⁺ ions. (A) Chemical structure of the GGH peptide. (B) Chemical structure of the GHHPH peptide. (C) Schematic illustration of the hydrogels based on the coordination interactions between the designed peptides and Zn²⁺ ions. (D) Images corresponding to GGH and GHHPH hydrogels. (E) G’ and G” of the hydrogels measured in a frequency sweep experiment (frequencies from 0.01 to 100 rad s⁻¹, 0.1% strain) at the peptide concentration of 50 mg mL⁻¹ while the concentration of acrylamide was always 25 mg mL⁻¹. The molar ratios of peptides and ZnCl₂ in GGH and GHHPH hydrogels were 15:3 and 15:9, respectively. (F) G’ and G” of the hydrogels measured in a strain sweep experiment (strains from 0.01 to 100%, a frequency of 6.28 rad s⁻¹) at the peptide concentration of 50 mg mL⁻¹, while the concentration of acrylamide was always 25 mg mL⁻¹ and molar ratio of peptides and ZnCl₂ were 15:3 and 15:9 for GGH and GHHPH hydrogels, respectively. (G) G’ and G” of the hydrogels measured in a destroy–recovery experiment at the peptide concentration of 50 mg mL⁻¹ while the concentration of acrylamide was always 25 mg mL⁻¹ and molar ratios of peptides and ZnCl₂ were 15:3 and 15:9 for GGH and GHHPH hydrogels, respectively. The strain was set to an amplitude of 1000% for 60 s to destroy the coordination interactions and switched back to an amplitude of 0.1% to monitor the recovery of the mechanical properties for 600 s. The G’ and G’’ were measured at a frequency of 6.28 rad s⁻¹ at 20 °C.

Figure 2

Tensile mechanical properties of GGH and GHHPH hydrogels. (A) Stress–strain curves (left) of GGH hydrogels and zoomed stress–strain curves (right) at the strain rate of 30% min⁻¹ with different mass ratios of GGH and acrylamide (1:1, 2:1, and 3:1). The solid lines in the right indicate the linear fitting of the elastic region. The concentrations of GGH peptides were 25 mg mL⁻¹, 50 mg mL⁻¹, and 75 mg mL⁻¹, respectively, while the concentration of acrylamide was always 25 mg mL⁻¹ and the molar ratios of peptides and ZnCl₂ were always 15:3. (B) Stress–strain curves of GGH hydrogels (m_GGH:m_acrylamide= 2:1) with different tensile strain rates (3%, 30%, 300% and 3000% per minute). (C) Stress–strain curves (left) of GHHPH hydrogels and zoomed stress–strain curves (right) at the strain rate of 30% min⁻¹ with different mass ratios of GHH and acrylamide (1:1, 2:1, and 3:1). The solid lines in the right indicate the linear fitting of the elastic region. The concentrations of GHHPH peptides were 25 mg mL⁻¹, 50 mg mL⁻¹, and 75 mg mL⁻¹, respectively, while the concentration of acrylamide was always 25 mg mL⁻¹ and the molar ratios of peptides and ZnCl₂ were always 15:9. (D) Stress–strain curves of GHHPH hydrogels (m_GHHPH:m_acrylamide = 2:1) with different tensile strain rates (3%, 30%, 300% and 3000% min⁻¹).

Figure 3

Self-healing properties of GGH and GHHPH hydrogels. (A) Stretching photograph of the GGH hydrogel before and after healing. The reconnected points are highlighted with a green cycle. Scale bar = 5 mm. (B) Stress–strain curves of GGH hydrogels at the strain rate of 30% min⁻¹ healed for different times at room temperature. The concentrations of GGH peptides and acrylamide were 50 mg mL⁻¹ and 25 mg mL⁻¹, respectively, while the molar ratios of peptides and ZnCl₂ were always 15:3. (C) Normalized recovery percentages of fracture strain, fracture stress and toughness with different healing time corresponding to (B). (D) Stretching photograph of the GHHPH hydrogel before and after healing. The reconnected points are highlighted with a green cycle. Scale bar = 5 mm. (E) Stress–strain curves of GHHPH hydrogels at the strain rate of 30% min⁻¹ healed for different times at room temperature. The concentrations of GHHPH peptides and acrylamide were 50 mg mL⁻¹ and 25 mg mL⁻¹_, respectively, while the molar ratios of peptides and ZnCl₂ were always 15:9. (F) Normalized recovery percentages of fracture strain, fracture stress and toughness with different healing time corresponding to (E).

Figure 4

Self-healing properties of GGH and GHHPH hydrogels with different molar ratios of peptide and Zn²⁺ ions. (A) Stress–strain curves of GGH hydrogels at the strain rate of 30% min⁻¹ before and after healing with different molar ratios of peptide and Zn²⁺ ions (15:1 and 15:4). The concentrations of GGH peptides and acrylamide were 50 mg mL⁻¹ and 25 mg mL⁻¹ respectively. (B) Stress–strain curves of GHHPH hydrogels at the strain rate of 30% min⁻¹ before and after healing with different molar ratios of peptide and Zn²⁺ ions (15:3, 15:12). The concentrations of GGH peptides and acrylamide were 50 mg mL⁻¹ and 25 mg mL⁻¹, respectively. (C) Normalized recovery percentages of fracture strain, fracture stress and toughness with different ratios of GGH and Zn²⁺ ions. (D) Normalized recovery percentages of fracture strain, fracture stress and toughness with different ratios of GHHPH and Zn²⁺ ions.