Diabetic Wound Healing with Adhesive Hydrogels

By Surbhi JainReviewed by Susha Cheriyedath, M.Sc.Apr 29 2022

In an article recently published in the journal Acta Biomaterialia, researchers discussed the preparation of antibacterial, sticky, and self-healing hydrogels for the healing of diabetic wounds.

Study: Antibacterial adhesive self-healing hydrogels to promote diabetic wound healing. Image Credit: Billion Photos/Shutterstock.com

Background

Long-term diabetes impairs wound healing, resulting in chronic non-healing wounds and other complications. The treatment period for diabetic wound disease is long, and the medical treatment cost is considerable due to its intricacy. Effective therapeutic techniques are urgently needed to ensure patients' decreased pain, increased quality of life, and the speeding of wound healing.

Wound dressings, such as hydrogel dressings, transparent film dressings, liquid dressings, and foam dressings are designed and applied to aid in the healing of injured wounds.

Hydrogel wound dressings are one of the most promising materials in wound care. Gelatin is a very cost-effective basic material for making diabetic wound hydrogel dressings. An adenine can give adhesion by forming hydrogen bonds and metal complexes with material components due to its unique molecular structure.

Cu²⁺ doping in gelatin/adenine-derived hydrogels not only ensures the hydrogel's integrity to prevent wound infection but also endows the hydrogel with angiogenic and antibacterial capabilities, which could aid diabetic wound healing. Such multi-functional hydrogels, however, have yet to be discovered.

About the Study

In this study, the authors discussed the development of a variety of sticky, self-healing, and antibacterial hydrogels based on adenine acrylate (AA), gelatin methacrylate (GelMA), and CuCl₂ to promote diabetic wound healing through coordination complexation of Cu²⁺ and carboxyl groups, covalent bonding, and hydrogen bonding.

The team used hydrogen bonding, free radical polymerization, and ionic bonding to design and prepare a variety of adhesive, self-healing, and antibacterial hydrogels. Through radical polymerization, gelatin was changed by methacrylic anhydride to produce hydrogels with improved stability and mechanical characteristics. Free radical polymerization was used to incorporate adenine into the hydrogel network after it had been modified by acryloyl chloride. Cu²⁺ was also introduced into the GelMA/AA hydrogel via the coordination of Cu²⁺ with the carboxyl groups of gelatin, which resulted in the development of GelMA/AA/Cu hydrogels.

The researchers tested the developed hydrogels for self-healing, mechanical properties, Cu²⁺ release, antibacterial capabilities, biocompatibility, and hemostasis in vivo. Furthermore, diabetic mice with full-thickness skin defects were created, and the GelMA/AA/Cu hydrogel's effect on diabetic wound healing was assessed.

Observations

After 12 hours of incubation, S. aureus had a survival rate of 11.1%, while E. coli was entirely suppressed. After 3 hours of incubation, nearly half of the bacteria in the GelMA/AA/Cu1.0 group were killed, and the bacterial survival ratios for S. aureus and E. coli were both around 50.0%. The survival ratios of S. aureus and E. coli after 9 hours of incubation were 7.5% and 0.0%, respectively. In addition, the GelMA/AA/Cu1.0 hydrogel could completely destroy germs in about 12 hours. After 3 hours of incubation, the hydrogel GelMA/AA/Cu1.5 group totally prevented the development of S. aureus and E. coli.

With the increase in Cu²⁺ concentrations, the GelMA/AA/Cu hydrogels' adhesive strength increased from 3.4 0.4 kPa to 9.3 0.1 kPa. In the control group, blood loss was 224.0 ± 39.9 mg, while in the GelMA/AA/Cu1.0 hydrogel group, blood loss was 23.0 ± 31.9 mg. The collagen content of the GelMA group, control group, GelMA/AA/Cu1.0 group, and GelMA/AA/Cu0 group, respectively, were 110.1 ± 14.3%, 99.9 ± 18.0%, 160.1 ± 14.9%, and 108.4 ± 14.5%.

Due to the metal-ligand interaction and hydrogen bond provided by the Cu²⁺ and the carboxyl group, the developed hydrogels had excellent fatigue resistance, rapid self-healing characteristics, and good adhesion qualities. In a mouse liver trauma model, the GelMA/AA/Cu1.0 hydrogel comprised of 1.0 mg/mL Cu²⁺ with well-balanced antibacterial and biocompatibility properties demonstrated excellent hemostatic performance and greatly aided wound healing in a full-thickness skin diabetic wound model.

When compared to the Tegaderm^TM Film, the immunohistochemistry results of GelMA, and GelMA/AA/Cu0 hydrogel revealed that the GelMA/AA/Cu1.0 hydrogel could promote normal collagen deposition and epithelialization. The GelMA/AA/Cu1.0 hydrogel could lower the expression of proinflammatory factors and increase angiogenesis, according to immunofluorescence data.

Conclusions

In conclusion, this study elucidated that the prepared adhesive, self-healing, and antibacterial GelMA/AA/Cu hydrogel wound dressing proved successful in facilitating diabetic skin wound regeneration.

Hydrogen bonding and metal-ligand coordination provided outstanding self-healing characteristics. In comparison to the TCP group, GelMA/AA/Cu hydrogels demonstrated good biocompatibility in the L929 cell cytocompatibility test. The inclusion of Cu²⁺ facilitated the GelMA/AA/Cu hydrogel’s remarkable antibacterial characteristics, which helped to prevent infection in diabetic wounds. The GelMA/AA/Cu hydrogel also performed well in terms of hemostasis. Furthermore, the GelMA/AA/Cu1.0 hydrogel's superior wound healing impact on diabetic wounds was demonstrated by the downregulation of IL-6 and the acceleration of vascular regeneration in wound healing (α-SMA and CD31).

The authors emphasized that the GelMA/AA/Cu hydrogels are promising materials for diabetic wound healing.

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