CMC-containing hydrogels for the repair of skin injuries

Deeper skin injuries require appropriate wound dressings to promote healing. In the presented study, CMC-containing hyaluronic acid-dopamine hydrogels were synthesized, characterized and investigated in vivo for their wound healing properties.

INJECTEBLE MULITFUNCTIONAL CMC/HA-DA HYDROGEL FOR SKIN INJURY REPAIR

Longlong Cui, Jiankang Li, Shuaimeng Guan, Kaixiang Zhang, Kun Zhang, Jingan Li, Injectable multifunctional CMC/HA-DA hydrogel for repairing skin injury, Materials Today Bio, Volume 14, 2022, 100257, ISSN 2590-0064, https://doi.org/10.1016/j.mtbio.2022.100257

The skin provides the body with protection from germs, serves as a sensory organ, and maintains homeostasis. However, it is susceptible to external injury. While minor wounds heal quickly, deeper injuries affecting all layers of the skin can lead to infection and scarring. In these cases, suitable wound dressings are essential.
Injectable hydrogels offer many advantages over conventional wound dressings, such as formation of a 3D porous matrix structure, a moist wound healing climate, high water content, good biocompatibility, adaptable mechanical properties and the ability to fill wounds. Nevertheless, the majority of hydrogels do not have the ideal properties for wound healing. There, an anti-inflammatory and hemostatic effect, good adhesion and antioxidant properties play an important role.
Hyaluronic acid (HA), as a component of the extracellular matrix, has good biocompatibility and promotes wound healing. However, as a hydrogel, it has poor adhesion. To improve this, HA can be coupled with dopamine (DA). This is used, for example, by mussels to adhere to moist surfaces. Another component of interest for hydrogels is carboxylmethylchitosan (CMC). This chitosan derivative has improved solubility at neutral and basic pH compared to conventional chitosan, but has hemostatic and anti-inflammatory effects as well. In addition, it also promotes wound healing and can be degraded by the body upon healing.
Therefore, in the presented study, multifunctional hydrogels of HA, DA and CMC were synthesized by enzymatic coupling through the horseradish and hydrogen peroxidase. To investigate the effect of hydrogel composition on wound healing, 2%, 4%, and 6% HA-DA were coupled with 6% CMC (CMC/HA-DA1, CMC/HA-DA2, and CMC/HA-DA3), respectively. In addition to analyzing physical and chemical properties of the hydrogels, cytotoxicity in vitro and healing of multilayer wounds in vivo were studied using a mouse model.

RESULTS

• Evidence of successful coupling of HA-DA via ¹H-NMR, UV, and FTIR spectra, and formation of a porous 3D crosslinked hydrogel with CMC
• Positive effect of higher HA-DA content on gelation time, mechanical strength, degradability, antioxidant properties, and adhesion to organic and inorganic surfaces
• In vitro: over 80% survival rates of L929 cells and HaCaT cells after 24 and 72 h incubation, and hemolysis rates between 0.36-0.54
• Best physical, chemical and biological properties with CMC/HA-DA₃, however CMC/HA-DA₂ used for in vivo experiments due to longer gelation time
• In vivo: wound healing rates of 55% (day 3), 77% (day 7) and nearly 100% after 14 days
• Decreased concentration of IL-6, IL-10, VEGF, MMP-9 cells, and increased expression of PCNA protein compared to control group confirmed the anti-inflammation and angiogenesis promotion by CMC/HA-DA₂

Summary: In the presented study, multifunctional hydrogels were successfully prepared by enzymatic synthesis from CMC and dopamine-coupled hyaluronic acid. Besides the formation of a porous 3D matrix, the gelation time, adhesive and antioxidant properties as well as the degradation could be adjusted via the DA-HA content. Moreover, the hydrogels exhibited low cytotoxicity and almost no hemolysis properties in vitro. Significantly improved wound healing was observed in vivo. Overall, the CMC/HA-DA hydrogels showed great potential for skin and tissue regeneration. Link to article: Injectable multifunctional CMC/HA-DA hydrogel for repairing skin injury - ScienceDirect