• Infusing hydrogel dressings with NMN speeds restorative skin healing in a mouse model for diabetic skin wounds.
  • Higher NMN doses added to the hydrogel dressing increase the synthesis and thickness of skin collagen — a structural protein for skin and connective tissue — during healing.
  • Elevated NMN doses in the hydrogel dressing increase gene activity for two skin-regenerating proteins — VEGF and TGF-ꞵ.

Wound repair falters in those with diabetes, especially for potentially deadly diabetic foot ulcers. Oxidative stress from highly reactive, oxygen-containing molecules called reactive oxygen species at the site of ulcers makes the healing process and ulcer resolution difficult. Clinicians frequently apply dressings to diabetic ulcers to serve as a barrier against infection, but testing whether loading hydrogel dressings with the antioxidant NMN speeds healing hadn’t been done, until now.

Published in Biomedicine & Pharmacotherapy, Zhu and colleagues from Fudan University in China show that applying a hydrogel matrix loaded with NMN to diabetic wounds speeds healing in a mouse model for diabetic wounds. Additionally, at higher doses loaded to the hydrogel matrices, the synthesis and thickness of skin collagen increases during healing. Furthermore, higher NMN doses increase gene activity for two proteins playing key roles in skin regeneration — VEGF and TGF-ꞵ. With the inadequate efficacy of current diabetic wound treatments, the findings suggest that adding NMN to hydrogel dressings provides a potent and affordable way to speed healing.

NMN Enhances Skin Structural Protein Synthesis to Accelerate Diabetic Wound Healing

To test whether adding NMN to hydrogel dressings speeds up slow-healing wounds in diabetes, Zhu and colleagues loaded hydrogels with varying doses of NMN. They applied the loaded hydrogels to mice injected with streptozotocin — a diabetes-inducing agent — with full-blown, 1 cm diameter wounds on their backs. They found that higher NMN doses sped up healing so that the wounds resolved about 30% faster than applying hydrogel dressings without NMN. These results show that NMN-loaded hydrogel dressings initiate faster healing compared to hydrogel dressings without NMN.

(Liang et al., 2023 | Biomedicine & Pharmacotherapy) NMN-loaded hydrogel dressings applied to wounds in diabetic mice speed healing. Compared to no treatment (black line) and hydrogel dressing treatment without NMN (purple line), NMN-loaded hydrogel application (yellow line) substantially accelerated diabetic wound healing.

Since adding NMN to the hydrogels triggers faster healing, the China-based researchers sought to determine whether NMN speeds healing by enhancing collagen synthesis and increasing the thickness of the skin’s outermost layer — the epidermis. Interestingly, by comparing NMN-loaded hydrogel dressing groups to dressings without NMN during healing, the researchers showed increasing NMN wound dressing doses enhanced collagen synthesis. Moreover, the NMN-loaded hydrogel dressings increased epidermal thickness during the healing process. These findings show that adding NMN to hydrogel wound dressings enhances collagen synthesis and increases epidermal thickness to speed wound healing.

(Liang et al., 2023 | Biomedicine & Pharmacotherapy) Applying an NMN-loaded hydrogel dressing to diabetic wounds significantly increases the thickness of the skin’s outermost epidermal layer. A high NMN dose added to hydrogel dressings (checkered bar) significantly increased epidermal thickness compared to no treatment (gray bar showing zero thickness) and adding a skin growth-promoting protein, recombinant human basic fibroblast growth factor (rh-bFGF; black bar).

To pinpoint how adding NMN to hydrogel dressings speeds diabetic wound healing, Zhu and colleagues measured gene activity for skin growth-promoting proteins, VEGF and TGF-ꞵ. The researchers found that the NMN-loaded hydrogel wound dressings almost doubled VEGF and significantly enhanced TGF-ꞵ gene activity compared to dressings without NMN. These data suggest that adding NMN to hydrogel dressings increases skin growth-promoting VEGF and TGF-ꞵ to speed up diabetic wound healing.

(Liang et al., 2023 | Biomedicine & Pharmacotherapy) Adding NMN to hydrogel dressing applications enhances gene activation for skin growth-promoting proteins VEGF and TGF-ꞵ. Graph on left) Compared to rh-bFGF (black bar) and no treatment (gray bar), high dosage NMN added to hydrogels (checkered bar) significantly increased VEGF gene activity. Graph on right) High dose NMN added to hydrogels (checkered bar) also increased TGF-ꞵ compared to no treatment (gray bars).

“This study was the first report that the NMN-loaded temperature-sensitive hydrogel dressings have a promoting effect in the healing of diabetic foot wounds,” said Zhu and colleagues.

NMN As a Means to Promote Skin Healing and Rejuvenation

Wounds can last a long time for those with diabetes, often becoming chronic, tough-to-treat ailments, especially when they present as diabetic foot ulcers. Current treatment options like topical cream therapies and drainage techniques that extract fluids from ulcers come with high costs and limited efficacy. In light of these treatment obstacles, applying NMN, with antioxidant properties, to wound dressings to promote healing may serve as a new, low cost treatment option to alleviate diabetic wounds and ulcers.

Another study showed that NMN along with another nicotinamide adenine dinucleotide (NAD+) precursor with antioxidant properties, nicotinamide riboside (NR), promotes skin wound healing in aged mice. Along those lines, adding NMN to any type of wound may serve as a way to promote healing and rejuvenation.