A nicotinamide mononucleotide (NMN)-loaded hydrogel dressing — a wound-covering matrix mostly composed of water — speeds diabetic wound healing and restores skin thickness in a diabetic skin wound mouse model.
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.
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.
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.
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.
“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.
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.
Model: C57BL/6J mice fed a high-fat, high-sugar diet and injected with diabetes-inducing streptozotocin
Dosage: Hydrogel dressings loaded with 200 µg/mL of NMN applied for 14 days