Rational Design of Human Hair Keratin-Driven Proteins for Hair Growth Promotion

Area of Science:

• Biochemistry
• Dermatology
• Biomaterials Science

Background:

• Keratins are key hair nutrients, but extracts are complex and pure recombinant keratins have poor solubility, limiting their hair growth application.
• Investigating keratin's mechanism for hair growth is challenging due to extract complexity and solubility issues of pure recombinant forms.

Purpose of the Study:

• To design water-soluble recombinant keratins (RKs) for enhanced hair growth studies.
• To investigate the efficacy of novel water-soluble RKs in promoting hair follicle (HF) activity and hair regeneration.
• To compare the hair growth-promoting effects of RK81 and RK31 and their mechanism of action.

Main Methods:

• Rational design of water-soluble recombinant keratins (RKs) K31 and K81 using QTY Code methodology.
• Fabrication of microneedles using designed RKs for topical delivery.
• Assessment of hair follicle anagen entry, new hair diameter, and HF activity.
• Analysis of the PI3K/AKT/Nf-κB signaling pathway upregulation.

Main Results:

• RK81 significantly promoted HF anagen entry (over 40% by day 12) and increased new hair diameter (15.10 ± 2.45 µm) compared to RK31.
• Water-soluble RKs demonstrated superior enhancement of HF activity and hair regeneration compared to traditional keratin extract and minoxidil.
• Upregulation of the PI3K/AKT/Nf-κB signaling axis was observed, indicating a key mechanism for enhanced hair growth.

Conclusions:

• Designed water-soluble recombinant keratins, particularly RK81, show significant potential for promoting hair growth and improving hair quality.
• The QTY Code methodology enables the creation of soluble recombinant proteins with enhanced therapeutic efficacy for hair regeneration.
• This study opens new possibilities for developing advanced keratin-based therapies targeting hair loss and improving hair health.