Keratin Microspheres as Promising Tool for Targeting Follicular Growth.

Skin is the body barrier that constrains the infiltration of particles and exogenous aggression, in which the hair follicle plays an important role. Recent studies have shown that small particles can penetrate the skin barrier and reach the hair follicle, making them a potential avenue for delivering hair growth-related substances. Interestingly, keratin-based microspheres are widely used as drug delivery carriers in various fields. In this current study, we pursue the effect of newly synthesized 3D spherical keratin particles on inducing hair growth in C57BL/6 male mice and in human hair follicle dermal papilla cells. The microspheres were created from partially sulfonated, water-soluble keratin. The keratin microspheres swelled in water to form spherical gels, which were used for further experiments. Following topical application for a period of 20 days, we observed a regrowth of hair in the previously depleted area on the dorsal part of the mice in the keratin microsphere group. This observation was accompanied by the regulation of hair-growth-related pathways as well as changes in markers associated with epidermal cells, keratin, and collagen. Interestingly, microsphere keratin treatment enhanced the cell proliferation and the expression of hair growth markers in dermal papilla cells. Based on our data, we propose that 3D spherical keratin has the potential to specifically target hair follicle growth and can be employed as a carrier for promoting hair growth-related agents.

Triethylene Glycol Squalene Improves Hair Regeneration by Maintaining the Inductive Capacity of Human Dermal Papilla Cells and Preventing Premature Aging.

De novo hair follicle (HF) regeneration, achieved through the replenishment of the dermal papilla (DP), acknowledged as the principal orchestrator of the hair growth cycle, is emerging as a prospective therapeutic intervention for alopecia. Nonetheless, multiple attempts have shown that these cells lose key inductive properties when cultured in a two-dimensional (2D) monolayer, leading to precocious senescence engendered by oxidative stress and inflammatory processes. Consequently, the three-dimensional (3D) spheroid technique is presently widely employed for DP cell culture. Nevertheless, substantiating the regenerative potential of these cells within the hair follicle (HF) milieu remains a challenge. In this current study, we aim to find a new approach to activate the inductive properties of DP cells. This involves the application of hair-growth-stimulating agents that not only exhibit concurrent protective efficacy against the aging process but also induce HF regeneration. To achieve this objective, we initially synthesized a novel highly amphiphilic derivative derived from squalene (SQ), named triethylene glycol squalene (Tri-SQ). Squalene itself is a potent antioxidant and anti-inflammatory compound traditionally employed as a drug carrier for alopecia treatment. However, its application is limited due to its low solubility. Subsequently, we applied this newly synthesized derivative to DP cells. The data obtained demonstrated that the derivative exhibits robust antioxidant and anti-inflammatory activities while concurrently promoting the expression of genes associated with hair growth. Moreover, to further assess the hair regrowth inductive properties of DP cells, we cultured the cells and treated them with Tri-SQ within a 3D spheroid system. Subsequently, these treated cells were injected into the previously depilated dorsal area of six-week-old male C57BL/6 mice. Results revealed that 20 days postinjection, a complete regrowth of hair in the previously hairless area, particularly evident in the case of 3D spheroids treated with the derivative, was observed. Additionally, histological and molecular analyses demonstrated an upregulation of markers associated with hair growth and a concurrent decrease in aging hallmarks, specifically in the 3D spheroids treated with the compound. In summary, our approach, which involves the treatment of Tri-SQ combined with a 3D spheroid system, exhibited a notably robust stimulating effect. This effect was observed in the induction of inductive properties in DP cells, leading to HF regeneration, and concurrently, it demonstrated an inhibitory effect on cellular and follicular aging.