A Novel Hair Restoration Technology Counteracts Androgenic Hair Loss and Promotes Hair Growth in A Blinded Clinical Trial.

Androgenic alopecia (AGA) is a genetically predetermined condition that occurs as a result of stepwise miniaturization of the dermal papilla. During this process, the hair follicle suffers from increasing malnutrition and eventually dies, causing progressive hair loss. We recently highlighted that HIF-1α modulation may counteract hair loss. Here, we aim to demonstrate the positive influence of Tomorrowlabs HIF strengthening factor [HSF] hair restoration technology on hair biology in a monocentric blinded clinical trial over a total period of 9 months. A trial with 20 subjects (4 female and 16 male) and once-daily application of [HSF] hair restoration technology to the scalp was conducted. To assess the tolerability and efficacy of [HSF], testing included dermatological assessment, determination of hair loss by counting after combing, macro images of the head and TrichoScan evaluation of hair density as well as the proportion of anagen hair versus telogen hair. The clinical data show Tomorrowlabs [HSF] hair restoration to be safe and effective to counteract AGA. The use of Tomorrowlabs [HSF] hair restoration resulted in improvements in the clinical parameters of hair quality such as thickness (+7.2%), hair density (+14.3%) and shine and elasticity (+20.3%) during the test period. The effectiveness of the test product was further determined by a significant reduction in hair loss of an average of 66.8% in treatment-responsive subjects after 6 months and an increase in hair growth reaching up to 32.5%, with an average percentage change of 8.4% in all participants and 10.8% in the responsive patients (85% of the study cohort) after 9 months on TrichoScan evaluation. The hair growth cycle was harmonized with the result of an average anagen hair percentage increase of +8.0% and telogen hair percentage reduction of -14.0% shown in the test area. Applicable for both sexes in an alcohol-free formulation, beneficial to scalp health and free of complications or side effects, this novel product provides objectively measurable results counteracting hair loss paired with an improved look and feel of the hair.

Deferiprone Stimulates Aged Dermal Fibroblasts via HIF-1α Modulation.

BACKGROUND: Hypoxia-inducible factor 1α (HIF-1α), a transcription factor responsible for tissue homeostasis and regeneration, presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator deferiprone (DFP) at stimulating dermal fibroblasts. OBJECTIVES: The main objective of this study was to quantify the DFP concentrations capable of stimulating dermal fibroblasts in vitro and to correlate the effective DFP concentrations with the ability of DFP to penetrate the epidermis, reach the dermis, and activate HIF-1α in vivo. METHODS: We measured cell proliferation, metabolic activity, HIF-1α expression, and lactate dehydrogenase levels of both young and aged fibroblasts after a 24-hour in vitro preconditioning with DFP. In addition, we evaluated cell survival rates and morphology with different cellular stainings. Finally, we performed a transdermal permeation study with a 1% DFP topical formulation to quantify the concentration required to reach the dermis. RESULTS: In vitro administration of iron-chelation therapy (156-312.5 µg/mL DFP ) on aged fibroblasts resulted in activation of various antiaging processes. The concentration required to reach the dermis within 24 hours was 1.5% (0.15 mg/mL), which corresponds well with the effective doses of our laboratory analyses. CONCLUSIONS: The activation of HIF-1α by DFP enhances cell metabolism, proliferation, and survival of fibroblasts while reducing lactate dehydrogenase levels. Modulation of HIF-1α is linked to activation of key regeneration enzymes and proteins, and by proxy, antiaging. Therefore, the antiaging properties of DFP and its satisfactory dermal penetration make it a promising regenerative agent.

HIF-1α Stimulators Function Equally to Leading Hair Loss Agents in Enhancing Dermal Papilla Growth.

INTRODUCTION: Androgenic alopecia (AGA) occurs due to progressive miniaturization of the dermal papilla (DP). During this process the hair follicle loses nutrition over time and eventually dies, causing the hair to fall out. Recent evidence suggests that hypoxia-inducible factor-1a (HIF-1α) modulation may counteract hair loss. This study aims to evaluate the proliferation of dermal papilla cells (DPCs) under the influence of a selection of commercially available topical hair loss drugs, compared to HIF-1α-stimulating agents. MATERIALS AND METHODS: Using the hanging drop method, DPCs self-organized into spheroid shape, mirroring the three-dimensional (3D) structure of the DP in vivo. DP analogs were treated with established substances against AGA (minoxidil and caffeine) compared to HIF-1α-stimulating agents (deferoxamine [DFO] and deferiprone [DFP]), at 10 mM doses. DP analogs were simultaneously stained with 5-bromo-2'-deoxyuridine (BrdU) to evaluate impact of drug compounds on DP daughter cell production. Concurrently, fluorescent microscopy visualization of migration of daughter cells after 48 h in culture was performed. RESULTS: DPC proliferation within the spheroid structure was significantly enhanced by caffeine, minoxidil, and the HIF-1α-stimulating agent DFP when compared to control. Highest proliferation was seen in the DFP-treated DP analogs. Migration of peripheral DP daughter cells was highest in control and DFO groups. CONCLUSION: Here we demonstrate a significantly enhanced proliferative activity for both established substances against AGA (minoxidil and caffeine) and the HIF-1α-stimulating agent DFP in a 3D DPC spheroid culture model with equal results for DFP and minoxidil. These favorable characteristics make such compounds potential water-soluble alternatives to minoxidil.

A single-center blinded randomized clinical trial to evaluate the anti-aging effects of a novel HSF™-based skin care formulation.

BACKGROUND: Similar to chronic wounds, skin aging is characterized by dysfunction of key cellular regulatory pathways. The hypoxia-inducible factor-1 alpha (HIF-1α) pathway was linked to both conditions. Recent evidence suggests that modulating this pathway can rejuvenate aged fibroblasts and improve skin regeneration. Here, we describe the application of a novel HIF stimulating factor (HSF™)-based formulation for skin rejuvenation. METHODS: Over a period of 6 weeks using a split-face study design, the effects on skin surface profile, skin moisture, and transepidermal water loss were determined in 32 female subjects (mean age 54, range 32-67 years) by Fast Optical in vivo Topometry of Human Skin (FOITSHD ), Corneometer, and Tewameter measurements. In addition, a photo documentation was performed for assessment by an expert panel and a survey regarding subject satisfaction was conducted. RESULTS: No negative skin reactions of dermatological relevance were documented for the test product. A significant reduction in skin roughness could be demonstrated. The clinical evaluation of the images using a validated method confirmed significant improvement of wrinkles, in particular of fine wrinkles, lip wrinkles, and crow's feet. A significant skin moisturizing effect was detected while skin barrier function was preserved. The HSF™-based skin care formulation resulted in a self-reported 94% satisfaction rate. CONCLUSION: With no negative skin reactions and highly significant effects on skin roughness, wrinkles, and moisturization, the HSF™-based skin care formulation achieved very satisfying outcomes in this clinical trial. Given the favorable results, this approach represents a promising innovation in aesthetic and regenerative medicine.

Molecular Mechanisms of Hair Growth and Regeneration: Current Understanding and Novel Paradigms.

Hair is a defining feature of mammals and has critical functions, including protection, production of sebum, apocrine sweat and pheromones, social and sexual interactions, thermoregulation, and provision of stem cells for skin homeostasis, regeneration, and repair. The hair follicle (HF) is considered a "mini-organ," consisting of intricate and well-organized structures which originate from HF stem and progenitor cells. Dermal papilla cells are the main components of the mesenchymal compartments in the hair bulb and are instrumental in generating signals to regulate the behavior of neighboring epithelial cells during the hair cycle. Mesenchymal-epithelial interactions within the dermal papilla niche drive HF embryonic development as well as the postnatal hair growth and regeneration cycle. This review summarizes the current understanding of HF development, repair, and regeneration, with special focus on cell signaling pathways governing these processes. In particular, we discuss emerging paradigms of molecular signaling governing the dermal papilla-epithelial cellular interactions during hair growth and maintenance and the recent progress made towards tissue engineering of human hair follicles.

Polydioxanone Threads for Facial Rejuvenation: Analysis of Quality Variation in the Market.

BACKGROUND: Beside botulinum-toxin injections and hyaluronic acid fillers, thread lifts have established themselves as the third column of minimally invasive facial rejuvenation. Most commonly, barbed threads for this approach are made out of polydioxanone, a material known for decades from application in resorbable sutures. The clinical efficacy and the putative material safety of polydioxanone have fueled the popularity of thread lifts. METHODS: The present study highlights significant variation among six commercially available threads in microstructure, tensile strength, elasticity, anchoring capacity in human tissue, and biocompatibility. RESULTS: Despite their license to be marketed and sold in the European Union, some products performed significantly worse than others on material testing, and even displayed cytotoxic characteristics. CONCLUSION: The results of this study are highly relevant for clinicians and may be linked to various typical side effects of polydioxanone threads for facial rejuvenation.

Skin Rejuvenation through HIF-1α Modulation.

The constant intrinsic and extrinsic stress the skin is exposed to leads to significant impairments of the regenerative capacity of aging skin. Current skin rejuvenation approaches lack the ability to holistically support the biological processes that exhaust during aging skin degeneration, such as collagen production, cell migration and proliferation, and new vessel formation. Similar to chronic wounds, aged skin is characterized by dysfunction of key cellular regulatory pathways impairing regeneration. Recent evidence suggests that the same mechanisms hindering a physiologic healing response in chronic wounds are the basis of impaired tissue homeostasis in aged skin. Dysfunction of a main response-to-injury pathway, the hypoxia-inducible factor (HIF)-1α regulatory pathway, has been identified as pivotal both in chronic wounds and in aging skin degeneration. HIF-1α signaling is significantly involved in tissue homeostasis and neovascularization, resulting in the production of new collagen, elastin, and nourishing blood vessels. Modulating the functionality of this pathway has been demonstrated to significantly enhance tissue regeneration. In this review, we present an overview of the regenerative effects linked to the up-regulation of HIF-1α functionality, potentially resulting in skin rejuvenation on both the cellular level and the tissue level.