Search Results (63)

Background/Objectives: Androgenetic alopecia (AGA) is the most common hair loss disorder in dermatological practice. Its primary pathogenesis involves the conversion of testosterone to dihydrotestosterone (DHT) by type II 5α-reductase upon reaching dermal papilla cells (DPCs). DHT impairs DPCs’ activity and inhibits hair growth. Although the FDA-approved drugs finasteride and minoxidil show certain efficacy, they are also associated with severe side effects. This study aims to explore the effects of Terminalia chebula fruit extract (TCFE) on hair growth and its underlying molecular mechanisms. Methods: We investigated the therapeutic potential of TCFE in hair follicle regeneration, employing a multi-level experimental approach combining in vitro analyses of DPCs, in vivo animal models of AGA, and ex vivo cultures of human hair follicles and scalp tissue. Results: First, RNA-seq analysis and RT-PCR validation revealed that TCFE treatment activated the Wnt and TGF-β3 signaling pathways in DPCs, particularly upregulating the AKR1C gene family, which is involved in DHT metabolism. TCFE also potently inhibited type II 5α-reductase activity and mitigated DHT-induced damage to DPCs. In an AGA mouse model, TCFE reversed the AGA phenotype with efficacy comparable to finasteride. However, unlike finasteride, TCFE specifically enhanced the expression of AKR1C1 and AKR1C3, indicating a distinct mechanism. Finally, in ex vivo organ cultures, TCFE suppressed hair follicle cell apoptosis, promoted proliferation, and thereby stimulated hair growth. Conclusions: These findings suggest that TCFE is a promising natural treatment for AGA, likely acting through multiple mechanisms, including Wnt pathway activation, 5α-reductase inhibition, and enhanced DHT degradation. Full article

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Androgenetic alopecia (AGA) is a common form of hair loss characterized by androgen-driven tissue remodeling, including progressive follicular miniaturization and dermal fibrosis, which is accompanied by low-grade immune activation. However, the molecular mechanisms underlying this fibroimmune dysfunction remain poorly understood. Dermal fibroblasts (DFs) have been suggested as androgen-responsive stromal cells and a potential source of CXCL12, a chemokine implicated in fibroimmune pathology, but their precise role in AGA has not been fully established. In this study, we performed single-cell transcriptomic profiling of a testosterone-induced mouse model of AGA, with or without treatment of CXCL12-neutralizing antibody, to elucidate the pathological role of CXCL12 in mediating stromal-immune interactions. Our analysis suggested that DFs are the primary androgen-responsive population driving CXCL12 expression. Autocrine CXCL12-ACKR3 signaling in DFs activated TGF-β pathways and promoted fibrotic extracellular matrix deposition. In parallel, paracrine CXCL12-CXCR4 signaling reprogrammed Sox2⁺Twist1⁺ dermal papilla cells (DPCs) and promoted the accumulation of pro-fibrotic Trem2⁺ macrophages, contributing to impaired hair follicle regeneration. Notably, CXCL12 blockade attenuated these stromal and immune alterations, restored the regenerative capacity of DPCs, reduced pro-fibrotic macrophage infiltration, and promoted hair regrowth. Together, these findings identify CXCL12 as a central mediator of androgen-induced fibroimmune remodeling and highlight its potential as a therapeutic target in AGA. Full article

Background: The aim of the present narrative review is to synthesize the available scientific evidence on the minimally invasive surgical techniques for periodontal regeneration preserving the entire papilla without dissection. Surgical treatment of intrabony defects may result in compromising the integrity of the interdental tissues and subsequent papilla loss. Therefore, it is indicated to investigate the approaches avoiding papillary incision over the osseous defect, thus optimizing wound healing conditions. Methods: Authors performed a search of literature via electronic databases such as PubMed, Web of Science, Cochrane, and Scopus, and extended by manual searching with a stop date of February 2025. Based on inclusion criteria only randomized clinical trials (RCT), cohort studies, case–control studies, and case series were included, and 106 records were initially identified. Various aspects of described novel approaches preserving the entire papilla were finally discussed. Results: A total of 12 studies were evaluated. There is a significant lack of randomized controlled clinical trials on minimally invasive techniques without incision in the papilla. However, numerous modifications of existing techniques have emerged, mainly in the form of case series and case reports with short-term data. Among them, some authors stated that the entire papilla preservation approaches may facilitate early soft tissue healing, reduce papilla trauma and the risk of gingival recession, minimize procedure time, improve flap stability, and alleviate discomfort and side effects, while others reported similar outcomes to conventional approaches and emphasize the need for further comparative clinical trials. Conclusions: Preserving papilla integrity and the soft tissue profile is essential for minimizing complications, especially in the esthetic zone. Within the limitations of this narrative review, presented findings emphasize the effectiveness of entire papilla preservation techniques in preventing post-surgery tissue loss compared to conventional incisions and flaps. Randomized controlled trials with longer follow-up periods and larger sample sizes are necessary to validate the efficacy of these approaches in comparison to established papilla preservation techniques. Full article

Androgenetic alopecia (AGA) is a prevalent form of non-scarring hair loss, affecting approximately 32.13% of the population. Seborrheic alopecia is the most frequently observed among its various types, contributing to over 25% of hair loss cases in men. Identifying effective natural compounds or therapeutic agents that stimulate hair growth remains a key research focus. Platycladus orientalis L., known for its medicinal properties, shows potential in promoting hair darkening and regeneration, although its mechanisms remain unclear. In this study, Fr2 of Platycladus orientalis L. was found to significantly enhance hair growth in mice. Similarly, (7E)-7,8-Dehydroheliobuphthalmin (DHHB) was successfully isolated and purified for the first time through a combination of medium-pressure liquid chromatography and two-dimensional high-performance liquid chromatography. In an alopecia areata (AGA) model using dermal papilla cells (DPCs), DHHB was found to significantly promote cell proliferation and differentiation by down-regulating the expression of androgen receptor (AR) proteins, and activating the Wnt/β-catenin signaling pathway, as compared with the dihydrotestosterone-induced model group. These results indicate that DHHB is a major bioactive compound in Platycladus orientalis L. and represents a promising candidate for promoting hair growth. Full article

Hair loss is often associated with oxidative stress and mitochondrial dysfunction in human follicle dermal papilla cells (HFDPCs), resulting in impaired cellular function and follicle degeneration. Thus, many studies have been conducted on natural plants aimed at inhibiting hair loss. This study investigated the therapeutic potential of exosomes derived from the rhizomes of Iris germanica L. (Iris-exosomes) in HFDPCs damaged by dihydrotestosterone (DHT). Iris-exosomes significantly reduced reactive oxygen species (ROS) levels, restoring mitochondrial membrane potential and ATP production, thereby mitigating oxidative stress and improving mitochondrial function. These effects occurred alongside enhanced cellular processes critical for hair follicle regeneration, including increased cell migration, alkaline phosphatase (ALP) activity, and three-dimensional (3D) spheroid formation, which replicates the follicle-like microenvironment and promotes inductive potential. Furthermore, Iris-exosomes stimulated the Wnt/β-catenin signaling pathway by enhancing glycogen synthase kinase-3β (GSK-3β), AKT, and extracellular signal-regulated kinase (ERK), leading to β-catenin stabilization and nuclear translocation, thereby supporting the expression of genes essential for hair growth. Taken together, these findings suggest that Iris-exosomes can be promising ingredients for alleviating hair loss. Full article

As an endogenous metabolite, α-ketoglutarate (AKG) exhibits potent antioxidant properties, yet its molecular mechanisms remain unclear. Dermal Papilla Cells (DPCs), functioning as the regulatory hub of hair follicle morphogenesis, serve as a pivotal model system for deciphering follicular functionality and regeneration mechanisms through their orchestration of signaling networks. Using a hydrogen peroxide (H₂O₂)-induced oxidative stress model in DPCs, we investigated AKG’s protective effects. AKG attenuated H₂O₂-triggered reactive oxygen species (ROS) overproduction, restored mitochondrial membrane potential, and suppressed apoptosis-related protein dysregulation. It enhanced cellular stress resistance by increasing the Bcl-2/Bax ratio, boosting antioxidant levels, and inhibiting inflammation. Mechanistically, H₂O₂ activated the Nrf2 pathway, while AKG amplified Nrf2 nuclear translocation and expression. Crucially, ERK inhibition abrogated AKG-mediated Nrf2 regulation, intensifying ROS accumulation and cell death. These results identify the ERK/Nrf2 axis as central to AKG’s antioxidative cytoprotection. This study advances AKG’s therapeutic potential and deepens insights into its multifunctional roles. Full article

Advanced bioengineering, popularly known as regenerative dentistry, has emerged and is steadily developing with the aim of replacement of lost or injured tissues in the mouth using stem cells and other biomaterials. Conventional therapies for reparative dentistry, for instance fillings or crowns, mainly entail the replenishment of affected tissues without much concern given to the regeneration of tissues. However, these methods do not enable the natural function and aesthetics of the teeth to be maintained in the long term. There are several regenerative strategies that offer the potential to address these limitations to the extent of biologically restoring the function of teeth and their components, like pulp, dentin, bone, and periodontal tissues. Hence, stem cells, especially dental tissue derived stem cells, such as dental pulp stem cells, periodontal ligament stem cells, or apical papilla stem cells, are quite promising in this regard. These stem cells have the potentiality of generating precise dental cell lineages and thus are vital for tissue healing and renewal. Further, hydrogels, growth factors, and synthetic scaffolds help in supporting the stem cells for growth, proliferation, and differentiation into functional tissues. This review aims at describing the process of stem cell-based tissue repair biomaterials in dental regeneration, and also looks into the practice and prospects of regenerative dentistry, analysing several case reports and clinical investigations that demonstrate the efficacy and limitations of the technique. Nonetheless, the tremendous potential for regenerative dentistry is a reality that is currently challenged by biological and technical constraints, such as scarcity of stem cell sources, inadequate vascularization, and the integration of the materials used in the procedure. As we move forward, the prospects for regenerative dentistry are in subsequent developments of stem cell technology, biomaterial optimization, and individualized treatment methods, which might become increasingly integrated in dental practices globally. However, there are regulatory, ethical and economic issues that may pose a hurdle in the further advancement of this discipline. Full article

Background/Objectives: A novel 3D-printed, bioresorbable bone graft, made of nanohydroxyapatite (nHAP) covered by poly(lactide-co-glycolide) (PLGA), showed strongly expressed osteoinductive properties in our previous investigations. The current study examines its application in the dual regeneration of bone and cartilage by combining with nHAP gel obtained by nHAP enrichment with hydroxyethyl cellulose, sodium hyaluronate, and chondroitin sulfate. Methods: In the in vitro part of the study, the mitochondrial activity and osteogenic and chondrogenic differentiation of stem cells derived from apical papilla (SCAPs) in the presence of nHAP gel were investigated. For the in vivo part of the study, three rabbits underwent segmental osteotomies of the lateral condyle of the femur, and defects were filled by 3D-printed grafts customized to the defect geometry. Results: In vitro study revealed that nHAP gel displayed significant biocompatibility, substantially increasing mitochondrial activity and facilitating the osteogenic and chondrogenic differentiation of SCAPs. For the in vivo part of the study, after a 12-week healing period, partial resorption of the graft was observed, and lamellar bone tissue with Haversian systems was detected. Histological and stereological evaluations of the implanted grafts indicated successful bone regeneration, marked by the infiltration of new bone and cartilaginous tissue into the graft. The existence of osteocytes and increased vascularization indicated active osteogenesis. The hyaline cartilage near the graft showed numerous new chondrocytes and a significant layer of newly formed cartilage. Conclusions: This study demonstrated that tailored 3D-printed bone grafts could efficiently promote the healing of substantial bone defects and the formation of new cartilage without requiring supplementary biological factors, offering a feasible alternative for clinical bone repair applications. Full article

Hair loss disorders pose a substantial global health burden, affecting millions of individuals and significantly impacting quality of life. Despite the widespread use of approved therapeutics like minoxidil and finasteride, their clinical efficacy remains limited. These challenges underscore the pressing need for more targeted and effective therapeutic solutions. This review examines the latest innovations in hair loss drug discovery, with a focus on small-molecule inhibitors, biologics, and stem cell-based therapies. By integrating insights from molecular mechanisms and leveraging advancements in research methods, the development of next-generation therapeutics holds the potential to transform the clinical management of hair loss disorders. Future drug development for hair loss disorders should prioritize antibody therapy and cell-based treatments, as these approaches offer unprecedented opportunities to address the limitations of existing options. Antibody therapies enable precise targeting of key molecular pathways involved in hair follicle regulation, providing highly specific and effective interventions. Similarly, cell-based therapies, including stem cell transplantation and dermal papilla cell regeneration, directly address the regenerative capacity of hair follicles, offering transformative potential for hair restoration. Full article

The root walls of immature permanent teeth are often weak, thin, and short, making regenerative endodontic treatment (RET) necessary. The goal of RET is to create a favorable environment for further root development. A biomimetic approach is essential for thorough disinfection, followed by the preservation and potential stimulation of stem cells from surrounding tissue to enable root regeneration and continued development. The objective of this study was to assess temperature changes on the external root surface, structural alterations in the internal root walls following irradiation with a 940 nm diode laser, and the biocompatibility of stem cells from the apical papilla (SCAPs). Irradiation was performed with varying output powers (0.5 W, 1 W, 1.5 W, and 2 W) in continuous mode for 5 s over four consecutive cycles. Thermographic measurements during irradiation, the micro-CT analysis of root samples, and mitochondrial activity of SCAPs were evaluated. The heating effect correlated directly with a higher output power and thinner root walls. A 1 W output power was found to be safe for immature teeth, particularly in the apical third of the root, while 1.5 W could be safely used for mature mandibular incisors. Diode laser irradiation at 1 W and 1.5 W significantly stimulated SCAPs’ mitochondrial activity within 24 h post-irradiation, indicating a potential photobiostimulatory effect. However, no significant changes were observed at lower (0.5 W) and higher (2 W) output powers. The area of open tubular space inside the root canal was significantly reduced after irradiation, regardless of the applied power. Additionally, irradiation contributed to the demineralization of the dentin on the inner root walls. Future studies should explore the impact of irrigants used between irradiation cycles, the potential benefits of conical laser tips for more even energy distribution, and a thorough analysis of how disinfection protocols affect both the dentin structure and stem cell viability. Full article

How to elicit and harness regeneration is a major issue in wound healing. Skin injury in most amniotes leads to repair rather than regeneration, except in hair and feathers. Feather follicles are unique organs that undergo physiological cyclic renewal, supported by a dynamic stem cell niche. During normal feather cycling, growth-phase proximal follicle collar bulge stem cells adopt a ring configuration. At the resting and initiation phases, these stem cells descend to the dermal papilla to form papillary ectoderm and ascend to the proximal follicle in a new growth phase. Plucking resting-phase feathers accelerates papillary ectoderm cell activation. Plucking growth-phase feathers depletes collar bulge stem cells; however, a blastema reforms the collar bulge stem cells, expressing KRT15, LGR6, Sox9, integrin-α6, and tenascin C. Removing the follicle base and dermal papilla prevents feather regeneration. Yet, transplanting an exogenous dermal papilla to the follicle base can induce re-epithelialization from the lower follicle sheath, followed by feather regeneration. Thus, there is a stepwise regenerative strategy using stem cells located in the collar bulge, papillary ectoderm, and de-differentiated lower follicle sheath to generate new feathers after different levels of injuries. This adaptable regenerative mechanism is based on the hierarchy of stem cell regenerative capacity and underscores the remarkable resilience of feather follicle regenerative abilities. Full article

The absence of interdental papillae in dental prosthetics often leads to unsatisfactory esthetic outcomes, such as black triangles and elongated clinical crowns. While previous research has demonstrated that papillae can regenerate in a coronal direction, the underlying mechanisms remain incompletely understood. Several theories have been proposed to explain this phenomenon, but no clear cause–effect relationship has been established among the various factors involved in spontaneous papilla growth around implants. This study aims to identify and classify the factors influencing this process. Various potential contributors were analyzed, including adjacent elements, buccal–lingual papilla width, contact point position, convergent neck design, crown overcontour, intraoral negative pressure, and others. To systematically organize these factors, a modified Overton Window and a mind map were employed. The factors were categorized as cause-related, essential, or influencing based on the collective opinion of the research group following a comprehensive review of the relevant literature. In the absence of clear evidence supporting a definitive cause–effect relationship, Occam’s Razor (the principle of parsimony) was applied to identify the most plausible cause-related factors. Full article

This study explored the role of Piezo1 in the odontogenic differentiation of dental papilla cells (DPCs) and tissue, focusing on a mechanism involving family with sequence similarity 83, member G (FAM83G). Here, we found Piezo1, a mechanosensitive cation channel, was upregulated during odontogenesis in DPCs and dental papilla tissues. Knockdown of Piezo1 impaired odontogenic differentiation, while its activation by Yoda1 enhanced the process. Using a 3D culture model and an ectopic transplantation model, we confirmed Piezo1’s role in vivo. RNA sequencing (RNA-seq) analysis revealed that FAM83G was upregulated in Piezo1-knockdown cells, and FAM83G silencing enhanced odontogenesis in DPCs. These findings indicate that Piezo1 positively regulates odontogenesis by inhibiting FAM83G in DPCs both in vitro and in vivo, with Piezo1 representing a potential target for dental tissue regeneration. Full article

Cell homing, a process that leverages the body’s natural ability to recruit cells and repair damaged tissues, presents a promising alternative to cell transplantation methods. Central to this approach is the recruitment of endogenous stem/progenitor cells—such as those from the apical papilla, bone marrow, and periapical tissues—facilitated by chemotactic biological cues. Moreover, biomaterial scaffolds embedded with signaling molecules create supportive environments, promoting cell migration, adhesion, and differentiation for the regeneration of the pulp–dentin complex. By analyzing in vivo animal studies using cell homing strategies, this review explores how biomolecules and scaffold materials enhance the recruitment of endogenous stem cells to the site of damaged dental pulp tissue, thereby promoting repair and regeneration. It also examines the key principles, recent advancements, and current limitations linked to cell homing-based regenerative endodontic therapy, highlighting the interplay of biomaterials, signaling molecules, and their broader clinical implications. Full article