Dermal Research Articles

Inhibition of Adipocyte-Derived FABP4 Reduces Adipocyte Inflammation, Improves Angiogenesis, and Facilitates Wound Healing in Metabolic Dysfunctions

Dermal white adipose tissue may participate in the wound healing process. Obesity-mediated chronic low-grade inflammation impairs wound healing by suppressing vascularity. Given that fatty-acid-binding protein (FABP) 4 is upregulated in the skin tissue of obese animals, this study aimed to investigate the effects of FABP4 inhibition on wound healing in high-fat-diet (HFD)-induced metabolic dysfunction mice in vivo. The interaction between adipocyte-derived FABP4 and vascular endothelial cell function was also investigated. In HFD-induced metabolic dysfunction mice, FABP4 inhibition increased angiogenesis and facilitated wound healing with reduced wound inflammation. FABP4 inhibition not only attenuated systemic inflammation, decreased body weight, and reduced insulin resistance, but also improved the sizes of adipocytes and hypoxic conditions in dermal white adipose tissue. The in vitro hypoxia was used to induce adipocyte inflammation, and the supernatants from hypoxia-stimulated adipocytes impaired the function and angiogenetic capability of human dermal microvascular endothelial cells. Both of them were improved by FABP4 inhibition. Altogether, FABP4 inhibition reduced systemic and adipocyte inflammation, improved vascular endothelial cell function, and facilitated wound healing in metabolic dysfunctions. Given the complex involvement of wound healing, future studies may be required to validate FABP4 as a potential therapeutic target for wound repair in metabolic dysfunctions.

Analysis of the Long Non-Coding and Messenger RNA Expression Profiles in the Skin Tissue of Super Merino and Small-Tailed Han Sheep.

Wool quality and yield are two important economic livestock traits. However, there are relatively few molecular studies on lncRNA for improving sheep wool, so these require further exploration. In this study, we examined skin tissue from the upper scapula of Super Merino (SM) and Small-Tailed Han (STH) sheep during the growing period. The apparent difference was verified via histological examination. High-throughput RNA sequencing identified differentially expressed (DE) long non-coding (lncRNAs) and messenger RNAs (mRNAs). The target gene of DE lncRNA and DE genes were enrichment analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify randomly selected DE lncRNAs and mRNAs. Finally, the DE, RAC2, WNT11, and FZD2 genes, which were enriched in the Wnt signaling pathway, were detected via immunohistochemistry. The results showed that a total of 20,888 lncRNAs and 31,579 mRNAs were identified in the skin tissues of the two sheep species. Among these, 56 lncRNAs and 616 mRNAs were differentially expressed. Through qRT-PCR, the trends in the randomly selected DE genes' expression were confirmed to be aligned with the RNA-seq results. GO and KEGG enrichment analysis showed that DE lncRNA target genes were enriched in GO terms as represented by epidermal and skin development and keratin filature and in KEGG terms as represented by PI3K-Akt, Ras, MAPK, and Wnt signaling pathways, which were related to hair follicle growth and development. Finally, immunohistochemistry staining results indicated that RAC2, WNT11, and FZD2 were expressed in dermal papilla (DP). The lncRNAs MSTRG.9225.1 and MSTRG.98769.1 may indirectly participate in the regulation of hair follicle growth, development, and fiber traits by regulating their respective target genes, LOC114113396(KRTAP15-1), FGF1, and IGF1. In addition, MSTRG.84658.1 may regulate the Wnt signaling pathway involved in the development of sheep hair follicles by targeting RAC2. This study provides a theoretical reference for improving sheep breeding in the future and lays a foundation for further research on the effects of MSTRG.84658.1 and the target gene RAC2 on dermal papilla cells (DPC).

A bioswitchable delivery system for microRNA therapeutics based on a tetrahedral DNA nanostructure.

As microRNAs (miRNA) regulate almost all physiopathological activities in the human body, miRNA therapeutics that deliver miRNA regulators have attracted considerable attention in the field of nucleic acid drug development. The use of tetrahedral DNA nanostructures to deliver miRNA regulators is promising because of their simple fabrication, enhanced cell entry, effective tissue penetration, biocompatibility and functional editability. This protocol extension builds on our previous protocol for the use of tetrahedral DNA nanostructures and was designed to establish an updated bioswitchable delivery system (BDS) for achieving controlled cargo loading and release. A ribonuclease H-sensitive sequence is designed as a bioswitchable apparatus for the targeted release of the miRNA regulator. The functional sequence of the miRNA regulator and minimal secondary structure formation tendency during annealing are two key points in cargo design. We provide two BDS design strategies; BDS-A comprises an intact DNA tetrahedron with the RNA cargo hanging outside, offering the merits of lower cost, simplicity, and more direct structural design. In the BDS-B design, the RNA regulators are embedded into the DNA tetrahedron, which is beneficial for dermal tissue permeation applications. Following sequence design in Oligo 7 and Tiamat, the BDS assembly is completed and then ribonuclease H achieves controlled release of the miRNA regulator by triggering the bioswitchable apparatus. This is verified via polyacrylamide and agarose gel electrophoresis or fluorophore modifications. Both BDSs show promising cellular membrane permeability, tissue permeability and target inhibition in vitro and in vivo. The assembly and characterization of the BDS can be completed in 4 d, and the validation time for biostability and biological applications will depend on the specific use.

Comparative morphology of the rhinarium and upper lip in sigmodontine rodents: Refined nomenclature, intertribal variation in a phylogenetic framework, and functional inferences.

Rodents have received substantial attention in the study of olfaction. However, the rhinarium, the naked part of the nose, which plays an important role in chemical, tactile, and thermal perception, has been relatively overlooked. This study presents a comprehensive analysis of the rhinarium morphology and spatially associated structures (i.e., upper lip, and philtrum) in sigmodontines, a diverse group within the Cricetidae rodents. The research covers 483 specimens representing 145 species, accounting for 74% of genera in the clade, including all 13 recognized tribes, three incertae sedis genera, and the murid representatives Mus musculus and Rattus norvegicus. The inconsistent use of terminology in describing rhinarium traits across the literature poses a challenge for comparative analyzes. To address this issue, a standardized terminology was proposed to characterize the rhinarium. A paired complex protuberance typically with epidermal ridges (i.e., rhinoglyphics), termed here the tubercle of Hill, was identified as a distinctive feature in muroid rhinaria. Comparative assessments among tribes revealed unique sets of features defining each major clade, encompassing variations in hairiness, dorsum nasi complexity, size and positioning of the tubercle of Hill, and other key attributes. Two primary rhinarium configurations were discerned: one shared by Oryzomyalia and Sigmodontini and another specific to Ichthyomyini. The former groups display a ventrally positioned rhinarium prominently featuring the tubercle of Hill and sculptured areola circularis. In contrast, Ichthyomyini exhibit a frontally directed rhinarium characterized by an enlarged dorsum nasi fused to the tubercle of Hill, resulting in a distinctive "cherry" appearance. Convergent rhinarium structures observed in fossorial species, characterized by well-developed plica alaris and hair fringes, are presumed to mitigate potential damage during digging. Conversely, semiaquatic carnivorous sigmodontines showcase an integrated apical structure in their rhinarium, facilitating enhanced somatosensory capabilities crucial for predation activities during diving expeditions.

Experimental Study of Ultra-Pulsed CO 2 Fractional Laser Combined With Recombinant Human Epidermal Growth Factor Gel in the Treatment of Eyelid Keloid.

Keloid (KD) and hypertrophic scars are prevalent and result from excessive growth of dermal tissue after skin damage. This review focused on the clinical application of the ultra-pulsed CO 2 fractional laser combined with recombinant human epidermal growth factor (rHEGF) gel in patients with eyelid KD. Patients (N = 98) with KD who underwent surgery were randomly divided into a study group (ultra-pulsed CO 2 fractional laser combined with rHEGF gel therapy, N = 49) and a control group (ultra-pulsed CO 2 fractional laser therapy, N = 49). Besides, 5 cases dropped out of the study, including 2 cases in the study group and 3 cases in the control group. Finally, 47 cases of the study group and 46 cases of the study group were included in the analysis. The clinical baseline data such as sex, age, body mass index, scar area, etiology, Vancouver Scar Scale score, Patient and Observer Scar Assessment Scale score, four-item itch questionnaire score, serum interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α level expression were recorded in the study group (N = 47) and the control group (N = 46). There was no significant difference in gender, age, body mass index, scar area, etiology, Vancouver Scar Scale score, Patient and Observer Scar Assessment Scale score, 4-item itch questionnaire score, IL-6, IL-10, and tumor necrosis factor-α levels between the patients treated with ultra-pulse CO 2 fractional laser + rHEGF gel and those only treated with ultra-pulse CO 2 fractional laser ( p > 0.05). Vancouver Scar Scale scores, Patient and Observer Scar Assessment Scale scores, and four-item itch questionnaire scores of patients with eyelid KD decreased to a greater extent than those treated with ultra-pulsed CO 2 fractional laser combined with rHEGF gel ( p <0.01). Compared with ultra-pulsed CO 2 fractional laser treatment, ultra-pulsed CO 2 fractional laser combined with rHEGF gel was more efficacious in treating patients with eyelid KD, with a lower incidence of adverse effects and a 1-year recurrence rate. Ultra-pulsed CO 2 fractional laser combined with rHEGF gel can significantly improve the scar status and scar itching in patients with eyelid KD, with an obvious therapeutic effect, a low incidence of adverse effects, a 1-year recurrence rate, and high safety, which is worthy of popularization and application.

Exosomal miR-222-3p derived from dermal papilla cells inhibits melanogenesis in melanocytes by targeting SOX10 in rabbits.

Dermal papilla cells (DPCs) play a pivotal role in hair follicle development and can modulate melanogenesis in melanocytes (MCs) through their microenvironment. Our previous studies have demonstrated that the level of exosomal miR-222-3p derived from DPCs of white Rex rabbits are significantly higher than those of black Rex rabbits. However, the specific role and underlying molecular mechanisms of exosomal miR-222-3p in melanogenesis remain elusive. DPCs and MCs were isolated from hair follicles of Rex rabbits and identified using western blotting (WB) and immunofluorescent staining. Exosomes derived from DPCs (DPCs-exos) were characterized using nanoparticle tracking analysis, transmission electron microscopy, and WB. To investigate cell-cell crosstalk mediated by exosomes, MCs were co-cultured with CM-Dil-labeled DPCs-exos. The expression of miR-222-3p in skin tissue and exosomes was quantitatively assessed using quantitative real-time PCR (qRT-PCR). The transmission of DPCs-secreted exosomal miR-222-3p to MCs was demonstrated using Cy3-labeled miR-222-3p in conjunction with transwell assays. The impact of miR-222-3p on melanin synthesis was evaluated using the NaOH method, CCK-8, and Annexin V-FITC/PI assays. SOX10, a potential target gene regulated by miR-222-3p, was validated using a dual-luciferase reporter assay, site-specific mutation, and WB. Increased levels of miR-222-3p were observed in the skin and DPCs-exos of white Rex rabbits compared to those of black Rex rabbits. Effective internalization of CM-Dil-labeled DPCs-exos by MCs was observed. Furthermore, exosomal miR-222-3p derived from DPCs was transferred to MCs. Functionally, miR-222-3p significantly inhibited MCs proliferation, induced apoptosis and inhibited melanin synthesis. SOX10 was confirmed as a direct target of miR-222-3p in this regulatory cascade. The findings demonstrate that exosomal miR-222-3p, derived from DPCs, suppresses melanogenesis in MCs by targeting SOX10, thus unveiling a novel mechanism of exosome involvement in melanogenesis.

Identification of Fingerprint Pattern and Lip Print Pattern in Females of Type 2 Diabetes Mellitus as a Biomarker

Diabetes mellitus (D.M.) is a chronic metabolic disorder that has increased worldwide. Fingerprints and lip prints are noninvasive procedures that are genetically used in criminal cases and to determine genetic disorders such as Diabetes mellitus type 2. Dermatoglyphics is the epidermal ridge configuration, the ridged skin on our fingertips, palms, and toes. There are three types (Whorl, et al.). Cheiloscopy, derived from the Greek word (cheilos), which means lip, is the study of crinkles and grooves that are perceptible on our lips and unique. We conducted our research with 90 females, 45 were with (DMT2), and 45 were normal females over 30 years old. The samples were collected in different Kurdistan regions (Erbil City, Qaladza Town, Koya Town, and Koya University). We collected all 10 (ten) fingerprint patterns and divided them into Whorl, loop, and arch using an ink pad. Also, lip samples were collected by using lipstick on A4 paper. According to our research, the predominant fingerprints and lip prints in females with type 2 diabetes were loops for both hands (right (31.1%) and left (28.4%)), and for lips, the print was intersected grooves (28.9%). The predominant fingerprint and lip print for normal females were also loops in both hands (right (28%) and left (25%)), and the lip print was complete vertical grooves (42.2%). The study showed no association between fingerprint pattern and diabetes mellitus type 2 and cannot be used as a biomarker for it. However, there is a clear association between lip print pattern and diabetes mellitus type 2, and it can be used as a specific biomarker.

Novel Synergistic Approach for Bioactive Macromolecules: Evaluating the Efficacy of Goat Placenta Extract in PEGylated Liposomes and Microspicules for Chemotherapy-Induced Hair Loss.

Chemotherapy-induced hair loss is a distressing side effect of cancer treatment, and medical interventions are often needed to address this problem. The objectives of this study were to evaluate the bioactivity of goat placenta (GP) extract on both normal and chemotherapy-induced hair cells and to develop PEGylated liposomes (PL) and microspicule (MS) formulations for promoting hair growth in patients with chemotherapy-induced hair loss. The bioactivities of GP extract on human follicle dermal papilla (HFDP) cells and cells damaged by chemotherapy were assessed. GP extract was incorporated into PLs and MS gel (PL-MS) and then investigated in vitro skin permeation and in vivo studies on the scalps of patients with chemotherapy-induced hair loss. GP extract stimulated HFDP cell proliferation in both normal and cisplatin-damaged cells. PL nanovesicles and MS gel worked synergistically to deliver macromolecular proteins into the skin and hair follicles. The application of GP extract-loaded PL-MS to the scalps of chemotherapy-treated patients for 12 weeks significantly enhanced the hair growth rate, without causing skin irritation. In conclusion, GP extract promoted the proliferation of hair cells damaged by chemotherapy, when this extract, combined with PL-MS, effectively delivered bioactive macromolecules across the skin and hair follicles, resulting in successful regrowth of hair post-chemotherapy.

Chitinase 3-Like 1 and C-X-C motif chemokine ligand 5 proteins and the hair cycle.

Dermal papilla cells (DPCs) exhibit self-recovery ability, which may be involved in hair growth. Therefore, we tested whether DPCs subjected to temporary growth-inhibiting stress (testosterone, 17β-estradiol, mitomycin C, or undernutrition) treatments exhibit self-recovery behavior that can activate hair follicle growth, and examined the changes in cell proliferation capacity and gene expression. Related proteins were identified and their relationships with the hair cycle was examined using a mouse model. Recovery-period DPCs (i.e., from day 3 after loading) were subjected to microarray analysis to detect genetic variations common to each stress treatment. Co-culture of recovery-period DPCs and outer root sheath cells (ORSCs) confirmed the promotion of ORSC proliferation, suggesting that the activation of hair follicle growth is promoted via signal transduction. Chitinase 3-like 1 (CHI3L1) and C-X-C motif chemokine 5 (CXCL5) exhibited ORSC proliferation-promoting effects. Measurement of protein content in the skin during each phase of the hair cycle in mice revealed that CHI3L1 and CXCL5 secretion increased immediately after anagen transition. In a hair-loss mouse model treated with testosterone or 17β-estradiol, CHI3L1 and CXCL5 secretion was lower in treated telogen skin than in untreated skin. Our results suggest that CHI3L1 and CXCL5 secreted by recovery-state DPCs promote hair growth.

Ionic Liquid-Based Extraction of Fulvic-like Substances from Wood Sawdust: Reproducing Unique Biological Activities of Fulvic Acids Using Renewable Natural Sources.

Fulvic acids (FAs) have been commercially used in cosmetics and agronomy due to their unique biological activities, such as plant stimulation and anti-inflammatory effects. However, the extraction sources of FAs, such as peat, are currently limited. Consequently, new extraction methods using renewable resources need to be developed, while reproducing the biological functions. Here, ionic liquids (ILs) effectively extracted fulvic-like substances (FLSs) from wood sawdust. The overall molecular weight distributions of FLSs were similar to those of commercial FAs, and key organic groups (e.g., aromatic, phenolic, and methoxy groups) were also found to be shared between commercial FAs and FLSs. Detailed compositional analysis revealed by high-resolution mass spectrometry showed that the extracts contain both lignin-like and lipid-like molecules, while commercial FAs are biased toward lignin-like and carbohydrate-like molecules. FLSs generally showed better and similar performance in radical scavenging activity against ABTS+· and H2O2. Fibroblast proliferation and lettuce growth enhancements were also observed with the extract containing 1-ethyl-3-methylimidazolium acetate and triethylammonium hydrogen sulfate, respectively, which performed better than commercial FAs. Immunofluorescence staining of in vitro human follicle dermal papilla cells supports that coexpression of hair growth-related proteins can be accelerated with FLSs, and this effect was further evidenced by in vivo mouse model experiments. Finally, the reusability of ILs in the extraction process was confirmed by analyzing the structural features of FLSs from each recycling. Our findings indicate that ILs are useful for obtaining biologically functional fulvic analogs from renewable plant sources.

Role of Umbilical Cord Mesenchymal Derived Exosomes in Diseases

Stem cells are divided into embryonic stem cells and adult stem cells. Mesenchymal stem cells (MSCs) are one of the most important adult stem cells. These cells possess characteristic plastic adhesion properties, the ability to differentiate into osteoblasts, chondrocytes and adipocytes in vitro, are positive for CD73, CD90 and CD105, major histocompatibility complex class II, and negative for CD11b, CD14, CD31, CD34 and CD45. MSCS can be isolated from different sources, such as umbilical cord, umbilical cord blood, bone marrow (BM), adipose tissue, cervical tissue, placenta, skeletal muscle tissue, liver tissue, dental pulp, synovium, saphenous vein, lung and dermal tissue and periodontal ligament. They have many abilities, such as the ability to differentiate, expand in vitro, produce nutrients and regulate immunity. Therefore, bone marrow mesenchymal stem cells can help in tissue repair and treatment, such as diabetes, cardiovascular diseases, diseases of the liver, lung, kidney, nervous system, and other systems, and of course, bone. As a noninvasive method, there is no ethical issues, low immunogenicity, self-renewal ability faster, more stable, doubling time proliferation ability is higher, compared with other sources, the treatment of human umbilical cord MSC is based on cells and regenerative medicine preferred candidates. However, hucMscs have relative limitations in maintaining biological activity, quantifying bioactive substances, and clinical therapeutic logistics. Therefore, it seems necessary to find a cell-free method with the same output and efficacy. Exosomes are one of the members of extracellular vesicles, and due to their many biological activities and cell communication, they have attracted the attention of researchers as a new strategy for cell-based cell-free therapies. In the study of HUCMSCexo, all the advantages of HUCMSC, such as the therapeutic factor transfer of low immunogenicity HUCMSC, the prominent self-renewal and immunomodulatory properties have been reported to be conserved. In addition, no tumorigenic outcome was found in these studies. Therefore, this article reviews the application of HUCMSC-EXO in different diseases.

Panax notoginseng saponins loaded W/O microemulsion for alopecia therapy with panthenol as cosurfactant to reduce skin irritation

The etiology of alopecia is so complex that current therapies with single-mechanism and attendant side-effects during long-term usage, are insufficient for treatment. Panax notoginseng saponins (PNS) is supposed to treat alopecia with multiple mechanisms, but difficult to penetrate skin efficiently due to water-solubility. Here, we designed water-in-oil microemulsion (PNS ME) using jojoba oil, fractioned coconut oil, RH 40 + Span 80 and cosurfactant D-panthenol, to help PNS penetrating the skin. Particularly, D-panthenol not only enlarges the microemulsion area, reduces the usage amounts of surfactants thus relieves skin irritation, but stimulates the migration of dermal papilla cells (DPCs), displaying cooperative effects on anti-alopecia. PNS ME penetrates through sebum-rich corneum via high-affinity lipid fusion, targets to hair follicles (HFs), where it resides in skin for sustained drug release, accelerates angiogenesis to build well-nourished environment for HFs, and facilitates the proliferation and migration of DPCs in vitro. PNS ME markedly improved hair density, skin pigmentation, new hair weight, skin thickness, and collagen generation of telogen effluvium mice. Moreover, PNS also took outstanding curative effects on androgenetic alopecia mice. Upon further exploration, PNS ME caused dramatic upregulations of β-catenin, VEGF and Ki67, suggesting it might function by triggering Wnt/β-catenin pathway, accelerating vessels formation, and activating the hair follicle stem cells. Notably, PNS ME indicated longer-term safety than minoxidil tincture. Together, PNS ME provides a comprehensive strategy for alopecia, especially it avoids defects by high-proportioned surfactants in traditional microemulsion, exhibiting milder and safer, which shows bright prospect of applying microemulsion in hair growth promotion.

The synergistic effect of phototherapy and active substances on hair growth

Androgenic alopecia (AGA) typically manifests post-puberty, resulting in decreases in hair density, disruptions in the hair growth cycle, and alterations in hair follicle micro structure. Dihydrotestosterone (DHT) is a key hormone implicated in hair loss, especially on male. In this study, we found that each of arginine (Arg), arterial extract (AE) or biotin tripeptide-1 (BT-1), when combined with low level light therapy (LLLT, at 630 nm, 2 J/cm2), showed the efficacy in enhancing mitochondrial functions, cell proliferation and collagen synthesis in fibroblasts. Additionally, CARRIPOWER (the complexes of AE, BT-1, Arg, and Diaminopyrimidine derivatives), in conjunction with LLLT (630 nm, 2 J/cm2), showed promising results in dermal papilla cells (DPCs). The promising results contained not also inflammatory cytokines (IL-1β and IL-6) and cell pro apoptotic factor (TGF-β2) reduction, but also Wnt pathway inhibition by decreasing DKK1 level, and pro-hair growth factors (vascular endothelial growth factor (VEGF) and β-catenin) increase. This innovative combination therapy offers a potential solution for the treatment of AGA, addressing both hormonal and cellular factors involved in hair loss.

Use of VAC System and Dermal Matrix as a Surgical Alternative for Lower Extremity Degloving Treatment

Introduction: Soft tissue degloving injuries are the result of high-energy forces that produce compression, twisting or friction of tissues causing soft tissue avulsion, in which a large portion of skin and subcutaneous tissue is detached from the underlying fascia and muscles with musculocutaneous damage and perforating fasciocutaneous vessels. Case Report: The case of a 67-year-old female patient was reported, who as a result of a traffic accident (run over) suffered cutaneous loss (degloving) of the left lower limb. The patient underwent surgical cleaning with debridement of dead tissue plus full-thickness skin autograft for partial coverage of the exposed area in the proximal region. At the same time the surgery was performed, the VAC system was placed. After multiple surgical cleanings, scarce granulation tissue was revealed in the middle and distal third of the left leg. Therefore, it was decided to cover the exposed area with dermal matrix for later definitive coverage. The patient is being followed up by outpatient service. It is revealed that the patient already performs assisted mobility, and the grafts are assimilated. Conclusions: Traffic accidents are a major problem worldwide, especially those of high-energy may require multidisciplinary treatment, prolonged surgical time until recovery and return to daily activities. The initial treatment for degloving has to be performed by trained professionals since the criterion for assessing flap vitality is indispensable. When complex skin grafts are not an option, advanced wound treatment should be used, as in this case, where VAC therapy and permanent synthetic substitute were used for the total coverage of a major defect with lost dermal tissue.

GelMA loaded with platelet lysate promotes skin regeneration and angiogenesis in pressure ulcers by activating STAT3

Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL’s therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.

Glycogen Phosphorylase Inhibitor Promotes Hair Growth via Protecting from Oxidative-Stress and Regulating Glycogen Breakdown in Human Hair follicles.

Hair growth cycles are mainly regulated by human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). Protecting hDPCs from excessive oxidative stress and hORSCs from glycogen phosphorylase (PYGL) is crucial to maintaining the hair growth phase, anagen. In this study, we developed a new PYGL inhibitor, Hydroxytrimethylpyridinyl Methylindolecarboxamide (HTPI) and assessed its potential to prevent hair loss. HTPI reduced oxidative damage, preventing cell death and restored decreased level of anagen marker ALP and its related genes induced by hydrogen peroxide in hDPCs. Moreover, HTPI inhibited glycogen degradation and induced cell survival under glucose starvation in hORSCs. In ex-vivo culture, HTPI significantly enhanced hair growth compared to the control with minoxidil showing comparable results. Overall, these findings suggest that HTPI has significant potential as a therapeutic agent for the prevention and treatment of hair loss.

Electrospun 3D multi-scale fibrous scaffold for enhanced human dermal fibroblasts infiltration

Electrospun polymeric nanofibrous scaffold possesses significant potential in the field of tissue engineering due to its extracellular matrix mimicking topographical features that modulate a variety of key cellular activities. However, traditional two-dimensional (2D) electrospun scaffolds are generally close-packed fiber mats which prohibit cell infiltration and proliferation. Consequently, the applications of electrospun scaffolds in regenerative medicine are limited. In this study, we detail the use of a needle collector to fabricate three-dimensional (3D) electrospun poly-&amp;epsilon;-caprolactone (PCL) scaffolds with multi-scale fiber dimensions. The resultant pore size is 4 times larger than conventional 2D electrospun scaffolds with interweaving micro (3.3 &amp;plusmn; 0.6 &amp;micro;m) and nano (240 &amp;plusmn; 50 nm) fibers. The scaffold was surface modified by grafting with gelatin molecules. It was found that surface modification significantly improved human dermal fibroblasts (HDFs) cell infiltration throughout the 3D multi-scale scaffold. Even after an extended culture period of up to 28 days, cell proliferation was well supported in the surface-modified 3D multi-scale scaffold as confirmed by Ki67 staining. Extracellular matrix proteins secreted by the HDFs was evident on the 3D multi-scale PCL scaffold showing promising potential to facilitate tissue regeneration, in particular dermal tissue engineering.

A Natural deep eutectic solvent as an effective material for dual debridement and antibiofilm effects in chronic wound treatment

In chronic wound treatment, the debridement of devitalized tissue and the eradication of the biofilm must balance aggressiveness with care to protect regenerating tissues. In this study, urea, a potent chaotropic molecule, was modulated through the formation of a Natural Deep Eutectic Solvent (NADES) with betaine to develop a new debriding material (BU) suitable for application into injured dermal tissues. To evaluate BU’s debriding capacity, along with its antibiofilm effect and biocompatibility, pre-clinical to clinical methods were employed. In vitro determinations using artificial and clinical slough samples indicate that BU has a high debriding capacity. Additionally, BU’s de-structuring effects lead to a strong antibiofilm capability, demonstrated by a reduced bacterial load compared to the antiseptic PHMB-Betaine or medical honey, evaluated in artificial slough and ex vivo human skin. Furthermore, BU’s efficacy was evaluated in a murine model of diabetic wound, demonstrating significant effects on debriding and antibiofilm capacity, similar to those observed in PHMB-Betaine and medical honey-treated animals. Finally, BU was clinically evaluated in leg ulcers, showing superiority in reduction of bacterial load and wound area compared to honey, with no adverse effects. Thus, BU represents a simple and non-biocidal option that could contributes to chronic wound care.

Cellulose nanocrystal-stabilized Pickering emulsion gels as vehicles for follicular delivery of minoxidil

Minoxidil (MXD) is the only topical over-the-counter medicine approved by the United States Food and Drug Administration for the treatment of androgenetic alopecia. For the purpose of targeting the delivery of MXD to dermal papilla in the hair follicle, MXD Pickering emulsion gels were fabricated based on the designability of deep eutectic solvent (DES) and the versatility of cellulose nanocrystal (CNC) and sodium carboxymethyl cellulose (CMC-Na). Structural studies and theoretical calculations results suggest that CNC can stabilize the interface between the MXD-DES and water, leading to the formation of Pickering emulsions. The rheological properties and stabilities of MXD Pickering emulsions were enhanced through gelation using CMC-Na, which highlights the good compatibility and effectiveness of natural polysaccharides in emulsion gels. Due to the particle size of emulsion droplets (679 nm) and the rheological properties of emulsion gel, the fabricated MXD formulations show in vivo hair regrowth promotion and hair follicle targeting capabilities. Interestingly, the MXD Pickering emulsion-based formulations exert therapeutic effects by upregulating the expression of hair growth factors. The proposed nanodrug strategy based on supramolecular strategies of CNC and CMC-Na provides an interesting avenue for androgenetic alopecia treatment.

The metabolites of Bifidobacterium longum BB536 alleviate DHT-damaged human dermal papilla cells by activating WNT/β-catenin signaling

Probiotics have numerous biological functions and clinical studies have reported that consuming probiotic foods could promote hair growth and hair follicle health. Bifidobacterium longum BB536 was selected to investigate the possibility of treating hair loss with Cell-Free Supernatant (CFS) of B. longum BB536 and the alleviation mechanism of CFS on dihydrotestosterone (DHT)-damaged human dermal papilla cells (HDPCs). The results showed that HDPCs treated with 10% CFS of B. longum BB536 for 24 h could significantly promote cell proliferation, repair cell damage, accelerate the process of cell cycle and increase the secretion of VEGF. The CFS of B. longum BB536 reduced the apoptosis rate of DHT-damaged HDPCs. In addition, it could reduce the level of pro-inflammatory factors and improve the alkaline phosphatase (ALP) activity. Metabolites of B. longum BB536 may increase the protein expression of Wnt10b, β-catenin and LEF-1 by activating Wnt/β-catenin signaling pathway and inhibit the expression of DHT-induced negative feedback factors DKK1 and GSK-3β, which alleviates the damage of DHT on HDPCs, some protein expression levels such as LEF-1 are close to minoxidil (common drugs for hair loss). So, metabolites of B. longum BB536 can be used as new treatment for hair loss due to its safety. This study provides theoretical basis for probiotics to prevent androgenic alopecia.