Effect on the Skin Microbiota of Oral Minocycline for Rosacea.

In the rosacea an unstable skin microbiota is significant for disease progression. However, data on the influence on the skin microbiota of treatment with systemic antibiotics are limited. This single-arm trial recruited patients with rosacea. Oral minocycline 50 mg was administered twice daily for 6 weeks. The lesions on the cheek and nose were sampled for 16S rRNA amplicon sequencing and metagenomic sequencing at baseline, 3 weeks and 6 weeks of treatment. Physiological parameters were detected using non-invasive instruments. After treatment, distribution of the Investigator Global Assessment scores changed significantly. For the skin microbiota, a notable increase in α-diversity and a shift of structure were observed after treatment. Treatment was accompanied by a reduction in the relative abundance of Cutibacterium and Staphylococcus, indicating negative correlations with increased bacterial metabolic pathways, such as butyrate synthesis and L-tryptophan degradation. The increased butyrate and tryptophan metabolites would be conducive to inhibiting skin inflammation and promoting skin barrier repair. In addition, the abundance of skin bacterial genes related to tetracycline resistance and multidrug resistance increased notably after antibiotic treatment.

Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.

Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor ß and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.

Biophysical and ultrasonographic changes in early patch/plaque stage of mycosis fungoides, compared with uninvolved skin.

BACKGROUND: The goal of this study was evaluation of the skin biophysical properties in early patch/plaque stage of mycosis fungoides (MF) and its comparison with uninvolved skin in order to gain a better understanding of the pathogenesis of diseases. MATERIALS AND METHODS: The stratum corneum hydration, transepidermal water loss (TEWL), surface friction, pH, sebum, melanin, erythema, temperature, elasticity parameters (R0, R2, R5), thickness, and echo density of epidermis and dermis were measured on lesions of 21 patients and compared with controls (average measures of uninvolved perilesional and symmetrical skins) by paired sample t test. RESULTS: Stratum corneum hydration (P < 0.001) and echo density of dermis (P = 0.044) were significantly lower, whereas pH (P-value = 0.007), erythema (P < 0.001), and melanin content (P = 0.007) were significantly higher in lesions. There was not any significant difference in TEWL, friction index, sebum, temperature, R0, R2, R5, thickness of epidermis and dermis, and echo density of epidermis between lesions and normal skin. CONCLUSION: Parapsoriasis/MF lesions are specified by a set of certain changes in biophysical properties which are mainly correlated with histological changes. These sets of alterations may help in noninvasive, early diagnosis of parapsoriasis/MF.

Skin trophicity improvement by mechanotherapy for lipofilling-based breast reconstruction postradiation therapy.

BACKGROUND: Post-mastectomy irradiation severely impairs skin trophicity resulting in poor prosthetic implant outcome. Autologous fat grafting improves skin quality allowing minimally invasive approach with prosthetic reconstruction. Here, we report our pilot experience of preoperative mechanotherapy to optimize lipofilling and subsequent prosthetic reconstruction outcome. METHODS: We retrospectively included 65 women that had breast reconstruction using autologous fat grafting and implant placement from 2012 to 2018 benefiting or not from mechanotherapy before the reconstructive procedure. Demographic and surgical outcomes were recorded. RESULTS: The volume of fat injected was significantly superior in the mechanotherapy group compared with the controls for the first and second lipofilling (259.3 mL vs 150.6 mL and 251.8 mL vs 154 mL, respectively). Sixteen patients among controls required a pre-expansion prosthesis compared with none in the endermology group. The prosthesis volume was smaller in the endermology group. Six patients in the endermology group had a reconstruction without prosthesis. The aesthetic score evaluated by patients was 4.8 with no statistically significant difference between the two groups. CONCLUSION: Preoperative skin mechanotherapy and postoperative skin mechanotherapy increase skin compliance. It is associated with a higher volume of fat injection and lower prosthesis volume. If confirmed in a prospective study, endermology could become a standard in patients' preparation for lipofilling-based reconstruction.

Rosacea is associated with conjoined interactions between physical barrier of the skin and microorganisms: A pilot study.

BACKGROUND: Rosacea is a common condition characterized by transient or persistent central facial erythema, and often papules and pustules. Currently, the role of bacterium in the development and progression of rosacea remains controversial. This study aimed to investigate the difference in the physiological conditions and microorganisms between the lesional and non-lesional areas of papulopustular rosacea. METHODS: Twenty-five French patients with papulopustular rosacea were enrolled in this pilot study. Each patient was subjected to clinical assessment, and the skin barrier function was tested in lesional and non-lesional areas. In addition, samples from the lesional and non-lesional areas were collected for bacterial culturing. RESULTS: Of all subjects included in the study, a lower skin conductivity was measured in lesional areas than in non-lesional areas (43.5 ± 12.4 vs. 57.2 ± 11.6 U, P < .05), and a higher transepidermal water loss (TEWL) value was found in lesional areas than in non-lesional areas (17.2 ± 5.9 vs. 14.2 ± 4.1 g/(m2  h), P < .05). We found a lower TEWL in lesions in rosacea patients with bacterial dysbiosis than in those with bacterial balance (P < .05). In addition, there were significant differences in the skin conductivity and TEWL between lesional and non-lesional areas in patients with bacterial dysbiosis (P < .001), and no significant differences were seen in patients with bacterial balance (P < .05). CONCLUSION: The results of the present study demonstrate that the physiological features of rosacea are closely associated with the interactions between the host and the microorganisms.

Comparison of biophysical, biomechanical and ultrasonographic properties of skin in chronic dermatitis, psoriasis and lichen planus.

Background: Skin biometrology is a useful method for evaluation of inflammatory skin disorders such as dermatitis, psoriasis, and lichen planus. The current study tries to compare the biophysical features of skin in dermatitis, psoriasis, and lichen planus. Methods: By a convenient sampling method, 22 mild to moderate chronic dermatitis, 26 psoriasis, and 21 lichen planus patients were recruited in the study. Stratum corneum (S.C.) hydration, Transepidermal water loss (TEWL), pH, erythema, melanin, sebum, friction, elasticity parameters (R0, R2, and R5), skin temperature, skin thickness, and echo-density of epidermis and dermis were measured on the lesional (selected active lesion), uninvolved perilesional, and uninvolved symmetrical skin. The average of perilesional and symmetrical uninvolved parameters was used as control, while the percentage change of each parameter [(lesion - control / control) ×100] was calculated, and compared among three diseases by ANOVA test using SPSS software version 18. The significance level was set at α=0.05. Results: Comparison of percentage changes showed that the changes in TEWL, friction index, sebum content, R2 (gross elasticity), R5 (net elasticity), skin temperature, dermal thickness, and epidermal density are not significantly different among three skin diseases. But there were significant differences in three diseases considering the decrease in S.C. hydration (p<0.001), R0 (opposed to firmness) (p<0.001), and dermal density (p<0.001) compared to control skin. Moreover, the increase in skin pH (p<0.001), melanin content (p=0.048), erythema (p=0.023), and epidermal thickness (p <0.001) significantly differed among these diseases. Conclusion: Dermatitis, psoriasis and lichen planus lesions had specific biophysical changes. It may be helpful in their differential diagnosis.

Biological processes in solar lentigo: insights brought by experimental models.

Common in ageing patient, the solar lentigo is a macular hyperpigmented skin lesion that results from chronic exposure to ultraviolet irradiations. Despite sharing numerous features with other pigmented spots, the diagnostic of this benign lesion is well characterized at the tissue level. Recent studies shed lights on several factors and their pathogenic mechanisms involved in the development of the solar lentigo. This review summarizes how diverse experimental approaches allowed the identification of several biomarkers, which contribute to a better understanding on the initiation and the maintenance of this pigmentary disorder.

The topical corticosteroid classification called into question: towards a new approach.

Vasoconstrictor assay described in 1962 was an interesting assessment of potency of topical corticosteroids at the beginning of these new therapies, however knowledge and technology have evolved and the classification should follow. A topical corticosteroids with a strong vasoconstrictor effect, as determined by vasoconstrictor assay, has not necessary a strong anti-inflammatory effect. Therefore a specific classification adapted to the therapeutic target is needed to be more efficient and thus reduce side effects and corticophobia.

Effects of anti-TNF-α agents on circulating endothelial-derived and platelet-derived microparticles in psoriasis.

Psoriasis involves TNF-α secretion leading to release of microparticles into the bloodstream. We investigated the effect of TNF blockers on microparticles levels before and after treatment in patients (twenty treated by anti-TNF-α agents and 6 by methotrexate) with severe psoriasis. Plasmatic microparticles were labelled using fluorescent monoclonal antibodies and were analysed using cytometry. Three months later, 70% of patients treated with anti-TNF-α agents achieved a reduction in PASI score of at least 75%. The clinical improvement in patients treated with anti-TNF-α agents was associated with a significant reduction of the mean number of platelet microparticles (2837/µl vs 1849/µl, P = 0.02) and of endothelial microparticles (64/µl vs 22/µl, P = 0.001). Microparticles are significantly decreased in psoriatic patients successfully treated by anti-TNF-α. Microparticles levels as circulating endothelial cells represent signs of endothelial dysfunction and are elevated in psoriasis. Then, TNF blockade may be effective to reduce cardiovascular risk through the reduction of circulating microparticles.

Lack of expression of an alternative CD20 transcript variant in circulating B cells from patients with pemphigus.

We have identified a spliced mRNA transcript of CD20 (named D393-CD20) which was associated with resistance to RTX in primary B cell from patients with lymphoma and leukaemia. In the present work, we wished to investigate whether D393-CD20 variant was expressed by B cells from patients with pemphigus. Ten patients with bullous pemphigoid and twenty-five patients with pemphigus were included. All patients were responder to conventional immunosuppressive agents or rituximab (n = 11). Efficacy of B-cell activation by pokeweed mitogen was assessed by CD86 expression using a FACS Canto II flow cytometer. mRNA CD20 expression study was then performed using RT-PCR assay allowing first to discriminate wild-type (wt)-CD20 and D393-CD20 transcript. Although wt-CD20 expression was always detected, we were unable to detect D393-CD20, even after B-cell activation or RTX treatment. Our results suggest that D393-CD20 transcript may be a molecular marker of B-cell malignancies rather than autoimmune disease like pemphigus. Further study of RTX non-responders or non-escaping PV patients is thus still required to appreciate whether D393-CD20 expression may be detected under the pressure of RTX therapy.

Influence of skin extension upon the epidermal morphometry, an in vivo study.

BACKGROUND: The Dermal-Epidermal Junction (DEJ) is characterized by undulations whose apices are called papillae. With aging, epidermis becomes thinner, together with a flattening of the DEJ, leading to a decreased density of papillae. The causes of these modifications are likely as multiple as uncertain. The present paper deals with in vivo morphometric characterization of the DEJ and its changes following a skin surface deformation. METHODS: Living epidermis of human adults was examined by means of in vivo Reflectance Confocal Microscopy. Distances between skin surface and papillae apex and pegs of the DEJ were, respectively, recorded in both relaxed and stretched skin situation. The number of papillae present within a single image (field of view, 500 × 500 µm) was also measured. RESULTS: Skin extension has no effect upon the distance between skin surface and the apex of papillae. In contrast, the distance between skin surface and the pegs of papillae decreases. On the other hand, skin extension leads to a significant decrease in the number of papillae within a single image. CONCLUSION: Epidermal atrophy and structural changes observed in the DEJ with aging may be, by some extent, related to daily and repetitive skin deformations all along the life span.

A skin substitute based on human amniotic membrane.

Human amniotic membrane (HAM) has biological properties which are useful for wound healing. HAM is notably one of the therapeutic alternatives for venous leg ulcer care. Indeed, a prospective clinical study has demonstrated that cryopreserved HAM transplantation for leg ulcer is feasible, safe and has beneficial effects: 80 % of the patients had a significant clinical response. Nevertheless, at the end of the 3-month follow-up period, only 20 % of the ulcers were totally closed. The aim of this work was to create and characterize a model of epidermized HAM. The method of HAM desepithelialization was validated by histology, immunohistochemistry and scanning electron microscopy. Then, de-epithelialized HAM was seeded with primary keratinocytes. After 21 days of culture, 15 at the air-liquid interface, the model obtained was analyzed histologically and by immunohistochemistry. The amniotic basement membrane was preserved during enzymatic desepithelialization of HAM. Primary keratinocytes proliferated on HAM: the model obtained showed involucrin expression and had a good basement membrane. As re-epithelialization is an important step for ulcer closure, a model of epidermized HAM could be used to speed up the healing of such wounds.

Exploratory study of the typology of various grades of mature skin.

BACKGROUND: Post-menopausal skin aging has intrinsic as well as extrinsic origins, and this process induces important disparities of appearance and feeling within an age range. OBJECTIVE: The objective of this study was to identify 3 grades of maturity of the facial skin of menopausal women. MATERIAL AND METHOD: One hundred and fifty women aged between 50 and 80 (63 ± 7 years) were enrolled. The investigations combined clinical scoring, biometrological measurements (corneometry, cutometry, digital photography, and 3D analysis by fringe projection), and questionnaires. Images elaborated from photographs and 3D views were scored by 2 investigators to classify the subjects according to 3 grades of skin maturity. RESULTS: STEPDISC statistical analysis revealed that the most relevant variables to differentiate the maturity grades were elastosis, wrinkles on the cheeks, wrinkles on the upper lip, roughness, spots, and elasticity. CONCLUSION: The age does not reveal the degree of maturity of mature skin. Three grades of skin maturity in menopausal women, based on clinical and physiological patterns, have been differentiated in this study. Cosmetic treatments specifically adapted to the needs of menopausal women can therefore be developed.

Dermal equivalents in oncology: benefit of one-stage procedure.

BACKGROUND: In oncology, dermal equivalent may be indicated to cover losses of substance related to skin tumors or after the removal of skin flaps. OBJECTIVE: To report our experience of two dermal equivalents, Matriderm 1 mm with a one-stage graft (DE1) and Integra DL with a two-stage graft (DE2) in oncology. PATIENTS AND METHOD: Retrospective, single-center study involving 16 patients. RESULTS: Sixteen patients received dermal equivalents as an alternative to flaps (7 cases), over tendinous areas (7 cases), and for cosmetic purposes (2 cases). Twelve patients received DE1 and four DE2. Wound healing times with DE1 were 4 weeks less than those with DE2. Three cases of infection were noted with DE2. The use of dermal equivalents as an alternative to skin flaps was effective, and no adhesions were found over the tendinous areas. CONCLUSION: The learning curve, the two-stage graft required with DE2, and not using a vacuum-assisted closure system can explain the high infection rate. The use of dermal equivalents is particularly indicated in the treatment of skin defect in oncology. The possibility of a one-stage graft with DE1 and combination with negative pressure therapy is beneficial.

Clinical equivalence of conventional OnabotulinumtoxinA (900 KDa) and IncobotulinumtoxinA (neurotoxin free from complexing proteins - 150 KDa): 2012 multidisciplinary French consensus in aesthetics.

Botulinum neurotoxins are the most popular non-surgical treatments for aesthetic indications, but there is uncertainty about whether certain formulations are comparable in efficacy and safety and can be substituted for one another by a simple one to one dose conversion ratio. An expert panel of French practitioners was convened to establish a consensus on the clinical equivalence in efficacy and safety of OnabotulinumtoxinA (900 KDa) and IncobotulinumtoxinA (neurotoxin free from complexing proteins - 150 KDa). The consensus was divided into three sections incorporating a biological, bibliographic and clinical analysis of the two toxins. This included a review of the published data that have directly compared the two toxins for aesthetic indications and a survey of the panel's extensive clinical experience with the two toxins in terms of efficacy and safety. All panel members reviewed and endorsed the content of each section. Among this expert panel of French aesthetic physicians and biologists there was consensus that OnabotulinumtoxinA and IncobotulinumtoxinA are clinically equivalent in terms of efficacy and safety, and that a switch from one drug to the other can be made using a simple 1:1 conversion ratio.

Efficacy and safety of a gauze pad containing hyaluronic acid in treatment of leg ulcers of venous or mixed origin: a double-blind, randomised, controlled trial.

Topical hyaluronic acid (HA) is routinely used in the local treatment of chronic wounds, but few data have been reported to date. A 60-day double-blind, randomised, controlled superiority trial was designed to investigate the efficacy and safety of a gauze pad containing HA in local treatment of venous leg ulcers, compared with its neutral vehicle. The primary endpoint was the percentage of wound size reduction after 45 days. Totally 89 patients were included. At day 45, the percentage of ulcer surface reduction was significantly greater in the HA group (73 ± 4·6%) versus neutral vehicle group (46 ± 9·6%) (P = 0·011). The number of healed ulcers was significantly higher in the HA group at day 45 (31·1% versus 9·3% respectively) and day 60 (37·8% versus 16·3% respectively; P < 0·05). At day 30, pain intensity based on visual analogue scale was significantly lower in the HA group (12·4 mm ± 2·6 versus 22·8 mm ± 3·8; P = 0·026). Tolerance of both treatments was comparable in the two groups. HA gauze pad, in local treatment of venous leg ulcers, was significantly more effective than the neutral vehicle on wound size reduction, healed ulcers rate and pain management with a good safety profile.

Evaluation of the Performance and Tolerance of the Combination of an HA-based Filler with Tri-Hyal Technology and a Skin Biorevitalizer on Skin Aging Parameters.

Background: Biorevitalization solutions contain numerous nutritive compounds to improve skin quality. Dermal fillers like HA (hyaluronic acid), depending on rheological characteristics, are used to fill large static defaults with a sustained long-term efficacy. Treatments with either dermal filler or biorevitalization solutions alone are not enough to bring a global facial aging approach. Objective: To demonstrate the anti-aging performance and safety of a new protocol, BIONUTRILIFT, which combined an HA-based filler with Tri-Hyal technology and a skin biorevitalizer, to target the skin quality and wrinkles correction at the same time. Materials and Methods: Eligible subjects were enrolled based on a score of 2, 3, 4, or 5 on Bazin cheek folds wrinkle scale. Safety outcomes measured were immediate and local tolerability. Performance outcomes measured included: proportion of subjects in whom the severity of cheeks folds, nasolabial folds, marionette lines, upper lip wrinkles and skin radiance remained at least one point below the baseline measurement (Bazin scale) Global Aesthetic Improvement Scale scores by subjects and investigators. Results: In performance analyses with the combined protocol, skin radiance and cheek folds wrinkle correction sustained during the four-month study and decrease by 61% and 55%, respectively. 96% and 77% of subjects respectively showed at least a one-point decrease in the mean skin radiance score and Bazin score compared with baseline. Interestingly, the BIONUTRILIFT protocol showed the distance effect of vector A (cheek injection) and vector B (mandibular injection) on perioral zone and remained significant even 120 days after injections. Adverse events (AEs) were consistent with the expected AEsthat occurred after dermal injections. No serious AEswere recorded. Conclusion: BIONUTRILIFT may satisfy the subjects' demand by obtaining in the same session a simple, personalized, noninvasive, atraumatic, and reproductible technique.

Effects of Investigational Moisturizers on the Skin Barrier and Microbiome following Exposure to Environmental Aggressors: A Randomized Clinical Trial and Ex Vivo Analysis.

The skin microbiota barrier participates in skin barrier function in addition to the physical, chemical, and immunological protective barriers, and is affected by environmental aggressors and skincare regimens. To better understand the exact effects of real-life environmental conditions on the skin and determine the protective methods, this study investigates the effects of three topical cosmetic moisturizers (water gel moisturizers with/without yeast extract (Moisturizers K and C) and a thick-emulsion cream moisturizer (Moisturizer L)) on clinical and skin microbiome endpoints in the presence of environmental aggressors during an 8-week, randomized controlled, triple-blind clinical trial with 110 participants, and molecular- as well as biomarker-level endpoints on ex vivo skin explants after exposure to simulate urban environmental conditions. The results show that all moisturizers are well-tolerated and improve skin barrier function and surface moisture content from the baseline, and the improvement is maintained at the last analysis point (3 days after trial completion). Compared with the untreated control areas (samples taken from the upper chest), treatment with Moisturizer K prevented a reduction in bacterial and fungal richness, and increased the change ratio of the relative abundance of commensal bacteria, such as Staphylococcus epidermidis and Ralstonia, at the treated sites (samples taken from the forehead). Moreover, Moisturizer K-treated ex vivo skin explants had higher levels of caspase 14 (a marker of skin barrier function), collagen I, and elastin (structure components), and lower levels of aryl hydrocarbon receptor (AHR; activated by air pollutants) and interleukin-6 (IL-6) than those in explants treated with other moisturizers and in the untreated areas of the skin. These results suggest that a skin postbiotic moisturizer with yeast extract supports the regulation of the skin's microbiome balance and may provide a holistic barrier (involving skin microbiome, physical, chemical, and immune barriers) to protect the skin against environmental aggressors.

Polymeric Nanoparticles' Accumulation in Atopic Dermatitis: Clinical Comparison between Healthy, Non-Lesional, and Lesional Skin.

A major limitation in the current topical treatment strategies for inflammatory skin disorders is the inability to selectively target the inflamed site with minimal exposure of healthy skin. Atopic dermatitis is one of the most prevalent types of dermatitis. The use of polymeric nanoparticles for targeting inflamed skin has been recently proposed, and therefore the aim of this proof-of-concept clinical study was to investigate the skin penetration and deposition of polymeric biodegradable nanoparticles in the atopic dermatitis lesions and compare the data obtained to the deposition of the particles into the healthy skin or lesion-free skin of the atopic dermatitis patients. For that, fluorescent PLGA nanoparticles in sizes of approximately 100 nm were prepared and applied to the skin of healthy volunteers and the lesional and non-lesional skin of atopic dermatitis patients. Skin biopsies were examined using confocal laser scanning microscopy to track the skin deposition and depth of penetration of the particles. Immunohistochemistry was performed to investigate the alteration in tight-junction protein distribution in the different types of skin. Results have shown that nanoparticles were found to have higher deposition into the atopic dermatitis lesions with minimal accumulation in healthy or non-lesional skin. This has been primarily correlated with the impaired barrier properties of atopic dermatitis lesions with the reduced production of Claudin-1. It was concluded that polymeric nanoparticles offer a potential tool for selective drug delivery to inflamed skin with minimal exposure risk to healthy skin.

Role of neurotrophins on dermal fibroblast survival and differentiation.

Neurotrophins (NTs) belong to a family of growth factors that play a critical role in the control of skin homeostasis. NTs act through the low-affinity receptor p75NTR and the high-affinity receptors TrkA, TrkB, and TrkC. Here we show that dermal fibroblasts (DF) and myofibroblasts (DM) synthesize and secrete all NTs and express NT receptors. NTs induce differentiation of DF into DM, as shown by the expression of α-SMA protein. The Trk inhibitor K252a, TrkA/Fc, TrkB/Fc, or TrkC/Fc chimera prevents DF and DM proliferation. In addition, p75NTR siRNA inhibits DF proliferation, indicating that both NT receptors mediate DF proliferation induced by endogenous NTs. Autocrine NTs also induce DF migration through p75NTR and Trk, as either silencing of p75NTR or Trk/Fc chimeras prevent this effect, in absence of exogenous NTs. Finally, NGF or BDNF statistically increase the tensile strength in a dose dependent manner, as measured in a collagen gel through the GlaSbox device. Taken together, these results indicate that NTs exert a critical role on fibroblast and could be involved in tissue re-modeling and wound healing.