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Facial Skin Density Enhancement Using Hyaluronic Acid—Based Bioactive Hydrogel: Cannula-Assisted Delivery and Ultrasound Evaluation in a Retrospective Controlled Study
Pharmaceutics
Abstract
Background: Hyaluronic acid (HA) – based bioactive hydrogels have emerged as multifunctional platforms for skin bioregeneration. While traditional mesotherapy using multicomponent substances has been widely practiced for improving skin quality, the time-consuming nature of this approach has led to exploration of alternative delivery methods. Aims: This study evaluated the clinical effectiveness of an HA bioactive hydrogel-based bioregeneration system (containing non-stabilized hyaluronic acid and 14 bioactive ingredients) administered via cannula and its impact on facial skin density as assessed by ultrasound imaging. Methods: We conducted a retrospective review of data from 20 female patients aged 30–42 years who received a single cannula-delivered injection of a bioactive hyaluronic acid hydrogel (TEOSYAL® Redensity [I]) in the midface region. The formulation combines the structural benefits of hyaluronic acid with the biochemical stimulation provided by amino acids, antioxidants, minerals, and vitamins. Skin density was measured using high-frequency ultrasound at baseline, immediately post-procedure, and at 3–4 weeks follow-up. A control group of seven individuals received no treatment. Results: Ultrasound assessments revealed a statistically significant increase in skin density (92.7%, p < 0.001) within the treated area compared to no significant changes in the control group. This substantial improvement in dermal architecture demonstrates the efficacy of bioactive hydrogels in stimulating fibroblast function and extracellular matrix regeneration. Patient satisfaction was high, with 85% of patients reporting being satisfied or very satisfied. Side effects were minimal, with minor bruising (10%) and transient swelling (15%). Conclusions: Cannula-delivered bioactive hyaluronic acid hydrogel effectively enhances facial skin density with high patient satisfaction and minimal downtime, demonstrating the potential of advanced hydrogel formulations as multifunctional therapeutic platforms that extend beyond traditional applications into aesthetic and regenerative dermatology.
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Objective. This single-center, prospective, open-label randomized study aimed to produce a repeatable procedure for isolating platelet-rich plasma (PRP), maximizing platelet recovery and concentration parameters from the collected material, and to assess the effectiveness of autologous platelet-rich plasma (concentrated platelet rich plasma C-PRP and platelet rich plasma low centrifugation concept PRP LCC) and platelet-rich fibrin (injectable platelet rich fibrin I-PRF and fluid platelet rich fibrin F-PRF) injections on skin density and thickness in facial aesthetic treatments. Methods. Twenty participants aged 30–60 underwent a series of three treatments (intervals: 4–6 weeks). The study encompassed the following two stages: a laboratory and a clinical one. In the first stage, the aim was to optimize centrifugation parameters (time and speed) of whole blood to produce the highest quality product for use in aesthetic treatments. Double centrifugation of blood produced the following four types of plasma fractions with different parameters: platelet-rich plasma (C-PRP and PRP LCC) and platelet-rich fibrin (I-PRF and F-PRF) each with two different platelet concentrations (202% in the first centrifugation and 148% in the second centrifugation). The total PLT recovery in the procedure was 76%, with an average of 32% in the first centrifugation and that of 44% in the second one. In the clinical stage, treatments involved C-PRP, PRP LCC, I-PRF, and F-PRF injections in the forehead, lower eyelid, and cheek areas. In ultrasound skin examination with randomly assigned measurements for each patient, a series of acoustic density values directly proportional to tissue density was obtained. Thickness of the skin was also determined (µm) by summation of the epidermis and dermis thickness. Measurements were made in the lateral forehead, lower eyelids, and cheek regions. Results. Statistical analysis elucidates the effectiveness of blood-derivatives therapy in the introduced regiment. The increase in skin density was statistically significant after the following treatment: three sessions in 4–6 week intervals, each consisting of 1 mL of C-PRP injections in the forehead area, 1 mL of I-PRF injections in the lower eyelid area, and 3.5 mL of PRP LCC and 3.5 mL of F-PRF injections in the cheek area. Furthermore, significant improvements in skin density were recorded in the cheek and forehead areas (F(3, 24) = 4.5170 with p=0.011971 for cheeks and F(3, 24) = 9.2327 with p=0.000305 for forehead). Lower eyelid skin density and thickness also increased significantly (F(3, 24) = 3.2653, p=0.038881). No significant changes were noted in skin thickness in the forehead and cheek areas (F(3, 6) = 1.438771, p=0.321616 for cheeks; F(3, 6) = 2.383248, p=0.168172 for forehead). Patient satisfaction was high, as evidenced by a GAIS average score of 2.75. Conclusion. The study confirms the efficacy of C-PRP, PRP LCC and I-PRF, and F-PRF injections in increasing skin density and, to a lesser extent, skin thickness in specific facial areas. As a result of this research, ready-to-use kits (PLASMOO) for obtaining PRP and PRF were developed and put into production. These findings underscore the potential of autologous plasma and fibrin formulations in aesthetic medicine, which offer substantial improvements in skin quality and patient satisfaction. This trial is registered with ISRCTN10538865.
The primary aim of this retrospective study was to investigate the potential effectiveness of autologous platelet gel as a method for facial volume restoration and skin rejuvenation. High-frequency ultrasonography was utilized to assess the outcomes of the treatment. The study included a cohort of ten female patients aged between 40 and 50 who actively participated in the research. They reported moderate-to-severe static and dynamic wrinkles, volume loss, thinning, and roughness of the skin. Each patient received one session of autologous platelet gel injections. The gel was prepared accordingly with the manufacturer’s (INNMEDIS, ATR™) instructions. Medium viscosity gel was injected into the superficial subdermal fat pads in the temples, as well as in the middle and lower face areas, to improve facial volume. A high-frequency ultrasound (US) device was employed to quantify skin density, skin thickness, and the depth of nasolabial folds. The US images were captured at three time points: before gel administration, one month after the procedure, and three months after the procedure. The imaging focused on the nasolabial folds area to monitor changes and assess the effectiveness of the treatment over time. Based on the analyses, the use of autologous platelet gel is beneficial towards improving skin density and decreasing nasolabial fold depth. However, further research should be conducted into the gel’s effects on dermis thickness to achieve a stronger, more statistically significant conclusion. The level of satisfaction of the enrolled patients regarding their facial appearance was evaluated using the visual analogue scale (VAS). The VAS assessment revealed an average score of 4.1 before the commencement of the treatment, an average score of 7.9 one month after the treatment, and an average score of 7.5 three months following the treatment. The results indicate a significant increase in patient satisfaction following treatment completion. Autologous platelet gel appears to hold promise as a treatment option for volume replacement and skin rejuvenation, making it an attractive choice for individuals seeking natural skin treatments. Despite the encouraging findings from this observation, further validation is required through a larger controlled study to definitively confirm whether autologous platelet gel is indeed an effective method for volume replacement and skin rejuvenation.
Introduction
Nowadays patients want to get an immediate result from skin rejuvenation techniques without sign of injections and consequent limitations in social life. Therefore, the least traumatic, more effective, and longer lasting treatment approach for skin quality improvement should be favored.
Purpose
Assess skin quality outcomes by clinical examination and self-reporting in patients treated with two non-crosslinked hyaluronic acid (HA) products, injected by cannula. Investigate the skin thickness and the longevity of dermal fillers in soft tissues by ultrasound examination.
Patients and Methods
Fifteen female patients (mean age 41 years) were selected for injection with two non-crosslinked HA products (one for each hemiface and hemi neck). Subdermal injections were performed bilaterally and the retrograde linear fanning technique with a 25G 50 mm cannula from three entry points was used. An ultrasound examination of the skin layers thickness was carried out before the procedure and every 6–7 days up to three weeks, when patients skin quality improvement was assessed by GAIS (Global Aesthetic Improvement Scale) and patients asked about their satisfaction level.
Results
On the right hemiface, the use of the non-crosslinked HA-product with lidocaine was not associated with pain in the sites of injection. On both face sides, the signs of bruising or edema were minor and not associated with downtime or social life limitation after the procedure. After three weeks, despite both injected products could not be detected by ultrasound technique, signs of skin stimulation and skin layers hydration were still observed: The dermis became thicker on both hemifaces while the epidermis became thinner but showed more pronounced radiance and densification effect on the right hemiface.
Conclusion
Subdermal injections of non-crosslinked HA “skin boosters” could be a good option for minimal traumatic and effective 3-week lasting skin quality improvement.
Hyaluronic acid (HA) is a glycosaminoglycan widely distributed in the human body, especially in body fluids and the extracellular matrix of tissues. It plays a crucial role not only in maintaining tissue hydration but also in cellular processes such as proliferation, differentiation, and the inflammatory response. HA has demonstrated its efficacy as a powerful bioactive molecule not only for skin antiaging but also in atherosclerosis, cancer, and other pathological conditions. Due to its biocompatibility, biodegradability, non-toxicity, and non-immunogenicity, several HA-based biomedical products have been developed. There is an increasing focus on optimizing HA production processes to achieve high-quality, efficient, and cost-effective products. This review discusses HA’s structure, properties, and production through microbial fermentation. Furthermore, it highlights the bioactive applications of HA in emerging sectors of biomedicine.
The objective of this retrospective study was to verify with the use of high-frequency ultrasonography whether Platelet-Rich Fibrin (PRF) can increase skin density and become an effective method of skin revitalization as well as to determine an optimal procedure protocol for the use of Platelet-Rich Fibrin to revitalize skin of the periorbital region. Ten patients (women, age 32–45) were assigned for the observation. They reported thinning and wrinkles of the skin in the periorbital area. For each individual two vials (18 mL) of peripheral blood were collected and placed in preprogrammed centrifuge ( 60 g , 3 minutes). After centrifugation injectable-PRF (i-PRF, 2 mL) was collected and injected intradermally in the periorbital area, using the mesotherapy technique with 4 mm 30 G needles. The patients underwent four procedures in one month intervals. A high-frequency ultrasound device was used to measure skin density. Skin density analyses were performed before PRF administration, a month after the second and a month after the third procedure in the crow’s feet area. The results demonstrated an increase in skin density in all patients after just one procedure: on average it was 1.66 times higher compared to the baseline after the second and 5.08 times higher after the third treatment which was visualized using the DUB SkinScanner imaging. The enrolled patients’ satisfaction with their facial skin appearance was measured with the visual analogue scale (VAS). Digital photographs were taken before the first treatment and a month after the last treatment. The VAS assessment results were as follows: the average score before the treatment was 4 and the average score after the treatment was 8.5, indicating a significant increase in patient satisfaction. i‐PRF seems to be a promising treatment modality for skin rejuvenation in the periorbital area and might be a solution for those seeking natural methods. Although the results of this observation are very promising, there is need for larger controlled research to definitely confirm Platelet-Rich Fibrin efficacy in the skin revitalization processes.
Purpose
Cannulas are increasingly used for injecting hyaluronic acid fillers, as they are thought to improve patient comfort safety and treatment tolerability. This study aimed to demonstrate the non-inferiority of a Resilient Hyaluronic Acid 4 (RHA 4) filler injected with a cannula versus a needle for the treatment of moderate to severe nasolabial folds (NLF).
Patients and Methods
A total of 50 subjects were included in a randomized, evaluator-blinded, split-face trial. The NLF were injected with RHA 4 using a cannula on one side of the face and using a needle on the other side on Day 0. A touch-up could be performed 4 weeks later. The subjects were followed up for 12 weeks after the last injection, ie, injection on Day 0 or touch-up. Efficacy was evaluated using a Wrinkle Severity Rating Scale (WSRS), the Global Aesthetic Improvement Scale (GAIS), and patient-reported outcomes. Safety assessments included the injection-site pain, common treatment reactions (CTRs), and adverse events (AEs).
Results
Twelve weeks after the last injection, the efficacy of the cannula treatment was found to be non-inferior to that of the needle treatment, based on the WSRS score improvements. The other study endpoints showed the equivalent efficacy and safety of the two methods. No serious or unexpected AEs were reported.
Conclusion
RHA 4 may be effectively and safely injected into the NLF using a cannula or a needle, provided it is administrated by a trained practitioner.
Objective:
The aim of this investigation was to assess the effectiveness of a combined treatment with stabilized and non-stabilized HA soft tissue fillers in the correction of midfacial volume and improving skin condition in the treated area.
Materials and methods:
A total of 10 Caucasian female patients participated in the study, with a mean age of 42,2 years. They received stabilized and non-stabilized HA soft tissue fillers in the midface. Non-stabilized HA soft tissue filler was placed unilaterally. Skin density and thickness were measured with an ultrasound device. Aesthetic improvement and patient satisfaction were also assessed 3 weeks post treatment.
Results:
side treated with stabilized and non-stabilized HA showed 65,40% increase in skin density versus the baseline and 7,02% increase in skin thickness versus the baseline. Side treated with stabilized HA showed 26,55% increase in skin density versus the baseline and 4,83% increase in skin thickness versus the baseline. After 3 weeks 62,5% of the patients stated that they were satisfied with the treatment and 37,5% of the patients were very satisfied with the treatment.
Conclusion:
skin density and thickness significantly increased in the treated regions. Combined therapies based on stabilized and non-stabilized HA soft tissue fillers appear to be an optimal solution for facial volume and skin quality enhancement and seem to be more effective than stabilized HA soft filler alone. The procedure is safe and satisfactory to the treated subjects. This article is protected by copyright. All rights reserved.
Skin aging is one of the most evident signs of human aging. Modification of the skin during the life span is characterized by fine lines and wrinkling, loss of elasticity and volume, laxity, rough-textured appearance, and pallor. In contrast, photoaged skin is associated with uneven pigmentation (age spot) and is markedly wrinkled. At the cellular and molecular level, it consists of multiple interconnected processes based on biochemical reactions, genetic programs, and occurrence of external stimulation. The principal cellular perturbation in the skin driving senescence is the alteration of oxidative balance. In chronological aging, reactive oxygen species (ROS) are produced mainly through cellular oxidative metabolism during adenosine triphosphate (ATP) generation from glucose and mitochondrial dysfunction, whereas in extrinsic aging, loss of redox equilibrium is caused by environmental factors, such as ultraviolet radiation, pollution, cigarette smoking, and inadequate nutrition. During the aging process, oxidative stress is attributed to both augmented ROS production and reduced levels of enzymatic and non-enzymatic protectors. Apart from the evident appearance of structural change, throughout aging, the skin gradually loses its natural functional characteristics and regenerative potential. With aging, the skin immune system also undergoes functional senescence manifested as a reduced ability to counteract infections and augmented frequency of autoimmune and neoplastic diseases. This review proposes an update on the role of oxidative stress in the appearance of the clinical manifestation of skin aging, as well as of the molecular mechanisms that underline this natural phenomenon sometimes accelerated by external factors.
Hyaluronic acid (HA) plays multifaceted role in regulating the various biological processes such as skin repairmen, diagnosis of cancer, wound healing, tissue regeneration, anti-inflammatory, and immunomodulation. Owing to its remarkable biomedical and tissue regeneration potential, HA has been numerously employed as one of the imperative components of the cosmetic and nutricosmetic products. The present review aims to summarize and critically appraise recent developments and clinical investigations on cosmetic and nutricosmetic efficacy of HA for skin rejuvenation. A thorough analysis of the literature revealed that HA based formulations (i.e., gels, creams, intra-dermal filler injections, dermal fillers, facial fillers, autologous fat gels, lotion, serum, and implants, etc.) exhibit remarkable anti-wrinkle, anti-nasolabial fold, anti-aging, space-filling, and face rejuvenating properties. This has been achieved via soft tissue augmentation, improved skin hydration, collagen and elastin stimulation, and face volume restoration. HA, alone or in combination with lidocaine and other co-agents, showed promising efficacy in skin tightness and elasticity, face rejuvenation, improving aesthetic scores, reducing the wrinkle scars, longevity, and tear trough rejuvenation. Our critical analysis evidenced that application/administration of HA exhibits outstanding nutricosmetic efficacy and thus is warranted to be used as a prime component of cosmetic products.
There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life-and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant Solidago virgaurea subsp. alpestris, which exhibited weak senolytic activity, delayed the acquisition of a senescent phenotype and induced a papillary phenotype with improved functionality in human dermal fibroblasts. When administered to stress-induced premature senescent fibroblasts, this extract changed their global mRNA expression profile and particularly reduced the expression of various SASP components, thereby ameliorating the negative influence on nearby cells. Thus, the investigated plant extract represents a promising possibility to block age-related loss of tissue functionality.
The dermal extracellular matrix (ECM) comprises the bulk of skin and confers strength and resiliency. In young skin, fibroblasts produce and adhere to the dermal ECM, which is composed primarily of type I collagen fibrils. Adherence allows fibroblasts to spread and exert mechanical force on the surrounding ECM. In this state, fibroblasts display a “youthful” phenotype characterized by maintenance of the composition and structural organization of the dermal ECM. During aging, fibroblast-ECM interactions become disrupted due to fragmentation of collagen fibrils. This disruption causes loss of fibroblast spreading and mechanical force, which inextricably lead to an “aged” phenotype; fibroblasts synthesize less ECM proteins and more matrix-degrading metalloproteinases. This imbalance of ECM homeostasis further drives collagen fibril fragmentation in a self-perpetuating cycle. This article summarizes age-related changes in the dermal ECM and the mechanisms by which these changes alter the interplay between fibroblasts and their extracellular matrix microenvironment that drive the aging process in human skin.
Hyaluronic acid (HA) is used extensively in aesthetic medicine thanks to its documented role in skin rejuvenation. The specific applications of HA-based products are not always fully acknowledged due to a lack of consistent recommendations. In this paper, the authors have summarized available published data on the range of applications of non-animal stabilized hyaluronic acid (NASHA®) gel skin boosters (NSBs) in several anatomical areas and types of patient, as well as their own recommendations. Overall, the panel agreed that a standard initial protocol treatment of up to 3 sessions, followed by a maintenance schedule, would allow patients to improve and then preserve skin quality over time. Indeed, distinct effects are evident after the first session, but a progressive enhancement of skin texture is detectable for up to 12 months after repeat treatment at 4 to 6 month intervals. Moreover, the authors agreed that the NASHA gel, reaching the dermis, is able to reestablish a greater degree of hydration and stimulate collagen that, in turn, restores the volume and density of the skin. Thus, a strong consensus was reached that NSB procedures are minimally invasive, safe, and effective, and designed to improve skin texture and maintain skin quality.
J Drugs Dermatol. 2018;17(1):83-88.
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Skin aging can largely be attributed to dermal fibroblast dysfunction and a decrease in their biosynthetic activity. Regardless of the underlying causes, aging fibroblasts begin to produce elements of the extracellular matrix in amounts that are insufficient to maintain the youthful appearance of skin. The goal of mesopreparations is primarily to slow down and correct changes in skin due to aging. The rationale for developing complex polycomponent mesopreparations is based on the principle that aging skin needs to be supplied with the various substrates that are key to the adequate functioning of the fibroblast. The quintessential example of a polycomponent formulation – NCTF® (New Cellular Treatment Factor) – includes vitamins, minerals, amino acids, nucleotides, coenzymes and antioxidants, as well as hyaluronic acid, designed to help fibroblasts function more efficiently by providing a more optimal environment for biochemical processes and energy generation, as well as resisting the effects of oxidative stress. In vitro experiments suggest that there is a significant increase in the synthetic and prophylactic activity of fibroblasts with treated NCTF, and a significant increase in the ability of cells to resist oxidative stress. The current article looks at the rationale behind the development of polycomponent mesopreparations, using NCTF as an example.
The dermal extracellular matrix (ECM) provides strength and resiliency to skin. The ECM consists mostly of type I collagen fibrils, which are produced by fibroblasts. Binding of fibroblasts to collagen fibrils generates mechanical forces, which regulate cellular morphology and function. With aging, collagen fragmentation reduces fibroblast-ECM binding and mechanical forces, resulting in fibroblast shrinkage and reduced function, including collagen production. Here, we report that these age-related alterations are largely reversed by enhancing the structural support of the ECM. Injection of dermal filler, cross-linked hyaluronic acid, into the skin of individuals over 70 years of age stimulates fibroblasts to produce type I collagen. This stimulation is associated with localized increase in mechanical forces, indicated by fibroblast elongation/spreading, and mediated by upregulation of type II TGF-β receptor and connective tissue growth factor. Interestingly, enhanced mechanical support of the ECM also stimulates fibroblast proliferation, expands vasculature, and increases epidermal thickness. Consistent with our observations in human skin, injection of filler into dermal equivalent cultures causes elongation of fibroblasts, coupled with type I collagen synthesis, which is dependent on the TGF-β signaling pathway. Thus, fibroblasts in aged human skin retain their capacity for functional activation, which is restored by enhancing structural support of the ECM.Journal of Investigative Dermatology advance online publication, 25 October 2012; doi:10.1038/jid.2012.364.
Reduced synthesis of collagen types I and III is characteristic of chronologically aged skin. The present report provides evidence that both cellular fibroblast aging and defective mechanical stimulation in the aged tissue contribute to reduced collagen synthesis. The reduction in collagen synthesis due to fibroblast aging was demonstrated by a lower in vitro production of type I procollagen by dermal fibroblasts isolated from skin of young (18 to 29 years) versus old (80+ years) individuals (82 +/- 16 versus 56 +/- 8 ng/ml; P < 0.05). A reduction in mechanical stimulation in chronologically aged skin was inferred from morphological, ultrastructural, and fluorescence microscopic studies. These studies, comparing dermal sections from young and old individuals, demonstrated a greater percentage of the cell surface attached to collagen fibers (78 +/- 6 versus 58 +/- 8%; P < 0.01) and more extensive cell spreading (1.0 +/- 0.3 vs. 0.5 +/- 0.3; P < 0.05) in young skin compared with old skin. These features are consistent with a lower level of mechanical stimulation on the cells in old versus young skin. Based on the findings presented here, we conclude that reduced collagen synthesis in chronologically aged skin reflects at least two different underlying mechanisms: cellular fibroblast aging and a lower level of mechanical stimulation.
This article summarizes important molecular mechanisms that drive aging in human skin from the perspective of dermal fibroblasts. The dermis comprises the bulk of the skin and is largely composed of a collagen-rich extracellular matrix (ECM). The dermal ECM provides mechanical strength, resiliency, and an environment that supports the functions of ibroblasts and other types of dermal cells. Fibroblasts produce the dermal ECM and maintain its homeostasis. Fibroblasts attach to the ECM and this attachment controls their morphology and function. During aging, the ECM undergoes gradual degradation that is nitiated by matrix metalloproteinases (MMPs). This degradation alters mechanical forces within the dermal ECM and disrupts he interactions between fibroblasts and the ECM thereby generating an aged fibroblast phenotype. This aged fibroblast phenotype is characterized by collapsed morphology, altered mechanosignaling, induction of CCN1, and activation of transcription factor AP-1, with consequent upregulation of target genes including MMPs and pro-inflammatory mediators. The TGF-beta pathway coordinately regulates ECM production and turnover. Altered mechanical forces, due to ECM fragmentation, down-regulate the type II TGF-beta receptor, thereby reducing ECM production and further increasing ECM breakdown. Thus, dermal aging involves a feed-forward process that reinforces the aged dermal fibroblast phenotype and promotes age-related dermal ECM deterioration. As discussed in the article, the expression of the aged dermal fibroblast phenotype involves both adaptive and cell-autonomous mechanisms.
The extracellular matrix (ECM) is a complex assembly of hundreds of proteins forming the architectural scaffold of multicellular organisms. In addition to its structural role, the ECM conveys signals orchestrating cellular phenotypes. Alterations of ECM composition, abundance, structure, or mechanics, have been linked to diseases and disorders affecting all physiological systems, including fibrosis and cancer. Deciphering the protein composition of the ECM and how it changes in pathophysiological contexts is thus the first step toward understanding the roles of the ECM in health and disease and toward the development of therapeutic strategies to correct disease-causing ECM alterations. Potentially, the ECM also represents a vast, yet untapped reservoir of disease biomarkers. ECM proteins are characterized by unique biochemical properties that have hindered their study: they are large, heavily and uniquely post-translationally modified, and highly insoluble. Overcoming these challenges, we and others have devised mass-spectrometry-based proteomic approaches to define the ECM composition, or "matrisome", of tissues. This review provides a historical overview of ECM proteomics research and presents the latest advances that now allow the profiling of the ECM of healthy and diseased tissues. The second part highlights recent examples illustrating how ECM proteomics has emerged as a powerful discovery pipeline to identify prognostic cancer biomarkers. The third part discusses remaining challenges limiting our ability to translate findings to clinical application and proposes approaches to overcome them. Last, the review introduces readers to resources available to facilitate the interpretation of ECM proteomics datasets. The ECM was once thought to be impenetrable. MS-based proteomics has proven to be a powerful tool to decode the ECM. In light of the progress made over the past decade, there are reasons to believe that the in-depth exploration of the matrisome is within reach and that we may soon witness the first translational application of ECM proteomics.
Background:
Mesotherapy is a method of treatment in which biocompatible substances are injected in small aliquots into different levels of skin. This technique can be used for facial rejuvenation.
Aim:
To comprehensively evaluate efficacy of different hyaluronic acid (HA) materials for skin rejuvenation, and discuss longevity of these products, potential adverse effects and different injection techniques.
Material and methods:
We searched Pubmed, Scopus, Web of science, Google Scholar, Embase, Cochrane Library and Science direct until April of 2022. Thirty-four articles were selected including twenty-three articles about non-cross-linked HA and eleven articles about cross-linked HA.
Results:
Eleven and five different non-cross-linked HA and cross-linked HA materials were utilized, respectively. Treatment sessions for non-cross-linked HA were between 1 and 6 at weekly-to-bimonthly interval, and for cross-linked HA were 1-3 at 4-36 weeks apart. In most of the studies, serial micropuncture technique with 23-32 gauge needles was used for injection. Other injection techniques were Nappage (picotage), depot and micro-linear.
Conclusion:
Mesotherapy with HA-based fillers is a favorable method for restoring youthful appearance, rejuvenation and revitalization of skin. Proper selection and precise placement of HA in desired level of dermis is an essential key to optimize improvement and minimize side effects including skin irregularities and Tyndall effect. Adjuvant therapy with additional rejuvenation procedures to enhance esthetic results is required especially in elderly individuals with severe photodamaged skin. Moreover, preservation of esthetic results requires maintenance therapy every few months.
Background
Pneumatic‐assisted high velocity jet injections are an alternative method for intradermal delivery of hyaluronic acid (HA) and demonstrated efficacy in dermal thickening and scar remodeling with minimal side effects. Investigation into the clinical efficacy comparing non‐crosslinked HA (NCL‐HA) and crosslinked HA (CL‐HA) for aesthetic skin concerns is limited.
Methods
We retrospectively analyzed charts of 115 patients treated with jet injected NCL‐HA and CL‐HA for skin rejuvenation, age‐related laxity and rhytidosis, hypertrophic and acne scars and striae.
Global Aesthetic Improvement Scale (GAIS) and the 5‐grade patient satisfaction scale were used for assessment of the treatment efficacy at the 3‐month follow‐up. Efficacy was separately analyzed between patients receiving NCL‐HA vs. CL‐HA. Longevity of treatment effect was measured by the time to voluntary return for repeat treatment.
Results
An average of 2.8 treatments was completed per patient with a low incidence of side effects including bruises (7%) and temporary local edema (1%). Patients were highly‐satisfied with the treatment results in all categories with the average satisfaction scores of 3.68 (NCL‐HA) and 3.76 (CL‐HA). An average GAIS score of 1.7 (“much improved”) was calculated for neck, décolleté and perioral areas. An overall GAIS score averaged as 1.78 (NCL‐HA) and 1.6 (CL‐HA). Longevity of the effect averaged 13.1 months for NCL‐HA and 13.2 months for CL‐HA groups.
Conclusion
Our retrospective data showed similar significant improvement of all aesthetic skin concerns in 115 subjects treated with either NCL‐HA or CL‐HA delivered intradermally by a high velocity jet‐injector device with minimal downtime, pain or side‐effects.
Importance
Soft-tissue augmentation with skin fillers can be delivered with needles or microcannulas, but unwanted vascular occlusions are possible.
Objective
To determine whether filler-associated vascular occlusion events of the face occur more often with injections performed with needles than with microcannulas.
Design, Setting, and Participants
This retrospective cohort study included a random sample of board-certified dermatologists deemed eligible based on membership in relevant professional societies and attendance at relevant national professional meetings. Participants completed detailed forms in which they could enter deidentified data and volume statistics pertaining to patients undergoing filler procedures in their practices. Data were collected from August 2018 to August 2019.
Exposures
Injectable fillers approved by the US Food and Drug Administration delivered via needles or microcannulas.
Main Outcomes and Measures
The primary outcome measure was intravascular occlusion. Occlusion events were graded by severity (no sequelae, scar, and ocular injury or blindness).
Results
A total of 370 dermatologists (mean [SD] years in practice, 22.3 [11.1] years) participated and reported 1.7 million syringes injected. The risk of occlusion with any particular filler type using needle or cannula never exceeded 1 per 5000 syringes injected. Overall, 1 occlusion per 6410 per 1-mL syringe injections was observed with needles and 1 per 40 882 with cannulas (P < .001). Of the 370 participants, 106 (28.6%) reported at least 1 occlusion. Multivariate analysis found that injections with cannula had 77.1% lower odds of occlusion compared with needle injections. Participants injecting fillers for more than 5 years had 70.7% lower odds of occlusion than those who were less experienced. For each additional injection per week, the odds of occlusion decreased by 1%, and 85% of occlusions had no long-term sequelae. Nasolabial folds and lips were most likely to be occluded, with mean severity level of occlusions highest at the glabella.
Conclusions and Relevance
In this cohort study, filler injections with either needles or cannulas were associated with a very low risk of intravascular occlusion events. Moreover, the vast majority of such events were minor and resolved without scar or other injury. Injections with microcannulas were less often associated with occlusion events than injections with needles. Occlusion risk per syringe appeared decreased after the first few years of clinical practice and was also lower among those who more frequently inject fillers. Whether a needle or cannula is most appropriate for injection may depend on patient factors, anatomic site, and the type of defect being treated.
Advanced therapeutic dressings that take active part in wound healing to achieve rapid and complete healing of chronic wounds is of current research interest. There is a desire for novel strategies to achieve expeditious wound healing because of the enormous financial burden worldwide. This paper reviews the current state of wound healing and wound management products, with emphasis on the demand for more advanced forms of wound therapy and some of the current challenges and driving forces behind this demand. The paper reviews information mainly from peer-reviewed literature and other publicly available sources such as the US FDA. A major focus is the treatment of chronic wounds including amputations, diabetic and leg ulcers, pressure sores, and surgical and traumatic wounds (e.g., accidents and burns) where patient immunity is low and the risk of infections and complications are high. The main dressings include medicated moist dressings, tissue-engineered substitutes, biomaterials-based biological dressings, biological and naturally derived dressings, medicated sutures, and various combinations of the above classes. Finally, the review briefly discusses possible prospects of advanced wound healing including some of the emerging physical approaches such as hyperbaric oxygen, negative pressure wound therapy and laser wound healing, in routine clinical care.
The extracellular matrix (ECM) is critically important for many cellular processes including growth, differentiation, survival, and morphogenesis. Cells remodel and reshape the ECM by degrading and reassembling it, playing an active role in sculpting their surrounding environment and directing their own phenotypes. Both mechanical and biochemical molecules influence ECM dynamics in multiple ways; by releasing small bioactive signaling molecules, releasing growth factors stored within the ECM, eliciting structural changes to matrix proteins which expose cryptic sites and by degrading matrix proteins directly. The dynamic reciprocal communication between cells and the ECM plays a fundamental roll in tissue development, homeostasis, and wound healing.
Background:
Microcannulas with blunt tips for filler injections have recently been developed for use with dermal fillers. Their utility, ease of use, cosmetic outcomes, perceived pain, and satisfaction ratings amongst patients in terms of comfort and aesthetic outcomes when compared to sharp hypodermic needles has not previously been investigated.
Objective:
To compare injections of filler with microcannulas versus hypodermic needles in terms of ease of use, amount of filler required to achieve desired aesthetic outcome, perceived pain by patient, adverse events such as bleeding and bruising and to demonstrate the advantages of single-port injection technique with the blunt-tip microcannula.
Materials and methods:
Ninety-five patients aged 30 to 76 years with a desire to augment facial, décolleté, and hand features were enrolled in the study. Subjects were recruited in a consecutive manner from patients interested in receiving dermal filler augmentation. Each site was cleaned with alcohol before injection. Anesthesia was obtained with a topical anesthesia peel off mask of lidocaine/tetracaine. Cross-linked hyaluronic acid (20 mg to 28 mg per mL) was injected into the mid-dermis. The microcannula or a hypodermic needle was inserted the entire length of the fold, depression or lip and the filler was injected in a linear retrograde fashion. The volume injected was variable, depending on the depth and the extent of the defect. The injecting physician assessed the ease of injection. Subjects used the Visual Analog Scale (0-10) for pain assessment. Clinical efficacy was assessed by the patients and the investigators immediately after injection, and at one and six months after injection using the Global Aesthetic Improvement Scale (GAIS) and digital photography.
Results:
Overall, the Global Aesthetic Improvements Scale (GAIS) results were excellent (55%), moderate (35%), and somewhat improved (10%) one month after the procedure, decreasing to 23%, 44%, and 33%, respectively, at the six month evaluation. There was no significant differences in the GAIS score between the microcannula and the hypodermic needle. However, the Visual Analog Scale for pain assessment during the injections was quite different. The pain was described as 3 (mild) for injections with the microcannula, increasing to 6 (moderate) for injections with the hypodermic needle. Bruising and ecchymosis was more marked following use of the hypodermic needle.
Conclusion:
Using the blunt-tip microcannula as an alternative to the hypodermic needles has simplified filler injections and produced less bruising, echymosis, and pain with faster recovery.
As blunt injection microcannulas increase in popularity, clinicians may find it of value to have a systematic review of their current uses. This consensus document is derived from a roundtable discussion between a multi-specialty faculty comprising two U.S.-based dermatologists, one U.S.-based plastic surgeon, and one European cosmetic surgeon, all of whom were early adopters of blunt microcannulas for alloplastic fillers. The purpose of this consensus document is to provide an overview of the utility and clinical applications of blunt microcannulas, guidelines for their safe and efficacious use, and recommendations for the further evidence that needs to be accrued to substantiate the claims that have been made in regard to their superior safety profile and other benefits.
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