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OBJECTIVE: Following previous clinical trials, an antiaging product (Restorative Skin complex [RSC]; Alastin Skin Care Carlsbad, a Galderma company), was investigated for its effects on Klotho gene regulation, telomere length, and histological biopsy changes to provide a comprehensive picture of the mechanism and efficacy of its anti-aging effect. METHODS: Neonatal human fibroblasts were used for telomere length studies to examine the effect of the full RSC formulation and the amino acid components Tripeptide-1 and Hexapeptide-12 (TriHex™) on these cellular aging mechanisms. In addition, RNA sequencing was conducted using human keratinocytes specifically investigating Klotho and related genes. This was supplemented by a clinical study using biopsy samples. RESULTS: TriHex™ significantly upregulated the Klotho gene and related FGF23, FGFR1 and FOXO3B anti-aging genes. Significant telomere shortening reduction over control was demonstrated with the RSC formulation at four weeks and with TriHex™ at six weeks for all percentiles tested. Previous clinical studies demonstrated that the use of the antiaging regimen for 12 weeks produced a statistically significant improvement in scores for all evaluated parameters. Restaining of previous biopsy blocks from the clinical trial revealed positive ECM changes, stimulation of collagen, fibrillin, CD44 and elastin. LIMITATIONS: The study was limited by a relatively small numbers of patients in the clinical trial and the non-competitive nature of the trial. CONCLUSION: RSC anti-aging formulation and its TriHex™ components demonstrated significant reduction in telomere shortening, upregulation of Klotho and FOXO3 genes and biopsy validation of antiaging efficacy. This new science supplements previous trials that demonstrated clinical efficacy of the formulation

Background: The original TriHex combination-Tripeptide-1 and Hexapeptide-12 (TriHex) encompasses a peptide combination selected for its ability to modulate the extracellular matrix (ECM) by progressively eliminating clumped collagen and elastin fragments and then stimulating replacement with new collagen and elastin. Incorporation of a proprietary, patent-pending Octapeptide-45 (Octa) to the TriHex original provides potential for added benefit based on the peptide's capacity to stimulate hyaluronic acid (HA) and its anticipated added benefit in wound healing. This is named TriHex 2.0 in the paper., Materials and Methods: A full-scale validation process was structured to assess Octa synergy with TriHex using an ex vivo model, assessing ECM changes histologically in relation to elastin, HA and basement membrane components. In addition, gene expression studies were undertaken, including bulk and single cell sequencing analysis to assess the particular changes that occurred by adding Octa to the TriHex. Following the gene expression analysis, a further round of ex vivo studies was conducted to assess protein expression of the defined differentially expressed genes using histological staining., Results: Octa synergized with TriHex as demonstrated by significantly upregulated genes (p < 0.05) affecting the ECM and basement membrane. A histological assessment using the ex vivo model demonstrated tropoelastin intensity significantly increasing with TriHex (43%) and 2.0 (42%) (p < 0.05 for both) compared to untreated explants. HA levels (CD44 intensity) significantly increased with TriHex (69%; p < 0.01), while TriHex 2.0 demonstrated HA levels 160% greater (p < 0.001) than the untreated tissue. Single cell sequencing identified a gene expression profile upregulation relating to ECM modulation and wound healing in both TriHex and 2.0, but TriHex 2.0 showed additional activities in basement membrane physiology, stem cell recruitment, and protection of fibroblasts against cellular senescence., Conclusion: The addition of Octapeptide-45 to TriHex technology in the form of TriHex 2.0 is a significant advance to TriHex technology science. Both forms demonstrate ECM remodeling and positive wound healing, but supplementary benefits are evident including increased elastin and hyaluronic acid stimulation, added effects on the basement membrane, additional wound healing capacity in basal keratinocytes and anti-senescent effects in fibroblasts. This is helpful for pre-conditioning of the skin prior to procedures and post procedure related to additional ECM remodeling, wound healing advantages, senescent cell targeting and DEJ strengthening. Clinical studies to follow., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Skin atrophy and fragility associated with Dermatoporosis result from chronic extracellular matrix (ECM) degradation. A current marketed product, ReFORM & RePAIR COMPLEX with TriHex Technology&reg; (R&R, Alastin Skincare, Inc.), contains actives that aid in recycling the ECM with new matrix components that have been found to be deficient in patients with DP.1 This study evaluates the efficacy of R&R compared to a ceramide moisturizer for reducing acute episodic purpura events and improving atrophic skin associated with this condition over a 24-week period., Study Design: Participants were evaluated in a double-blind, 24-week split-arm study. Each participant applied R&R to one arm and a ceramide moisturizer on the opposite arm twice daily for 24 weeks. Participants&rsquo; arms were evaluated at screening/baseline and follow-up visits at weeks 4, 8, 12, 16, and 24. At all visits, different assessment parameters were evaluated at selected clinical trial centers including standardized photography, skin biopsies, skin barrier function, hydration/transepidermal water loss (TEWL) measurements, line-field confocal optical coherence tomography imaging (LC-OCT), and ultrasound imaging. Efficacy assessments were performed by blinded investigators, and participants completed global improvement questionnaires for each arm. Pre- and post-treatment biopsies were collected for histological evaluation in randomly selected consenting participants., Results: Thirty-eight (38) participants completed the study, and statistically significant improvements were seen across all arm skin parameters evaluated after 24 weeks of treatment. The R&R treatment arm achieved greater mean improvements and showed substantially better TEWL recovery compared to the ceramide moisturizer treatment arm. Ultrasound analysis revealed improvement in rete pegs and dermoepidermal junction (DEJ) undulation associated with the R&R-treated arm in 83% of study participants compared to the ceramide moisturizer-treated arm (17%). Significantly improved DEJ undulation and strengthening was seen in the R&R-treated arm, which was confirmed by LC-OCT imaging. Histology revealed improved collagen formation in the majority of R&R-treated arm case biopsies, as opposed to the comparator arms, which showed minimal improvements with early changes in elastin formation only evident in the R&R group. In addition, the R&R arms demonstrated more skin resilience and less bruising and skin fragility than the comparator arms., Conclusion: Dermatoporosis is a condition that takes years to evolve, and recovery is expected to take time. That noted, this study revealed that the DEJ is the first anatomic area to demonstrate improvement in DP status. This was evident in the R&R-treated arms. In addition, skin functionality related to TEWL measurements, overall texture, crepiness, and biopsy changes were all improved to a larger extent in the R&R-treated arms compared to the comparator arms, demonstrating the logical use of R&R for DP management. J Drugs Dermatol. 2024;23(12):1064-1071. doi:10.36849/JDD.8177.

Objective: Retention rates of lipotransfer remain variable, with the underlying cause associated with tissue oxygenation and blood supply barriers. One promising new method of improving tissue oxygenation is micro/nanobubbles (MNBs), which are small gas bubbles (<100 μm) generated within a saline solution. MNBs are stable and carry a significant amount of oxygen, and because of their negatively charged surface characteristics, they are an ideal oxygen-delivery solution. Thus, we hypothesize that washing/oxygenating lipoaspirate tissue prior to transplantation in a micro/nanobubble saline solution will improve graft survival and quality compared to a saline control., Methods: Human lipoaspirate samples obtained from healthy donors were washed with an oxygenated MNB or saline wash. These samples were then injected into the dorsum of sixteen 6-week-old male BALB/c mice, where each mouse received one saline and one MNB-washed graft. At 2-, 4-, 8-, and 12-week time points, the explants were harvested and weighed, and gas pycnometry was performed to assess graft volume. The tissues were also subjected to hematoxylin and eosin (HE) staining and immunohistochemistry to detect perilipin and blood vessels (CD31). These stains, as well as adipocyte count and area quantifications, were analyzed using ImageJ., Results: HE staining revealed that the control group demonstrated notable adipocyte hypertrophy, while MNB-washed samples had evident adipocyte hyperplasia. This observation was confirmed by an analysis of variance (ANOVA), which showed that the control group had a larger average graft mass and volume (P < 0.01). MNB-washed grafts also exhibited significantly greater adipocyte counts and smaller adipocytes (P < 0.001). Perilipin staining was also greater in the MNB group at the 2- and 4-week time point indicating improved de novo adipogenesis following implantation. Lastly, CD31 staining revealed a significantly greater core vessel density and angiogenesis at the 4-week and 12-week time points (P < 0.01)., Conclusions: Our study demonstrates that MNBs enhance tissue quality as indicated by a significant increase in de novo adipogenesis, higher vessel density, and decreased adipocyte hypertrophy. Additional studies are needed to evaluate the clinical effectiveness. Nevertheless, incorporating MNBs into procedures holds great promise in tackling the ongoing challenge of inconsistent outcomes in lipotransfer., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Utilizing biological scaffolds for cartilage tissue engineering is a promising tool for improving auricular reconstruction. Decellularized auricular scaffolds provide a means of regenerating cartilage for in vivo implantation, but identifying the ideal regenerative mix remains challenging., Methods: Human cadaver auricular cartilage was decellularized and recellularized with either auricular chondrocytes alone, auricular chondrocytes with adipose-derived stem cells, or both cells with platelet-rich plasma. Confirmation of decellularization and recellularization was done by hematoxylin and eosin staining. Extracellular matrix preservation and production were determined by Masson's trichrome, Alcian blue, and Verhoeff-van Gieson staining. Collagen II assessments were made using immunohistochemistry., Results: Decellularization of cadaver auricular cartilage was confirmed by the absence of cells, reduction in glycosaminoglycans, and the preservation of collagen and elastin. Recellularization was more efficient when chondrocytes were seeded with adipose-derived stem cells, which was enhanced by adding platelet-rich plasma. Coculture with platelet-rich plasma yielded better total collagen (56% increase) and glycosaminoglycan (47% increase) induction. Moreover, when platelet-rich plasma was added, collagen II induction was significantly increased (42%; P < 0.05)., Conclusion: We identified a regenerative protocol that included auricular chondrocytes, adipose-derived stem cells, and platelet-rich plasma, which stimulated chondrogenesis on decellularized auricular cartilage. This finding provides a model to explore cartilage formation and the potential for improving auricular and cartilage-based reconstruction., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dermatoporosis (DP) is a condition associated with thinning skin layers and resultant fragility. Much of the thinning is related to fibroblast dysfunction, production of destructive inflammatory cytokines, breakdown of the extracellular matrix (ECM), and weakening of the dermo-epidermal junction. A major contributor to this change in the ECM milieu, previously under-considered, is cellular senescence, particularly involving the papillary dermal fibroblasts., Methods: A series of experiments were undertaken to explore the impact of a combination of known actives on senescent cell status. Human keratinocytes and fibroblasts were cultured, and cytotoxicity tests were performed to determine the ideal concentration to avoid cell toxicity. Microdoses of Centella asiatica (0.005%) and mandelic acid (0.05%) were found to be ideal in avoiding any cytotoxicity. However, the challenge was then to assess the efficacy of these actives in this microdosed form. After exposing the cells to the compounds, RNA was isolated and sequenced. Moreover, a well-described ex vivo model using photodamaged skin was subjected to immunofluorescence to identify senescent cells (via p16INK4a), particularly in the papillary dermis, using the microdose formulation compared to untreated skin. In addition, JAG/NOTCH expression in the epidermal basal cells was evaluated to further understand the cellular senescence signaling mechanism., Results: Microdosing these two well-known agents had surprisingly significant synergistic effects in vitro, decreasing senescence-associated secretory phenotype (SASP) cytokines and the associated inflammation involved in the process. The ex vivo model revealed a significant (P&lt;0.05) decrease in senescent cells in the papillary dermis and a significant increase (P&lt;0.001) of JAG/NOTCH expression in the basal cells of the epidermis., Conclusion: Using microdoses of two known agents, a novel approach produced an unexpected effect of reversal of dermal senescent cells and promoting an anti-inflammatory milieu. A gene expression analysis of the individual and combined actives validated these observations, followed by full formulation testing in an ex vivo model. The approach of limiting cellular senescence in dermal fibroblasts for managing DP is novel and provides an exciting new direction to address dermatoporosis. Clinical studies will follow. J Drugs Dermatol. 2024;23(9):748-756. doi:10.36849/JDD.8388.

This paper outlines a process undertaken by a physician to design a peptide aimed at impacting the extracellular matrix. From a position of very little expertise, a new peptide was designed with amino acid constituents based on the structural proteins collagen and elastin. Sequencing was also considered, given the periodic repetition observed in these proteins, and a peptide with reasonable molecular weight and physical characteristics was designed using available software. The sequence of events concerning intellectual property, functionality investigation, and eventual use of the peptide in new formulations is detailed. This may be of interest to physicians who consider this exercise out of the scope of the usual practice. J Drugs Dermatol. 2024;23(5):347-352.&nbsp; &nbsp; doi:10.36849/JDD.7921.

Microtia and anotia are congenital auricular anomalies that negatively impact the psychosocial development of those affected. Because auricular cartilage is a type of elastic cartilage that lacks regenerative capacity, any notable defect in its structure requires a surgical approach to reconstructing the auricle. While there are several reconstructive options available between alloplastic and prosthetic implants, autologous rib cartilage grafts remain the most commonly used treatment modality. Still, this widely used technique is accompanied by significant patient discomfort in a young child and carries additional risks secondary to the traumatic process of rib cartilage extraction, such as pneumothorax and chest wall deformities, and the final esthetic results may not be ideal. To circumvent these limitations, tissue engineering approaches have been used to create a realistic-looking ear that mirrors the complex anatomy of the normal ear. This article reviews the biochemical and biomechanical properties of human auricular cartilage as they relate to design criteria. In addition, a variety of cell sources, biocompatible scaffolds, scaffold-free techniques, and mechanical and biological stimuli are discussed. This review aims to identify knowledge gaps in the literature related to auricular cartilage characteristics and make recommendations to drive the field of auricular tissue engineering., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: This study follows an initial scientific validation linking sodium ascorbate (SAC) with elastin conservation and the clinical trial histology observation that the full formulation tested there stimulated elastin development. In an effort to explain the increased elastin response, a candidate was sought that may provide synergy to SAC during elastin stimulation. Lactoferrin was the constituent chosen to explore in this realm., Materials and Methods: Using the previously described ex vivo skin model, freshly collected discarded human skin from 2 donors was used to evaluate the effects of lactoferrin and SAC alone and together, and L-ascorbate CE Ferulic formulation (CEF) on elastogenesis. Four skin explants were topically subjected to the treatments daily for 7 days and one group was left untreated as a negative control. The tissue was fixed and embedded. Sections were evaluated by immunofluorescence using antibodies targeting Tropoelastin and CD44, with DAPI counterstaining to observe nuclei. Images were then analyzed using ImageJ., Results: Treatment with SAC and lactoferrin demonstrated a significant synergistic effect on tropoelastin stimulation compared to the single treatments. In addition, this combination demonstrated intact and increased elastin fibers in contrast to the CEF, which portrayed fragmented elastin fibers. In addition, an additive effect of SAC also contributed to the enhanced CD44, suggesting an increased presence of hyaluronic acid, a new observation for this compound., Conclusion: This study complements a series of studies that have been undertaken to validate the efficacy of a novel antioxidant formulation. Aside from its efficacy in ROS management, the SAC constituent is unique in the different forms of Vitamin C for its ability to conserve elastin. Prior clinical studies demonstrated additive elastin stimulation on histology, not just conservation. From this current study, the combination of SAC with lactoferrin may be responsible for this additive stimulatory effect on elastin. This presents a significant advance in topical antioxidant formulations where the Vitamin C component provides antioxidant and collagen stimulation with additional elastin stimulation rather than degradation., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Dyschromia can be associated with increased production and/or reduced clearance of pigmentation in the skin. Multiple pathways are involved in causality. A novel topical product was recently developed, which contains actives that have been validated through in-vitro and clinical studies to counteract pigmentation related to photodamage, PIH, and melasma. This study further evaluates the safety and efficacy of this product for facial dyschromia during an additional 3-month extension period following the completion of the previous 12-week multi-center trial.&nbsp; Study Design: Subjects from the previous multi-center trial with mild to severe facial dyschromia at baseline were eligible to participate in this 3-month extension study upon completion of that trial. This extension study evaluated the continued use of the novel topical product with PATH-3 Technology (Alastin Skincare, Carlsbad, CA) over a 3-month period. Subjects who were previously randomized to the novel topical product continued using it and for those previously randomized to hydroquinone 4% discontinued its use. Both cohorts continued daily sunscreen use. Blinded investigators assessed subjects at follow-up visits at 16, 20, and 24 weeks., Results: Twenty-six (26) subjects completed the extension phase of the pivotal trial, with 13 subjects in each of the AL and HQ-BREAK cohorts. Significant improvements were seen within the AL cohort from weeks 12 to 24 for facial dyschromia (P=0.0158) and skin tone/clarity/evenness (P=0.0067), while there were no significant improvements seen in the HQ-BREAK cohort. The HQ-BREAK cohort had more subjects who worsened with facial dyschromia and skin tone/clarity/evenness. For the mMASI, the HQ-BREAK cohort demonstrated regression at week 24 compared to week 12, while the AL cohort instead experienced continued improvement. This difference was found to be significant (P=0.02). No study-related adverse events were reported for either cohort.&nbsp; Conclusion: A novel topical product designed to counteract various steps in pigmentation pathways using PATH-3 Technology has been demonstrated to be safe and effective in treating facial dyschromia on a long-term basis. In contrast to the significant rebound experienced by subjects with HQ, the AL cohort continued to demonstrate ongoing improvement. J Drugs Dermatol. 2024;23(1):1266-1270.&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.7622.

Background: A new antioxidant serum has been formulated with sodium ascorbate, a sodium salt of Vit C, which aims to address facial photodamage while maintaining a low irritation profile and preserving elastin. Detailed background science has been submitted in a previous publication. This open-label study was conducted to validate the science by demonstrating product efficacy and tolerability in patients with moderate to severe facial photodamage., Methods: A multicenter, open-label clinical study was undertaken over 5 months from March 2023 to July 2023. Thirty six eligible participants (35 female, 1 male), aged 38-69 years, and Fitzpatrick skin types II-V were enrolled into and completed the study following 12 weeks of the topical antioxidant serum use twice daily, along with the following supporting products (gentle cleanser, moisturizer, and sunscreen for as needed use). Follow-up visits were conducted in Weeks 2, 4, 8, and 12. At every visit, participants were evaluated for facial photodamage severity and test product tolerability. Additionally, study participants underwent subject assessments and satisfaction questionnaires, investigator assessments, biopsy collection, and photography., Results: Significant improvements in all evaluated facial photodamage parameters were observed at 12 weeks together with excellent tolerability and subject satisfaction persisting to Week 12 at study completion. Histology most notably revealed increased elastin fibers in 5 out of 5 post 12-week treatment biopsies on Movat staining, while Herovici stains revealed stimulation of collagen and early formation of new fibers., Conclusion: A novel antioxidant serum has demonstrated to be safe and effective for addressing facial photodamage, while stimulating the production of both elastin and collagen in the extracellular matrix (ECM)., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: This paper describes the background research and validation related to the formulation of a novel antioxidant product. Two defined outcomes were sought. Firstly, a combined efficacy of antioxidant ingredients in quenching free oxygen radicals. Secondly, the investigation into whether a vitamin C derivative sodium salt was elastin conserving in contrast to current vitamin C/l-ascorbic acid variations that have been reported to negatively affect elastin constitution and regeneration., Materials and Methods: A leading l-ascorbic acid antioxidant available on the market was compared with the experimental new product in two studies. In the first experiment, the products were compared to assess their antioxidant properties. The evaluated products TOPICAL ANTIOXIDANT 1 and TOPICAL ANTIOXIDANT 2 were applied to human skin cultures (25-30 mg/cm 2 ) for a total of 72 h of treatment and exposed to oxidative stress. The generation of free radicals was semi-quantitatively assessed by measuring the fluorescence intensity of the deacetylation and oxidation of the probe dichlorofluorescein diacetate (DCFH-DA). In the second experiment, an ex vivo skin model (derived from patients undergoing facelift procedures) was used to assess elastin preservation. Three skin explants were topically subjected to the two formulations daily for 7 days. The skin was then prepared and fixed for immunofluorescent assessment after staining with CD44 and tropoelastin antibodies. Images were then analyzed using ImageJ., Results: A full description of the different components selected for the new formulation is presented. In the first study, the experimental formulation performed with absolute equivalence to the comparator in its radical quenching capacity; both showed extremely effective antioxidant function. In the second study, the comparator negatively affected the existing elastin with areas of breakdown and diminished staining. In contrast, the new formulation showed good conservation of healthy elastin in all sections demonstrating elastin preservation., Conclusion: A new antioxidant formulation was carefully designed with multiple actives that show an equivalent antioxidant capacity to a leading product on the market. More importantly, the vitamin C component shows direct elastin conservation and improvement as opposed to the comparator, which had negative effects on elastin preservation. This is in keeping with little-known literature reports on vitamin C and its negative effects on elastin and validates the use of a sodium salt derivative, which appears to have protective effects on elastin. These findings support the overall regenerative extracellular matrix changes seen with TriHex® technology in other products., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Dermatoporosis as a disease entity is relatively newly described, the title conceived as recently as 2007. The background of chronic skin fragility, bruising, and atrophy appears to start in some patients as early as their mid-forties, but is full blown over the age of 65 years. The dehydration and fragility of the skin with recurrent bruising and breakdown were initially attributed to increased vessel fragility and permeability thought to be associated with inherent vascular tissue defects in a milieu of increased inflammation and extracellular matrix (ECM) degradation. It has subsequently been demonstrated that this ECM breakdown directly affects the structural support system of the superficial vessels, leading to stretch, increased permeability, and vulnerability to mechanical damage. Add to that the ECM atrophy and general accumulation of non-functional metabolic waste products in the form of fragmented collagen, elastin, and increased circulating glycation end products, and it becomes apparent that much of the problem resides in a structural defect, non-functioning, dehydrated, senescent cellular matrix and unsupported vascular system that presents as dermatoporotic characteristics. This paper describes a strategy of ECM replacement to counteract these foundational deficiencies. J Drugs Dermatol. 2023;22(9): doi:10.36849/JDD.7549.

Purpose: Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic growth factors are released when adipose-derived stem cells (ASCs) are cultured with platelet-rich plasma (PRP), a platelet concentration from whole blood. Reprograming myofibroblasts into adipocytes via growth factors is proposed as a powerful potential tool to target fibrosis. We aimed to assess whether the combination of ASCs and PRP reprograms DMFs into adipocytes in vitro and alters their contractile nature in vivo., Methods: Normal human dermal fibroblasts (NHDFs) and DMFs from Dupuytren patients were isolated and cocultured with ASCs and PRP either alone or together. Adipocytes were detected by Oil Red O and perilipin staining. DMFs and NHDFs were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]) and treated with saline, PRP+ASCs, or collagenase Clostridium histolyticum (clinical comparison) 2 months later. After 2 weeks, the tissue was harvested and subjected to Masson trichrome staining, and collagen I and III and alpha-smooth muscle actin detection by immunohistochemistry., Results: Myofibroblasts transform into adipocytes upon coculture with PRP+ASCs. DMFs show increased alpha-smooth muscle actin expression in vivo compared with NHDFs, which is significantly decreased after PRP+ASCs and collagenase Clostridium histolyticum treatments. DMFs induce collagen I and III expressions in rat paws compared with NHDFs, with a type III to I ratio increase. Treatment with PRP+ASC reduced the ratio, but collagenase Clostridium histolyticum did not., Conclusions: Treating DMFs with PRP+ASCs provides factors that induce myofibroblast to adipocyte transformation. This treatment reduces the contractile phenotype and fibrosis markers in vivo. Future studies should detail the mechanism of this conversion., Clinical Relevance: The combination of PRP and ASCs to induce the differentiation of DMFs into adipocytes may serve to limit surgery to a percutaneous contracture release and biological injection, rather than a moderate or radical fasciectomy, and reduce the recurrence of Dupuytren contracture., (Copyright © 2023. Published by Elsevier Inc.)

Approximately 20% of retained foreign bodies are surgical needles. Retained macro-needles may become symptomatic, but the effect of microsurgical needles is uncertain. We present the first animal model to simulate microsurgical needle retention. Given a lack of reported adverse outcomes associated with macro-needles and a smaller cutting area of microsurgical needles, we hypothesized that microsurgical needles in rats would not cause changes in health or neurovascular compromise., Methods: Male Sprague-Dawley rats (x̄ weight: 288.9 g) were implanted with a single, 9.0 needle (n = 8) or 8.0 needle (n = 8) orthogonal to the right femoral vessels and sutured in place. A control group (n = 8) underwent sham surgery. Weekly, a cumulative health score evaluating body weight, body condition score, physical appearance, and behavior for each rat was determined. Infrared thermography (°C, FLIR one) of each hindlimb and the difference was obtained on postoperative days 15, 30, 60, and 90. On day 90, animals were euthanatized, hindlimbs were imaged via fluoroscopy, and needles were explanted., Results: The mean, cumulative health score for all cohorts at each weekly timepoint was 0. The mean temperature difference was not significantly different on postoperative days 15 ( P = 0.54), 30 ( P = 0.97), 60 ( P = 0.29), or 90 ( P = 0.09). In seven of eight rats, 8.0 needles were recovered and visualized on fluoroscopy. In six of eight rats, 9.0 needles were recovered, but 0/8 needles were visualized on fluoroscopy., Conclusions: Microsurgical needle retention near neurovascular structures may be benign, and imaging for needles smaller than 8.0 may be futile. Further studies should explore microsurgical needle retention potentially through larger animal models., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. Disclosure statements are at the end of this article, following the correspondence information., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objective: Bioscaffolds for treating soft tissue defects have limitations. As a bioscaffold, allograft adipose matrix (AAM) is a promising approach to treat soft tissue defects. Previously, we revealed that combining superficial adipose fascia matrix with AAM, components of the hypodermis layer of adipose tissue, improved volume retention, adipogenesis, and angiogenesis in rats 8 weeks after it was implanted compared with AAM alone. Here, we modified the fascia matrix and AAM preparation, examined the tissue over 18 weeks, and conducted a deeper molecular investigation. We hypothesized that the combined matrices created a better scaffold by triggering angiogenesis and proregenerative signals., Methods: Human AAM and fascia matrix were implanted (4 [1 mL] implants/animal) into the dorsum of male Fischer rats (6-8 weeks old; ~140 g) randomly as follows: AAM, fascia, 75/25 (AAM/fascia), 50/50, and 50/50 + hyaluronic acid (HA; to improve extrudability) (n = 4/group/time point). After 72 hours, as well as 1, 3, 6, 9, 12, and 18 weeks, graft retention was assessed by a gas pycnometer. Adipogenesis (HE), angiogenesis (CD31), and macrophage infiltration (CD80 and CD163) were evaluated histologically at all time points. The adipose area and M1/M2 macrophage ratio were determined using ImageJ. RNA sequencing (RNA-seq) and bioinformatics were conducted to evaluate pathway enrichments., Results: By 18 weeks, the adipose area was 2365% greater for 50/50 HA (281.6 ± 21.6) than AAM (11.4 ± 0.9) (P < 0.001). The M1/M2 macrophage ratio was significantly lower for 50/50 HA (0.8 ± 0.1) than AAM (0.9 ± 0.1) at 6 weeks (16%; P < 0.05). This inversely correlated with adipose area (r = -0.6; P > 0.05). The RNA-seq data revealed that upregulated adipogenesis, angiogenesis, and macrophage-induced tissue regeneration genes were temporally different between the groups., Conclusions: Combining the fascia matrix with AAM creates a bioscaffold with an improved retention volume that supports M2 macrophage-mediated angiogenesis and adipogenesis. This bioscaffold is worthy of further investigation., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This review aims to evaluate the effectiveness of the two most commonly used oxygen delivery methods for the treatment of thermal burn wound healing: hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT)., Method: The PubMed database was searched for articles discussing the use of HBOT or TOT in the treatment of thermal burns., Results: The search yielded 43,406 articles, of which 28 (23 HBOT, 5 TOT) met the inclusion criteria. Both experimental and clinical studies have demonstrated conflicting results after treating thermal burns with HBOT or TOT. Overall, 14/23 studies demonstrated positive results for HBOT on the healing of burn wounds and associated complications, such as oedema and pain. Findings from these studies showed it can reduce morbidity and mortality in certain high-risk groups such as those with diabetes or extensive burns. Although the five studies (one human and four animal trials) reviewing TOT showed promising outcomes, this therapeutic modality has not been well investigated., Conclusion: Therapeutic use of HBOT in thermal burns has been popular in the past but its use remains controversial due to inconsistent results, serious side-effects, lack of convenience and high costs. The use of TOT in the management of burns needs further exploration by scientists and clinicians alike, in addition to the implementation of a standardised treatment protocol.

Background: Autologous fat grafting is commonly used for soft-tissue repair (approximately 90,000 cases per year in the United States), but outcomes are limited by volume loss (20% to 80%) over time. Human allograft adipose matrix (AAM) stimulates de novo adipogenesis in vivo, but retention requires optimization. The extracellular matrix derived from superficial fascia, interstitial within the adipose layer, is typically removed during AAM processing. Thus, fascia, which contains numerous important proteins, might cooperate with AAM to stimulate de novo adipogenesis, improving long-term retention compared to AAM alone., Methods: Human AAM and fascia matrix proteins (back and upper leg regions) were identified by mass spectrometry and annotated by gene ontology. A three-dimensional in vitro angiogenesis assay was performed. Finally, AAM and/or fascia (1 mL) was implanted into 6- to 8-week-old male Fischer rats. After 8 weeks, the authors assessed graft retention by gas pycnometry and angiogenesis (CD31) and adipocyte counts (hematoxylin and eosin) histologically., Results: Gene ontology annotation revealed an angiogenic enrichment pattern unique to the fascia, including lactadherin, collagen alpha-3(V) chain, and tenascin-C. In vitro, AAM stimulated 1.0 ± 0.17 angiogenic sprouts per bead. The addition of fascia matrix increased sprouting by 88% (2.0 ± 0.12; P < 0.001). A similar angiogenic response (CD31) was observed in vivo. Graft retention volume was 25% (0.25 ± 0.13) for AAM, significantly increasing to 60% (0.60 ± 0.14) for AAM/fascia ( P < 0.05). De novo adipogenesis was 12% (12.4 ± 7.4) for AAM, significantly increasing to 51% (51.2 ± 8.0) for AAM/fascia ( P < 0.001) by means of adipocyte quantification., Conclusions: Combining fascia matrix with AAM improves angiogenesis and adipogenesis compared to AAM alone in rats. These preliminary in vitro and pilot animal studies should be further validated before definitive clinical adoption., Clinical Relevance Statement: When producing an off-the-shelf adipose inducing product by adding a connective tissue fascial component (that is normally discarded) to the mix of adipose matrix, vasculogenesis is increased and, thus, adipogenesis and graft survival is improved. This is a significant advance in this line of product., Competing Interests: Disclosure : Dr. Widgerow is chief scientific officer of Galderma and receives royalties on technology from Skin Medica; he has no conflict of interest in this study. Dr. Banyard is a paid consultant for Recros Medica, Inc.; he has no conflict of interest in this study. Dr. Chnari is an employee of MTF Biologics and participated in the study design, protocol development, manuscript review, and write-up of the allograft adipose matrix preparation methods. She did not impact the analysis or interpretation of the study results. The remaining authors have no financial interest to declare in relation to the content of this study ., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Adipose tissue is an easily accessible source of stem and progenitor cells that offers exciting promise as an injectable autologous therapeutic for regenerative applications. Mechanical processing is preferred over enzymatic digestion, and the most common method involves shuffling lipoaspirate between syringes and filtering to produce nanofat. Although nanofat has shown exciting clinical results, the authors hypothesized that new device designs could enhance recovery of stem/progenitor cells through optimization of fluid dynamics principles, integration, and automation., Methods: The authors designed and fabricated the emulsification and micronization device (EMD) and the filtration device (FD) to replace the manual nanofat procedures. Using human lipoaspirate samples, the EMD and the FD were optimized and compared to traditional nanofat using ex vivo measurements of cell number, viability, and percentage of mesenchymal stem cells and endothelial progenitor cells., Results: The EMD produced results statistically similar to nanofat, and these findings were confirmed for a cohort of diabetic patients. Combining the FD with the EMD was superior to manually filtered nanofat in terms of both recovered cell percentages (>1.5-fold) and numbers (two- to three-fold). Differences were statistically significant for total mesenchymal stem cells and a DPP4 + /CD55 + subpopulation linked to improved wound healing in diabetes., Conclusions: The new EMD and the FD improved mechanical processing of human lipoaspirate in terms of mesenchymal stem cell enrichment and number compared to traditional nanofat. Future work will seek to investigate the wound healing response both in vitro and in vivo, and to refine the technology for automated operation within clinical settings., Clinical Relevance Statement: The new devices improved mechanical processing of human lipoaspirate in terms of stem cell enrichment and number compared to traditional methods. Future work will seek to validate wound healing response and refine the technology for automated operation within clinical settings., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Restorative Eye Treatment with TriHex Technology (RET) is a topical eye product with peptides and botanicals that reduce the appearance of crow's feet, under-eye bags, and dark circles. INhance with TriHex Technology (IH) is a topical product that has been clinically proven to accelerate the clearance of bruises and aid in the reduction of swelling. TriHex Technology has been shown to regenerate collagen and elastin., Objectives: Evaluate the use of RET compared to a bland moisturizer prior to blepharoplasty and the bilateral use of INhance postoperatively., Methods: Blepharoplasty patients were randomized to use either RET or a bland moisturizer, twice daily, on the designated periocular skin for 4 weeks prior to the procedure. Postoperatively, participants applied IH bilaterally, at least 4 times a day, and returned for follow-up on Days 1 or 3, 7, and 14. The removed upper-eyelid skin (13 patients) underwent independent dermatopathological evaluation., Results: Investigators noted no differences in peri-operative complications but observed faster improvement in swelling, bruising, discomfort on the treated side. 85% of participants had less edema and bruising on the RET pretreated side. Biopsy results revealed improved extracellular matrix appearance on the RET pretreated side. Participants agreed that IH alleviated their swelling and noted that their skin felt and appeared more hydrated., Conclusions: A regimen designed for eyelid surgery employing a pretreatment product component and a post treatment product appear to have a positive impact on measured outcomes in blepharoplasty patients including effects on bruising, swelling and patient comfort., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Aesthetic Society.)

Importance: In a patient-centered field such as plastic surgery, patient-reported satisfaction can measure the success and value of surgery, since it is not uncommon for patient and surgeon assessments to differ. Currently, there is no standard for evaluating patient-reported satisfaction postauricular reconstruction. Objective: To systematically review the literature regarding patient-reported satisfaction postauricular reconstruction in microtia patients. Evidence Review: The databases MEDLINE, EMBASE, Cochrane, and Scopus were searched and preferred reporting items for systematic reviews and meta-analyses guidelines were followed. Studies documenting patient-reported satisfaction postauricular reconstruction in microtia patients were included. All techniques for ear reconstruction have been included in this review. Findings: Nineteen studies utilizing autologous reconstruction technique, comprising 3694 patients, met inclusion criteria. No standardized patient satisfaction assessment was used throughout the studies, indicating criteria variability to measure outcomes. Auricular substructure analysis highlighted lower patient satisfaction with the tragus and antitragus compared with the upper units. In addition, satisfaction depended on patient perception, not on a low surgical complication rate. Conclusions: There is a clear need to incorporate a standardized validated surgery-specific questionnaire related to patient satisfaction in the auricular reconstruction protocol.

Background: A new hyaluronic acid (HA) formulation was developed based on high molecular weight (MW) compounds used on the surface of the skin while using peptides to stimulate the high MW HA production by fibroblasts and keratinocytes from within the skin layers. Detailed science has been submitted to this journal in a previous publication. This multicenter study aims to validate the science by demonstrating the safety and efficacy of the product in the clinical realm., Objectives: This study evaluated the efficacy and safety of a topical HA serum in facial skin., Methods: An open-label clinical study was undertaken over 4 months from November 2021 to March 2022. Participants applied the topical serum twice daily and were provided a gentle cleanser and an SPF 30+ to use in the morning. Follow-up visits were conducted at weeks 2, 4, and 8. At every visit, participants were measured for hydration post 15 minutes of cleansing the skin and post 15 minutes of product application for cumulative skin hydration sensor measurements. Additional procedures included participant assessments and satisfaction, investigator assessments, biopsies, and photography., Results: At each follow-up visit, there was an increase in hydration measurements compared to baseline, in both immediate scores and cumulative long-term scores. At weeks 4 and 8, there was a statistically significant increase in hydration compared to baseline and the prior visit. Participants' assessments progressively increased over 2-, 4-, and 8-week intervals with significantly favorable ratings in all measured parameters. Similarly, investigator assessment grades were statistically significant (p < 0.0001) for decreased fine lines/wrinkling, crepiness, texture, erythema, and dryness, and increased (p < 0.0001) for moisture/hydration. Histology revealed increased CD44 staining in 6 of the 7 participants biopsied, denoting increased HA stimulation. In all of the participant biopsies, H&E staining demonstrated improvement in solar elastosis. Photography revealed remarkable improvement in erythema, tone, and texture., Conclusions: The study results demonstrated that the formulation produced significant improvements in immediate and long-term hydration effects on the skin as measured by the skin hydration sensor, 'wearifi' technology, comparison of before and after biopsies, and participant and investigator assessments. This high MW HA formulation produced excellent clinical improvement in skin health and hydration., (© 2022 Alastin Skincare, Inc and The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: Hyaluronic acid (HA) plays an important role in cellular and extracellular matrix (ECM) homeostasis. Recent studies demonstrate that low molecular weight (MW) HA has pro-inflammatory characteristics while high MW HA is considered anti-inflammatory and regenerative. In formulating a topical HA product, the possibility of creating a focused high MW HA technology was posed, combining external surface high MW HA constituents with active agents promoting fibroblast production of high MW in the depths of the dermis., Methods: Human dermal fibroblasts and keratinocytes were treated with various agents, and RNA sequencing (RNA-seq) was conducted to identify genes involved in HA synthesis. HA production by fibroblasts was assessed by collecting the culture supernatant, concentrating the protein, and conducting polyacrylamide gel electrophoresis (PAGE). The gel was stained with Stains-All to identify bands relative to known HA products of different MWs. Subsequently, the supernatants were treated with hyaluronidase to confirm the bands corresponded to HA., Results: The RNA-seq results revealed a variety of agents upregulated HA-related genes. However, a potent upregulation of HA synthesis gene was observed by hexapeptide-11 in the keratinocytes and a newly identified proprietary octapeptide in the fibroblasts. PAGE demonstrated not only robust production of HA by octapeptide, but significantly, the HA produced was ~2 Mega Daltons in size. Octapeptide was the most potent stimulator among the tested agents., Conclusion: Comprehensive in vitro testing identified a group of active agents that stimulated high MW HA production. This novel approach to HA topical application with exclusively high MW HA production should maximize hydration capacity while encouraging regenerative activity within the ECM. Multi-center trials are underway., (© 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Skin preconditioning prior to and following procedures, has previously been demonstrated to hasten and optimize healing, and decrease the symptoms and signs associated with invasive surgery. These trials involved the use of multiple topical products. In an effort to control costs and to increase patient compliance, a single surgical product was developed, with actives aimed at decreasing swelling, bruising, induration, and internal fibrous banding., Objectives: This multi-center trial was designed to measure the efficacy of this single product in these mentioned parameters., Methods: A double-blind, randomized, split body, clinical study was undertaken in 29 patients involving 38 surgical procedures. Assessments included photography, biopsies, ultrasound imaging, and blinded investigator and participant assessments., Results: Differentiated results between test comparator sides became apparent at postop day 10-14 (as previously observed). Thus, blinded investigator and participant assessment scores demonstrated statistical significance exclusive to the test product side at postop day 10-14 for ecchymoses and then extending to skin discoloration, edema, induration and subcutaneous fibrous banding, at weeks 3, 4, 6, and 12. Ultrasound evaluation confirmed the earlier dissolution of fibrous banding on the test side in the subcutaneous tissue at the 3-6-week postop period. In addition, biopsies assessing the pre-conditioned period prior to surgery confirmed that the topical test product stimulated a remodeled extracellular matrix without comparative changes on the opposite side., Conclusions: A single peri-surgical product designed for the use with invasive surgery produced significant differences in ecchymosis, skin discoloration, edema, induration and ongoing resolution of fibrous banding over many weeks. This study validation provides an additional adjunct to surgical procedures., (© 2022 The Aesthetic Society.)

Background: Burns are devastating injuries, carry significant morbidity, and require long-term treatment or multiple reconstructive procedures. Wound healing and secondary insults caused by burn wound conversion are amendable to therapeutic intervention, where ischemia has been cited as one of the major factors (Dermatol Surg. 2008;34:1159-1169). Halting injury progression in the zone of stasis is crucial as conversion creates increased burn surface area and depth, leading to local and systemic consequences (J Burns Wounds. 2006;5:e2). Oxygen-carrying micro/nanobubbles, MNB(O2), offer a novel technology that can be used to effectively deliver oxygen to burn wounds and potentially counteract burn wound ischemia., Methods: Topical irrigation with MNB(O2) of full-thickness burn wounds on a rodent model (n = 3) was compared against saline-treated controls (n = 3). Tissue structure (reduced scattering coefficient, μs'), oxyhemoglobin concentration (cHbO2), and tissue perfusion were quantified over the course of 28 days through spatial frequency domain imaging and laser speckle imaging. Histological samples taken at the end of the experiment were examined for evidence of wound healing., Results: Findings in this preliminary study showed hastened healing with significant differences in spatial frequency domain imaging-measured μs' during wound healing (days 11-28) in MNB(O2) group. The healing "tipping point" seemed to occur at days 9 to 11 with increased collagen organization and increased cHbO2 occurring around that period confirming the gross healing improvements observed. In addition, histological evidence indicated that only the MNB(O2) burns had reached the remodeling phase by the end of 28-day study period., Conclusions: These preliminary findings propose the potential of MNB(O2) as a topical method for improving burn wound healing., Competing Interests: Conflicts of interest and sources of funding: Dr Durkin has a financial interest in Modulim, Inc, which developed the OxImager RS. However, Dr Durkin does not participate in the management of Modulim and has not shared these results with the company. Conflicts of interest have been disclosed and managed in accordance with the University of California and the National Institutes of Health policies. The other authors have no financial interests or commercial associations that might pose or create a conflict of interest with the information presented in this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The techniques used to make preoperative markings before soft tissue reconstruction have remained relatively unchanged since the earliest years of plastic surgery. Using skin-marking pens, many surgeons continue to draw markings freehand as "best estimates" before their first incisions. Although efficient for the experienced surgeon, this strategy may prove challenging for residents and trainees striving to learn and maintain consistency while replicating the intricate geometries of flap markings. To address this need, Operating Room Stencil was developed as a novel tool for digitally planning flap markings that may then be projected onto contoured surfaces such as the human body. As a cost-free mobile application, Operating Room Stencil is widely accessible to the medical community and offers educational captions for a majority of the flaps featured in its database. Users can plot relaxed skin tension lines onto uploaded facial images, thus enabling surgeons to orient surgical markings in a way that optimizes scar formation and reduces wound contraction. Although originally intended to appeal to trainees as a reliable way to learn about flaps and practice their technique, Operating Room Stencil may prove useful even among more experienced surgeons striving to further perfect their visualization and execution of flap markings., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article. The development of OR-Stencil was fully funded by a grant from the Aesthetic Surgery Education and Research Foundation entitled “New Innovation for Projected Flap Design.” The foundation had no involvement in project development., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

TriHex Technology (Alastin Skincare, Carlsbad, CA) has been shown clinically to promote healing and outcomes post procedures and has been demonstrated clinically to improve lipid droplet dissolution and patient-reported outcomes post procedure. Histologically, the formulations have proven to regenerate collagen and elastin. The use of the technology to prepare the skin for surgical procedures combined with its use post procedure was assessed through clinical study outcomes, histological evidence, and gene expression analyses and demonstrated remodeling of the extracellular matrix (ECM), accelerating healing, and initiation of anti-inflammatory genes. While the improvement in clinical signs and outcomes has been validated, the changes taking place at a molecular level need to be explored. The interaction of cells (adipocytes, macrophages, fibroblasts) and the ECM proteins (collagen, elastin) secondary to the effects of the topical agent application are discussed. It appears that the manipulation of fat during body contouring surgery and the resultant adipocytolysis precipitates a molecular profile that can be positively directed toward hastened healing by using adjuvant topical applications as preconditioning prior to surgery and after the surgical procedure. Here, we review the literature and underlying physiology relating to these products and describe how interleukin 6 appears to be the primary facilitator of these effects., (© 2021 The Aesthetic Society.)

Background: Photodamage creates changes within the skin layers known as solar elastosis. This presents as fragmentation of collagen and elastin fibers, decreases in the extracellular matrix (ECM) ground substance, as well as hyaluronic acid decrease in the thinning epidermis. Traditional immunohistochemistry (IHC) staining has failed to differentiate degenerated elastin from new elastin fibers generated with various topical strategies., Aims: A combination of stains that can offer a regenerative narrative distinguishing newly formed collagen and elastin from that of degenerated protein, thus distinguishing "good" vs "bad" elastin., Methods: A series of stains were explored based on their ability to identify early regenerative changes within epidermal, dermal, and ECM areas to examine consistency of outcomes and reliability., Results: A combination of Movat, fibrillin, elafin, and versican for elastogenesis and reversal of solar elastosis. CD44 for HA status (mainly epidermal) and Herovici stain for identifying early collagenesis in the ECM provides a comprehensive range of stains for identifying new elastin and collagen CONCLUSION: This suggested stain combination appears to offer an ideal collection of stains for identifying regenerative events within the skin layers., (© 2020 Wiley Periodicals LLC.)

Background: Microtia is an inherited condition that results in varying degrees of external ear deformities; the most extreme form is anotia. Effective surgical reconstruction techniques have been developed. However, these usually require multistage procedures and have other inherent disadvantages. Tissue engineering technologies offer new approaches in the field of external ear reconstruction. In this setting, chondrocytes are cultured in the laboratory with the aim of creating bioengineered cartilage matrices. However, cartilage engineering has many challenges, including difficulty in culturing sufficient chondrocytes. To overcome these hurdles, the authors propose a novel model of cartilage engineering that involves co-culturing chondrocytes and adipose-derived stem cells on an allograft adipose-derived extracellular matrix scaffold., Methods: Auricular chondrocytes from porcine ear were characterized. Adipose-derived stem cells were isolated and expanded from human lipoaspirate. Then, the auricular chondrocytes were cultured on the allograft adipose matrix either alone or with the adipose-derived stem cells at different ratios and examined histologically., Results: Cartilage induction was most prominent when the cells were co-cultured on the allograft adipose matrix at a ratio of 1:9 (auricular chondrocyte-to-adipose-derived stem cell ratio). Furthermore, because of the xenogeneic nature of the experiment, the authors were able to determine that the adipose-derived stem cells contributed to chondrogenesis by means of a paracrine stimulation of the chondrocytes., Conclusions: In this situation, adipose-derived stem cells provide sufficient support to induce the formation of cartilage when the number of auricular chondrocytes available is limited. This novel model of cartilage engineering provides a setting for using the patient's own chondrocytes and adipose tissue to create a customized ear framework that could be further used for surgical reconstruction., (Copyright © 2020 by the American Society of Plastic Surgeons.)

Background: Physicians strive to improve the postsurgical experience and optimize patient-reported recovery outcome measures (PROMs) following elective cosmetic surgical procedures. Our previous pilot feasibility study demonstrated that twice daily postoperative topical body treatment with tripeptide and hexapeptide (TransFORM Body Treatment with TriHex Technology [TFB, Alastin Skincare, Inc., Carlsbad, CA]) reduced PROMs of swelling, induration, soft tissue fibrosis, and pain as well as improved visible and palpable skin quality., Objectives: Evaluate whether adding a tripeptide/hexapeptide anhydrous gel (Regenerating Skin Nectar with TriHex Technology [RSN, Alastin Skincare, Inc., Carlsbad, CA]) pre- and post-procedure to the existing postsurgical regimen of TFB significantly improves 6 PROMs in patients undergoing neck and body contouring cosmetic surgical procedures., Methods: Ten female patients underwent 15 neck and body contouring procedures and were blindly randomized to 1 of 2 topical treatment protocols (1 [TFB] and 2 [RSN/TFB]) pre- and post-procedure. Patient-reported scores of 5 skin parameters (skin discoloration, ecchymosis, edema, induration, and subcutaneous fibrous banding) and pain scores using the Visual Analog Scale were collected at 8 intervals for 12 weeks post-procedure., Results: The treatment side that used both topicals showed significantly reduced scores of edema, induration, and subcutaneous fibrous banding compared with the side that only used 1 topical, on days 5-7 and 10-14 ( P < 0.05). All patients observed slower soft tissue recovery on the side that was treated with TFB alone and opted to break the code and use both topical treatments., Conclusions: Patients had statistically significant improved patient-reported measures of skin edema, skin induration, and subcutaneous banding on the operated side that used both topicals., (© 2020 The Aesthetic Society.)

Background: Skin topical preconditioning before and after surgical procedures is a relatively new concept, particularly in relation to the efficient removal of tissue breakdown products. Clinical trials demonstrate improvements, such as less induration, when surgery is combined with topical product preconditioning and with usage post-surgery., Objectives: This trial aimed to assess the efficacy of such a regimen at the molecular level through gene expression studies in combination with clinical assessments., Methods: Six women who underwent medial thigh liposuction administered either a bland moisturizer or the experimental topical products to each side of the surgical area twice daily. Biopsies were taken before any topical application, at 2 and 4 weeks after liposuction. An inflammation-related gene expression analysis was conducted to compare the different conditions. In addition, the degree of induration was assessed in a blinded manner., Results: Compared with the bland moisturizer, the experimental group demonstrated a hastened immune inflammatory response moving more rapidly to an anti-inflammatory reversal at 2 weeks followed by a wound healing extracellular remodeling effect at 4 weeks. This matched the clinical picture depicting less induration with the treatment., Conclusions: For patients undergoing body procedures, a topical treatment with the Alastin induces an accelerated healing response, inducing the clearance of "waste" products and the induction of anti-inflammatory genes. Furthermore, this topical treatment stimulates extracellular matrix remodeling, which ultimately leads to less induration., (© 2020 The Aesthetic Society.)

Injectable procedures have come to play an enormous part in everyday aesthetic medical practice. Whether its use is directed at volumizing with fillers, decreasing volume using enzymes, skin-tightening using multi-needle approaches, or neuromuscular blockade, the injectable route is the means of delivery in all these cases, making injectable procedures the most common aesthetic procedure performed. As with all procedures, expected and unexpected consequences may follow including bruising, swelling, discomfort, and the possibility of infection. This paper outlines the scientific process and validation of a product designed as an adjunct to injection therapy and the scientific deep dive needed to encompass both symptomatic and adjunctive purposes. On the symptomatic side, bruising, swelling, and pain were considered, while volumetric enhancement, regeneration, and anti-microbial/biofilm effects were desired outcomes from the adjunctive perspective. Utilizing peptides and active agents aimed at reducing excess residual iron and stimulating macrophage absorption of red blood cells, we were able to achieve efficient resolution of bruising. In addition, peptides were included to stimulate collagen, elastin, and hyaluronic acid in synergy with the injectable. Anti-inflammatory, antimicrobial, and antibiofilm agents were added to aid in the safety profile of the injectable. In vivo testing of bruising resolution demonstrated that at day 2/3, participants using the study product (INhance Post-Injection Serum with TriHex Technology®, Alastin Skincare, Inc. Carlsbad, CA) had 73% less bruise color intensity and statistically significant improvement over the bland moisturizer. Overall, 81% of subjects applying the study topical product had less bruising at day 2/3 compared to the bland moisturizer. J Drugs Dermatol. 2020;19(4):398-404. doi:10.36849/JDD.2020.5016.

Anti-aging strategies using topicals with active agents demand validation and proof of efficacy. One investigation in this realm involves gene expression testing. This study undertakes gene expression analysis of Alastin Skincare Regenerating Skin Nectar (RSN) using an in vitro human skin model. The current study is similar to other published human skin model studies, but with additional time periods beyond 24-hours (which are more appropriate for testing peptides) and a suitable control for the Alastin non-aqueous product. Results show the Alastin product upregulates a large array of genes within areas of skin renewal, extracellular matrix remodeling, barrier function, and inflammation after 72 hours. The study provides gene expression data that support the clinical success of the product. It also demonstrates the difficulty and vulnerabilities in assessing efficacies of products with certain in vitro investigations when the nuances of that product are not considered. J Drugs Dermatol. 2019;18(12):1255-1259.

Background: Ever since the classification of Dupuytren disease into the proliferative, involutional, and residual stages, extensive research has been performed to uncover the molecular underpinnings of the disease and develop better treatment modalities for patients. The aim of this article is to systematically review the basic science literature pertaining to Dupuytren disease and suggest a new approach to treatment., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted using the MEDLINE database to identify basic science literature on Dupuytren pathophysiology falling under 1 or more of the following categories: (1) Molecular alterations, (2) Structural alterations, and (3) Genetic predisposition., Results: A total of 177 articles were reviewed of which 77 studies met inclusion criteria. Articles were categorized into respective sections outlined in the study methods., Conclusion: The pathophysiological changes involved in Dupuytren's disease can be divided into a number of molecular and structural alterations with genetic predisposition playing a contributory role. Understanding these changes can allow for the development of biologics which may disrupt and halt the disease process.

Purpose: The preservation of transplantable tissue is directly tied to and limited by the ischemia time. Micro/nanobubbles (MNBs) are miniature gaseous voids that allow for the oxygenation of tissue given their high oxygen-carrying capacity. One of the current limitations of islet cell transplantation for type 1 diabetes is poor islet survival, caused by hypoxia, after harvesting the cells from pancreata. As such, the purpose of this study was to elucidate whether MNBs, when added to standard culture medium, improve islet cell survival postharvest., Materials and Methods: Islet cells were harvested from Sprague-Dawley rat pancreas tissue via a standard collagenase digestion and gradient purification. To create the MNB solution, a shear-based generation system was used to produce both air- and oxygen-filled MNBs in standard Connaught Medical Research Laboratories (CMRL) medium. Four groups, consisting of 500 islet equivalents, were cultured with either the standard CMRL medium, macrobubble-CMRL, MNB (air)-CMRL, or MNB (O2)-CMRL, and they were incubated at 37°C. Each treatment solution was replenished 24 hours postincubation, and after 48 hours of culture, dithizone staining was used to determine the islet cell counts, and the viability was assessed using Calcein AM/propidium iodide staining., Results: Islet cells that were preserved in macrobubble-CMRL, MNB (air)-CMRL, and MNB (O2)-CMRL conditions showed an increased survival compared with those cultured with standard CMRL. The islet cells cultured in the MNB (air)-CMRL condition demonstrated the greatest cell survival compared with all other groups, including the pure oxygen-carrying MNBs. None of the MNB treatments significantly altered the viability of the islet cells compared to the control condition., Conclusions: The addition of MNBs to culture medium offers an innovative approach for the oxygenation of transplantable tissue, such as islet cells. This study demonstrated that MNBs filled with air provided the most optimal addition to the islet cell culture medium for improving islet cell survival amongst the treatment groups we tested. Given these findings, we hypothesize that MNBs may also improve the oxygenation and survival of a variety of other tissues, including fat grafts from lipoaspirate, chronic wounds, and solid organs.

Mixed reality, a blending of the physical and digital worlds, can enhance the surgical experience, leading to greater precision, efficiency, and improved outcomes. Various studies across different disciplines have reported encouraging results using mixed reality technologies, such as augmented and virtual reality. To provide a better understanding of the applications and limitations of this technology in plastic surgery, we performed a systematic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The initial query of the National Center for Biotechnology Information database yielded 2544 results, and only 46 articles met our inclusion criteria. The majority of studies were in the field of craniofacial surgery, and uses of mixed reality included preoperative planning, intraoperative guides, and education of surgical trainees. A deeper understanding of mixed reality technologies may promote its integration and also help inspire new and creative applications in healthcare., (© 2019 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Introduction: Extracellular vesicles (EVs) are cell-secreted packages that deliver cargo to target cells to effect functional and phenotypic changes. They are secreted by many different cell types, including adipose-derived stem cells (ADSCs), which are a promising field of study in regenerative medicine. Our aim was to perform a systematic review of the literature to summarize the scientific work that has been conducted on ADSC EVs to date., Methods: The Pubmed database was queried with keywords (and variations of) "adipose derived stem cell," "stromal vascular fraction," and "extracellular vesicles." We excluded review papers, then manually screened articles based on title and abstract. Full-text articles were assessed for eligibility to include in final review., Results: While an extensive body of research exists on EVs, a much smaller proportion of that is original research on ADSC EVs. Of 44 manuscripts that met our database search criteria, 21 articles were selected for our systematic review., Conclusion: ADSC EVs were found to exert effects on angiogenesis, cell survival and apoptosis, inflammation, tissue regeneration, and reduction of disease pathology. Further studies examine characteristics of ADSC EVs. Future work should aim to further detail the safety profiles of ADSC EVs given their potential for cell-based therapies. The body of research studies characterizing ADSC EVs continues to expand, and much work remains to be done before human pilot studies can be considered. To our knowledge, we offer the first systematic review summarizing the research on ADSC EVs and their determined roles to date., (Copyright © 2019. Published by Elsevier Ltd.)

This paper introduces the concept of "skin bed preparation" prior to surgical procedures. Following the theory of chronic wound bed preparation and adapting the skin model to one of chronic wound changes related to extrinsic and intrinsic factors, a topical formulation aimed at recycling the extracellular matrix (ECM) from accumulated waste products is evaluated and discussed. The clearance of these products and stimulation of new replacements has the potential to change the regenerative milieu of the skin so that when procedures are carried out, cellular signaling and cross-talk at the dermal level are improved and healing is optimized. By introducing a combination of peptides and other synergistic active agents, a sequence of clearance, regeneration, and remodeling is initiated. This is confirmed and validated by a series of biopsies and clinical studies that demonstrate changes in the ECM as early as 2 to 3 weeks after application. Clinical studies related to resurfacing procedures show accelerated healing and improved symptomatic relief compared with standard of care by preconditioning the skin 2 weeks prior to the procedure. A similar approach is suggested as a potential advantage for invasive surgical procedures based on similar scientific principles elucidated on in the text., (© 2019 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Background: Non-surgical fat reduction through cold application, cryolipolysis, is an extremely popular procedure. Apoptosis of the fat cell content may take around 3 months to resolve. Objective: A topical test product was compared to a bland emollient as an adjunct to the cryolipolysis procedure of the upper arms to determine if the product could hasten outcomes in these patients. The product includes a peptide combination thought to stimulate autophagic breakdown of lipid droplets, thus speeding up the apoptotic process seen after cryolipolysis. Methods: A randomized, double-blind, comparator-controlled study in 11 patients compared the test product to a bland emollient on the upper arms of patients following cryolipolysis. Subjects were followed at 1, 4, 8, 12, and some at 24-weeks post treatment. Assessments were made through subjective and objective photographic analysis of the treated areas comparing changes in both arms. Results: The test product appeared to speed up the process of contour improvement with results at 8 weeks matching those attained at 12 weeks by the comparator and long-term results at 24 weeks appearing to maintain this advantage. When measured objectively using pixel analysis, 8 and 24-week contour improvement was statistically better than the comparator. Skin laxity was also improved. In additional assessments using 3D volume analysis, cases showed improved reduction of fat tissue on the treated sides. Conclusion: This pilot study introduces a potential advance in adjuvant topical therapy aiding the outcome of non-invasive fat reduction procedures. J Drugs Dermatol. 2019;18(4):342-348.

Non-surgical fat reduction procedures have gained in popularity over the past few years and remain in great demand. The process results in accumulation of breakdown products, lipid droplets, that are slowly absorbed over a period of months. This paper outlines the physiological process whereby lipid droplets are absorbed through a process of autophagy (lipophagy) involving a repackaging of these droplets to smaller sizes so that macrophages can then cope with digestion of these very large particles. Furthermore, a fat compartment is described within the dermis surrounding the tail of the hair follicle, which is attracting much attention due to its unique phenotype, function, and connection to the deeper subcutaneous fat compartment. This provides an entry route for direct signaling to the subcutaneous fat. Related to these novel concepts, peptides can be designed in liposomal delivery systems to target lipid droplet breakdown via the hair follicle entry route. This concept is elucidated in this paper. J Drugs Dermatol. 2019;18(4):375-380.

Introduction: An antiaging regimen that aids in clearing the matrix of waste products and stimulating neocollagenesis and neoelastogenesis was tested among a group of subjects over the course of 12 weeks to assess its efficacy in women with mild to moderate wrinkles and skin sagging on the face., Materials and Methods: The efficacy of the product regimen was tested in 22 subjects using investigator clinical grading measurements, raking light imaging, 3D imaging, biopsies, and self-assessment questionnaires at baseline and weeks 4, 8, and 12., Results: Clinical grading indicated that use of the antiaging regimen for 12 weeks produced a statistically significant improvement in scores for all evaluated parameters; the raking light image analysis demonstrated a statistically significant improvement in values for length, width, and area of wrinkles when compared with baseline values as did 3D imaging. Biopsy results in the 5 patients tested showed improvement in solar elastosis, collagen stimulation, and improvement in cornified layers in all 5 patients. Elastin stimulation was evident in 3 of 5 patients. Results from the self-assessment questionnaire analysis indicated favorable responses in a statistically significant proportion of subjects after 12 weeks of use for all inquiries., Conclusion: Use of this facial antiaging regimen was effective in improving visual facial photoaging conditions and well-perceived when used by women with mild to moderate wrinkles and skin sagging on the face under the conditions of this study., (© 2018 Wiley Periodicals, Inc.)

Diabetes mellitus (DM) is a chronic disease that results in a variety of systemic complications. Recently, stem cell-based therapies have been proposed as potential modalities to manage DM related complications. Mesenchymal stem cell (MSC) based therapies are often considered as an ideal stem cell-based treatment for DM management due to their immunosuppressive characteristics, anti-inflammatory properties and differentiation potential. While MSCs show tremendous promise, the underlying functional deficits of MSCs in DM patients is not well understood. Using the MEDLINE database to define these functional deficits, our search yielded 1826 articles of which 33 met our inclusion criteria. This allowed us to review the topic and illuminate four major molecular categories by which MSCs are compromised in both Type 1 DM and Type II DM models which include: (1) changes in angiogenesis/vasculogenesis, (2) altered pro-inflammatory cytokine secretion, (3) increased oxidative stress markers and (4) impaired cellular differentiation and decreased proliferation. Knowledge of the deficits in MSC function will allow us to more clearly assess the efficacy of potential biologic therapies for reversing these dysfunctions when treating the complications of diabetic disease.

Level of Evidence: 4.

Despite the vast amount of technological advancement seen in the operating room, surgical markings are still drawn as "best estimates" the same way Susruta drew them in the sixth century BC. Many of the flaps used in plastic surgery have precise geometries that are hard to replicate by hand. In this article, the authors describe a novel approach in making surgical markings more accurate by using a pico-projector to project a prefabricated flap, designed on Google Sketchup, as a stencil. Projected and hand-drawn rhomboid and bilobed flaps were tested on cadavers, with both quantitative and qualitative outcomes favoring the projected flaps. This unique concept can not only be used in the operating room but also serve as an educational tool for training plastic and reconstructive surgeons., Clinical Question/level of Evidence: Therapeutic, V.