Tissue Engineering Auricular Cartilage: A Review of Auricular Cartilage Characteristics and Current Techniques for Auricular Reconstruction.

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.

Combining Allograft Adipose and Fascia Matrix as an Off-the-Shelf Scaffold for Adipose Tissue Engineering Stimulates Angiogenic Responses and Activates a Proregenerative Macrophage Profile in a Rodent Model.

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.

Targeting Myofibroblasts as a Treatment Modality for Dupuytren Disease.

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.

The End of Roe v. Wade.

The Supreme Court seems poised to overrule Roe v. Wade and hold that there is no constitutional right to choose abortion. The reversal of Roe seems to run counter to public opinion in the United States-while many favor restrictions, a clear majority do not want Roe reversed and favor access to abortion early in pregnancy. The current Court's apparent willingness to run the risk of political pushback has a complex history. Scholars have long described the Court as a countermajoritarian institution, but in practice, as historians have shown, the Court tends not to stray too far from popular opinion. For a Court bent on reversing Roe and tackling a long list of other divisive topic, concerns about institutional legitimacy no longer appear to be an effective check. A post-Roe Court may be more unplugged from popular opinion, with unpredictable results for the future of the democracy.

Advances in Pigmentation Management: A Multipronged Approach.

BACKGROUND: Key cellular players regulating human skin pigmentation include melanocytes in the epidermis that synthesize melanin, neighboring keratinocytes that receive and distribute melanin in the upper layers, and fibroblasts in the dermis that affect overlying melanocytes and keratinocytes. In addition, endocrine factors from the blood supply (endothelial cells) and inflammation-related factors play a role. Thus, new strategies for affecting pigmentation need to consider these multiple cell lines to adequately cover various causes and disease processes associated with hyperpigmentation. METHODS: Pathophysiologic mechanisms and cellular pathways involved in melanogenesis were thoroughly reviewed with particular emphasis on the cellular interplay involved in the process. A complex system of interlinking and independent pathways was defined and described demonstrating differing pathways for altered pigmentary disorders - melasma associated with endothelial cell interactions; post inflammatory hyperpigmentation associated with keratinocyte inflammatory mediators (PGE2 in particular); and photodamage involving all 4 cell types. In vitro validation studies were then undertaken to define differing cell group gene expression profiles with selected peptides and other active agents. Melanocytic production of pigment was then tested with these agents to identify key potential players capable of limiting pigmentation. RESULTS: Hexapeptide-12 and lactoferrin (melanocytes), Hexapeptide-11 (in keratinocytes), and phosphatidylserine (endothelial cells) were identified as major inhibitors of melanogenesis based on their gene expression profiles. This was confirmed by secondary melanin production tests performed on melanocytic lines. Additional active agents were also identified as inhibitors of melanocytic production of melanin, and together, these constituents formed the basis for a novel formulation for use in pigmentary disorders. CONCLUSION: A comprehensive scientific narrative of the various facets relating to pigmentation has been presented including differing pathways affecting varied cell lines that effect pigment production. Based on this concept, actives were tested using gene expression studies as well as in vitro melanogenic model testing in different cell lines. Using this novel multi-faceted approach, we have selected and validated a series of active agents to be used in a formulation targeting the complex problem of hyperpigmentation. J Drugs Dermatol. 2022;21(11):1206-1220. doi:10.36849/JDD.7013.

Micro/nanobubbles: Improving Pancreatic Islet Cell Survival for Transplantation.

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.

Adipose-Derived Tissue in the Treatment of Dermal Fibrosis: Antifibrotic Effects of Adipose-Derived Stem Cells.

Treatment of hypertrophic scars and other fibrotic skin conditions with autologous fat injections shows promising clinical results; however, the underlying mechanisms of its antifibrotic action have not been comprehensively studied. Adipose-derived stem cells, or stromal cell-derived factors, inherent components of the transplanted fat tissue, seem to be responsible for its therapeutic effects on difficult scars. The mechanisms by which this therapeutic effect takes place are diverse and are mostly mediated by paracrine signaling, which switches on various antifibrotic molecular pathways, modulates the activity of the central profibrotic transforming growth factor ß/Smad pathway, and normalizes functioning of fibroblasts and keratinocytes in the recipient site. Direct cell-to-cell communications and differentiation of cell types may also play a positive role in scar treatment, even though they have not been extensively studied in this context. A more thorough understanding of the fat tissue antifibrotic mechanisms of action will turn this treatment from an anecdotal remedy to a more controlled, timely administered technology.

The New Threat to Abortion Access in the United States-The Comstock Act.

This Viewpoint explains the history of the Comstock Act, its use by those seeking to restrict abortion, and why it threatens abortion access in the US.

Platelet-Rich Plasma, Adipose Tissue, and Scar Modulation.

Level of Evidence: 4.

Topical oxygen therapy & micro/nanobubbles: a new modality for tissue oxygen delivery.

Up to 15 billion dollars of US health care expenditure each year is consumed by treatment of poorly healing wounds whose etiologies are often associated with aberrancies in tissue oxygenation. To address this issue, several modes of tissue oxygen delivery systems exist, including Hyperbaric Oxygen Therapy (HBOT) and Topical Oxygen Therapy (TOT), but their efficacies have yet to be fully substantiated. Micro/nanobubbles (MNBs), which range anywhere from 100 µm to <1 µm in diameter and are relatively stable for hours, offer a new mode of oxygen delivery to wounds. The aim of this article is to systematically review literature examining the use of TOT for wound healing and use of MNBs for tissue oxygenation using the MEDLINE database. The search yielded 87 articles (12 MNB articles and 75 TOT articles), of which 52 met the inclusion criteria for this literature review (12 MNB articles and 40 TOT articles). Additionally, we present an analysis on the efficacy of our MNB generating technology and propose its use as a wound healing agent.

Beyond Balancing: Rethinking the Law of Embryo Disposition.

Actress Sofia Vergara became the center of a new round of conflict about the disposition of embryos created using assisted reproductive technologies (ART): the conflict about the difference that abortion jurisprudence should make to case law on ART. This Article argues that the history of abortion jurisprudence sheds light on the problems with the leading approach to embryo-disposition cases like Vergara's. In many instances, courts first look for a clear, binding agreement and look to a balancing analysis if no such agreement exists. As this Article shows, this is not the first time that courts have applied a balancing analysis to deal with clashing rights to seek and avoid genetic parenthood. The Article explores the history of two balancing approaches that have played a pivotal role in abortion law. These approaches have led to inconsistent results and cater to the prejudices of judges who are asked to weigh the relative merits of individual parties' views on reproduction. This Article recommends that states adopt legislation detailing the requirements of an enforceable embryo disposition similar to the Uniform Premarital and Marital Agreements Act (UPMAA). In the embryo-disposition context, states should require parties to disclose legal rights and responsibilities rather than only finances. These disclosures should cover the preservation, implantation, or destruction of the embryos and the financial and legal responsibility for any resulting child. States should enforce an embryo-disposition agreement if it is voluntary, if the parties had counsel or the opportunity to access counsel, and if the parties had a full disclosure of the constitutional and common law rights implicated by the agreement.

mTORC2 mediates CXCL12-induced angiogenesis.

The chemokine CXCL12, through its receptor CXCR4, positively regulates angiogenesis by promoting endothelial cell (EC) migration and tube formation. However, the relevant downstream signaling pathways in EC have not been defined. Similarly, the upstream activators of mTORC2 signaling in EC are also poorly defined. Here, we demonstrate for the first time that CXCL12 regulation of angiogenesis requires mTORC2 but not mTORC1. We find that CXCR4 signaling activates mTORC2 as indicated by phosphorylation of serine 473 on Akt and does so through a G-protein- and PI3K-dependent pathway. Significantly, independent disruption of the mTOR complexes by drugs or multiple independent siRNAs reveals that mTORC2, but not mTORC1, is required for microvascular sprouting in a 3D in vitro angiogenesis model. Importantly, in a mouse model, both tumor angiogenesis and tumor volume are significantly reduced only when mTORC2 is inhibited. Finally, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), which is a key regulator of glycolytic flux, is required for microvascular sprouting in vitro, and its expression is reduced in vivo when mTORC2 is targeted. Taken together, these findings identify mTORC2 as a critical signaling nexus downstream of CXCL12/CXCR4 that represents a potential link between mTORC2, metabolic regulation, and angiogenesis.

Interferon-induced transmembrane protein 1 regulates endothelial lumen formation during angiogenesis.

OBJECTIVE: It is well established that angiogenesis is a complex and coordinated multistep process. However, there remains a lack of information about the genes that regulate individual stages of vessel formation. Here, we aimed to define the role of human interferon-induced transmembrane protein 1 (IFITM1) during blood vessel formation. APPROACH AND RESULTS: We identified IFITM1 in a microarray screen for genes differentially regulated by endothelial cells (ECs) during an in vitro angiogenesis assay and found that IFITM1 expression was strongly induced as ECs sprouted and formed lumens. We showed by immunohistochemistry that human IFITM1 was expressed by stable blood vessels in multiple organs. siRNA-mediated knockdown of IFITM1 expression spared EC sprouting but completely disrupted lumen formation, in both in vitro and in an in vivo xeno-transplant model. ECs lacking IFITM1 underwent early stages of lumenogenesis (ie, intracellular vacuole formation) but failed to mature or expand lumens. Coimmunoprecipitation studies confirmed occludin as an IFITM1 binding partner in ECs, and immunocytochemistry showed a lack of occludin at endothelial tight junctions in the absence of IFITM1. Finally, time-lapse video microscopy revealed that IFITM1 is required for the formation of stable cell-cell contacts during endothelial lumen formation. CONCLUSIONS: IFITM1 is essential for the formation of functional blood vessels and stabilizes EC-EC interactions during endothelial lumen formation by regulating tight junction assembly.

Vitamin C, lactoferrin and elastin-Advancing the science.

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.

Antioxidants with proven efficacy and elastin-conserving vitamin C-A new approach to free radical defense.

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/cm2 ) 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.

Deconstructing Allograft Adipose and Fascia Matrix: Fascia Matrix Improves Angiogenesis, Volume Retention, and Adipogenesis in a Rodent Model.

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.

HLA class I-mediated stress fiber formation requires ERK1/2 activation in the absence of an increase in intracellular Ca2+ in human aortic endothelial cells.

Following transplantation, HLA class I antibodies targeting donor endothelium stimulate cell proliferation and migration, which contribute to the development of transplant vasculopathy and chronic allograft rejection. Dynamic remodeling of the actin cytoskeleton regulates cell proliferation and migration in endothelial cells (ECs), but the mechanism(s) involved remain incompletely understood. We explored anti-HLA class I antibody-mediated alterations of the cytoskeleton in human aortic ECs (HAECs) and contrasted these findings to thrombin-induced cytoskeleton remodeling. Our results identify two different signaling pathways leading to myosin light chain (MLC) phosphorylation in HAECs. Stimulation of HAECs with thrombin at 1 U/ml induced a robust elevation of intracellular Ca(2+) concentration, increased MLC phosphorylation, and promoted stress fiber formation via MLC kinase (MLCK) and Rho kinase (ROK) in an ERK-independent manner. In contrast, HAECs stimulated with HLA class I antibodies did not promote any detectable change in intracellular Ca(2+) concentration but instead induced MLC phosphorylation and stress fiber assembly via MLCK and ROK in an ERK1/2-dependent manner. Stimulation of HAECs with low-dose thrombin (1 mU/ml) induced signaling cascades that were similar to stimulation with HLA class I antibodies. HLA class I antibodies also stimulated the translocation of mammalian target of rapamycin complex 2 (mTORC2) and ERK1/2 from the cytoplasm to the plasma membrane independently of stress fiber assembly. These findings identify novel roles for HLA class I signaling in ECs and provide new insights into the role of ERK1/2 and mTORC2 in cytoskeleton regulation, which may be important in promoting transplant vasculopathy, tumor angiogenesis, and atherosclerosis.

Patient-Reported Satisfaction After Autologous Auricular Reconstruction in Patients with Microtia: A Systematic Review.

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.

Effects of a Topical Anti-aging Formulation on Skin Aging Biomarkers.

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 anti-aging efficacy. This new science supplements previous trials that demonstrated clinical efficacy of the formulation.