Search

Martina Kerscher,1 Sylvia Wagner-Schiffler,2 Ernst Magnus Noah,3 Tanja Fischer,4 Daniela Greiner-Krüger,5 Sonja Sattler,6 Tanju Kaptan,7 Attyla Drabik,8 Glyn Hamed,9 Julio Reinecke,7 Jana Wehling10 1Division of Cosmetic Sciences, University of Hamburg, Hamburg, Germany; 2Dermatologische Praxis, Aachen, Germany; 3Noahklinik und Klinik für Plastische Chirurgie, Kassel, Germany; 4Haut und Lasercentrum, Potsdam, Germany; 5MediCorium, Zentrum für Dermatologie und Ästhetik, Oberursel, Germany; 6Rosenpark Klinik, Darmstadt, Germany; 7ORTHOGEN AG, Düsseldorf, Germany; 8Clinical Trial Support, Münster, Germany; 9Practice Dr. Wehling and Partner, Düsseldorf, Germany; 10Krankenhaus Neuwerk, Mönchengladbach, GermanyCorrespondence: Glyn Hamed, Email glyn.hamed@doctor-wehling.comBackground: The “Inflammation Theory of Ageing” identifies pro-inflammatory cytokines and oxidative damage as one cause of cellular and mitochondrial deterioration and aging. Cell-free blood cell secretome (BCS) also known as autologous conditioned serum (ACS) has shown anti-inflammatory and regenerative mode of action in musculoskeletal disorders and radicular compression.Aim: To confirm that BCS can improve signs of skin aging from a previous study in a multi-center setting.Methods: Prospective, one-armed, multi-center interventional therapeutic study. Ninety-five women with skin firmness loss were treated with four intra-dermal injection sessions in both cheeks at 0, 2, 4 and 6 weeks. BCS was processed with Exokine® medical device according to manufacturer’s instructions. Primary endpoints were cutometric R0 and R3 at 12 and 24 weeks. GAIS, FACE-QTM, Patient Attractivity Self-Assessment and safety were evaluated.Results: Mean skin firmness (R0) improved significantly from baseline 0.40 mm to 0.38 mm at week 12 and to 0.36 mm at week 24. Mean skin tiring (R3) improved significantly from baseline 0.45 mm to 0.42 mm at week 12 and to 0.40 at week 24. FACE-QTM “Satisfaction with Skin” significantly improved from baseline to weeks 12, 24 and 48. So did “Satisfaction with Facial Appearance” and “Psychological and Social Function”. “Satisfaction with Decision” and “Satisfaction with Outcome” were stable at week 24 and 48. At week 48 patients assessed their age 1.68 years younger vs Baseline. FACE-QTM aging appraisal improves from Baseline 52.94 to 65.23 at week 48. GAIS, by both physicians and patients, confirm improvement of skin.Conclusion: For up to 48 weeks four intra-dermal injections with cell-free BCS increase facial skin firmness and resilience to tiring and patients’ satisfaction with their facial appearance and skin. Patients perceive their face as younger. BCS has the ability to sustainably rejuvenate facial skin safely.Study Registration: Registration on German clinical trials register: DRKS00013014.Keywords: cell-free blood cell secretome, BCS, autologous conditioned serum, ACS, skin quality, regeneration, autologous, rejuvenation

Gerhard Sattler,1 Martina Kerscher,2 Ernst Magnus Noah,3 Welf Prager,4 Tanja C Fischer,5 Patricia Ogilvie,6 Matthias Hofmann,7 Hanna Dersch,7 Gemma Odena8 1Rosenparkklinik GmbH, Darmstadt, Germany; 2Division of Biochemistry and Molecular Biology, Cosmetic Science, University of Hamburg, Hamburg, Germany; 3Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, Kassel, Germany; 4Prager & Partner Dermatologische Praxis, Hamburg, Germany; 5Haut- Und Lasercentrum Berlin-Potsdam, Potsdam, Germany; 6SkinConcept, Munich, Germany; 7Merz Pharmaceuticals GmbH, Frankfurt Am Main, Germany; 8Merz North America, Inc., Raleigh, NC, USACorrespondence: Gerhard Sattler Email gerhard.sattler@rosenparkklinik.deBackground: Facial aging is characterized by increased prominence of nasolabial folds (NLFs), marionette lines, and thinning of the lips. Cross-linked hyaluronic acid injection is a very effective method for the temporary correction of these areas.Objective: To confirm the clinical performance and the safety of Etermis 3 (ET3) and/or Etermis 4 (ET4) in the treatment of moderate and severe wrinkles/folds, as well as lip volume enhancement.Methods: Subjects were treated in at least two facial areas (NLFs, marionette lines, lips). ET3 was used in facial moderate wrinkles while ET4 was used in severe facial skin volume loss. An optional touch-up 1 month after treatment was possible. A blinded investigator assessed improvement on Merz Aesthetic Scales (MAS). Subjects were followed-up for 12 months after the last treatment.Results: In total, 154 healthy subjects were enrolled. The proportion of subjects achieving ≥ 1 score improvement in MAS after treatment was above 60% for ET4 (Month 6/7: NLFs 94.9% and marionette lines 81.4%, p≤ 0.0004; Month 3/4: lips 63.0%, p=0.39) and ET3 (Month 6/7: marionette lines 79.4%, p=0.0005; Month 3/4: lips 65.5%, p=0.31). Facial improvement was still visible at Month 12/13 for ET4 (NLFs ≥ 76.6%, marionette lines ≥ 61%, lips ≥ 36%) and ET3 (marionette lines ≥ 50% and lips ≥ 21.9%). No treatment-related serious AEs occurred. The most frequent AEs were injection-site reactions.Conclusion: Etermis 3 and Etermis 4 demonstrated good clinical performance and safety for NLFs and marionette lines volume enhancement for up to 12 months. Both products can also be used safely to treat lips for volume augmentation.Keywords: hyaluronic acid, wrinkles, facial volume enhancement

Background The FACE-Q patient-reported outcome assesses patient experiences/outcomes with aesthetic facial procedure. A recent trial of abobotulinumtoxinA (ASI, liquid formulation) was the first to our knowledge to assess satisfaction with FACE-Q after glabellar line (GL) injection. Objectives The authors sought to evaluate patient satisfaction with ASI for GL treatment employing 3 FACE-Q scales: facial appearance, psychological well-being, and aging appearance. Methods This was a Phase 3, randomized, double-blind, placebo-controlled trial (NCT02353871) of ASI 50 units in adults with moderate-to-severe GL with 6-month follow-up. Results Significantly greater least squares mean changes from baseline were associated with ASI treatment (N = 125) vs placebo (N = 59) for satisfaction with facial appearance at all visits until day 148 (5 months; P < 0.0001-0.0037), psychological well-being at all visits (P < 0.0001-0.0279), and aging appearance at all visits except day 148 (P < 0.0001-0.0409). Significant differences (ASI vs placebo) were observed at all visits for individual items: “how rested your face looks” (P < 0.0001-0.0415), “I feel okay about myself” (P = 0.0011-0.0399), and “I feel attractive” (P < 0.0001-0.0102). Maximal least squares mean (standard error) changes in aging appearance score were −1.4 (0.3; ASI) and −0.3 (0.4; placebo). Investigators’ live assessment of GL at maximum frown significantly correlated with improvements in FACE-Q facial appearance and psychological scales (all patients: r = −0.41 and r = −0.36 [both P < 0.0001], respectively). Conclusions Significant improvements in patient satisfaction with aging, facial appearance, and, importantly, psychological well-being were demonstrated with ASI employing FACE-Q scales up to 5 to 6 months post-injection. Results support a long duration of efficacy with ASI and use of FACE-Q in future trials and clinical practice. Level of Evidence: 1

Background Safety and efficacy of botulinum toxin A for glabellar line (GL) treatment are well established. Currently approved formulations require reconstitution before injection. Objectives The authors sought to assess 6-month efficacy, safety, and patient satisfaction of new ready-to-use abobotulinumtoxinA solution for injection (ASI) in patients with moderate-to-severe GL at maximum frown. Methods The authors conducted a phase 3, double-blind, randomized, placebo-controlled trial (NCT02353871). Patients (N = 185) were randomized (2:1) to receive ASI 50 U or placebo. GL severity was evaluated at days 8, 15, 29, 57, 85, 113, 148, and 183 employing a 4-point scale for investigator’s live assessment (ILA) and subject's self-assessment (SSA). Primary endpoint was ILA of GL at maximum frown at day 29, and secondary endpoints were ILA and SSA of GL at maximum frown (all time points), patient satisfaction with GL appearance, time to onset, and duration of action. Results Responder rates were significantly higher for ASI vs placebo (88.3% vs 1.4%; P < 0.0001) at day 29 by ILA and all time points by ILA (P < 0.0001-0.0441) and SSA (P < 0.0001-0.0036). Sixty percent of patients reported onset of treatment response on or before day 3 (P < 0.0001 vs placebo), and in 5% of patients, efficacy by ILA lasted 6 months (day 183; P = 0.0441 vs placebo). Patient satisfaction rates were significantly higher for ASI vs placebo at all visits (P < 0.0001). Safety was comparable with the known abobotulinumtoxinA profile. Conclusions ASI was significantly efficacious for improving moderate or severe GL vs placebo by investigator and patient assessment. ASI was associated with high patient satisfaction, a long duration of action, and comparable safety profile to abobotulinumtoxinA. Level of Evidence: 1

The poor vascularization rate of matrices following cell invasion is considered to be one of the main shortcomings of scaffolds used in tissue engineering. In the past decade much effort has been directed towards enhancing the angiogenic potential of biomaterials. A great many studies have appeared reporting about enhancement of vascularization by immobilizing angiogenic factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor-2 (FGF-2). We have also tried to achieve this goal by modifying collagen matrices by covalent incorporation of heparin into the matrices and loading them with VEGF. We and others have observed that loading angiogenic factors to heparinized materials markedly increases angiogenic capacity. In the present paper we also investigated the angiogenic properties of collagen matrices which were only cross-linked, i.e. in the absence of heparin. The angiogenic capacity of the modified matrices was evaluated using the chorioallantoic membrane assay. Differences in angiogenic potential were deduced from macroscopic and microscopic analyses of the chorioallantoic membrane, as well as from dry weight changes. Cross-linked only matrices and matrices both cross-linked and heparinized appeared to show a significantly larger angiogenic potential than unmodified matrices. As previously observed, loading VEGF to these matrices further stepped up angiogenic potential. Quite surprisingly, cross-linking had a substantial impact on angiogenic potential. In terms of magnitude, this effect was similar to the effect of loading VEGF to heparinized matrices. Both modification procedures resulted in an increase of average pore size within the collagen matrices, and this observation may explain the more rapid invasion of mouse fibroblasts into cross-linked and heparinized matrices. Form changes of the implants were also monitored during the in vivo contacts: cross-linked and heparinized matrices showed far better resistance against contraction, as compared to unmodified matrices. Results from the chorioallantoic membrane assay experiments were compared with data obtained from rat model experiments, which confirmed the results from the chorioallantoic membrane assay. This relatively simple assay was again shown to be extremely helpful in evaluating and predicting the angiogenic capabilities of biomaterials for use in tissue engineering and wound healing.

Background: Major differences exist in residency training, and the structure and quality of residency programs differ between different countries and teaching centers. It is of vital importance that a better understanding of the similarities and differences in plastic surgery training be ascertained as a means of initiating constructive discussion and commentary among training programs worldwide. In this study, the authors provide an overview of plastic surgery training in the United States and Europe. Methods: A survey was sent to select surgeons in 10 European countries that were deemed to be regular contributors to the plastic surgery literature. The questions focused on pathway to plastic surgery residency, length of training, required pretraining experience, training scheme, research opportunities, and examinations during and after plastic surgery residency. Results: Plastic surgery residency training programs in the United States differ from the various (selected) countries in Europe and are described in detail. Conclusions: Plastic surgery education is vastly different between the United States and Europe, and even within Europe, training programs remain heterogeneous. Standardization of curricula across the different countries would improve the interaction of different centers and facilitate the exchange of vital information for quality control and future improvements. The unique characteristics of the various training programs potentially provide a basis from which to learn and to gain from one another.

Since the survival of ingrowing cells in biomaterials for regenerative processes largely depends on the supply of nutrients and oxygen, angiogenesis plays an important role in the development of new materials for tissue engineering. In this study we investigated the possibility of enhancing the angiogenic properties of collagen matrices by covalent incorporation of the vascular endothelial growth factor (VEGF). In a previous paper we already reported the use of homo- and heterobifunctional cross-linking agents for modifying collagen matrices [1]. In the present work the angiogenic growth factor was linked to the collagen with the homobifunctional cross-linker disuccinimidyldisuccinatepolyethyleneglycol (SS-PEG-SS) in a two step procedure. The efficiency of the first reaction step-the reaction of SS-PEG-SS with VEGF--was evaluated by western blot analysis. After 10 minutes virtually all of the dimeric molecules VEGF were on average modified by conjugation with 1 cross-linking molecule. The biological activity of the conjugate was investigated by exposing endothelial cells to non-modified VEGF and to VEGF conjugated to the cross-linker. The conjugation only had a limited effect on the mitogenic activity of VEGF. We therefore applied the cross-linking reaction to the VEGF-collagen system. In a first approach the changes were evaluated by the in vitro exposure of HUVECs to non-modified matrices, to matrices in which the VEGF was simply admixed and to matrices in which the VEGF was covalently incorporated. The angiogenic properties were evaluated in vivo with the chorioallantois membrane model. In this assay the chorioallantois membrane of the chicken embryo was exposed to the same set of matrices. The covalent incorporation of VEGF has a small but significant effect both on the formation of microvessels in the chorioallantois membrane and the tissue ingrowth into the implant. The covalent incorporation of angiogenic growth factors may thus be considered as a promising approach for enhancing the angiogenic capabilities of collagen matrices. Also the cross-linking with the homobifunctional cross-linking agent has a positive effect on the angiogenic potential of the collagen matrices.

This study investigates the impact of different sterilization processes on structural integrity and stability of collagen sponges designed for tissue engineering. Collagen sponges with uniform pore size (20 microm) were sterilized either with ethylene oxide (EO) or gamma irradiation (2.5 Mrad). Gamma-sterilized sponges showed a dramatic decrease of resistance against enzyme degradation and severe shrinkage after cell seeding. Collapsed porosity inhibited fibroblasts and barred completely the human umbilical vein endothelial cell ingrowth into the sponges. On the contrary, the porous structure and stability of EO-sterilized sponges remained almost unaltered. Fibroblasts and endothelial cells exhibited favorable proliferation and migration within sponges with normal morphology. Tubular formation by seeded endothelial cells occurred early in the first week. Therefore, we emphasize that the impact of sterilization of biomaterials is substantial and any new procedure has to be evaluated by correlating the impact of the procedure on the porous structure with cell proliferation behavior.

The realization of three-dimensional (3D) degradable matrices which slowly release bio-active components represents a major challenge in the field of tissue engineering. In this paper we report on the usage of commercially available bifunctional agents for both the covalent coupling of proteins to and the cross-linking of collagen matrices. Proteins – horse radish peroxidase (HRP) was used as a model protein – were cross-linked with either a homobifunctional (disuccinimidyldisuccinatepolyethylene-glycol) or a heterobifunctional (N-hydroxysuccinimidylvinylsulfonepolyethyleneglycol) agent. In the case of the heterobifunctional cross-linking agent the collagen matrices were previously modified with succinimidylacetylthioacetate in order to introduce sulfhydryl groups. As compared with control experiments a 10-fold and 50-fold increase of immobilized proteins were achieved with the homobifunctional and heterobifunctional cross-linker resp. The HRP–PEG conjugates demonstrated a better long-term stability as compared to the non-treated HRP. The effects of the cross-linking agents and the thiolation reagent succinimidylacetylthio acetate on the in vitro degradation of the collagen matrices by collagenase were also investigated. In particular the reaction with succinimidylacetylthio acetate appears to offer interesting opportunities both for coupling active proteins and modulating the degradation times of collagen matrices.

Soft tissue defects represent a challenge in plastic surgery. Therefore many research efforts have focused onto materials that support tissue formation and especially angiogenesis. But still most of the commercially available products can serve only as temporary coverage due to the small angiogenic potency.