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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

In general, matrices for tissue engineering must maintain structural integrity during the process of tissue formation and promote vascularization of developing tissue. Therefore, collagen sponges, manufactured by an approach that offers the potential of unidirectional pore size, were seeded with human umbilical vein endothelial cells (HUVEC) to demonstrate a positive effect on cell proliferation. In addition, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have been used to promote proliferation of HUVEC on optimized collagen sponges. Growth and viability of the cells were evaluated. Potential unidirectional pore structure demonstrated an improvement of both, endothelial cell growth and viability. Supplementation of growth factors showed an additional increase of endothelial cell growth on collagen sponges, which confirmed the high potential of combining this biomaterial with growth factors. The results suggest that a collagen sponge with a potential specific pore size could be a suitable scaffold for endothelial cells and might be a promising implantable biomaterial with enhanced angiogenic capabilities for future clinical applications.

Highly concentrated hyaluronic acid dermal fillers commonly contain 20 mg/ml sodium hyaluronate. The soft tissue filler SF 24 contains 24 mg/ml sodium hyaluronate. It is a viscoelastic gel, which is moderately cross-linked and specifically designed to correct moderate to deep wrinkles and folds of facial skin.To evaluate the long-term safety and effectiveness of the SF 24 for facial augmentation.The primary endpoints were effectiveness and safety, which were measured by investigators' assessment of wrinkle/ fold/ defect severity and reaction severity, respectively. The Global Esthetic Improvement Scale (GAIS) evaluated secondary endpoints, such as patient and physician satisfaction. Data collection occurred at treatment date (day 0) and at each visit set at an interval of 21 days, 121 days, 213 days, and 395 days. A total of 74 individuals (3 male and 71 female) received treatment with SF 24 across five sites. The baseline value (2. 70) of wrinkle and fold severity was reduced to 1.22 directly after treatment and remained improved even after 273 days at 1.59. The improvements compared to baseline were all significant (p .001). The injection-related reactions were mainly short-term (1-7 days), mild to moderate in severity, and resolved without intervention. SF 24 is safe and effective for facial volume augmentation. It shows long-lasting (9 months) results in treated patients.

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

BACKGROUND In clinical practice, different upper facial areas are commonly treated together. OBJECTIVE To evaluate the efficacy and safety of repeated incobotulinumtoxinA injections for the treatment of upper facial lines (UFL) in a 3-month open-label extension (OLEX) period. MATERIALS AND METHODS In the main study period (randomized, double blind, placebo controlled; n = 156), subjects with moderate-to-severe UFL (glabellar frown lines [GFL], horizontal forehead lines [HFL], and lateral periorbital lines [LPL]) on the 5-point Merz Aesthetics Scales (MAS) received 54 to 64 U incobotulinumtoxinA or placebo. In the OLEX, all subjects (n = 139) received 1 treatment with 54 to 64 U incobotulinumtoxinA. Investigator- and subject-assessed MAS scores were evaluated at rest and maximum contraction. Response was defined either as a MAS score of "none" or "mild" or a ≥1-point improvement in MAS scores. RESULTS A clear, rapid treatment response was seen in each individual treated area and for all areas combined. At Day 30, a response of none or mild at maximum contraction (investigator's rating) was reported for 80.1%, 77.2%, and 66.9% of subjects for GFL, HFL, and LPL, respectively. IncobotulinumtoxinA was well tolerated, with no evidence of an increase in adverse events with repeat injection. CONCLUSION IncobotulinumtoxinA is highly effective for the simultaneous treatment of UFL with a good safety profile (EudraCT Number: 2011-005887-20).

The literature reports many cases of cutaneous malignancy in the setting of skin tattoos. In this study, we review the reported incidence of and risk factors for tattoo-associated skin cancer. A PubMed literature review was performed for all cases of tattoo-associated skin cancer, including squamous cell carcinoma, basal cell carcinoma, malignant melanoma, keratoacanthoma, and other rare skin malignancies (source: PubMed/until June 2017). The authors identified 51 publications and 63 total cases of tattoo-associated skin cancer. We also report on a single new case of tattoo-associated skin cancer observed at one of our co-authors’ institutions. Among these 64 total cases, 58% were associated with black and blue inks and 34% were associated with red ink. Overall, while the strength of association remains unclear, the literature reports many cases of tattoo-associated skin cancer. Among these cases, black, blue, and red inks were particularly worrisome for their carcinogenic potential. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The performance of a transparent absorbent adhesive wound dressing (TAAWD) was observed over 7 days in five plastic surgery clinics across Germany. The study included 47 diverse postoperative linear wounds and donor sites with dry or minimal exudate levels. Data on ease of application and removal, adhesive strength, skin compatibility, conformability to the body, visual wound inspection and parameters of wound assessment were collected and analysed. At the end of the observation period, 100% of wounds were recorded as healing with no reported complications. Clinicians considered that the new dressing had predominantly met clinical needs in 89% of cases. The dressing was shown to be skin friendly, easy to apply, adhere and conform to the skin while protecting the wound and allowing the patient to shower. Due to its transparency, the dressing enabled direct wound surveillance without potential disruption to the wound and healing process.

Patienten informieren sich heute deutlich eingehender als vor zehn Jahren, bevor sie sich fur einen Eingriff oder einen Arzt entscheiden. Doch nach welchen Kriterien geschieht diese Arztselektion und wie konnen Sie diese beeinflussen? Der Beitrag gibt Ihnen aktuelle Antworten.

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.

One of the prominent shortcomings of matrices for tissue engineering is their poor ability to support angiogenesis. We report here on experiments to enhance the angiogenic properties of collagen matrices. Our aim is to achieve this goal by covalently incorporating heparin into collagen matrices and by physically immobilizing angiogenic vascular endothelial growth factor (VEGF) to the heparin. The immobilization of heparin was performed with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS). Carboxyl groups on the heparin are activated to succinimidyl esters, which react with amino functions on the collagen to zero length cross-links. This modification leads--in addition to the incorporation of heparin--to gross changes in in vitro degradation behavior and water-binding capacity. As a first approach to testing angiogenic capabilities, endothelial cells were exposed to nonmodified and heparinized collagen matrices. This exposure leads to an increase in endothelial cell proliferation. The increase can be further enhanced by loading the (heparinized) collagen matrices with VEGF. Evaluation of the angiogenic potential of heparinized matrices was further investigated by exposing them to the chorioallantoic membrane of chicken embryos and to the subcutaneous tissue of rats. Both approaches show that heparinized matrices have substantially increased angiogenic potential. In particular, the loading of heparinized matrices with VEGF invokes a further increase in angiogenic potential. It is apparent that the physical binding of VEGF to heparin allows for a release that is beneficial to angiogenesis. By varying the heparin and EDC/NHS concentrations during the modification process and by varying the loading with VEGF, the angiogenic potential as well as the degradation behavior can be adapted to obtain matrices that fulfill specific angiogenic requirements in the field of tissue engineering.

The clinical use of an artificial skin substitute (Integra®) has been celebrated enthusiastically as an improvement in burn therapy over a period of more than 10 years. Many case-reports have shown the positive effects of the treatment with Integra® as a skin substitute. In this study we examine the alterations of Integra®-usage in Germany. Fifteen German burn centres have been interviewed respectively over a time period of 6 years with interviews in the years 1999, 2001, and 2003. The goal of this study is to focus on the problems associated with the use of artificial skin and to create a manual for Integra®-therapy including indication, pre-, intra-, and postoperative treatment. Since the first Integra® Users seminar in Germany in 1999 repeated interviews have been conducted with fifteen German burn centres. The collected results of the last 6 years were evaluated. These results show a change in the indication for the therapy with artificial skin towards extensive full thickness burned patients and as extended indication especially for posttraumatic reconstruction. This article gives our guidelines for the usage and handling of Integra® and shows that Integra is an important reconstructive dermal substitute for the severely burned or posttraumatic patient if handled by a skilled surgeon in a correct way.

The surgical goal in Mobius patients is far more modest and differs from patients with unilateral developmental facial paralysis. It is impossible to restore a true smile in these mask-like, expressionless faces. Despite sophisticated microneurovascular transplantations, movement can only be restored along one vector and enhanced firmness in the cheeks, thus multiple differentiated facial animation is not achievable. A detailed neurological evaluation can identify possible motor donors or residual function, which can be used for additional dynamic restorations. Due to the multiple cranial nerve involvement a thorough clinical and electrophysiological examination is mandatory. In addition, electromyographic survey of the potential motor donors is very helpful to avoid weak wasted regeneration and prevent further downgrading of function. Because of the variety of cranial nerves involved in Möbius' syndrome, a standard procedure for dynamic restoration cannot and should not be promoted; instead, a careful preoperative objective and quantitative assessment should guide the reconstructive surgeon to the optimal reconstruction strategy. Useful movement can be restored in afflicted patients that may signal physical and psychological rehabilitation.

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.

This study investigated axonal regeneration in a denervated nerve graft sutured end-to-side with a main peripheral nerve trunk. To demonstrate morphologic changes, the peroneal nerve was severed in a rat and coapted end-to-side to the posterior tibial nerve. The integrity of the epineurial and perineurial sheath was altered in four different groups. Histologic evaluation 30 days after operation showed axonal regeneration in the nerve graft in all groups. Morphometric analysis of cross sections of the grafted nerve elucidated the importance of severance of the perineurium in end-to-side neurorrhaphy.

The vascularization of engineered tissues in many cases does not keep up with the ingrowth of cells. Nutrient and oxygen supply are not sufficient, which ultimately leads to the death of the invading cells. The enhancement of the angiogenic capabilities of engineered tissues therefore represents a major challenge in the field of tissue engineering. The immobilization of angiogenic growth factors may be useful for enhancing angiogenesis. The most potent angiogenic growth factor specific to endothelial cells, vascular endothelial growth factor (VEGF), occurs in several splice variants. The variant with 165 amino acids both has a high angiogenic activity and a high affinity for heparin. We therefore incorporated heparin molecules into collagen matrices by covalently cross-linking them to amino functions on the collagen. Physical binding of VEGF to the heparin may then prevent a rapid clearance from the implant, while the release rate may become coupled to the degradation of the collagen matrix. The modified matrices were characterized by determination of the extent of the heparin immobilization, the in vitro degradation rate by collagenase. For testing the angiogenic properties, non-modified and heparinized collagen specimens were – either loaded with VEGF or non-loaded – subcutaneously implanted on the back of rats. Specimens were explanted after varying periods of implantation, the dry weights and the hemoglobin contents, as well as immunostained histological sections were evaluated: heparinized collagen matrices loaded with VEGF are vascularized to a substantially higher extent as compared to non-modified 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.

The wound-healing process of patients with severe burns often leads to the formation of extensive fibrotic scars. In this study, serum concentrations of tissue inhibitors of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and amino-terminal propeptide of procollagen type III (PIIINP) were measured by enzyme-linked immunosorbent assay as markers for excessive cicatrization in 22 patients with acute burn injuries. All patients were followed up for 6 months to determine a fibrotic reaction during the wound-healing process after operative treatment using the Burn Scar Index. Blood samples were drawn immediately before the operation; at postoperative days 1, 3, 7, and 14; and 1, 3, and 6 months after the operation. Twenty patients who underwent elective plastic surgical operations served as the control group. There was a significant increase (p < 0.05) of TIMP-1 in the burned patients by the third postoperative day. Later in the follow-up period, the serum concentrations remained at a significantly elevated level (p < 0.05) compared with preoperative values. In comparison with the control group, the postoperative serum concentrations of TIMP-1 of the burned patients were significantly higher (p < 0.05) at any time and correlated with the total body surface area burned at the third and seventh postoperative days (p < 0.05; r2 = 0.46 versus r2 = 0.53) and the Burn Scar Index after 6 months (p < 0.05; r2 = 0.65). Serum levels of MMP-2 and MMP-9 showed a significant elevation (p < 0.05) only between postoperative days 3 and 14 in patients with burn wounds. PIIINP increased significantly (p < 0.05) in the sera of the burned patients at postoperative day 3 and remained significantly elevated up to 6 months after injury. At any time after trauma, PIIINP serum levels were significantly higher (p < 0.05) in the burned patients than in the control group and correlated with the total body surface area burned at postoperative days 3 and 7 (p < 0.05; r2 = 0.41 versus r2 = 0.44) and the Burn Scar Index after 6 months (p < 0.05; r2 = 0.5). Obviously, the physiological balance between matrix metalloproteinases and their endogenous inhibitors is disturbed after burn trauma. The elevated systemic TIMP-1 concentration might contribute to tissue fibrosis, leading to pathological scar formation. The increase of PIIINP after thermal trauma indicates a fibrogenic component of wound healing.

The present study investigates factors influencing the quality of life and social reintegration of burn victims. A study concept was developed to assess the functional and aesthetic long-term outcomes of burn victims. Objective data from a clinical examination was correlated with subjective data from completed questionnaires. The success of social rehabilitation was documented and an indicative profile of life quality evaluated. This profile could prompt early intervention if found necessary. Ninety-two patients were examined 5.4±1.1 years after trauma in relation to three factors: physical functions, localization of the burn injuries and extent of the body surface area burned. Physical functioning allows the best predictions for successful rehabilitation, because all areas of life quality are affected by it. Localization of burns in the face and hands creates disadvantages in social reintegration. Of less value in prediction is the extent of the body surface area burned, which is only closely linked to occupational rehabilitation and directly correlates to physical functional limitations. Our correlation showed, that even slight functional limitations were linked to severe depressions, similar to the values found with patients with serious functional impairment. Interdisciplinary cooperation between plastic surgeons and psychosomatic specialists will optimize early intervention with patients exposed to social maladaptation.

The amino-terminal propeptide of procollagen type III (PIIINP) has been proposed as a marker for fibrogenesis in patients with different fibroproliferative disorders, e.g. liver and lung fibrosis. In this study, serum concentrations of PIIINP were measured by ELISA as a marker for excessive cicatrization in burned patients before and after scar correction. All patients were followed 6 months to determine a new fibrotic reaction during the wound healing process using the Burn Scar Index and to correlate pre- and post-operative concentrations of PIIINP in their sera with the risk to develop a new severe tissue fibrosis leading to pathological scar formation. Furthermore, PIIINP was determined in the excised scar tissue by immunohistochemistry. The study included 38 patients. Nineteen patients (8 female, 11 male, average age 48.3+/-18.9 years) had hypertrophic scars after major burn injury (TBSA, 21+/-12%; Burn Scar Index, 10.4+/-3.7 points) and underwent scar correction. Nineteen patients (12 female, 7 male, average age 42.3+/-25.5 years) who underwent elective plastic-surgical operations served as the control group. Blood samples were drawn immediately before operation, at the 1st, 3rd, 7th, and 14th post-operative days, as well as 1st, 3rd, and 6th months after operation.Pre-operatively, PIIINP was significantly elevated (P

Life threatening burn injuries during vacations abroad raise special problems. Depending on the infrastructure of the country, adequate medical care can be delayed and communication between the patient and the medical staff is frequently impossible due to language barriers. Often the patient finds himself in a critical condition, isolated from supporting relatives and financial difficulties may occur. By summarising three cases referred to our centre, we aim to emphasise particularities of the primary management of burned victims at foreign hospitals, their transport, and following therapy at a domestic burn unit. Primary shock treatment and vital surgical interventions, e.g. escharotomy or treatment of the concomitant trauma, are subject to the facility of the hosting country. After management of the acute phase and initiation of local wound treatment, the next step should be to stabilise and prepare the patient for transport. Aeromedical transportation with physician attendency, as well as contact with a domestic burn centre can be established via responsible organisations. At the domestic hospital, every burn victim from abroad deserves special attention. Wound colonisation with different bacterial species or fungi than the usual spectrum of the centre and the risk of crossinfections should be taken in account of the treating medical team. An structure plan for appropriate and continuing surgical treatment is necessary to prevent deterioration of the patient's condition and to optimise wound closure with autologous skin grafts or allogenic materials.

Automobile air bags have gained acceptance as an effective measure to reduce the morbidity and mortality associated with motor vehicle accidents. As more cars have become equipped with them, new problems have been encountered that are directly attributable to the deployment of the bag itself. An increasing variety of associated injuries has been reported, including minor burns. We present two automobile drivers who were involved in front-impact crashes with air bag inflation. They sustained superficial and partial-thickness burns related to the deployment. The evaluation of these cases shows mechanisms involved in burn injuries caused by the air bag system. Most of the burns are chemical and usually attributed to sodium hydroxide in the aerosol created during deployment. Also direct thermal burns from high-temperature gases or indirect injuries due to the melting of clothing, as well as friction burns from physical contact are possible. However, the inherent risks of air bag-related burns are still outweighed by the benefits of preventing potentially life-threatening injuries.

This research group has introduced a model of end-to-side neurorrhaphy, in which reinnervation occurs without frank damage to donor axons. The current study used in situ hybridization to test the hypothesis that insulin-like growth factor (IGF-I and IGF-II) mRNA levels increase at the coaptation site and grafted nerve following end-to-side repair, and that this increase is associated with axonal sprouting and growth. One week after end-to-side coaptation, IGF-I mRNA was localized predominantly on the epineurial side of the graft perineurium, while IGF-II was seen mainly on the endoneurial side. IGF-I hybridization was greatest at this time and declined by 2 weeks post-procedure. No changes in IGF mRNA levels occurred in the distal donor nerve. The increase in IGF-I mRNA at 1 week preceded the appearance of myelinated axons. The presence of myelinated axons within the graft 2 weeks after end-to-side coaptation was associated with a decline in IGF-I mRNA. These data are the first to demonstrate increased IGF mRNA levels associated with axonal sprouting and growth following end-to-side neurorrhaphy. Moreover, the findings support those of earlier studies by others implicating IGFs in axonal regeneration. The increase in IGF mRNA during sprouting and axonal growth into an end-to-side coaptation indicates that the local therapeutic augmentation of endogenous IGF levels at the coaptation site may enhance axonal sprouting from a minimally injured donor nerve, and thereby increase the number of axons that reinnervate the graft.

Die Plastische Chirurgie, die oft nur als reine Schonheitschirurgie angesehen wird, beinhaltet die Versorgung von Handverletzungen, Verbrennungen sowie wiederherstellende Masnahmen am gesamten Korper. Plastische Chirurgen behandeln nicht nur akute Verletzungen, sondern rekonstruieren auch chronische Defekte und Fehlbildungen. Naturlich werden dabei neben der Wiederherstellung der Funktionen auch asthetische Grundprinzipien berucksichtigt.