Skin Wound Healing: Of Players, Patterns, and Processes.

BACKGROUND: Wound healing of the skin is a very complex biological activity. For a better understanding, an attempt is made to describe and subdivide the different players (cell types and signaling molecules), patterns (different regeneration or repair mechanisms), and processes (division of the overall process into categories, phases, and steps). However, this is always based on different points of view. On the one hand, the temporality of the phases and on the other hand, the dominant activity in each step can play a role. In addition, classifications according to wound theory and wound treatment are possible. SUMMARY: To gain an initial overview of (human) skin wound healing, simple classifications are advantageous for understanding and thus deserve to exist. The complexity of the underlying biology of skin wound healing takes on a multidimensional configuration upon closer examination, in which new actors are constantly being identified, making the events more precise and comprehensible but also significantly confusing when viewed as a whole. From this point of view, the healing process must be categorized so that the observer does not get lost in the multitude of interacting processes. In view of the steadily increasing knowledge, which includes in parallel the physiological as well as the pathophysiological processes of wound healing, the classification according to function in the sense of consecutive and overlapping phases seems the most convenient and considers the corresponding processes more precisely. Despite that many mechanisms and specific cellular functions in wound healing have been identified, many underlying (patho-)physiological processes still remain unknown. KEY MESSAGES: Currently, a substantial part of research activities in medicine is limited to molecular levels, while evidence for therapies currently in use is lacking or newly gained knowledge is quite far from clinical applicability and reality. This article aimed to shed more light on the various classifications of skin wound healing and presents the underlying paradigms starting from simple approaches and ending with more detailed concepts.

[Balancing Family and Career in Medicine: Greatly Desired but Given Little Consideration Results of the Study Arm VI of the KARiMED Study]. / Vereinbarkeit von Familie und Beruf in der Medizin: vom großen Wunsch und wenig Berücksichtigung.

AIM OF THE STUDY: Family life and professional practice are both highly important for young physicians. Accordingly, a good balancing of both areas of life is necessary. Despite political framework conditions and legal requirements that have been in place for years, implementation of measures to achieve this seems to be difficult, especially in medicine, and is associated with great reservations and problems on the part of those involved. METHODS: By means of an online survey, the medical mid-level staff from university and peripheral hospitals was questioned on topics related to family, children and professional biographical as well as career-relevant topics and subsequently analyzed on a gender-specific basis. RESULTS: Of the study participants, 65.1% were married and already had children or expressed a desire to have children (86.0%). Most were employed full-time (80.8%). The majority of part-time employees were female (87.4%). For 34.6%, there was a career break of 18.5±21.3 months, 87.8% of which were taken due to pregnancy or children. Female physicians generally took significantly more parental leave than male physicians (6-12 months: females 62.2%; males 22.4%; 12 months or more: females 25.2%; males 6.6%). Family planning received little support from superiors (21.2% much to very much support) and 45.6% reported having experienced problems with their return to work or career advancement. Almost 60% of the participants did not have any specific working time models in their own hospital for employees with children who need to be cared for. CONCLUSION: In order to implement a work-life balance for physicians, changes are first and foremost necessary on the part of the institutions. In addition, the respective superiors must rethink in order to enable a parallelization of these two areas of their employees' lives. However, young physicians must also rethink their view of this issue. Demanding changes in labor law while continuing traditional family constellations at home does not seem to do address this issue adequately.

[Academic Careers in Medicine: a Sex-Related Analysis of Career Goals]. / Akademische Karriere in der Medizin: eine geschlechterbezogene Analyse zu beruflichen Zielen.

AIM OF THE STUDY: For female and male physicians of the clinical-academic mid-level staff, working conditions as well as the attitude towards profession and career play a decisive role. For years, there has been an increasing proportion of women in medicine. Despite this increase, a significant sex incongruence is still evident, especially in academic medicine. The aim of this work was to analyze current opinions of female and male physicians on sex-related aspects for career. METHODS: By means of an online survey, medical mid-level staff from university and peripheral hospitals were asked about professional biographical as well as career-related topics and the data analyzed in terms of the sexes. RESULTS: Compared to their male counterparts, female physicians had lower career goals and mainly aimed to qualify as senior physicians. Women planned to have families and raise children earlier in their careers. Men were more likely to have their professional careers in mind during the same time period. Although only just under 47% of respondents considered an academic career to be worthwhile, 65% continued to rate the acquisition of an academic title highly. When evaluating equal treatment by superiors, female physicians tended to feel disadvantaged in their professional careers compared to male physicians. Thus, physicians rated the treatment by their respective superiors as characterized by the quality of the work (44% for both genders of superiors) or dependent on sympathy (female superiors 30%; male superiors 24%). Female physicians, however, saw a preference for male colleagues in 37% of male superiors. CONCLUSION: Despite a significantly larger proportion of women in medicine for decades, there is still an incongruence in sexes in favor of men in management positions. The professional and private goals of women and men differ significantly depending on their age decade. The academic career per se is increasingly losing importance, although the acquisition of academic degrees still seems to be desirable. Therefore, to improve the future of academic medicine, significant structural changes are needed to enable projectable career paths (e. g., tenure track, assistant professorship, young medical professionals model) for mid-level academic staff.

Focused electromagnetic high-energetic extracorporeal shockwave (ESWT) reduces pain levels in the nodular state of Dupuytren's disease-a randomized controlled trial (DupuyShock).

Dupuytren's disease is a progressive fibroproliferative disorder of the hand. In the nodular stage of Dupuytren's disease, pain might limit daily hand activities and progress to finger contractures. Focused electromagnetic high-energetic extracorporeal shockwave therapy (ESWT) may reduce pain in Dupuytren's nodules (Tubiana N). In this prospective, randomized, blinded, placebo-controlled single center trial, we enrolled 52 patients (mean age, 58.2 ± 9.2) with painful nodular Dupuytren disease Tubiana N. Randomization was done to either (group A) 3 treatments with focused electromagnetic high-energetic ESWT (2000 shots, 3 Hz, 0.35 mmJ/mm2/hand, Storz Duolith SD1, n = 27) or (group B) placebo ESWT (2000 shots, 3 Hz, 0.01 mJ/mm2/hand, n = 25) in a weekly interval. Primary outcome was the level of pain on a visual analogue scale (VAS 0-10) at 3/6/12/18 months, secondary outcomes were patient-related outcome measures (DASH score, MHQ score, URAM scale), grip strength, patient's satisfaction, and Dupuytren's disease progression over 18 months follow-up. Focused ESWT significantly improved outcomes. Pain was reduced from 3.6 ± 1.8 to 1.9 ± 1.2 at three, to 1.4 ± 0.7 at six, to 1.7 ± 1.6 after 12 months and 1.9 ± 0.8 after 18 months in the intervention group (47% reduction, p < 0.05). In the placebo group, pain on VAS increased from 2.2 ± 1.4 to 3.4 ± 1.7 at three, to 3.4 ± 1.8 at six, to 3.4 ± 1.4 at 12 and 3.1 ± 1.1 at 18 months (35% increase, p < 0.05). Quality-of-life score tended to improve in the intervention group (MHQ, 77 ± 19 to 83 ± 12; DASH, 12 ± 18 to 10 ± 9) while it deteriorated in the placebo group as Dupuytren's disease was progressing (MHQ, 79 ± 15 to 73 ± 17; DASH, 6 ± 10 to 14 ± 13). The strength of the affected hand and fingers did not change significantly in either of the groups. Patients' satisfaction was higher in the intervention group for symptom improvement (56% vs. 12%) and reduction of disease progression (59% vs. 24%). Any Dupuytren-related intervention was performed in 26% in the intervention group and in 36% in the placebo group within 18 months of follow-up (n.s.). Focused electromagnetic high-energetic ESWT can significantly reduce pain in painful nodules in Dupuytren's disease in an 18-month perspective. ( ClinicalTrials.gov Identifier: NCT01184586).

Effects of Extracorporeal Shock Waves on Microcirculation and Angiogenesis in the in vivo Wound Model of the Diver Box.

INTRODUCTION: Extracorporeal shock waves (ESWs) have been shown to have a positive effect on skin wound healing; however, little is known on the regeneration of the microcirculation and angiogenesis as well as the different application modes. METHODS: A total of 40 BALB/c mice were provided with dorsal skin fold chambers and were divided into 3 therapy groups (n = 30) and one control group (n = 10). The 3 therapy groups were treated with shock waves at different pulse rates (500-1,000 pulses/min) and application frequencies (day 0 and day 6 or day 0 only). Photographic documentation and intravital microscopy were carried out on day 1, 2, 4, and 6 after wounding. RESULTS: Using the newly developed Diver Box, shock waves could be applied in vivo without mechanical tissue damage. Shock wave therapy to skin wounds demonstrated to induce faster wound closure rates in the beginning than controls in groups with higher pulse rates and frequencies of the shock waves. Furthermore, the regeneration of microcirculation and perfusion in the healing skin was significantly improved after the application of, in particular, higher pulse rates as given by increased numbers of perfused capillaries and functional vessel density. The study of inflammation showed, especially in high-pulse ESW groups, higher leukocyte counts, and rolling leukocytes over time until day 6 as a response to the induction of inflammatory reaction after ESW application. Angiogenesis showed a marked increase in positive areas as given by sprouts, coils, and recruitments in all ESW groups, especially between days 4 and 6. CONCLUSION: The major findings of this trial demonstrate that ESW therapy to skin wounds is effective and safe. This is demonstrated by the initially faster wound closure rate, but later the same wound closure rate in the treatment groups than in controls. Furthermore, during the regeneration of microcirculation and perfusion in the healing skin, a significant improvement was observed after the application of, in particular, higher ESW pulse rates, suggesting an ESW-related increase in nutrient and oxygen supply in the wound tissue.

Panta Rhei: Neovascularization, Angiogenesis and Nutritive Perfusion in Wound Healing.

BACKGROUND: In response to tissue damage, angiogenesis is an extremely dynamic process that is finely regulated by signals from cells, the surrounding extracellular matrix (ECM), and derived mediators. As the only process, angiogenesis remains of decisive importance in the context of the entire wound healing process and is subject to constant change. The dissolution of the endothelial basement membrane, the migration of endothelial cells, and the development of new capillary vessels during wound healing depend not only on the cells and cytokines present, but also on the production and organization of ECM components in the immediate wound. SUMMARY: Angiogenesis in wound healing can be divided into two main phases. During the pro-angiogenic phase at the beginning of wound healing, excessive neo-formation of blood vessels, some of which are poorly differentiated, occurs, which restore blood flow and thus nutritive perfusion as quickly as possible. This is followed by an anti-angiogenic phase in which the initially established vascular network undergoes a maturing process, which, however, is accompanied by a significant reduction in the number of vessels. Key Messages: Although many mechanisms and specific cell functions in wound healing have already been described, many underlying pathophysiological processes remain unknown. Because angiogenesis and its maturation is a very fast but also very long-lasting process, the understanding of the underlying mechanisms is of crucial importance. This article will give an overview of the current understanding and controversy in this sub-step of wound healing.

Trendy Tattoos-Maybe a Serious Health Risk?

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. LEVEL OF EVIDENCE IV: 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 .

Skin Wound Healing: An Update on the Current Knowledge and Concepts.

BACKGROUND: The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention. Chronic conditions such as diabetes mellitus or peripheral vascular disease can lead to impaired wound healing. Acute trauma such as degloving or large-scale thermal injuries are followed by a loss of skin organ function rendering the organism vulnerable to infections, thermal dysregulation, and fluid loss. METHODS: For this update article, we have reviewed the actual literature on skin wound healing purposes focusing on the main phases of wound healing, i.e., inflammation, proliferation, epithelialization, angiogenesis, remodeling, and scarring. RESULTS: The reader will get briefed on new insights and up-to-date concepts in skin wound healing. The macrophage as a key player in the inflammatory phase will be highlighted. During the epithelialization process, we will present the different concepts of how the wound will get closed, e.g., leapfrogging, lamellipodial crawling, shuffling, and the stem cell niche. The neovascularization represents an essential component in wound healing due to its fundamental impact from the very beginning after skin injury until the end of the wound remodeling. Here, the distinct pattern of the neovascularization process and the special new functions of the pericyte will be underscored. At the end, this update will present 3 topics of high interest in skin wound healing issues, dealing with scarring, tissue engineering, and plasma application. CONCLUSION: Although wound healing mechanisms and specific cell functions in wound repair have been delineated in part, many underlying pathophysiological processes are still unknown. The purpose of the following update on skin wound healing is to focus on the different phases and to brief the reader on the current knowledge and new insights. Skin wound healing is a complex process, which is dependent on many cell types and mediators interacting in a highly sophisticated temporal sequence. Although some interactions during the healing process are crucial, redundancy is high and other cells or mediators can adopt functions or signaling without major complications.

Remote effects of extracorporeal shock wave therapy on cutaneous microcirculation.

BACKGROUND: Extracorporeal shock wave treatment (ESWT) has proven its clinical benefits in different fields of medicine. Tissue regeneration and healing is improved after shock wave treatment. Even in the case of burn wounds angiogenesis and re-epithelialization is accelerated, but ESWT in extensive burn wounds is impracticable. HYPOTHESIS: High energy ESWT influences cutaneous microcirculation at body regions remote from application site. METHODS: Eighteen Sprague Dawley rats were randomly assigned to two groups and received either high energy ESWT (Group A: total 1000 impulses, 10 J) or placebo shock wave treatment (Group B: 0 impulses, 0 J), applied to the dorsal lower leg of the hind limb. Ten minutes later microcirculatory effects were assessed at the contralateral lower leg of the hind limb (remote body region) by combined Laser-Doppler-Imaging and Photospectrometry. RESULTS: In Group A cutaneous capillary blood velocity was significantly increased by 152.8% vs. placebo ESWT at the remote body location (p = 0.01). Postcapillary venous filling pressure remained statistically unchanged (p > 0.05), while cutaneous tissue oxygen saturation increased by 12.7% in Group A (p = 0.220). CONCLUSION: High energy ESWT affects cutaneous hemodynamics in body regions remote from application site in a standard rat model. The results of this preliminary study indicate that ESWT might be beneficial even in disseminated and extensive burn wounds by remote shock wave effects and should therefore be subject to further scientific evaluation.

Coating of an anti-Fas antibody on silicone: first in vivo results.

BACKGROUND: Although the etiology of capsular contracture after breast augmentation has not yet been definitively clarified, the literature contains numerous reports placing the blame on a foreign body reaction. We have developed a procedure for covalently activating a silicone surface with an anti-Fas antibody, which might suppress the foreign body reaction on the silicone surface. OBJECTIVES: The authors evaluate whether surrounding tissue might be influenced by anti-Fas antibody coating on silicone disks in comparison to untreated silicone disks in an in vivo model. METHODS: During this study, 4-mm anti-Fas-coated silicone disks were implanted subcutaneously in the paravertebral region of mice (C57/BL6). Silicone disks passing the activation coating process without anti-Fas antibody incubation were defined as the control group. Twelve weeks after implantation, the disks were removed and the surrounding tissue examined. RESULTS: The tissue surrounding the silicone disks in the experimental group showed significantly increased levels of collagen type 3, elevated levels of matrix metalloproteinase 9, markedly decreased levels of transforming growth factor ß2, and a reduced CD68 expression in the pericapsular tissue. CONCLUSIONS: The first in vivo data reveal that the tissue surrounding a silicone surface can be influenced by the vectored binding of an anti-Fas antibody.

The nonhematopoietic effects of erythropoietin in skin regeneration and repair: from basic research to clinical use.

Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound-healing phases in a dose-dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound-healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.

Free Flaps for Skin and Soft Tissue Reconstruction in the Elderly Patient: Indication or Contraindication.

BACKGROUND: Increased lifespan and the improvement of medical treatment have given rise to research in reconstructive procedures in elderly patients. Higher postoperative complication rates, longer rehabilitation, and surgical difficulties remain a problem in the elderly. We asked whether a free flap in elderly patients is an indication or a contraindication and performed a retrospective, monocentric study. METHODS: Patients were divided into two groups (YOUNG 0-59 years; OLD > 60 years). The endpoint was the survival of flaps and their dependence on patient- and surgery-specific parameters using multivariate analysis. RESULTS: A total of 110 patients (OLD n = 59) underwent 129 flaps. The chance of flap loss increased as soon as two flaps were performed in one surgery. Anterior lateral thigh flaps had the highest chance for flap survival. Compared with the lower extremity, the head/neck/trunk group had a significantly increased chance of flap loss. There was a significant increase in the odds of flap loss in linear relation to the administration of erythrocyte concentrates. CONCLUSION: The results confirm that free flap surgery can be indicated as a safe method for the elderly. Perioperative parameters such as two flaps in one surgery and transfusion regimens must be considered as risk factors for flap loss.

[How important is an academic career in medicine today? A survey among medical students in Germany: Results of study arm XIII of the KARiMED study]. / Wie wichtig ist heute noch eine akademische Karriere in der Medizin? Eine Befragung von Medizinstudierenden in Deutschland: Ergebnisse des Studienarms XIII der KARiMED-Studie.

OBJECTIVE: Academic careers still play a significant role in medicine. Although the doctorate remains interesting for many students, there are no data available from medical students, for example, with regard to the interest in habilitation. In parallel, a good work-life/family balance is a key career element for young medical professionals. The aim was to obtain an up-to-date opinion on the academic career of medical students. METHODOLOGY: Using an online survey, medical students of all semesters in Germany were questioned on the topics of academic career, mentoring, and work-life balance from October 2017 to December 2018. For this purpose, the medical students were invited by e-mail to participate and answer an anonymized online questionnaire. RESULTS: A total of 1,775 participants from all 38 German medical faculties (68.3% female; age 23.3 ±â€¯4.0 years) were included. Almost half of the participants could envision working in a branch office after graduation. While a professional career appeared important to a clear majority (70.8%), leisure time was rated as even more important (84.3%), and work-life balance clearly prioritized personal life (41.2%) over career (9.6%). Acquiring a title was rated as important to one's career by 53.6%. However, while the acquisition of a doctorate was still an option for 88.0% of the respondents, the situation is significantly different for academic titles following a successful habilitation. Although the significance of a habilitation is rated as high to very high (66.1%), the titles of assistant professor ("yes": 13.0%), associate professor (6.0%) or university professor (7.0%) are much less likely to be considered by medical students and are therefore rated as "maybe" and "no". Nevertheless, almost 60% wished for better information and advice in their future field of work. CONCLUSION: Careers in medicine are undergoing a transformation where better compatibility of leisure/family and work is no longer the sole focus. On the contrary, work-life blending is sought, as a connection between work and life. Changes are therefore necessary for professional and especially academic careers in order to make working in science and research attractive again.

Diabetes and peripheral arterial occlusive disease impair the cutaneous tissue oxygenation in dorsal hand microcirculation of elderly adults: implications for hand rejuvenation.

BACKGROUND: In spite of potential implications for anti-aging therapy regarding the selection of the most suitable therapeutical method and potential perinterventional complications, cutaneous microcirculation of the aging hand in healthy individuals as well as in those with diabetes mellitus or peripheral arterial occlusive disease (PAOD) has never been evaluated. HYPOTHESIS: Functional microcirculation of the dorsal hand differs between healthy individuals and individuals with diabetes or PAOD at the same age. MATERIALS AND METHODS: Prospective controlled cohort study. One hundred ten individuals were allocated to group A (healthy individuals, n = 37), group B (diabetes mellitus, n = 36), and group C (PAOD, n = 37). Microcirculatory data were obtained using combined laser-Doppler and photospectrometry. RESULTS: Cutaneous oxygen saturation at the dorsal hand of healthy individuals was 11.1% higher than of those with diabetes mellitus (p = .04) and 18.8% higher than of those with PAOD (p = .001). Cutaneous capillary blood flow in participants with PAOD was 20% higher than in healthy individuals (p = .047). CONCLUSION: This is the first study demonstrating that capillary microcirculation of the dorsal hand differs between healthy individuals and those with diabetes or PAOD of the same age. Further studies should explore whether ameliorating cutaneous tissue oxygen saturation could emerge as a viable antiaging strategy for elderly hands.

Digitalization in Medicine: Are German Medical Students Well Prepared for the Future?

The German healthcare system is facing a major transformation towards digitalized medicine. The aim was to find out the attitude and the degree of preparation of upcoming medical professionals for digital medicine. By means of an online survey, medical students from 38 German faculties were asked about different topics concerning digitalization. Most students (70.0%) indicated that they had not had any university courses on digital topics. Thus, only 22.2% feel prepared for the technical reality of digitalized medicine. Most fear losing patient contact because of digitalized medicine and assume that the medical profession will not be endangered by digitalization. Security systems, data protection, infrastructure and inadequate training are cited as the top problems of digitalization in medicine. Medical students have major concerns about incorrect decisions and the consecutive medicolegal aspects of using digital support as part their treatment plans. Digitalization in medicine is progressing faster than it can currently be implemented in the practical work. The generations involved have different understandings of technology, and there is a lack of curricular training in medical schools. There must be a significant improvement in training in digital medical skills so that the current and future healthcare professionals are better prepared for digitalized medicine.

Improving Vascularization of Biomaterials for Skin and Bone Regeneration by Surface Modification: A Narrative Review on Experimental Research.

Artificial tissue substitutes are of great interest for the reconstruction of destroyed and non-functional skin or bone tissue due to its scarcity. Biomaterials used as scaffolds for tissue regeneration are non-vascularized synthetic tissues and often based on polymers, which need ingrowth of new blood vessels to ensure nutrition and metabolism. This review summarizes previous approaches and highlights advances in vascularization strategies after implantation of surface-modified biomaterials for skin and bone tissue regeneration. The efficient integration of biomaterial, bioactive coating with endogenous degradable matrix proteins, physiochemical modifications, or surface geometry changes represents promising approaches. The results show that the induction of angiogenesis in the implant site as well as the vascularization of biomaterials can be influenced by specific surface modifications. The neovascularization of a biomaterial can be supported by the application of pro-angiogenic substances as well as by biomimetic surface coatings and physical or chemical surface activations. Furthermore, it was confirmed that the geometric properties of the three-dimensional biomaterial matrix play a central role, as they guide or even enable the ingrowth of blood vessels into a biomaterial.

Facilitation of adhesion and spreading of endothelial cells on silicone oxide-coated dacron material by microwave-excited low-pressure plasma.

OBJECTIVES: Autologous transplants are still the means of choice for bypass surgery. In addition to good tolerability, there is a reduced thrombogenicity and fewer neointima hyperplasia compared to artificial materials. However, since viable transplants are limited, attempts are being made to improve existing artificial vascular prosthesis material. Next to the reduction of thrombogenicity, a rapid endothelialization of the vascular graft should reduce intimal hyperplasia and thus prevent stenoses. The effect of newly developed silicon oxide coatings on the growth of endothelial cells was therefore the goal of this work in a cell culture study. METHODS: A woven, uncoated polyethylene terephthalate (PET) vessel prosthesis was used. The coating process was carried out in a low-pressure plasma reactor in a multi-step process. After preparation of the vacuum chamber hexamethyldisiloxane (HDMSO) with oxygen was evaporated using argon plasma. By this an approx. 1 nm thin adhesion promoter layer was separated from plasma and HMDSO. The silicone oxide barrier layer was applied to the PET vessel samples. The carbon content of the layer could be selectively altered by changing the HMDSO oxygen flow ratio, resulting in coatings of 100 nm, 500 nm, and 1,000 nm. In addition, two different oxygen-to-HMDSO ratios were used. To achieve a carbon coating as low as possible, the ratio was set to 200:1. A carbon-rich layer was obtained with the 1:1 setting. The various coatings were then examined for their surface texture by scanning electron microscopy (SEM) as well as by cell culture experiments for cell viability and growth using EA.hy 926 cells. RESULTS: SEM showed no changes in the surface morphology; however a layer thickness of 1,000 nm showed peeled off coating areas. Alamar blue assays showed a significantly higher metabolic activity (p=0.026) for the coating 500 nm, ratio 200:1 compared to untreated control samples and a significantly lower metabolic activity (p=0.037) of the coating 500 nm, ratio 1:1 compared to the coating 500 nm, ratio 200:1. This underlines the apparent tendency of the 1:1 coating to inhibit the metabolic activity of the cells, while the 200:1 coating increases the activity. Fluorescence microscopy after calcein acetoxymethyl ester (AM) staining showed no significant difference between the different coatings and the uncoated PET material. However, a tendency of the increased surface growth on the coating 500 nm, ratio 200:1, is shown. The coatings with the ratio 1:1 tend to be less densely covered. CONCLUSIONS: The results of this work indicate a great potential in the silicon coating of vascular prosthesis material. The plasma coating can be carried out easy and gently. Cell culture experiments demonstrated a tendency towards better growth of the cells on the 200:1 ratio coating and a poorer growth on the carbon-rich coating 1:1 compared to the uncoated material. The coating with silicon oxide with a thickness of 500 nm and an oxygen-HMDSO ratio of 200:1, a particularly low-carbon layer, appears to be a coating, which should therefore be further investigated for its effects on thrombogenicity and intimal hyperplasia.

Intracardiac injection of matrigel induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model.

Matrigel promotes angiogenesis in the myocardium from ischemic injury and prevents remodelling of the left ventricle. We assessed the therapeutic efficacy of intracardiac matrigel injection and matrigel-mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, matrigel (250 µl) or phosphate-buffered solution (PBS) was delivered by intracardiac injection. Compared to the MI control group (MI-PBS), matrigel significantly improved left ventricular function (n= 11, P < 0.05) assessed by pressure-volume loops after 4 weeks. There is no significant difference in infarct size between MI-matrigel (MI-M; 21.48 ± 1.49%, n = 10) and MI-PBS hearts (20.98 ± 1.25%, n = 10). The infarct wall thickness of left ventricle is significantly higher (P < 0.01) in MI-M (0.72 ± 0.02 mm, n = 10) compared with MI-PBS (0.62 ± 0.02 mm, n = 10). MI-M hearts exhibited higher capillary density (border 130.8 ± 4.7 versus 115.4 ± 6.0, P < 0.05; vessels per high-power field [HPF; 400×], n = 6) than MI-PBS hearts. c-Kit(+) stem cells (38.3 ± 5.3 versus 25.7 ± 1.5 c-Kit(+) cells per HPF [630×], n = 5, P < 0.05) and CD34(+) cells (13.0 ± 1.51 versus 5.6 ± 0.68 CD34(+) cells per HPF [630×], n = 5, P < 0.01) were significantly more numerous in MI-M than in MI-PBS in the infarcted hearts (n = 5, P < 0.05). Intracardiac matrigel injection restores myocardial functions following MI, which may attribute to the improved recruitment of CD34(+) and c-Kit(+) stem cells.

Wound Healing and Therapy in Soft Tissue Defects of the Hand and Foot from a Surgical Point of View.

Wounds and tissue defects of the hand and foot often lead to severe functional impairment of the affected extremity. Next to general principles of wound healing, special functional and anatomic considerations must be taken into account in the treatment of wounds in these anatomical regions to achieve a satisfactory reconstructive result. In this article, we outline the concept of wound healing and focus on the special aspects to be considered in wounds of the hand and foot. An overview of different treatment and dressing techniques is given with special emphasis on the reconstruction of damaged structures by plastic surgical means.

Experimental Models to Study Skin Wound Healing with a Focus on Angiogenesis.

A large number of models are now available for the investigation of skin wound healing. These can be used to study the processes that take place in a phase-specific manner under both physiological and pathological conditions. Most models focus on wound closure, which is a crucial parameter for wound healing. However, vascular supply plays an equally important role and corresponding models for selective or parallel investigation of microcirculation regeneration and angiogenesis are also described. In this review article, we therefore focus on the different levels of investigation of skin wound healing (in vivo to in virtuo) and the investigation of angiogenesis and its parameters.