Maike Keck

Pathophysiology of burns

ZusammenfassungDas Verbrennungstrauma stellt weltweit ein bedeutendes Problem in der Medizin dar. Fortschritte im Bereich des therapeutischen Vorgehens, basierend auf einem besseren Verständnis der Pathophysiologie des Verbrennungs-traumas, haben den Therapieerfolg im Laufe der letzten Jahre deutlich verbessern können. Die folgende Arbeit beschreibt die Pathophysiologie des Verbrennungstraumas. Dargestellt werden neben der lokalen und systemischen Reaktion einige organspezifische Veränderungen, resultierend aus einer bestehenden Hypovolämie oder der Freisetzung von Mediatoren.SummaryBurn injury represents a significant problem worldwide. Advances in therapy strategies, based on better understanding of the pathophysiologic responses after burn injury have improved the clinical outcome of patients with burn injuries over the past years. This article describes the present understanding of the pathophysiology of a burn injury including both the local and systemic responses, focusing on the many facets of organ and systemic effects directly resulting from hypovolemia and circulating mediators following burn trauma.

Osteopontin Is an Activator of Human Adipose Tissue Macrophages and Directly Affects Adipocyte Function

Osteopontin (OPN) is highly up-regulated in adipose tissue in human and murine obesity and has been recently shown to be functionally involved in the pathogenesis of obesity-induced adipose tissue inflammation and associated insulin resistance in mice. OPN is a protein with multiple functions and acts as a chemokine and an inflammatory cytokine through a variety of different receptors (CD44, integrins). It is expressed in many cell types including adipose tissue macrophages (ATM). However, the target cells of OPN action in obese adipose tissue are still elusive. Here, we investigated expression of OPN receptors and the impact of OPN on ATM, adipocytes, and other cells of human adipose tissue. We found broad expression of OPN receptors in different adipose tissue cell types including adipocytes. OPN stimulated inflammatory signaling pathways and secretion of cytokines in model macrophages as well as isolated human ATM. Moreover, OPN impaired differentiation and insulin sensitivity of primary adipocytes as determined by peroxisomal proliferator-activated receptor-γ and adiponectin gene expression and insulin-stimulated glucose uptake. Furthermore, OPN induced inflammatory signaling in human adipocytes. In conclusion, OPN activates ATM and interferes with adipocyte function. Thus these data underline the potential of OPN as a therapeutic target for obesity-induced complications.

The use of Suprathel(®) in deep dermal burns: first results of a prospective study.

INTRODUCTION While autologous skin grafting has been the standard for coverage of full-thickness areas, several options for deep-partial-thickness defects exist. With regard to economising donor sites, we compared a copolymer based on DL-lactid acid (Suprathel(®)) as temporary wound dressing with autologous skin, and analysed time to healing and scar quality in matched areas of deep-partial-thickness burn. METHODS We recruited 18 patients with a median age of 45 years (range: 25-83 years), for this prospective, non-blinded controlled non-inferiority study, suffering from deep-partial-thickness burns from November 2009 to July 2010. After early tangential excision, matched deep-partial-thickness areas were covered with 1:1.5 meshed autologous skin grafts and the copolymer for direct intra-individual comparison. Scars were evaluated by means of the Vancouver Scar Scale (VSS), the Patient and Observer Scar Assessment Scale (POSAS) and suction cutometry (MPA 580, Courage and Khazaka Electronic GmbH, Cologne, Germany) on days 30 and 90, postoperatively. RESULTS Fifteen days after surgery, complete wound closure was present in 44.4% (8/18) of all areas covered with copolymer and 88.9% (16/18) in the split-thickness skin graft (STSG) area (p=0.008). Evaluation of the total VSS, POSAS and cutometry satisfied the criterion of non-inferiority for Suprathel(®) on day 30. Ninety days after surgery, only the Observer Scar Scale showed that Suprathel is non-inferior to STSG, albeit the mean total VSS and Patient Scar Scale were better in Suprathel(®) areas. CONCLUSION Suprathel(®) represents a solid, reliable epidermal skin substitute with longer healing times in comparison to skin grafts but comparable results concerning early scar formation. Suprathel(®) can serve as a tool in treatment portfolio for adult patients suffering from deep dermal burns. Especially in patients with extensive burns, Suprathel(®) can be used to cover the deep dermal burn wounds to save STSGs and its donor sites for the coverage of full-thickness burned areas.

Burn treatment in the elderly

The population of elderly patients is expected to rise continuously over the next decades due to global demographic changes. The elderly seem to be most vulnerable to burns and their management remains undoubtedly a challenge. A clear age margin for elderly patients is not yet defined, but most studies adhere to the inclusion of patients 65 years and above, but the general condition and social situation must be taken into account. The understanding of the physiological basis of aging and its related pathophysiological changes has only marginally influenced treatment and decision making in elderly burn patients. When looking at treatment regimens currently applied in elderly burn patients, the discussion of standards in intensive care as well as surgical strategies is ongoing. However, trends towards a moderate, non-aggressive resuscitation approach and careful inclusion of key parameters like physiological age, pre-burn functional status and premorbid conditions, seem to be useful guidelines for interdisciplinary treatment decisions. Once ordered for surgical treatment, the amount of body surface area operated in one session should be adapted to the general status of the patient. Even if older burn victims have a reported higher mortality rate than younger patients, improved therapeutic options have contributed to a reduced mortality rate even in the elderly over the last decades. As a result of improved outcome, more attention has to be given to a comprehensive rehabilitation program. This review will give an overview of the current literature and will draw attention to specific topics related to this important subpopulation of burn patients.

Adipose tissue engineering: three different approaches to seed preadipocytes on a collagen-elastin matrix.

Background:Millions of plastic and reconstructive surgical procedures are performed each year to repair soft-tissue defects that result from significant burns, tumor resections, or congenital defects. Tissue-engineering strategies have been investigated to develop methods for generating soft-tissue. Preadipocytes represent a promising autologous cell source for adipose tissue engineering. These immature precursor cells, which are located between the mature adipocytes in the adipose tissue, are much more resistant to mechanical stress and ischemic conditions than mature adipocytes. To use preadipocytes for tissue-engineering purposes, cells were isolated from human adipose tissue and seeded onto scaffolds. Once processed, preadipocytes become subject to the human tissue act and require handling under much tighter regulations. Therefore, we intended to identify any influence caused by processing of preadipocytes prior to seeding on the reconstructed adipose tissue formation. Material and Method:Human preadipocytes were isolated from subcutaneous adipose tissue obtained from discarded tissue during abdominoplasties of healthy men and women. Preadipocytes were divided into 3 groups. Cells of group I were seeded onto the scaffold directly after isolation, cells of group II were proliferated for 4 days before seeding, and cells of group III were proliferated and induced to differentiate before seeded onto the scaffold. A 3-dimensional scaffold (Matriderm, Dr. Otto Suwelack Skin and Health Care GmbH, Billerbeck, Germany) containing bovine collagen and elastin served as a carrier. Fourteen days after isolation, all scaffolds were histologically evaluated, using hematoxylin and eosin, anti-Ki-67 antibody, as well as immunofluorescence labeling with Pref-1 antibody (DLK (C-19), peroxisome proliferator-activated receptor gamma antibody, and DAPI (4′,6-diamidino-2-phenylindole). Results:Cells of all groups adhered to the scaffolds on day 21 after isolation. Cells of groups I (freshly isolated preadipocytes) and II (proliferated preadipocytes) adhered well and penetrated into deeper layers of the matrix. In group III (induced preadipocytes), penetration of cells was primarily observed to the surface area of the scaffold. Discussion/Conclusion:The collagen-elastin matrix serves as a useful scaffold for adipose tissue engineering. Freshly isolated preadipocytes as well as proliferated preadipocytes showed good penetration into deeper layers of the scaffold, whereas induced preadipocytes attached primarily to the surface of the matrix. We conclude that there might be different indications for each approach.

Electrical injury: a long-term analysis with review of regional differences.

Due to its relatively small share among burn injuries, published data on electrical injuries remain scarce, and differ in patient collectives due to infrastructural differences. We have retrospectively analyzed records of 56 patients who were admitted because of electrical injury to our burn center from 1994 to 2008, compared results with the current literature, and focused our review on regional differences. Patients in our collective were predominantly young men (71%, n = 40/56) and those who resulted from work-related accidents (59%, n = 33/56). The mean total burn surface area was 26%. In all, 93% of patients needed at least 1 operation, with 43% of patients requiring at least 1 surgical intervention during a follow-up hospital stay. The mean length-of-stay was 44 days. Two patients died, accounting for a mortality rate of 3.6%. When comparing high to low-voltage injuries, patients in the former group were significantly younger, had more operations, and required a longer length-of-stay. With respect to work-related high-voltage injuries, job-specific male-predominance explains for the demographic distribution of admissions. Low-voltage injuries continue to have low mortality rates in this part of Europe, most likely as a result of established high security standards as well as access to emergency treatment with subsequent intensive and specialist surgical care.

Electrospun Poly(ester-Urethane)- and Poly(ester-Urethane-Urea) Fleeces as Promising Tissue Engineering Scaffolds for Adipose-Derived Stem Cells

An irreversible loss of subcutaneous adipose tissue in patients after tumor removal or deep dermal burns makes soft tissue engineering one of the most important challenges in biomedical research. The ideal scaffold for adipose tissue engineering has yet not been identified though biodegradable polymers gained an increasing interest during the last years. In the present study we synthesized two novel biodegradable polymers, poly(ε-caprolactone-co-urethane-co-urea) (PEUU) and poly[(L-lactide-co-ε-caprolactone)-co-(L-lysine ethyl ester diisocyanate)-block-oligo(ethylene glycol)-urethane] (PEU), containing different types of hydrolytically cleavable bondings. Solutions of the polymers at appropriate concentrations were used to fabricate fleeces by electrospinning. Ultrastructure, tensile properties, and degradation of the produced fleeces were evaluated. Adipose-derived stem cells (ASCs) were seeded on fleeces and morphology, viability, proliferation and differentiation were assessed. The biomaterials show fine micro- and nanostructures composed of fibers with diameters of about 0.5 to 1.3 µm. PEUU fleeces were more elastic, which might be favourable in soft tissue engineering, and degraded significantly slower compared to PEU. ASCs were able to adhere, proliferate and differentiate on both scaffolds. Morphology of the cells was slightly better on PEUU than on PEU showing a more physiological appearance. ASCs differentiated into the adipogenic lineage. Gene analysis of differentiated ASCs showed typical expression of adipogenetic markers such as PPARgamma and FABP4. Based on these results, PEUU and PEU meshes show a promising potential as scaffold materials in adipose tissue engineering.

Adipose-derived stem cells cultivated on electrospun L-lactide/glycolide copolymer fleece and gelatin hydrogels under flow conditions - aiming physiological reality in hypodermis tissue engineering

INTRODUCTION Generation of adipose tissue for burn patients that suffer from an irreversible loss of the hypodermis is still one of the most complex challenges in tissue engineering. Electrospun materials with their micro- and nanostructures are already well established for their use as extracellular matrix substitutes. Gelatin is widely used in tissue engineering to gain thickness and volume. Under conventional static cultivation methods the supply of nutrients and transport of toxic metabolites is controlled by diffusion and therefore highly dependent on size and porosity of the biomaterial. A widely used method in order to overcome these limitations is the medium perfusion of 3D biomaterial-cell-constructs. In this study we combined perfusion bioreactor cultivation techniques with electrospun poly(l-lactide-co-glycolide) (P(LLG)) and gelatin hydrogels together with adipose-derived stem cells (ASCs) for a new approach in soft tissue engineering. METHODS ASCs were seeded on P(LLG) scaffolds and in gelatin hydrogels and cultivated for 24 hours under static conditions. Thereafter, biomaterials were cultivated under static conditions or in a bioreactor system for three, nine or twelve days with a medium flow of 0.3ml/min. Viability, morphology and differentiation of cells was monitored. RESULTS ASCs seeded on P(LLG) scaffolds had a physiological morphology and good viability and were able to migrate from one electrospun scaffold to another under flow conditions but not migrate through the mesh. Differentiated ASCs showed lipid droplet formations after 21 days. Cells in hydrogels were viable but showed rounded morphology. Under flow conditions, morphology of cells was more diffuse. DISCUSSION ASCs could be cultivated on P(LLG) scaffolds and in gelatin hydrogels under flow conditions and showed good cell viability as well as the potential to differentiate. These results should be a next step to a physiological three-dimensional construct for soft tissue engineering and regeneration.

Wharton’s jelly mesenchymal stem cells promote wound healing and tissue regeneration

Wound healing requires an orchestrated integration of complex biological and molecular events, which include inflammation, proliferation and remodeling. Wharton’s jelly mesenchymal stem cells seem to promote wound healing and tissue repair. Wharton’s jelly stem cells promote fibroblast proliferation and migration, accelerate re-epithelialization and promote overall wound repair by pcrine signaling. Wharton’s jelly is an advantageous mesenchymal stem cell source because the harvest of this type of stem cells is not painful or invasive and because, beside their effect on wound healing, they seem to have a significant impact on the treatment of keloids. Furthermore, they led to better nerve regeneration, better neuroprotection and less inflammation.

Tissue expansion for correction of scars due to burn and other causes: a retrospective comparative study of various complications.

BACKGROUND Tissue expansion is associated with a relatively high complication rate. The aim of this study was to quantify the complication risk of burn scar patients who underwent tissue expansion in comparison to patients with other indications such as skin tumors. Furthermore it was attempted to compare the complication rates in children and adults. METHODS A retrospective analysis was performed on 148 expanders implanted in 73 patients during the years 1994-2011. Two patient cohorts (burn scar cohort n=31 and other indication cohort n=42) were identified and analyzed. RESULTS 27 male and 46 female patients with a median age of 21 years were included. No statistically significant difference for complication risk between the burn and other indication cohorts could be found (p=0.1412). Statistical analyses revealed a higher complication rate (52%) in the lower limb compared to all other anatomic sites (29%) (p=0.1746). In addition, statistical analyses revealed a significantly higher total complication rate in children younger than 10 years (p=0.0043). Moreover a greater TBSA was accompanied by a higher complication rate (p=0.0258). CONCLUSION This set of data suggests that the burn scar patient is at no greater risk to suffer complications from tissue expansion. Other factors like age, TBSA and anatomical site have far more influence on the expander complication rate than the initial indication for tissue expansion.