Force distribution of a cylindrical grip differs between dominant and nondominant hand in healthy subjects.

INTRODUCTION: Grip strength and load distribution of the hand are important parameters for evaluating hand function. The purpose of this study was to analyze and compare grip force and load distribution of dominant and nondominant hands in right-handed healthy subjects. METHODS: Gripping measurements were performed on 40 healthy right-handed subjects using a cylindrical gripping device. Two different cylinders with circumferences of 150 mm (small cylinder) and 200 mm (large cylinder), respectively, were used for the measurements. Subjects were assigned to either the small or the large cylinder with respect to their hand size. Maximum and mean force applied during three intervals of gripping as well as the percent contribution of each digit, thenar, and hypothenar in relation to the total load applied were acquired. Values of dominant and nondominant hands were compared. RESULTS: Percent contribution of mean grip strength differed for the thumb (p = 0.007), ring finger (p < 0.001), little finger (p = 0.047), and palm (p < 0.001). Comparing the dominant and nondominant side, the dominant hand showed a lower contribution of the thumb, ring finger, and little finger, but a higher contribution of the palm. When analyzing maximum grip, percent contribution of the small fingers was equal between dominant and nondominant side (p = 0.1). Differences between dominant and nondominant thumb, ring finger, and palm persisted (p = 0.007, p = 0.001, p = 0.005, respectively). No differences could be shown for the index finger, middle finger, thenar, and hypothenar when analyzing both mean and maximum force. DISCUSSION AND CONCLUSION: Percent contribution of the thumb and the fingers to total grip strength differed between dominant and nondominant hands with a change in distribution when assessing maximum grip force. In right-handed subjects, thumb and ring finger have important roles during gripping.

Mesenchymal stem cells and myoblast differentiation under HGF and IGF-1 stimulation for 3D skeletal muscle tissue engineering.

BACKGROUND: Volumetric muscle loss caused by trauma or after tumour surgery exceeds the natural regeneration capacity of skeletal muscle. Hence, the future goal of tissue engineering (TE) is the replacement and repair of lost muscle tissue by newly generating skeletal muscle combining different cell sources, such as myoblasts and mesenchymal stem cells (MSCs), within a three-dimensional matrix. Latest research showed that seeding skeletal muscle cells on aligned constructs enhance the formation of myotubes as well as cell alignment and may provide a further step towards the clinical application of engineered skeletal muscle. In this study the myogenic differentiation potential of MSCs upon co-cultivation with myoblasts and under stimulation with hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) was evaluated. We further analysed the behaviour of MSC-myoblast co-cultures in different 3D matrices. RESULTS: Primary rat myoblasts and rat MSCs were mono- and co-cultivated for 2, 7 or 14 days. The effect of different concentrations of HGF and IGF-1 alone, as well as in combination, on myogenic differentiation was analysed using microscopy, multicolour flow cytometry and real-time PCR. Furthermore, the influence of different three-dimensional culture models, such as fibrin, fibrin-collagen-I gels and parallel aligned electrospun poly-ε-caprolacton collagen-I nanofibers, on myogenic differentiation was analysed. MSCs could be successfully differentiated into the myogenic lineage both in mono- and in co-cultures independent of HGF and IGF-1 stimulation by expressing desmin, myocyte enhancer factor 2, myosin heavy chain 2 and alpha-sarcomeric actinin. An increased expression of different myogenic key markers could be observed under HGF and IGF-1 stimulation. Even though, stimulation with HGF/IGF-1 does not seem essential for sufficient myogenic differentiation. Three-dimensional cultivation in fibrin-collagen-I gels induced higher levels of myogenic differentiation compared with two-dimensional experiments. Cultivation on poly-ε-caprolacton-collagen-I nanofibers induced parallel alignment of cells and positive expression of desmin. CONCLUSIONS: In this study, we were able to myogenically differentiate MSC upon mono- and co-cultivation with myoblasts. The addition of HGF/IGF-1 might not be essential for achieving successful myogenic differentiation. Furthermore, with the development of a biocompatible nanofiber scaffold we established the basis for further experiments aiming at the generation of functional muscle tissue.

[Surgical treatment of burns : Special aspects of pediatric burns]. / Chirurgische Behandlung von Verbrennungen : Besonderheiten bei Kindern.

BACKGROUND: Treatment of pediatric burn patients is very important because of the sheer frequency of burn wounds and the possible long-term ramifications. Extensive burns need special care and are treated in specialized burn centers. OBJECTIVES: The goal of this work is to present current standards in burn therapy and important innovations in the treatment of burns in children so that the common and small area burn wounds and scalds in pediatric patients in day-to-day dermatological practice can be adequately treated. MATERIALS AND METHODS: Analysis of current literature, discussion of reviews, incorporation of current guidelines. RESULTS: Burns in pediatric patients are common. Improvement of survival can be achieved by treatment in burn centers. The assessment of burn depth and area is an important factor for proper treatment. We give an overview for outpatient treatment of partial thickness burns. New methods may result in better long-term outcome. CONCLUSIONS: Adequate treatment of burn injuries considering current literature and guidelines improves patient outcome. Rational implementation of new methods is recommended.

[Palmar dislocation of the proximal interphalangeal joint and traumatic boutonnière deformity]. / Palmare Luxation im proximalen Interphalangealgelenk und traumatische Knopflochdeformität.

Injury to the central slip of the extensor tendon may occur with open and also with closed injuries, such as volar dislocation of the proximal interphalangeal (PIP) joint. For adequate treatment, it is necessary to identify all injured structures. Without appropriate primary management, the patient is likely to develop a subacute to chronic posttraumatic boutonnière deformity. A fixed boutonnière deformity requires recovery of joint mobility. Once joint mobility is achieved, secondary surgical reconstruction of the central slip can be performed with a tendon transfer or a tendon transplant.

Automatic quantification of angiogenesis in 2D sections: a precise and timesaving approach.

INTRODUCTION: The standardized characterization of angiogenesis is crucial in the field of tissue engineering as sufficient blood supply is the limiting factor of mass transfer. However, reliable algorithms that provide a straight forward and observer-independent assessment of new vessel formation are still lacking. We propose an automatic observer-independent quantitative method (including downloadable source code) to analyze vascularization using two-dimensional microscopic images of histological cross-sections and advanced postprocessing, based on a 'positive- and negative-experts' model and a (corrected) nearest neighbour classification, in a vascularized tissue engineering model. MATERIALS AND METHODS: An established angioinductive rat arteriovenous loop model was used to compare the new automatic analysis with a common 2D method and a µCT algorithm. Angiogenesis was observed at three different time points (5, 10 and 15 days). RESULTS: In line with previous results, formation of functional new vessels that arose from the venous graft was evident within the three-dimensional construct and a significant (p < 0.05) increase in vessel count and area was observed over time. The proposed automatic analysis obtained precise values for vessel count and vessel area that were similar to the manually gained data. The algorithm further provided vectorized parameterization of the newly formed vessels for advanced statistical analysis. Compared to the µCT-based three-dimensional analyses, the presented two-dimensional algorithm was superior in terms of small vessel detection as well as cost and time efficiency. CONCLUSIONS: The quantitative evaluation method, using microscopic images of stained histological sections, 'positive- and negative-experts'-based vessel segmentation, and nearest neighbour classification, provides a user-independent and precise but also time- and cost-effective tool for the analysis of vascularized constructs. Our algorithm, which is freely available to the public, outperforms previous approaches especially in terms of unambiguous vessel classification and statistical analyses.

A hundred patients with vertical rectus abdominis myocutaneous (VRAM) flap for pelvic reconstruction after total pelvic exenteration.

PURPOSE: We analysed the outcomes of a series of 100 consecutive patients with anorectal cancer with neoadjuvant radiochemotherapy and abdominoperineal exstirpation or total pelvic exenteration, who received a transpelvic vertical rectus abdominis myocutaneous (VRAM) flap for pelvic, vaginal and/or perineal reconstruction and compare a cohort to patients without VRAM flaps. METHODS: Within a 10-year period (2003-2013) in our institution 924 patients with rectal cancer stage y0 to y IV were surgically treated. Data of those 100 consecutive patients who received a transpelvic VRAM flap were collected and compared to patients without flaps. RESULTS: In 100 consecutive patients with transpelvic VRAM flaps, major donor site complications occurred in 6 %, VRAM-specific perineal wound complications were observed in 11 % of the patients and overall 30-day mortality was 2 %. CONCLUSIONS: The VRAM flap is a reliable and safe method for pelvic reconstruction in patients with advanced disease requiring pelvic exenteration and irradiation, with a relatively low rate of donor and recipient site complications. In this first study, to compare a large number of patients with VRAM flap reconstruction to patients without pelvic VRAM flap reconstruction, a clear advantage of simultaneous pelvic reconstruction is demonstrated.

[Extended skin and soft tissue defects after vascular wounds: plastic surgical concepts]. / Ausgedehnte Gewebedefekte bei vaskulären Wunden--Möglichkeiten der plastischen Chirurgie.

INTRODUCTION: Skin and soft-tissue defects at the ischaemic lower extremity represent a challenging condition. Major amputations can be prevented by optimised surgical therapy. The aim of any intervention is the revascularisation and defect reconstruction of the extremity. METHODS: This article aims to provide a structured overview on up-to-date therapeutic strategies and differentiated indications for certain surgical flaps in combination with bypass surgery for the treatment of chronic "vascular" wounds. RESULTS: Optimised conservative wound therapy, skin grafts, pedicled or microsurgical free flaps in combination with vascular bypasses can be applied to salvage ischaemic extremities. These operations require an interdisciplinary cooperation between vascular surgeons and plastic surgeons. DISCUSSION: These procedures should accordingly only be performed in specialised high-volume centres with significant vascular surgical and microsurgical expertise.

Anconeus epitrochlearis muscle (epitrochlearisanconeus muscle; Musculus epitrochleoanconeus) with cubital tunnel syndrome - a rare but relevant clinical entity.

BACKGROUND: Compression of the ulnar nerve at the elbow within the cubital tunnel is related to the anatomical structures and is generally believed to be caused by Osborne's ligament (also known as the cubital retinaculum). However, in rare cases an anatomical variation of the developmental peculiarity of a remaining anconeus epitrochlearis muscle may be responsible for the disease. METHODS: We present a series of five cases in which an anconeus epitrochlearis muscle was found as the cause of illness. RESULTS: All patients presented with typical symptoms of numbness and tingling in the hand and ulnar fingers, and recurring pain as well as weakness of the ulnar innervated muscles. With neurophysiologically confirmed diminished nerve conduction velocity and unsuccessful conservative treatment, surgical decompression revealed an anconeus epitrochlearis muscle as the reason of compression. Full symptom relief was achieved immediately after the procedure in all cases. CONCLUSIONS: This article strives to call attention to this entity when diagnosing ulnar nerve compression. Myectomy and medial epicondylectomy is the preferred treatment option in such cases.

[Registry Research Funding of the German Society of Plastic, Reconstructive and Aesthetic Surgery (DGPRÄC) and Research Funding Report 2021/2022]. / Register Forschungsförderung der Deutschen Gesellschaft für Plastische, Rekonstruktive und Ästhetische Chirurgie (DGPRÄC) und Forschungsförderungs-Bericht 2021/2022.

BACKGROUND: Research is an integral part of academic medicine. In plastic surgery, it sets the course for innovations in the specialty. The purpose of this study is to present the research performance of plastic surgeons in Germany for the period 2021/2022 and to compare it with previous periods. MATERIALS AND METHODS: The directors of plastic surgical academic institutions reported all requested/approved and rejected research applications to public, non-public and industrial funding organizations. Data was gathered within an established online database. In addition, the DFG´s public database GEPRIS was screened for plastic surgical research grants. Data was also collected regarding research infrastructure and organization at the participating centers. RESULTS: 105 applications were reported to 54 different funding agencies from 20 plastic surgery centers. 37 funding applications were submitted to the major public funding agencies DFG, BMBF, BMWi, BMG, BMVg, G-BA and EU. Of these, 59,5% (22/37) were DFG, 13,5% (5/37) each BMBF and EU, 5,4% (2/37) BMWi, and 2,7% (1/37) each BMG, BMVg, and G-BA applications. The average funding volume of these proposals was 401,515 euros. Approved DFG proposals were most frequently assigned to the review board 205-27 Orthopedics, Trauma Surgery, Reconstructive Surgery (n=10/16, 62,5%). Over time, the research registry shows an increase in the number of proposals in general and those granted. 70,0% (14/20) of participating sites had their own experimental research laboratory, while only 40,0% (8/20) had their own clinical trial center. CONCLUSION: The 2021/2022 Research Funding Report once again highlights the impressive research accomplishments of the plastic surgery community.

Laparoscopic abdominoperineal resection with open posterior cylindrical excision and primary transpelvic VRAM flap.

BACKGROUND: In our own experience over the last 15 years, the primary transpelvic vertical rectus abdominis myocutaneous (VRAM) flap is a reliable tool to prevent perineal wound complications after cylindrical excision in radical anorectal tumor surgery. To minimize the operative trauma in such patients, we performed a laparoscopic abdominoperineal resection combined with an open posterior cylindrical excision and a primary transpelvic vertical rectus abdominis myocutaneous (VRAM) flap via a minimal supraumbilical incision, which is described here for the first time. METHODS: A 49-year-old patient with recurrent anal cancer received radiochemotherapy with curative intention and underwent laparoscopic abdominoperineal rectal excision with posterior cylindrical excision combined with a primary transpelvic vertical rectus abdominis myocutaneous (VRAM) flap. The rectal stump was clipped and pulled through the pelvis together with the VRAM flap, which was then placed into the sacral defect. RESULTS: We found that the combined operative technical approaches with laparoscopy and minimal incisions for flap harvest and cylindrical excision were technically feasible, and no mesh was needed to close the small-sized laparotomies. We achieved complete tumor removal and flap perfusion, and healing was uneventful. The patient showed no relapse at 3 years postoperative. CONCLUSIONS: Our report of the operative technique shows that the combination of minimally invasive methods together with transpelvic VRAM flap transposition is technically feasible, can be performed with operative efficiency, and may become a valuable tool to minimize perioperative complications in advanced colorectal tumor surgery.

Axially vascularized bone substitutes: a systematic review of literature and presentation of a novel model.

INTRODUCTION: The creation of axially vascularized bone substitutes (AVBS) has been successfully demonstrated in several animal models. One prototypical indication is bone replacement in patients with previously irradiated defect sites, such as in the mandibular region. The downside of current clinical practice, when free fibular or scapular grafts are used, is the creation of significant donor site morbidity. METHODS: Based on our previous experiments, we extended the creation of an arterio-venous loop to generate vascularized bone substitutes to a new defect model in the goat mandibula. In this report, we review the literature regarding different models for axially vascularized bone substitutes and present a novel model demonstrating the feasibility of combining this model with synthetic porous scaffold materials and biological tissue adhesives to grow cells and tissue. RESULTS: We were able to show the principal possibility to generate axially vascularized bony substitutes in vivo in goat mandibular defects harnessing the regenerative capacity of the living organism and completely avoiding donor site morbidity. CONCLUSION: From our findings, we conclude that this novel model may well offer new perspectives for orthopedic and traumatic bone defects that might benefit from the reduction of donor site morbidity.

Leaving the perfusion zones? Individualized flap design in 100 free DIEP and ms-TRAM flaps for autologous breast reconstruction using indocyanine green angiography.

BACKGROUND: There is still no consensus regarding the ideal zoning in abdominal-based autologous breast reconstruction using free DIEP or ms-TRAM flaps. In particular, the perfusion pattern of the flap according to the number of perforators used and their location remains controversial. In this study, the perfusion of free DIEP and ms-TRAM flaps is assessed intraoperatively and analyzed with regard to different perfusion patterns. METHODS: A retrospective analysis of 100 free flaps for breast reconstruction was performed. Following complete flap harvest, we used indocyanine green angiography for perfusion analysis. By applying two different contour levels, DIEP flaps with lateral or medial perforators and ms-TRAM flaps were assessed for their respective perfusion patterns. RESULTS: No statistically significant differences were found in the size of the perfusion area between the different flap types when applying the contour level of 20% (p >0.05). For the contour level of 30%, however, statistically significant differences were found between DIEP flaps with medially or laterally located perforators (p = 0.038). Laterally or medially located perforators in DIEP flaps showed no significant differences in their ability to cross the midline (contour level 20%, p = 0.068; contour level 30%, p = 0.058). CONCLUSION: Considering the variability of the perfusion of the abdominal wall and the high sensitivity of indocyanine green angiography for their detection, the abdominal zonings play a minor role. By using intraoperative indocyanine green angiography, a precise and patient-specific free flap surgery for autologous breast reconstruction is possible independent of perforator location.

The Value of Negative-Pressure Wound Therapy and Flap Surgery in Hidradenitis Suppurativa - A Single Center Analysis of Different Treatment Options.

Background: Hidradenitis suppurativa is manifested by painful abscesses and scarring of sweat glands. Axillary, inguinal and genital regions are mostly affected. Multiple options exist in the treatment of hidradenitis suppurativa. The aim of this retrospective, mono-center cohort study was to analyze the outcome of different treatment methods after radical excision of hidradenitis suppurativa. Methods: We retrospectively evaluated the treatment strategy and recurrence rate of hidradenitis suppurativa. We included all eligible patients of legal age between February 2003 and October 2021, with the diagnosis of Hidradenitis suppurativa and the necessity for surgical treatment. All patients with surgical treatment and direct wound closure by suture were excluded. Bacterial load and flora were analyzed for primary and secondary reconstruction in combination with negative-pressure wound therapy. Patient data were analyzed for recurrence rate and remission time according to different reconstructive techniques. Results: In 44 affected anatomical sites (n = 23 patients) we treated 15 patients with negative-pressure wound therapy. Bacterial load and flora were lower in the last wound swab of patients with multi-surgical procedures (22 localizations) compared to the first wound swab independent of the use of negative-pressure wound therapy.Wound closure, independent of a direct and multi-stage procedure was achieved by local fasciocutaneous flaps (n = 12), secondary intention healing (n = 7), secondary intention healing with buried chip skin grafts (n = 10), or split-thickness skin grafts (n = 15). Radical excision combined with split-thickness skin grafts showed the lowest recurrence rate in the follow-up (16%; n = 4). Conclusion: Radical excision of hidradenitis suppurativa as gold standard for surgical treatment combined with negative-pressure wound therapy as multi-stage procedures ultimately reduced bacterial load and flora in our study. The use of split-thickness skin grafts showed the lowest recurrence rate.

The impact of VEGF and bFGF on vascular stereomorphology in the context of angiogenic neo-arborisation after vascular induction.

The aim of this in vivo study was to gather quantitative information on the three-dimensional morphology of a new vascular network under the influence of angioactive growth factors. For this purpose, the arteriovenous loop model was used in 10 Lewis rats to generate a bioartificial vascular assembly by means of vascular induction. In this model, an isolated organoid is created in the medial thigh of the animal by methods of tissue engineering. A fibrin gel containing vascular endothelial growth factor (VEGF(165)) and basic fibroblastic growth factor (bFGF) was used as a matrix in the effect group (GF+). Fibrin matrices devoid of growth factors were used as controls (GF-). A microvascular replica of the organoid was created by means of corrosion casting and the network was investigated on stereo-paired images obtained by scanning electron microscopy. Vectors of intercapillary and interbranching distances as well as the diameter of the pores in the intussusceptive events diameter and the ratio of sprouting versus intussusceptive angiogenic events were compared in the two groups. The results were highly significant. In the GF+ group there were more profound three-dimensional morphological traits of angiogenesis, whereas advanced neovascularisation in the phase of remodelling was demonstrated by a higher incidence of intussusception, compared to control. These results illustrate the importance of morphological studies with focus on the generation of three-dimensional vascular networks.

De novo generation of an axially vascularized processed bovine cancellous-bone substitute in the sheep arteriovenous-loop model.

BACKGROUND/AIMS: The aim of this study was to generate an axially vascularized bone substitute. The arteriovenous (AV)-loop approach in a large-animal model was applied in order to induce axial vascularization in a clinically approved processed bovine cancellous bone (PBCB) matrix of significant volume with primary mechanical stability and to assess the course of increasing axial vascularization. METHODS: PBCB constructs were implanted into 13 merino sheep together with a microsurgically created AV loop in an isolation chamber. The vascularization process was monitored by sequential magnetic resonance imaging (MRI) scans. Explants were subjected to micro-computed tomography (micro-CT) analysis, histomorphometry and immunohistochemistry for CD31 and CD45. RESULTS: Increasing axial vascularization in PBCB constructs was quantified by histomorphometry and visualized by micro-CT scans. Intravital sequential MRI scans demonstrated a significant progressive increase in perfused volume within the matrices. Immunohistochemistry confirmed endothelial lining of newly formed vessels. CONCLUSION: This study demonstrates successful axial vascularization of a clinically approved, mechanically stable bone substitute with a significant volume by a microsurgical AV loop in a large-animal model. Thus microsurgical transplantation of a tissue-engineered, axially vascularized and mechanically stable bone substitute with clinically relevant dimensions may become clinically feasible in the future.

Calcium, magnesium and aluminium ions as decontaminating agents against dermal fluoride absorption following hydrofluoric acid exposure.

The fluoride ions of the industrially largely irreplaceable, locally corrosive hydrofluoric acid (HF) can scavenge cations in biological tissues, which explains their high toxic potential, and also leads to local acidification through proton release. The influence of three complexing agents, calcium (Ca2+) gluconate (as 2.5% Ca2+gel and individually (2.84%) or commercially (10%) formulated Ca2+solution), magnesium (Mg2+) gluconate (2.84%) solution and aluminium (Al3+) solution (Hexafluorine®, pure and diluted) on the absorption of fluoride following HF exposure (1-3 min, 100 µl, 30%/0.64 cm2) through human skin was investigated in an ex-vivo diffusion cell model. Fluoride absorption was assessed over 6-24 h and analysed with a fluoride electrode. Decreasing the contamination time reduced the fluoride absorption distinctly which was further reduced by the application of fluoride-binding decontamination agents (Ca2+, Mg2+, Al3+) or water alone without being significantly different. Ca2+ appeared slightly more effective than Mg2+ in reducing fluoride absorption. Moreover, the addition of pH adjusting buffer promoted the decontamination efficacy. Fluoride-binding agents can facilitate the decontamination of dermal HF exposure. However, prompt decontamination appeared to be the key to successful limitation of fluoride absorption and pushes the choice of decontamination agent almost into the background.

[Registry Research Funding of the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC) and Research Funding Report 2019/2020]. / Register Forschungsförderung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC) und Forschungsförderungsbericht 2019/2020.

BACKGROUND: Since 2015/16 the DGPRÄC collects, evaluates and publishes the research activities of academic sections, departments and clinics for plastic surgery at university hospitals in Germany, in order to raise the awareness of plastic surgical research performance. MATERIALS AND METHODS: The directors of plastic surgical academic institutions were contacted via the DGPRÄC and asked to report any requested/approved and rejected research applications to public, non-public and industrial funding organizations. Data was collected in our previously established online database: https://docs.google.com/forms/d/e/1FAIpQLSe6F5xmTyw-k7VKJx_2jkPA4LBXsA0sgBGMrC3rx_4bHj6uzQ/viewform?usp=sf_link. In addition, applications were identified via the DFG's public database GEPRIS. RESULTS: A total of 41 funding applications to the public funding institutes DFG, BMBF, BMWi, BMG and EU were identified. 75.6 % (31/41) of the applications had already been approved at the time of data collection, of which 77.4 % (24/31) were DFG, 9.7 % (3/31) were BMWi, 6.5 % (2/31) were EU and 3.2 % (1/31) were BMBF or BMG applications. The average funding amounted to 358 301 Euro. In 50.0 % (12/24) of the cases, the approved DFG proposals were assigned to the subject review board 205-27 Orthopedics, Trauma Surgery, Reconstructive Surgery. CONCLUSION: The continuous publication of plastic surgical research funding reports submitted by the convention of university plastic surgeons of the DGPRÄC portraits the excellent, collaborative research activity in the field of plastic surgery.

Regenerative medicine: then and now--an update of recent history into future possibilities.

The fields of tissue engineering (TE) and regenerative medicine (RegMed) are yet to bring about the anticipated therapeutic revolution. After two decades of extremely high expectations and often disappointing returns both in the medical as well as in the financial arena, this scientific field reflects the sense of a new era and suggests the feeling of making a fresh start although many scientists are probably seeking reorientation. Much of research was industry driven, so that especially in the aftermath of the recent financial meltdown in the last 2 years we have witnessed a biotech asset yard sale. Despite any monetary shortcomings, from a technological point of view there have been great leaps that are yet to find their way to the patient. RegMed is definitely bound to play a major role in our life because it embodies one of the primordial dreams of mankind, such as: everlasting youth, flying, remote communication and setting foot on the moon. The Journal of Cellular and Molecular Medicine has been at the frontier of these developments in TE and RegMed from its beginning and reflects recent scientific advances in both fields. Therefore this review tries to look at RegMed through the keyhole of history which might just be like looking 'back to the future'.

Foetal hepatocyte transplantation in a vascularized AV-Loop transplantation model in the rat.

The use of foetal liver cells (FLC) in the context of hepatic tissue engineering might permit efficient in vitro expansion and cryopreservation in a cell bank. A prerequisite for successful application of bioartificial liver tissue is sufficient initial vascularization. In this study, we evaluated the transplantation of fibrin gel-immobilized FLC in a vascularized arterio-veno-venous (AV)-loop model. FLC were isolated from embryonic/foetal (ED 16) rat livers and were enriched by using magnetic cell sorting (MACS). After cryopreservation, FLC were labelled by pkh-26. Cells were transplanted in a fibrin matrix into a subcutaneous chamber containing a microsurgically created AV-loop in the femoral region of the recipient rat. The chambers were explanted after 14 days. Subcutaneous implants without an AV-loop and cell-free implants served as controls. Fluorescence microscopy of the constructs was used to identify pkh-26(+)- donor cells. Characterization was performed by RT-PCR and immunhistology (IH) for CK-18 and CD31. Transplantation of FLC using the AV-loop permitted a neo-tissue formation in the fibrin matrix. A high-density vascularization was observed in the AV-loop constructs as shown by CD31 IH. Viable foetal donor cells were detected which expressed CK-18. FLC can be successfully used for heterotopic transplantation. Fibrin matrix permits rapid blood vessel ingrowth from the AV-loop and supports engraftment of FLC. It is therefore an appropriate environment for hepatocyte transplantation in combination with microsurgical vascularization strategies. Transplantation of fibrin gel-immobilized FLC may be a promising approach for the development of highly vascularized in vivo tissue-engineering-based liver support systems.

Impact of physiologically relevant temperatures on dermal absorption of active substances - an ex-vivo study in human skin.

Skin temperature plays a certain role in the dermal absorption of substances, but the extent and mechanisms of skin temperatures-induced modulation in ranges caused by physiological thermoregulation or environmental conditions are largely unknown. The influence of dermal temperature on the absorption of the model lipophilic compound (anisole) and the model hydrophilic compounds (1,4-dioxane, ethanol) through human skin was investigated at three dermal temperatures (25, 32 and 39 °C) in an ex-vivo diffusion cell model. The substances were applied to the skin and transdermal penetration was monitored. All substances showed temperature dependent variations in their penetration behavior (3 h: 25-39 °C: 202-275% increase in cumulative, transdermally penetrated amounts). The relative differences in absorption in relation to temperature were greatest within 45 min after exposure (25-39 °C: 347-653% rise in cumulated penetration), although absolute amounts absorbed were small (45 min vs. 3 h: 4.5-14.5%). Regardless of blood circulation, skin temperature significantly influences the amount and kinetics of dermal absorption. Substance-dependent, temperature-related changes of the lipid layer order or the porous pathway may facilitate penetration. The early-stage modulation of transdermal penetration indicates transappendageal absorption, which may be relevant for short-term exposures. For both, toxicological evaluation and perfusion cell studies, it is important to consider the thermal influence on absorption or to perform the latter at a standardized temperature (32±1 °C).