An in vivo mouse model for human cartilage regeneration.

Cartilage regeneration methods have been examined in various animal models. The major limitation of those studies is the biological difference between human and animal cartilage. We propose an in vivo model for human chondrocytes in a human cartilage defect environment.

Mechanical and flow characterization of Sponceram carriers: Evaluation by homogenization theory and experimental validation.

The experimental evidence of the dependence of cell proliferation and differentiation in vitro on the mechanical environment aims to the need of characterization of porous scaffolds in terms of mechanical and flow properties. In this sense, the Young's modulus and intrinsic permeability for three types of Sponceram(R) cell carriers developed for in-vitro applications are here analyzed. Young's modulus and ultimate compression stress were obtained by performing a two-plates compression test carried out in a universal microtester machine Instron(R) for several representative samples of each specimen.

Depletion of NK cells in a murine polytrauma model is associated with improved outcome and a modulation of the inflammatory response.

Sepsis and associated diseases such as systemic inflammatory response syndrome and multiple organ dysfunction syndrome represent common posttraumatic complications on intensive care units induced by a variety of body defense mechanisms. Natural killer (NK) cells are part of the innate immune system. They are thought to play an important role in the development of such syndromes by interplay with other immune cell types and subsequent activation of the inflammatory cascade.

Effects of repetitive and short time strain in human bone marrow stromal cells.

For the long-term objective to engineer a functional bone construct, we applied unidirectional cyclic mechanical strain to human bone marrow stromal cells. Two strain regimes were applied comprising single and repetitive strain, respectively. For the single strain, we applied 15 and 60 min of mechanical load (1 Hz, 5% elongation).

Design and characterization of a rotating bed system bioreactor for tissue engineering applications.

The main challenge in the development of bioreactors for tissue engineering is the delivery of a sufficient nutrient and oxygen supply for cell growth in a 3D environment. Thus, a new rotating bed system bioreactor for tissue engineering applications was developed. The system consists of a culture vessel as well as an integrated rotating bed of special porous ceramic discs and a process control unit connected with the reactor to ensure optimal culturing conditions.

Femoral nailing-related coagulopathy determined by first-hit magnitude: an animal study.

We asked whether coagulopathy worsened during femoral intramedullary nailing in the presence of lung contusion and hemorrhagic shock and whether reamed or unreamed nailing influenced these results. In 30 Merino sheep, we induced hemorrhagic shock and/or standardized lung contusion followed by femoral nailing. Six groups of five each were assigned as follows: thoracotomy control groups treated with reamed or unreamed nailing, lung contusion groups treated with reamed or unreamed nailing, and shock and lung contusion groups treated with reamed or unreamed nailing.

The genetic predisposition to adverse outcome after trauma.

Technological advances and shorter rescue times have allowed early and effective resuscitation after trauma and brought attention to the host response to injury. Trauma patients are at risk of progressive organ dysfunction from what appears to be an uncontrolled immune response. The availability of improved techniques of molecular diagnosis has allowed investigation of the role of genetic variations in the inflammatory response to post-traumatic complications and particularly to sepsis.

Impact of the method of initial stabilization for femoral shaft fractures in patients with multiple injuries at risk for complications (borderline patients).

Objectives: The timing of definitive fixation for major fractures in patients with multiple injuries is controversial. To address this gap, we randomized patients with blunt multiple injuries to either initial definitive stabilization of the femur shaft with an intramedullary nail or an external fixateur with later conversion to an intermedullary nail and documented the postoperative clinical condition.

Methods: Multiply injured patients with femoral shaft fractures were randomized to either initial (<24 hours) intramedullary femoral nailing or external fixation and later conversion to an intramedullary nail.

FTY720 improves survival after transient ischemia and reperfusion of the hind limbs.

Background: Ischemia and reperfusion (I/R) damage involves adhesion and transmigration of lymphocytes and neutrophils. FTY720 is an immunosuppressive agent that reduces the number of neutrophils and monocytes in peripheral blood as well as tissue lymphocyte infiltration. This study investigated the effect of FTY720 during hind limb I/R.

Osteoinduction in human fat-derived stem cells by recombinant human bone morphogenetic protein-2 produced in Escherichia coli.

Bioactive recombinant human bone morphogenetic protein-2 (rhBMP-2) was obtained using Escherichia coli pET-25b expression system: 55 mg purified rhBMP-2 were achieved per g cell dry wt, with up to 95% purity. In murine C2C12 cell line, rhBMP-2 induced an increase in the transcription of Smads and of osteogenic markers Runx2/Cbfa1 and Osterix, measured by semi-quantitative RT-PCR. Bioassays performed in human fat-derived stem cells showed an increased activity of the early osteogenic marker, alkaline phosphatase, and the absence of cytotoxicity.

Chronic headache after cranio-cervical trauma--hypothetical pathomechanism based upon neuroanatomical considerations.

Background: Chronic headache after whiplash injury is common, but the underlying mechanisms have not yet been elucidated. On the basis of human neuroanatomy, we hypothesize that rear-end collision can cause leakage of the cerebrospinal fluid (CSF) into the epidural space most frequently at the lumbosacral level, inducing chronic headache.

Methods: We considered that the following phenomena would be evident in patients with chronic headache after rear-end collision: (1) orthostatic headache with early onset and long duration, (2) low intracranial pressure (ICP =or< 60 mm H2O), (3) CSF leakage mainly in the lumbosacral region on radioisotope-myelocisternography, and (4) diffuse pachymeningeal enhancement (DPE) on gadolinium enhanced magnetic resonant image (Gd-MRI).

Adverse effects associated with the use of porcine cross-linked collagen implants in an experimental model of incisional hernia repair.

Background: Porcine cross-linked collagen (PermaCol, PCL; TSL, Aldershot, United Kingdom) has been proposed as permanent biomaterial in incisional hernia repair. We evaluated the biocompatibility of PCL in an established animal model.

Material And Methods: In 10 Sprague Dawley rats, two hernias per animal were created in the abdominal wall left and right of the linea alba (1.

Tissue engineering of tendons and ligaments by human bone marrow stromal cells in a liquid fibrin matrix in immunodeficient rats: results of a histologic study.

Introduction: The original complex structure and mechanical properties are not fully restored after ligament and tendon injuries. Due to their high proliferation rate and differentiation potential, Bone Marrow Stromal Cells (BMSC) are considered to be an ideal cell source for tissue engineering to optimize the healing process. Ideal matrices for tissue engineering of ligaments and tendons should allow for homogenous cell seeding and offer sufficient stability.

Dose-dependent immunomodulatory effect of human stem cells from amniotic membrane: a comparison with human mesenchymal stem cells from adipose tissue.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been used for allogeneic application in tissue engineering but have certain drawbacks. Therefore, stem cells (SC)s derived from other adult tissue sources have been considered as an alternative. However, there is only limited knowledge on their immunomodulatory properties.

Inflammatory peritoneal reaction after perforated appendicitis: continuous peritoneal lavage versus non lavage.

Introduction: Bacterial peritonitis is a severe medical condition associated with a natural mortality rate of 80-100%. Progress in surgical techniques, new developments in intensive care medicine and antibiotic therapy reduced this rate significantly. Aim of this study was to evaluate sepsis parameter in perforated appendicitis and different postoperative management.

Association of IL-8-251A/T polymorphism with incidence of Acute Respiratory Distress Syndrome (ARDS) and IL-8 synthesis after multiple trauma.

Introduction: Interleukin-8 (IL-8) is regarded as one of the most important mediators in the pathogenesis of Adult Respiratory Distress Syndrome (ARDS). However, knowledge regarding the influence of genetic variations within the IL-8 gene either on the development of ARDS or on IL-8 production in the traumatic setting is sparse.

Patients And Methods: In this prospective cohort study, patients were included if the following criteria were fulfilled: Injury Severity Score (ISS) >16, age 18-60 years and a survival >48 h after injury.

The phosphatidylinositol 3-kinase signaling pathway exerts protective effects during sepsis by controlling C5a-mediated activation of innate immune functions.

The PI3K/Akt signaling pathway has been recently suggested to have controversial functions in models of acute and chronic inflammation. Our group and others have reported previously that the complement split product C5a alters neutrophil innate immunity and cell signaling during the onset of sepsis and is involved in PI3K activation. We report in this study that in vivo inhibition of the PI3K pathway resulted in increased mortality in septic mice accompanied by strongly elevated serum levels of TNF-alpha, IL-6, MCP-1, and IL-10 during sepsis as well as decreased oxidative burst activity in blood phagocytes.

FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia; impact on long-term survival and T-lymphocyte tissue infiltration.

Background: Organ dysfunction due to ischemia-reperfusion (I/R) injury is a common problem in transplant, liver, trauma, and heart surgery. I/R injury is mediated by upregulated expression of endothelial cell surface adhesion molecules and subsequent adhesion and activation of circulating leukocytes. The purpose of this study was to evaluate the effect of an intraoperative administration of FTY720 in an animal model with controlled bilateral warm kidney ischemia compared to steroids or placebo application.

FTY720 application following isolated warm liver ischemia improves long-term survival and organ protection in a mouse model.

Background: Ischemia-reperfusion-Injury (I/RI) is a common complication in transplant-, liver-, and heart surgery. The I/RI is mediated and aggravated by different types of leukocytes such as lymphocytes, monocytes, and neutrophil granulocytes, with consecutive enlargement of the expression of adhesion molecules. This study shows an organ-protective effect of an intraoperative FTY720 administration following warm liver ischemia (Pringle's maneuver).

Influence of sex and age on mods and cytokines after multiple injuries.

Although salutary effects of female sex steroids have been demonstrated not only in proestrus females but also in male animals treated with estradiol in different models of trauma, it remains unknown whether sex hormones influence post-traumatic immune response in humans. We therefore investigated the effect of sex and age on organ dysfunction and clinical course in patients with multiple injuries. Polytraumatized patients (injury severity score>16) between 16 and 65 years old admitted to the Hannover Medical School Level 1 trauma center between January 1997 and December 2001 were included.

Comparison of whole blood interleukin-8 and plasma interleukin-8 as a predictor for sepsis in postoperative patients.

Objective: Interleukin-8 (IL-8, also known as neutrophil-activating peptide 1, NAP1 and CXCL8, CXC chemokine ligand 8) is recognized as a potent effector of neutrophil functions. IL-8 is a major response factor following NfkB activation by cytokines or lipopolysaccharide and several different cell types T lymphocytes, monocytes, epithelial and endothelial cells secrete this polypeptide. IL-8 is not to be determined at significant concentrations in plasma due to its receptor binding but may play a major role in tissues.

The long-term neurocompatibility of human fibrin sealant and equine collagen as biomatrices in experimental spinal cord injury.

Introduction: While fibrin sealant (FS) and equine collagen (EC) have been used as scaffold materials in experimental spinal cord injury (SCI), questions concerning neurocompatibility still remain. In this study, we assessed potential adverse effects, as well as functional and histological impact of FS and EC in subtotal hemisection of the thoracic spinal cord (SC) in rats.

Methods: 124 male rats were randomly assigned to four main groups (n=31): Sham (SH), Lesion only (L), fibrin sealant (GFS) and equine collagen group (GEC).

Labelling of human adipose-derived stem cells for non-invasive in vivo cell tracking.

Human adipose-derived stem cells (ASC) can be expanded in an undifferentiated state or differentiated along the osteogenic, chondrogenic, adipogenic, myogenic, endothelial and neurogenic lineage. To test their in vivo and in situ regenerative potential, their fate needs to be traced after application in suitable defect models. Non-invasive imaging systems allow for real time tracking of labelled cells in the living animal.