Optimizing Bone Scaffold Porosity Distributions

We consider a simple one-dimensional time-dependent model for bone regeneration in the presence of a bio-resorbable polymer scaffold. Within the framework of the model, we optimize the effective mechanical stiffness of the polymer scaffold together with the regenerated bone matrix. The result of the optimization procedure is a scaffold porosity distribution which maximizes the stiffness of the scaffold-bone system over the regeneration time, such that the propensity for mechanical failure is reduced

Application of Stem Cells in Orthopedics

Stem cell research plays an important role in orthopedic regenerative medicine today. Current literature provides us with promising results from animal research in the fields of bone, tendon, and cartilage repair. While early clinical results are already published for bone and cartilage repair, the data about tendon repair is limited to animal studies. The success of these techniques remains inconsistent in all three mentioned areas. This may be due to different application techniques varying from simple mesenchymal stem cell injection up to complex tissue engineering. However, the ideal carrier for the stem cells still remains controversial. This paper aims to provide a better understanding of current basic research and clinical data concerning stem cell research in bone, tendon, and cartilage repair. Furthermore, a focus is set on different stem cell application techniques in tendon reconstruction, cartilage repair, and filling of bone defects

Morphology, mechanical characterization and in vivo neo-vascularization of chitosan particle aggregated scaffolds architectures

The present study intended to evaluate the performance of chitosan-based scaffolds produced by a particle aggregation method aimed to be used in tissue engineering applications addressing key issues such as morphological characteristics, mechanical performance and in vivo behaviour. It is claimed that the particle aggregation methodology may present several advantages, such as combine simultaneously a high interconnectivity with high mechanical properties that are both critical for an in vivo successful application. In order to evaluate these properties, micro-Computed Tomography (micro-CT) and Dynamical Mechanical Analysis (DMA) were applied. The herein proposed scaffolds present an interesting morphology as assessed by micro-CT that generally seems to be adequate for the proposed applications. At a mechanical level, DMA has shown that chitosan scaffolds have an elastic behaviour under dynamic compression solicitation, being simultaneously mechanically stable in the wet state and exhibiting a storage modulus of 4.21 ! 1.04 MPa at 1 Hz frequency. Furthermore, chitosan scaffolds were evaluated in vivo using a rat muscle-pockets model for different implantation periods (1, 2 and 12 weeks). The histological and immunohistochemistry results have demonstrated that chitosan scaffolds can provide the required in vivo functionality. In addition, the scaffolds interconnectivity has been shown to be favourable to the connective tissues ingrowth into the scaffolds and to promote the neo-vascularization even in early stages of implantation. It is concluded that the proposed chitosan scaffolds produced by particle aggregation method are suitable alternatives, being simultaneously mechanical stable and in vivo biofunctional that might be used in load-bearing tissue engineering applications, including bone and cartilage regeneration.The authors would like to acknowledge the Portuguese Foundation for Science and Technology for the PhD Grant to Patricia B Malafaya (SFRH/BD/11155/2002). This work was partially supported and carried out under the scope of the European STREP Project HIPPOCRATES (NMP3-CT-2003-505758) and European NoE EXPERTISSUES (NMP3-CT-2004-500283). The authors also thank Prof. Heinz Redl for the collaboration in the in VIVO Studies, as well as Bernhard Horing for the surgical procedures both from LBI, Austria and Joao Oliveira from 3B's Research Group, Portugal for the initial assistance with the DMA equipment

Dehydroepiandrosterone administration modulates endothelial and neutrophil adhesion molecule expression in vitro

INTRODUCTION: The steroid hormone dehydroepiandrosterone (DHEA) exerts protecting effects in the treatment of traumatic and septic complications in several animal models. This effect goes along with reduced amounts of infiltrating immune cells in organs such as lung and liver. However, the underlying mechanisms of DHEA action are still not known. Adhesion molecules are important for the extravasation of neutrophils into organs where they may exhibit detrimental effects. Therefore, we investigated the in vitro effect of DHEA on the expression pattern of adhesion molecules of human endothelial cells and neutrophils. METHODS: Endothelial cells derived from human umbilical cord were subjected to an lipopolysaccharide (LPS) challenge. DHEA was administered in two different concentrations, 10(-5 )M and 10(-8 )M, as a single stimulus or in combination with LPS challenge. After two, four and 24 hours, fluorescence activated cell sorter (FACS) analysis for vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-selectin was performed. Neutrophils were freshly isolated from blood of 10 male healthy volunteers, stimulated the same way as endothelial cells and analyzed for surface expression of L-selectin, CD11b and CD18. RESULTS: In the present study, we were able to demonstrate effects of DHEA on the expression of every adhesion molecule investigated. DHEA exhibits opposite effects to those seen upon LPS exposure. Furthermore, these effects are both time and concentration dependent as most DHEA specific effects could be detected in the physiological concentration of 10(-8 )M. CONCLUSION: Thus, we conclude that one mechanism by which DHEA may exert its protection in animal models is via the differential regulation of adhesion molecule expression

IL-6 predicts organ dysfunction and mortality in patients with multiple injuries

<p>Abstract</p> <p>Background</p> <p>Although therapeutic concepts of patients with major trauma have improved during recent years, organ dysfunction still remains a frequent complication during clinical course in intensive care units. It has previously been shown that cytokines are upregulated under stress conditions such as trauma or sepsis. However, it is still debatable if cytokines are adequate parameters to describe the current state of trauma patients. To elucidate the relevance of cytokines, we investigated if cytokines predict development of multiple organ dysfunction syndrome (MODS) or outcome.</p> <p>Methods</p> <p>A total of 143 patients with an injury severity score ≥ 16, between 16 and 65 years, admitted to the Hannover Medical School Level 1 Trauma Center between January 1997 and December 2001 were prospectively included in this study. Marshall Score for MODS was calculated for at least 14 days and plasma levels of TNF-α, IL-1β, IL-6, IL-8 and IL-10 were measured. To determine the association between cytokine levels and development of MODS the Spearman rank correlation coefficient was calculated and logistic regression and analysis were performed.</p> <p>Results and Discussion</p> <p>Patients with MODS had increased plasma levels of IL-6, IL-8 and IL-10. IL-6 predicted development of MODS with an overall accuracy of 84.7% (specificity: 98.3%, sensitivity: 16.7%). The threshold value for development of MODS was 761.7 pg/ml and 2176.0 pg/ml for mortality during the in patient time.</p> <p>Conclusion</p> <p>We conclude that plasma IL-6 levels predict mortality and that they are a useful tool to identify patients who are at risk for development of MODS.</p

Predictors of poor outcomes after significant chest trauma in multiply injured patients: a retrospective analysis from the German Trauma Registry (Trauma Register DGU (R))

Background: Blunt thoracic trauma is one of the critical injury mechanisms in multiply injured trauma victims. Although these patients present a plethora of potential structural damages to vital organs, it remains debated which injuries actually influence outcome and thereby should be addressed initially. Hence, the aim of this study was to identify the influence of critical structural damages on mortality. Methods: All patients in the database of the TraumaRegister DGU (R) (TR-DGU) from 2002-2011 with AIS Chest >= 2, blunt trauma, age of 16 or older and an ISS >= 16 were analyzed. Outcome parameters were in-hospital mortality as well as ventilation time in patients surviving the initial 14 days after trauma. Results: 22613 Patients were included (mean ISS 30.5 +/- 12.6; 74.7% male; Mean Age 46.1 +/- 197 years; mortality 17.5%; mean duration of ventilation 7.3 +/- 11.5; mean ICU stay 11.7 +/- 14.1 days). Only a limited number of specific injuries had a significant impact on survival. Major thoracic vessel injuries (AIS >= 5), bilateral lung contusion, bilateral flail chest, structural heart injury (AIS >= 3) significantly influence mortality in study patients. Several extrathoracic factors (age, blood transfusion, systolic blood pressure and extrathoracic severe injuries) were also predictive of increased mortality. Most injuries of the thoracic wall had no or only a moderate effect on the duration of ventilation. Injuries to the lung (laceration, contusion or pneumothoraces) had a moderate prolonging effect. Cardiac injuries and severe injuries to the thoracic vessels induced a substantially prolonged ventilation interval. Conclusions: We demonstrate quantitatively the influence of specific structural damages of the chest on critical outcome parameters. While most injuries of the chest wall have no or only limited impact in the study collective, injuries to the lung overall show adverse outcome. Injuries to the heart or thoracic vessels have a devastating prognosis following blunt chest trauma