Due to their immunomodulatory and regenerative capacity, human bone marrow-derived mesenchymal stromal cells (hBMSCs) are promising in the treatment of polytrauma patients. However, few studies evaluated the effects of sera from polytraumatized patients on hBMSCs. The aim of this study was to explore changes in hBMSCs exposed to serum from polytrauma patients from different time points after trauma. Sera from 84 patients on day 1 (D1), 5 (D5) and 10 (D10) after polytrauma (ISS ≥ 16) were pooled respectively to test the differential influence on hBMSC. As a control, sera from three healthy age- and gender-matched donors (HS) were collected. The pooled sera were analyzed by Multicytokine Array for pro-/anti-inflammatory cytokines. For the cell culture experiments, hBMSCs from four healthy donors were used. The influence of the different sera on hBMSC regarding cell proliferation, colony forming unit-fibroblast (CFU-F) assay, cell viability and toxicity, cell migration, as well as osteogenic and chondrogenic differentiation was analyzed. One-Way-ANOVA and LSD-test were used for the parametric, Kruskal-Wallis-test for non-parametric data. p≤0.05 was considered as statistically significant. The results showed that D5 serum reduced hBMSCs cell proliferation capacity by 41.26% (p=0.000) compared with HS and increased the proportion of dead cells by 3.19% (p=0.008) and 2.25% (p=0.020) compared with D1 and D10. The frequency of CFU-F was reduced by 49.08% (p=0.041) in D5 and 53.99% (p=0.027) in D10 compared with HS, whereas the other parameters were not influenced. The serological effect of polytrauma on hBMSCs was related to the time after trauma. It is disadvantageous to use BMSCs in polytraumatized patients five days after the incidence as obvious cytological changes could be found at that time point. However, it is promising to use hBMSCs to treat polytrauma after 10 days, combined with the concept of “Damage Control Orthopaedics” (DCO).
In multiple trauma patients, as well as in the healing of isolated fractures (Fx) with heavy bleeding (trauma haemorrhage, TH), complications occur very often. This is particularly evident in elderly patients over 65 years of age. Since these accompanying circumstances strongly influence the clinical course of treatment, the influence of age on bone regeneration after femoral fracture and severe blood loss was investigated in this study. 12 young (17–26 weeks) and 12 old (64–72 weeks) male C57BL / 6J mice per group were examined. The fracture group Fx underwent an osteotomy after applying an external fixator. The THFx group also received blood pressure-controlled trauma hemorrhage (35 mmHg for 90 minutes) and reperfusion with Ringer's solution for 30 minutes. The Sham group received only the catheter and one external fixator. μCT scans of the femora were performed in vivo after 2 weeks and ex vivo after 3 weeks. Histological and biomechanical examinations were also carried out. The statistical significance was set at p ≤ 0.05. The non-normally distributed data were analyzed using the Mann-Whitney-U or Kruskal-Wallis test.Introduction and Objective
Materials and Methods
In patients with multiple trauma delayed fracture healing is often diagnosed, but the pathomechanisms are not well known yet. The purpose of the study is to evaluate the effect of a severe hemorrhagic shock on fracture healing in a murine model. 10 male C57BL/6N mice per group (Fx, TH, THFx, Sham) and point in time were used. The Fx-group received an osteotomy after implantation of a fixateur extern. The TH-group got a pressure controlled hemorrhagic shock with a mean arterial blood pressure of 35 mmHg over 90 minutes. Resuscitation with 4 times the shed blood volume of Ringer solution was performed. The THFx group got both. Sham-animals received the implantation of a catheter and a fixateur extern but no blood loss or osteotomy. After 1, 2, 3, 4 or 6 weeks the animals were sacrificed. For the biomechanics the bones were analyzed via X-ray, µCT and underwent a 3-point bending test. The nondecalcified histology based on slices of Technovit 9100. The signaling pathway was analyzed via RT2 Profiler™ PCR Array Mouse Osteoporosis, Western Blot and Quantikine ELISA for RankL and OPG. Statistical significance was set at Purpose
Methods
Human bone marrow-derived mesenchymal stem cells (hBMSCs) can adopt either an immune suppressive or stimulative phenotype in response to cytokines and pathogen-associated molecular patterns (PAMPs). It is known that the glycoprotein CD24 allows for the discrimination between PAMPs and DAMPs in dendritic cells. We were able to show previously that CD24 is expressed by hBMSCs and found that its overexpression leads to the downregulation of NF-kB-regulated genes, as well as induction of the anti-inflammatory TGF beta. In the present study the influence of various PAMPs and cytokines on the expression of CD24 in hBMSCs was analysed. Furthermore, it was tested whether hBMSCs were enriched by density gradient centrifugation, cultured Introduction
Methods
The aims of this study were to determine whether the administration of anti-inflammatory and antifibrotic agents affect the proliferation, viability, and expression of markers involved in the fibrotic development of the fibroblasts obtained from arthrofibrotic tissue Dexamethasone, diclofenac, and decorin, in different concentrations, were employed to treat fibroblasts from arthrofibrotic tissue (AFib). Cell proliferation was measured by DNA quantitation, and viability was analyzed by Live/Dead staining. The levels of procollagen type I N-terminal propeptide (PINP) and procollagen type III N-terminal propeptide (PIIINP) were evaluated with enzyme-linked immunosorbent assay (ELISA) kits. In addition, the expressions of fibrotic markers were detected by real-time polymerase chain reaction (PCR). Fibroblasts isolated from healthy tissue (Fib) served as control. Further, a rabbit model of joint contracture was used to evaluate the antifibrotic effect of the three different agents.Objectives
Methods
To test whether there are differences in postoperative mechanical and component alignment, and in functional results, between conventional, navigated and patient-specific total knee arthroplasties in a low-volume centre? Retrospective cohort study of 391 patients who received conventional, navigated or patient- specific primary cemented TKA in a low-volume hospital.INTRODUCTION
MATERIAL AND METHODS
High tibial osteotomy (HTO) is a commonly used surgical technique for treating moderate osteoarthritis (OA) of the medial compartment of the knee by shifting the center of force towards the lateral compartment. The amount of alignment correction to be performed is usually calculated prior to surgery and it's based on the patient's lower limb alignment using long-leg radiographs. While the procedure is generally effective at relieving symptoms, an accurate estimation of change in intraarticular contact pressures and contact surface area has not been developed. Using electromyography (EMG), Meyer et al. attempted to predict intraarticular contact pressures during gait patterns in a patient who had received a cruciate retaining force-measuring tibial prosthesis. Lundberg et al. used data from the Third Grand Challenge Competition to improve contact force predictions in total knee replacement. Mina et al. performed high tibial osteotomy on eight human cadaveric knees with osteochondral defects in the medial compartment. They determined that complete unloading of the medial compartment occurred at between 6° and 10° of valgus, and that contact pressure was similarly distributed between the medial and lateral compartments at alignments of 0° to 4° of valgus. In the current study, we hypothesised that it would be possible to predict the change in intra-articular pressures based on extra-articular data acquisition. Seven cadavers underwent an HTO procedure with sequential 5º valgus realignment of the leg up to 15º of correction. A previously developed stainless-steel device with integrated load cell was used to axially load the leg. Pressure-sensitive sensors were used to measure intra-articular contact pressures. Intraoperative changes in alignment were monitored in real time using computer navigation. An axial loading force was applied to the leg in the caudal-craneal direction and gradually ramped up from 0 to 550 N. Intra-articular contact pressure (kg) and contact area (mm2) data were collected. Generalised linear models were constructed to estimate the change in contact pressure based on extra-articular force and alignment data.Introduction
Methods
The timing of definitive fixation for major fractures in polytrauma patients is controversial. To clarify this aspect of trauma management, we randomised patients with blunt multiple injuries to either initial definitive stabilisation of the femur shaft with an intramedullary nail or an external fixator which was converted to an intramedullary nail at a secondary procedure and documented the post-operative clinical condition. Multiply injured patients with femoral shaft fractures were randomised to either initial (<24 hours) intramedullary femoral nailing or to initial external fixation and conversion to an intramedullary nail at a later phase. Inclusion criteria: New Injury Severity Score >16 points, or 3 fractures and Abbreviated Injury Scale score >2 points and another injury (Abbreviated Injury Scale score >2 points), and age 18 to 65 years. Exclusion criteria: unstable or patients in extremis. Patients were graded as stable or borderline (increased risk of systemic complications). OUTCOMES: Incidence of acute lung injuries.Purpose
Methods
We aimed to investigate the treatment and outcome of patients over 65 years of age with tibial Pilon fracture. Patients were treated by primary open reduction and internal fixation or external fixation (EF) as determined by local soft tissue conditions. Patient course, incidence of radiological osteoarthritis and functional outcome using the SF-36 questionnaire were recorded. All patients were evaluated serially until discharge from final follow-up. The mean follow-up time was 28 months (12-45). Statistical analysis was performed using Analyse-it(tm) software for Excel. In total 25 patients were studied. Two patients died before completion of treatment and were excluded from the final analysis. Therefore, 23 patients (10 male) were included with a mean age of 70.9 years (range 66-89) and a mean ISS of 10.25 (range 9-22). There were 4 grade IIIb open injuries. Three patients suffered superficial tibial wound infection. Two patients underwent early secondary amputation due to deep bone sepsis within 8 weeks of injury. One patient in the ORIF group underwent primary arthrodesis, which was subsequently revised due to non-union. 3 patients underwent secondary bone grafting to enhance healing, performed at 2, 6 and 9 weeks. 2 patients with metal work failure underwent subsequent revision of ORIF and progressed to union; the mean time to union was 33.8 weeks. At final follow-up 7 (28%) patients had radiological features of osteoarthritis but none had symptoms severe enough to warrant ankle arthrodesis. There were significant differences from the USA norm in physical function score, role physical score, and physical component score, (p< 0.01). In older patients local complications are relatively common and clinical vigilance must be maintained in order to allow appropriate intervention during their post-operative course. Despite the incidence of radiological post-traumatic arthrosis, none of the patients progressed to ankle fusion.Conclusion/Significance
Patients with bilateral femur shaft fractures are known to have a higher rate of complications when compared with those who have unilateral fractures. Many contributing factors have been considered responsible, however due to the heterogeneity of the studied populations solid conclusions cannot be substantiated. Patients included in our study were separated according to the presence of a unilateral (group USF) (n=146) versus bilateral femur shaft fracture (group BSF) (n=19)Endpoints of the study included the incidence of systemic (SIRS, Sepsis, Acute Lung Injuries) complications. The perioperative assessment included documentation of clinical and laboratory data assessing blood loss, coagulopathy, wound infection, and pneumonia. Local (wound infection, compartment syndrome etc.) and systemic complications (ALI, MOF, Sepsis) were documented. Statistical analyses were conducted to examine the relation between the occurrence of unilateral versus bilateral femoral fractures and variables indexing patient demographic characteristics and other indicators of initial injury severity. Independent sample t-tests were used to examine treatment group differences for variables that approximated a Gaussian distribution. For non-normal indicators of injury severity Mann-Whitney tests were performed. Pearson chi-square tests were performed for binary indicators of injury severity, except when expected cell counts did not exceed 5 participants. When this occurred, the Fisher exact test was used Evidence indicated that patients who suffered a bilateral femoral fracture were significantly more likely to have hemothorax and receive a blood transfusion upon admission to the hospital in comparison to patients who suffered a unilateral femoral fracture. Bivariate analyses also indicated that patients with bilateral femoral fractures exhibited a longer clinical recovery time and were more likely to experience clinical complications in comparison to those with unilateral fractures. However, there were no significant differences between the fracture groups in terms of the number of hours spent on a ventilator or the occurrence of pneumonia, acute lung injury, acute respiratory distress, sepsis, and multiple organ failure following surgery. Patients in borderline condition spent significantly more time in the ICU in comparison to those in stable condition. The high incidence of posttraumatic complications in poly-trauma patients with bilateral femur shaft fractures is caused by the accompanying injuries rather than by the additional femur fracture itself. It also documents that a thorough preoperative assessment can help differentiate those who have a high like hood of developing systemic complications from those who do not.
Tests were done on 10 intact specimen and the process included the initial drilling and final placement of an osteosynthetic screw. Postoperative placement was controlled with a 3-D scan. Results concerning a defined optimal screw positioning and drill failures attempts were done by another independent surgeon.
The 3-D imaging modality allows a direct control of the reduction and screw placement intraoperatively. Our tests did not include simulated fracture conditions, a general use of our new technique can now only be implemented to non displaced fracture types, while clinical and further laboratory tests have to improve our findings for all types of scaphoid fractures.
Movement of the limb during computer aided arthroplasty may cause soft tissue impingement on the reference marker(RM) and consequently alter the spatial relationship between RM and bone with resulting inaccuracies in navigation. The purpose of this study was to investigate the effect of different degrees of soft tissue dissection on the stability of reference markers during limb movement. The stability of both one- and two-pin RM systems inserted using three different levels of soft-tissue dissection was analysed in relation to a super-stable RM in fresh cadaver lower limbs. The spatial relationship of the two RMs was analysed using the VectorVision® system (BrainLAB, Germany) during multiple repetitions of four predefined limb movements. All tests were done with RMs inserted in both the distal-anterior femur and distal-lateral femur. Analysis of movements of the test RM in relation to the super-stable RM showed that rotations of less than 0.15o and translations of less than 0.4mm occurred in most test combinations. The combination that showed the greatest instability was when a stab incision was used to insert a pin in the distal/lateral femur (translation 0.73mm+/− 0.05, rotation 0.25o+/− 0.05)(p<
0.001). This instability occurred in both single and double pin RMs(p=0.21). RM pins can be placed in the anterior distal femur through simple stab incisions without resulting in significant soft tissue impingement during limb movement. If pins are placed in the lateral distal femur through stab incisions, impingement may occur from the fascia lata. Release of the fascia lata 1cm either side of the pin prevents significant impingement. Wide skin incision is unnecessary in any location.
In computer assisted orthopaedic surgery, rigid fixation of the Reference Marker (RM) system is essential for reliable computer guidance. A minimum shift of the RM can lead to substantial registration errors and inaccuracies in the navigation process. Various types of RM systems are available but there is little information regarding the relative stabilities of these systems. The aim of this study was to test the rotational stability of three commonly used RM systems. One hundred and thirty Synbones and 15 cadavers were used to test the rotational stability of three different RM systems (Schanz’ screw, Brain-Lab MIRA and Stryker adjustment system). Using a specially developed testing device, the peak torque sustained by each RM system was assessed in various anatomical sites. Comparison of means for Synbone showed that the BrainLab MIRATM system was the most stable (mean peak torque 5.60+/− 1.21 Nm) followed by the Stryker systemTM (2.53+/− 0.53 Nm) and the Schanz screw(0.77+/− 0.39 Nm)(p<
0.01). The order of stability in relation to anatomical site was femoral shaft, distal femur, tibial shaft, proximal tibia, anterior superior iliac spine, iliac crest and talus. Results from the cadaver experiments showed similar results. Bi-cortical fixation was superior to mono-cortical fixation in the femur(p<
0.01) but not the tibia(p=0.22). The RM system is the vital link between bone and computer and as such the stability of the RM is paramount to the accuracy of the navigation process. In choosing RM systems for computer navigated surgery surgeons should be aware of their relative stability. Anatomical site of RM placement also affect the stability. Mono-cortical fixation is generally less stable than bi-cortical.
The integration of mechanical stimulation in the tissue engineering process may lead to a progress in the structural and biomechanical properties of these tissues and offers new possibilities in the management of bone injuries and degenerative diseases.
Tibial rotation and translation provide important stability parameters after ACL reconstruction. An accurate tool for a combined pre- intra- and postoperative stability measurement is not in clinical use so far. Navigation of the drill canals for the ACL placement and evaluation of possible impingement problems has been introduced for some years already, while measurement of the tibial translation and rotation is only available for a short time and only available for a few navigation modules. Navigation provides an accuracy of 1mm/1°, therefore navigated measurement of tibial rotation and translation were evaluated in this study with a new developed mechanical device and directly compared to conventional measurement techniques. Accuracy of navigation was compared with the KT1000 for the anterior-posterior (AP) translation and to a new developed goniometer tool concerning the rotational range of motion. Comparative tests included plastic whole leg models and specimens. Tests were repeated with intact and dissected ACL′s. A conventional navigation system (Vector Vision, Brainlab, Germany) was used in all cases. This included software developed for fluoroscopy based navigated ACL reconstruction. The following knee kinematics were detectable with the navigation system: Flexion/Extension degrees of the knee joint (°); AP translation of the tibia in relation to the femur (mm); Axial tibial rotation relative to the femur (°). Validation of Navigation: first neutral tibial rotation was defined and marked in the knee joint in neutral position. All rotational measurements were done with a new developed goniometer tool and compared to the navigated technique. Then the knee was rotated externally until 45° (maximum) and internally 45° (maximum), by single 2.5° steps. These measurements were repeated in 0°, 30°, 60° and 80° knee flexion. All tests were repeated three times and performed by 3 different observers. A total of 1296 measurements were done. Measurements of the tibial translation were compared with the KT 1000 for the specimen testing. Results revealed: accurate navigated measurement of tibial rotation in plastic and specimen models; variation of absolute AP translation values between KT1000 and navigation; variation of the AP translation corresponding to the ACL condition; increased range of total tibial rotation after dissecting the ACL compared to the intact ligament. Restoration of the rotational stability and limiting of the AP translation is necessary to provide normal knee kinematics after ACL reconstructions. Intraoperative measurements of these stability parameters are demanding and so far not established with navigation systems or conventionally. As our results show, navigation offers an accurate technique for measurement of the AP translation and rotation of the knee with intact and dissected ACL’s under laboratory conditions. General use in the evaluation of a successful ACL reconstruction becomes possible intraoperative and might be reproducible for further measurements. Clinical studies are needed to improve our results.
Anatomic reduction and appropriate implant placement is essential for optimal treatment of intraarticular tibial plateau fractures. Standard intraoperative fluoroscopy provides limited visualization of the reduction and hardware placement compared with pre- or postoperative 3-D imaging modalities. As such, post-operative computer tomography (CT) has become a common procedure to evaluate the quality of the reduction and fixation. The Iso-C3D provides 3-D intraoperatively imaging to dynamically assess the surgical reduction and fixation at different anatomic regions. We report on our first 19 clinical tibial plateau fractures scanned intra-operatively with the Iso-C 3D. Between January and November 2003, 19 intraarticular tibia plateau fractures were scanned intraoperatively with the Iso-C3D (Siemens, Germany). No formal selection criteria were utilised except for the presence of a tibial plateau fracture. Operative procedures included 14 cases of open reduction internal fixation and 5 cases of internal fixation with arthroscopic assisted reduction. Imaging Technique: All patients were positioned on full-carbon tables for the operative procedure. After initial operative reduction and fixation, conventional two-dimensional fluoroscopic imaging was performed using standard AP and lateral projections. These images were evaluated by the operating surgeon; if the reduction and fixation was judged to be appropriate, Iso-C3D imaging was initiated In 21% (n=4) of all cases an immediate revision of the operative procedure was performed after Iso-C3D imaging. These revisions were not deemed necessary with conventional fluoroscopy alone. In two cases, significant intra-articular incongruencies (greater than two millimetres) were noted. Additionally, in two cases, implant mal-position was detected. All patients had a postoperative CT scan. All CT scans confirmed the intraoperative Iso-C imaging, no further additional articular incongruencies or malpositioned implants were identified. When compared to conventional C-arm images, the Iso-C 3D scans demonstrated improved ability to identify the articular malreduction and implant mal-position in all cases. We have demonstrated that the Iso-C3D provides reliable intraoperative evaluation of reduction and hardware placement compared to traditional CT scans for tibial plateau fractures. In addition, clinically relevant intra-operative information was gained with its use in this study. In four (21%) cases, the operative treatment was modified due to the use of the multiplanar imaging modality. On average, 10 minutes of additional operative time was required for the use of Iso-C3D scanning and the evaluation of the images. Further prospective clinical studies are needed to improve our findings.