Martin Lucke

Gentamycin delivered from a PDLLA coating of metallic implants: In vivo and in vitro characterisation for local prophylaxis of implant-related osteomyelitis

Locally applied antibiotics support prophylaxis of highly feared implant associated infections. Implant coatings with poly(D,L-lactide) (PDLLA)/gentamicin seem to be a promising approach. Aims of this study were to analyse the release kinetics of gentamicin in vivo, in vitro, to analyse the antibacterial efficacy,the resistance development and its impact on osteoblasts. For the in vitro release experiments titanium implants were coated with PDLLA/gentamicin and the antibiotic release in aqueous solution was analysed at 20 time points (from 10 s to 110 days). For the in vivo experiments PDLLA/gentamicin-coated kirschner wires were implanted in the tibiae of 18 rats. Gentamicin concentration in the bone was analysed at several time points (n = 3 each, 1 h to 7 days). Bactericidal efficacy, bacterial adhesion on the implants and resistance development were tested. AP activity, cell count and CICP expression of osteoblasts were analysed. Gentamicin was released rapidly with an initial burst in aqueous solution and followed by a slow release. Similarly, in vivo gentamicin concentration reached a high peak initially followed by a decrease to a low level. No development of resistance was observed in the investigated setting, the antibacterial efficacy was not affected by the coating process and significantly fewer bacteria were attached to the implant. Osteoblasts were not negatively affected by the gentamicin released from the coating. PDLLA/gentamicin coating resulted in a desired antibiotic peak concentration within the bone. Bacterial adhesion was successfully prevented. No bacterial resistances were developed. This coating seems to be a suitable supplement for prophylaxis of implant-associated infections.

TGF-β1 As Possible Link between Loss of Bone Mineral Density and Chronic Inflammation

Background The TGF family plays a key role in bone homeostasis. Systemic or topic application of proteins of this family apparently positively affects bone healing in vivo. However, patients with chronic inflammation, having increased TGF-β1 serum-levels, often show reduced bone mineral content and disturbed bone healing. Therefore, we wanted to identify intracellular mechanisms induced by chronic presence of TGF-β1 and their possible role in bone homeostasis in primary human osteoblasts. Methodology/Principal Findings Osteoblasts were isolated from femur heads of patients undergoing total hip replacement. Adenoviral reporter assays showed that in primary human osteoblasts TGF-β1 mediates its signal via Smad2/3 and not Smad1/5/8. It induces proliferation as an intermediate response but decreases AP-activity and inorganic matrix production as a late response. In addition, expression levels of osteoblastic markers were strongly regulated (AP↓; Osteocalcin↓; Osteopontin↑; MGP↓; BMP 2↓; BSP2↓; OSF2↓; Osteoprotegerin↓; RANKL↑) towards an osteoclast recruiting phenotype. All effects were blocked by inhibition of Smad2/3 signaling with the Alk5-Inhibitor (SB431542). Interestingly, a rescue experiment showed that reduced AP-activities did not recover to base line levels, even 8 days after stopping the TGF-β1 application. Conclusions/Significance In spite of the initial positive effects on cell proliferation, it is questionable if continuous Smad2/3 phosphorylation is beneficial for bone healing, because decreased AP-activity and BMP2 levels indicate a loss of function of the osteoblasts. Thus, inhibition of Smad2/3 phosphorylation might positively influence functional activity of osteoblasts in patients with chronically elevated TGF-β1 levels and thus, could lead to an improved bone healing in vivo.

Comminuted fractures of the proximal ulna—Preliminary results with an anatomically preshaped locking compression plate (LCP) system

INTRODUCTION The purpose of this investigation was to review the preliminary results and patients outcome following treatment with an anatomically preshaped LCP in patients with comminuted fractures of the proximal ulna. We hypothesized that this fixation system provides equal or superior results in fracture care when compared with other available plating devices, but results in better patients comfort due to its low-profile design. PATIENTS AND METHODS Between 2007 and 2009, 15 patients with comminuted fractures of the proximal ulna including three posterior Monteggia fractures were managed with the preshaped LCP olecranon plate. The patients were invited for clinical examination at a mean duration of 16 months, retrospectively. Validated patient-oriented assessment scores involving the Mayo Elbow Performance Index (MEPI) and the shortened Disability of the Arm, Shoulder and Hand (Quick-DASH) score, postoperative range of motion, objective muscle-strengths testing and patients satisfaction were evaluated. All patients had follow-up radiographs. RESULTS Fourteen patients were available for evaluation. The mean arc of elbow motion was 129°. The mean MEPI was 97 with good results in two patients and excellent results in 12 patients. The mean Quick-DASH was 13. Thirteen of fourteen patients documented satisfaction with their elbow outcome. There was one patient with symptomatic hardware and one patient complained about deficit of motion. In four patients the hardware was removed including two patients with elective removal. Fourteen fractures healed with ulnohumeral congruity after a mean time to union of 11 weeks. One fracture non-union occurred without mechanical failure or loss of reduction. CONCLUSION Anatomically preshaped LCP olecranon plating is an effective fixation method for comminuted fractures of the proximal ulna allowing reliable stability for early elbow motion. The functional results are comparable with formerly described plating systems. A low rate of symptomatic hardware removal suggests better patients compatibility.

Medial migration of lag screw with intrapelvic dislocation in gamma nailing--a unique problem? A report of 2 cases.

Within the last decade, intramedullary nailing systems have gained popularity in the treatment of unstable fractures of the trochanteric region with good clinical results. However, these implants are not free of complications. Commonly reported treatment failures include implant cutout through the femoral neck, stress-derived femur fractures at the distal end of the nail, and secondary rotational displacement and varus deformity of the femoral neck and head. Only few reports exist on primary medial migration of the lag screw after treatment with intramedullary implants. We report on a rarely described complication in 2 patients who underwent osteosynthesis with a Gamma 3 nail (Stryker, Mahwah, NJ). Both patients presented with implant failures due to primary medial migration of the lag screw. Complete separation of the implant occurred, and the lag screw penetrated through the acetabulum into the pelvis. The patients histories and course of treatment are reported. The literature on this topic is discussed.

New method for detection of complex 3D fracture motion - Verification of an optical motion analysis system for biomechanical studies

BackgroundFracture-healing depends on interfragmentary motion. For improved osteosynthesis and fracture-healing, the micromotion between fracture fragments is undergoing intensive research. The detection of 3D micromotions at the fracture gap still presents a challenge for conventional tactile measurement systems. Optical measurement systems may be easier to use than conventional systems, but, as yet, cannot guarantee accuracy. The purpose of this study was to validate the optical measurement system PONTOS 5M for use in biomechanical research, including measurement of micromotion.MethodsA standardized transverse fracture model was created to detect interfragmentary motions under axial loadings of up to 200 N. Measurements were performed using the optical measurement system and compared with a conventional high-accuracy tactile system consisting of 3 standard digital dial indicators (1 μm resolution; 5 μm error limit).ResultsWe found that the deviation in the mean average motion detection between the systems was at most 5.3 μm, indicating that detection of micromotion was possible with the optical measurement system. Furthermore, we could show two considerable advantages while using the optical measurement system. Only with the optical system interfragmentary motion could be analyzed directly at the fracture gap. Furthermore, the calibration of the optical system could be performed faster, safer and easier than that of the tactile system.ConclusionThe PONTOS 5 M optical measurement system appears to be a favorable alternative to previously used tactile measurement systems for biomechanical applications. Easy handling, combined with a high accuracy for 3D detection of micromotions (≤ 5 μm), suggests the likelihood of high user acceptance. This study was performed in the context of the deployment of a new implant (dynamic locking screw; Synthes, Oberdorf, Switzerland).

Compartment syndrome of the thigh. A case report with delayed onset after stable pelvic ring fracture and chronic anticoagulation therapie

Compartment syndrome of the thigh is a rare occurrence potentially leading to devastating functional restrictions. There is a wide spectrum of reported conditions leading to increased tissue pressure in the thigh possibly resulting in a compartment syndrome, ranging from deep venous thrombosis to blunt injuries and femoral fractures. We report a case of a delayed development of a compartment syndrome of the thigh secondary to an undisplaced anterior pelvic ring fracture and chronic anticoagulation therapy in a 94-year-old woman. Regarding anticoagulation therapy there are numerous reports about the spectrum of bleeding complications during therapy, however this severe complication has to our knowledge not been reported previously. Treatment consisted in immediate fasciotomy and subsequently secondary wound closure.

Antimicrobial formulations of absorbable bone substitute materials as drug carriers based on calcium sulfate

ABSTRACT Substitution of bones is a well-established, necessary procedure to treat bone defects in trauma and orthopedic surgeries. For prevention or treatment of perioperative infection, the implantation of resorbable bone substitute materials carrying antibiotics is a necessary treatment. In this study, we investigated the newly formulated calcium-based resorbable bone substitute materials containing either gentamicin (CaSO4-G [Herafill-G]), vancomycin (CaSO4-V), or tobramycin (Osteoset). We characterized the released antibiotic concentration per unit. Bone substitute materials were implanted in bones of rabbits via a standardized surgical procedure. Clinical parameters and levels of the antibiotic-releasing materials in serum were determined. Local concentrations of antibiotics were measured using antimicrobial tests of bone tissue. Aminoglycoside release kinetics in vitro per square millimeter of bead surface showed the most prolonged release for gentamicin, followed by vancomycin and, with the fastest release, tobramycin. In vivo level in serum detected over 28 days was highest for gentamicin at 0.42 μg/ml, followed by vancomycin at 0.11 μg/ml and tobramycin at 0.04 μg/ml. The clinical parameters indicated high biocompatibility for materials used. None of the rabbits subjected to the procedure showed any adverse reaction. The highest availability of antibiotics at 14.8 μg/g on day 1 in the cortical tibia ex vivo was demonstrated for gentamicin, decreasing within 14 days. In the medulla, vancomycin showed a high level at 444 μg/g on day 1, decreasing continuously over 14 days, whereas gentamicin decreased faster within the initial 3 days. The compared antibiotic formulations varied significantly in release kinetics in serum as well as locally in medulla and cortex.

Ellenbogenluxationsverletzungen beim Trendsport Bouldern

Bouldering is a new trend sport which has become popular in recent years. From April 2011 to June 2012 a total of 5 patients with elbow dislocations from bouldering were admitted to our level 1 trauma center. The injuries varied from simple elbow dislocations to complex fracture dislocations. Elbow dislocations occurred during falling backwards when patients tried to protect themselves by retroversion of both arms. In all cases the falling height was less than 4 meters. The bouldering injury pattern, the diagnostic and therapeutic management as well as the rehabilitation program are described in detail in this article. To the best of our knowledge this is the first report on the special danger of bouldering for complex elbow injuries.

Monocytes Do Not Transdifferentiate into Proper Osteoblasts

Recent publications suggested that monocytes might be an attractive cell type to transdifferentiate into various cellular phenotypes. Aim was, therefore, to evaluate the potential of blood monocytes to transdifferentiate into osteoblasts. Monocytes isolated from peripheral blood were subjected to two previously published treatments to obtain unique, multipotent cell fractions, named programmable cells of monocytic origin (PCMOs) and monocyte-derived mesenchymal progenitor cells (MOMPs). Subsequently, MOMPs and PCMOs were treated with osteogenic differentiation medium (including either vitamin D or dexamethasone) for 14 days. Regarding a variety of surface markers, no differences between MOMPs, PCMOs, and primary monocytes could be detected. The treatment with osteogenic medium neither resulted in loss of hematopoietic markers nor in adoption of mesenchymal phenotype in all cell types. No significant effect was observed regarding the expression of osteogenic transcription factors, bone-related genes, or production of mineralized matrix. Osteogenic medium resulted in activation of monocytes and appearance of osteoclasts. In conclusion, none of the investigated monocyte cell types showed any transdifferentiation characteristics under the tested circumstances. Based on our data, we rather see an activation and maturation of monocytes towards macrophages and osteoclasts.

Traumatic elbow dislocations in bouldering

Bouldering is a new trend sport which has become popular in recent years. From April 2011 to June 2012 a total of 5 patients with elbow dislocations from bouldering were admitted to our level 1 trauma center. The injuries varied from simple elbow dislocations to complex fracture dislocations. Elbow dislocations occurred during falling backwards when patients tried to protect themselves by retroversion of both arms. In all cases the falling height was less than 4 meters. The bouldering injury pattern, the diagnostic and therapeutic management as well as the rehabilitation program are described in detail in this article. To the best of our knowledge this is the first report on the special danger of bouldering for complex elbow injuries.