Biomedical subjects

Britt Wildemann

Publications and source records attributed to Britt Wildemann.

9 recordsLinked to original sources

PubMed2006

Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review.

Implant-related infection is a feared complication in orthopedic and trauma surgery with tremendous consequences for the patient. To reduce this risk, administration of perioperative antibiotic prophylaxis is a routine procedure in orthopedic surgery. A local delivery system for antibiotics based on a polymer implant coating has been developed to optimize the prophylaxis. In an animal experiment, the efficacy of local prophylaxis of gentamicin was compared to a systemic single shot of gentamicin and to a combination of both administrations. The medullary cavities of rat tibiae were contaminated with Staphylococcus aureus and titanium K-wires were implanted into the medullary canals. For local antibiotic therapy, the implants were coated with poly(D,L-Lactide) (PDLLA) loaded with gentamicin. All the animals not treated with local and systemic application of the antibiotic developed osteomyelitis and all cultures of the implants tested positive for S. aureus. Onset of infection was prevented in 80-90% of animals treated with gentamicin-coated K-wires, with and without systemic prophylaxis. Gentamicin-coated intramedullary tibial nails are CE-certified for Europe and Canada and several patients have already been treated for implant-related infection. Up to now, eight patients with open tibia fractures have been treated with an unreamed tibial nail (UTN) coated with PDLLA and gentamicin. In the 1-year follow up, none of the patients developed an infection. A prospective randomized clinical documentation is currently in progress. So far, the results suggest that a local application of gentamicin from PDLLA-coated implants might support systemic antibiotic prophylaxis in preventing implant-associated osteomyelitis.

Animals↗

PubMed2006

Biodegradable polylactide membranes for bone defect coverage: biocompatibility testing, radiological and histological evaluation in a sheep model.

Large bony defects often show a delayed healing and have an increasing risk of infection. Several materials are used for the coverage of large defects. These materials must be biocompatible, easy to use, and must have an appropriate stability to present a mechanical hindrance. Aim of this study was to investigate two different biodegradable membranes for defect coverage in a sheep model. Round cranial defects (1.5 cm diameter) were created in sheep. Six different treatments were investigated: defects without membrane, defects covered with a poly(D,L-lactide) or with a 70/30 poly(L/D,L-lactide) membrane and all defects with or without spongiosa filling. The sheep were sacrificed 12 or 24 weeks postoperatively. Bone formation in the defects was quantified by computer-assisted measurements of the area of the residual defect on CT radiographs. Histomorphometry and host-tissue response were evaluated by light microscopy. The biocompatibility was investigated by analyzing the amount of osteoclasts and foreign body cells. Both membranes served as a mechanical hindrance to prevent the prolapse of soft tissue into the defect. The biocompatibility test revealed no differences in the amount and distribution of osteoclasts at the two investigated time points and between the investigated groups. No negative effect on the tissue regeneration was detectable between the investigated groups related to the type of membrane, but a foreign body reaction around the two membrane types was observed. In the membrane-covered defects, the spongiosa showed a progressing remodeling to the native bony structure of the cranium. The groups without spongiosa partly revealed new bone formation, without complete bridging in any group or at any time point. Comparing the 12 and 24 weeks groups, an increased bone formation was detectable at the later time point. In conclusion, the results of the present in vivo study reveal a good biocompatibility and prevention of soft tissue prolapse of the two used membranes without differences between the membranes. An enhanced remodeling of the spongiosa into native bony structures under the membranes was detectable, but no osteopromoting effect was observed due to the membranes.

Absorbable Implants↗

PubMed2006

Collective review: bioactive implants coated with poly(D,L-lactide) and growth factors IGF-I, TGF-beta1, or BMP-2 for stimulation of fracture healing.

Demographic data reveal that due to the increasing aging of the population, complications with the musculoskeletal system will increase in the next years. One major problem in orthopedic and trauma surgery are the delayed healing or non-unions of long bone fractures. The exogenous application of growth factors can stimulate the bone healing to reduce these complications. Beside the choice of the optimal growth factor the application system is important. Therefore, we developed a new bioactive coating method for implants, which is based on a biodegradable poly(D,L-lactide) (coating thickness: 10 mum). This coating allows the incorporation of growth factors and the controlled release of these factors during the healing process without the need for further devices. The effect of different growth factors (IGF-I, TGF-beta1, and BMP-2) locally released from coated intramedullary implants on fracture healing was investigated with biomechanical and histological analysis in rats. All investigated growth factors stimulated the fracture healing as assessed with biomechanical tests and histological analysis. The local application of combined IGF-I and TGF-beta1 had the most stimulating effect on fracture healing, followed by the effect of BMP-2, IGF-I, and TGF-beta1 alone. Bioactive coating of biomechanical well-established implants can on the one hand stabilize the fracture and on the other hand stimulate healing processes to increase healing and to reduce the rate of complications.

Absorbable Implants↗

PubMed2005

Proteasome inhibitors abrogate osteoclast differentiation and osteoclast function.

Cancer-induced bone disease results in bone destruction, pathological fractures, and pain. We hypothesized that the inhibition of the proteasome-ubiquitin system in osteoclasts could abolish the receptor activator of NF-kappaB ligand (RANKL) mediated osteoclast differentiation and function, since RANKL-mediated downstream signaling plays a crucial role in osteoclast life cycle. In this study, we examined the effects of the proteasome inhibitors MG-132 and MG-262 on RANKL-induced osteoclast differentiation and function. Osteoclast precursors from peripheral blood mononuclear cells were cultured in the presence of RANKL and M-CSF. Osteoclasts were identified as multi-nucleated TRAP-positive cells. Osteoclast function was quantified with the extent of dentine resorption and TRAP activity in culture supernatants. For the evaluation of the effects of proteasome inhibitors towards osteoclastogenesis, sub-apoptotic concentrations of MG-132 and MG-262 were used. Effects on NF-kappaB were obtained in treated and untreated osteoclasts. MG-132 and MG-262 inhibit both osteoclast differentiation and osteoclast function. 0.01 microM MG-132 induced a 3.2-fold (P = 0.004) and 0.001 microM MG-262 a 3.3-fold (P = 0.004) reduction of osteoclast differentiation, respectively. The resorption capacity was decreased 2.6- and 11.1-fold (P = 0.003) by treatment with 0.01 and 0.1 microM MG-132, and 14.2- and 16.6-fold (P = 0.003) by 0.001 and 0.01 microM MG-262, respectively. This decrease correlated with the extent of NF-kappaB binding capacity. In conclusion, this study shows for the first time that proteasome inhibitors act on osteoclast development and function at low concentrations and should be considered as potential drugs for the treatment of cancer-induced osteolytic bone disease.

Bone Resorption↗

PubMed2005

Short term in vivo biocompatibility testing of biodegradable poly(D,L-lactide)--growth factor coating for orthopaedic implants.

Fracture healing can be stimulated by exogenous application of growth factors. Using porcine and rat models the efficacy of locally delivered IGF-I and TGF-beta1 from an implant coating has been demonstrated. A thin and biomechanical stable biodegradable poly(D,L-lactide) was used to coat implants and serve as a drug carrier. Due to reports of possible foreign body reactions caused by polymer materials in orthopedic surgery, this study investigated the biocompatibility of the polylactide implant coating and the locally released growth factors during the time course of rat tibial fracture healing (days 5, 10, 15, and 28 after fracture). Monocytes/macrophages and osteoclast were detected using an monoclonal antibody against ED1 (comparable to CD68 in mice and human). The antibody ED1 stains monocytes, macrophages and osteoclast in the bone marrow and in the newly formed fracture callus. A moderate density of the monocytes/macrophages was seen in the proximal part of the medullary canal, but almost no cells were detectable in the region distal to the fracture. The amount of stained cells increased during the observation time with a maximum at days 10 and 15 followed by a decrease at day 28. No differences were detectable between the investigated groups from day 5 to 15 post fracture indicating, that the used poly(D,L-lactide) or the incorporated growth factors do not evoke an elevated immunological response compared to the uncoated titanium implant at the investigated time points. A significantly higher amount of ED1 positive cells was measured 28 days after fracture in the control group compared to the groups with the coated implants. In conclusion, no indication of a foreign body reaction due to the use of the polylactide or the growth factors was found indicating a good short-term biocompatibility of this bioactive coating.

Absorbable Implants↗

PubMed2004

Long-term effects of local growth factor (IGF-I and TGF-beta 1) treatment on fracture healing. A safety study for using growth factors.

Previous studies showed that growth factors dramatically stimulate healing processes in bone. However, the long-term effect of locally applied growth factors on fracture healing remains unclear. In considering the safety of using growth factors, it is necessary to elucidate that after initial stimulation, the effect stops and the result is a normally healed tissue. Therefore, the purpose of the present study was to investigate the long-term time course of healing processes during growth factor (GF) stimulated and unstimulated fracture healing in a closed tibial fracture model in rats. A well established local drug delivery system was used. IGF-I (50 microg) and TGF-beta 1 (10 microg) were locally applied using a 10 microm thin polylactide (PDLLA) coating on intramedullary implants. The biomechanical and histomorphometrical results demonstrated a significant stimulation of the fracture healing due to the locally applied growth factors compared to control at days 28 and 42 in agreement with the literature. At the last time point, 84 days after fracture, no differences were measurable in the biomechanical testing and the callus composition between the groups. The callus was consistently in the late phase of remodeling with no remaining cartilage. In conclusion, local growth factor application enhances the healing in the early phase without alteration of the normal healing process.

Animals↗

PubMed2003

The angiogenic peptide pleiotrophin (PTN/HB-GAM) is expressed in fracture healing: an immunohistochemical study in rats.

INTRODUCTION: Formation of new blood vessels is essential for the process of fracture healing. MATERIALS AND METHODS: We investigated the expression of the angiogenic factor pleiotrophin/HB-GAM in a closed fracture model in rats by immunohistochemical methods. RESULTS: Histologically, 5 days after fracture the callus was predominantly composed of fibrous tissue. On day 10 a prominent chondral callus connected both ends of the fractured tibia. There was a continuous transition from the chondral callus to the newly formed bone adjacent to the corticalis of the tibia. On day 15 the amount of woven bone had increased, and in 3 of 5 animals the proximal and distal tibiae were connected by a bridge of woven bone. Pleiotrophin could be immunostained in fibroblasts and endothelial cells of the fibrous tissue between the fractured tibia ends. The chondral callus remained largely pleiotrophin-negative. Only single chondrocytes adjacent to the newly formed bone were pleiotrophin-positive. On days 10 and 15 strong immunoreactivity for pleiotrophin in the well vascularized, newly formed, woven bone was detectable. Osteoblasts, endothelial cells and fibroblasts were strongly pleiotrophin-positive. CONCLUSIONS: These results show the presence of the angiogenic peptide pleiotrophin during fracture healing.

Angiogenesis Inducing Agents↗

PubMed2003

Synergistic effect of IGF-I and TGF-beta1 on fracture healing in rats: single versus combined application of IGF-I and TGF-beta1.

During the last few decades, knowledge about growth factors and their function has increased. However, little is known about the interaction of these factors during bone growth and fracture healing. In vitro studies have shown a higher rate of cell proliferation and cell metabolism after the use of IGF-I and TGF-beta1 in combination, as compared to the single use of these factors. The purpose of this study was to investigate a possible synergistic effect of these growth factors in vivo, using a fracture model. A midshaft fracture of rat tibia (n = 84) was intramedullary stabilized with poly(D,L-lactide)-coated or uncoated titanium K-wires. The growth factors IGF-I and TGF-beta1, singly or in combination, were incorporated in the coating and continuously released during fracture healing. 28 days after fracture, we performed mechanical tests and histomorphological analyses. We found a greater stimulating effect of IGF-I on fracture healing than of TGF-beta1. The combined application of both growth factors resulted in a significantly higher maximum load and torsional stiffness than the use of only one of them. The histomorphometric analyses showed an increase in remodeling of the fracture callus in this group with less cartilaginous and more mineralized tissue than in the other groups. Both growth factors seem to have a synergistic effect on fracture healing in this model.

Animals↗

PubMed2002

Quantitative measurement of the splice variants 120 and 164 of the angiogenic peptide vascular endothelial growth factor in the time flow of fracture healing: a study in the rat.

Formation of new blood vessels is essential for the process of wound and fracture healing. Little is known about the time-dependent expression and the involved splice variants of the vascular endothelial growth factor (VEGF). We therefore quantified and differentiated the angiogenic factor VEGF and its receptors (VEGFR) in a rat fracture model by immunohistochemical, biochemical and molecular biological methods. VEGF could be immunostained in chondrocytes and osteoblasts of the callus, but not in fibrous callus. In the capillaries, VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR) were also visualized. Both receptors were also detectable in some chondrocytes and in osteoclasts. Enzyme-linked immunosorbent assay (ELISA) measurements showed high levels of VEGF in fractured tibiae and negligible ones in non-injured bone. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed expression of the rat splice variants VEGF(120) and VEGF(164) during the course of fracture healing, which corresponds to human VEGF121 and VEGF165 splice variants. VEGF plays the most important role during the early phase of fracture healing, but VEGF concentrations decrease further after day 5.

Alternative Splicing↗