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Biomedical subjects

M Raschke

Publications and source records attributed to M Raschke.

At least 19 recordsLinked to original sources
PubMed2006

[Fracture of the tibial head].

Fractures of the tibial head are severe injuries, characterized by enormous variety. Fractures can be classified into fractures of the tibial plateau, luxation fractures, and comminuted fractures. Due to the mechanism of injury luxation fractures are frequently associated with lesions of the menisci and intra- and extra-articular ligaments. Multiple factors can be etiologic for post-traumatic gonarthrosis: nonanatomic reduction of the joint surface, malalignment, and unaddressed associated injuries. Therefore in addition to diagnostic steps such as X-ray, CT scan, and MRI a sophisticated therapeutic regime is necessary. In cases with severely damaged soft tissue or unstable patients, the fracture should initially be reduced and fixed with an external fixator and the definite fixation should be performed in a second setting. Arthroscopically assisted treatment is reserved for fractures of the tibial eminence, crack fractures, and impression fractures. Comminuted and bilateral fractures can be addressed via different incisions. New locking plates with angular stability allow avoidance of bilateral plating in most situations. In specific cases such as compound fractures and for patients with low compliance, a hybrid fixator may be a well-chosen alternative.

Arthroscopy↗
PubMed2005

Systemic versus local application of gentamicin in prophylaxis of implant-related osteomyelitis in a rat model.

Administration of perioperative antibiotic prophylaxis is a routine procedure in orthopedic surgery. Besides systemic prophylaxis, only few techniques are established for local application of antibiotics to reduce infection related to orthopedic implants. The aim of this study was to evaluate the efficacy of locally versus systemically applied gentamicin in a rat model (n = 60). For local application, the antibiotic was delivered from a biodegradable poly(D,L-lactide) (PDLLA) coating of titanium implants. The efficacy of local prophylaxis was compared to a systemic single shot application of gentamicin as well as a combination of both administrations. Half of the animals received a weight-adopted single shot application of gentamicin 30 min prior to surgery. At surgery, the medullary cavities of the tibiae were contaminated with Staphylococcus aureus (10(2) colony forming units /CFU) and titanium Kirschner wires were implanted into the medullary canals. The implants were either uncoated, PDLLA coated, or coated with PDLLA + 10% w/w gentamicin. The animals were followed up for 42 days. X-ray examinations were performed; body weight, temperature, and the clinical condition were determined. After sacrifice, infection was evaluated by histological and microbiological analysis. All animals treated with uncoated or PDLLA-coated Kirschner wires without systemic application of the antibiotic developed osteomyelitis and all cultures of implants were tested positive on S. aureus. Implant-related osteomyelitis could be prevented by prophylaxis of systemically applied gentamicin in 15% of animals. In contrast, local application of gentamicin delivered from a PDLLA coating was more effective. Onset of infection could be prevented in 90% of animals treated with gentamicin coated Kirschner wires, and in 80% of the animals that were treated with a combination of local and systemic application. The local application from PDLLA-coated implants might support systemic antibiotic prophylaxis in preventing implant-associated osteomyelitis.

Animals↗
PubMed2004

Differences in the fusion and resorption activity of human osteoclasts after stimulation with different growth factors released from a polylactide carrier.

Previous in vivo studies were able to demonstrate the efficacy of locally released growth factors IGF-I, TGF-beta1, and BMP-2 from a poly(D,L-lactide) (PDLLA) implant coating on fracture healing. In vitro studies using human osteoblast-like cells showed an enhanced collagen-1 production due to growth factor application without an effect of the PDLLA on the investigated parameter. Both bone-forming osteoblasts and bone-resorbing osteoclasts are important during bone formation and fracture healing. The aim of this study was to investigate the influence of different growth factors and the polylactide coating into which they were incorporated on isolated osteoclasts. In vitro studies using human osteoclast-like cells derived from peripheral blood mononuclear cells (PBMNCs) were performed. Titanium K-wires coated with the lactide loaded with IGF-I and TGF-beta1 (alone and in combination) or BMP-2 were added to the culture in a non-contact manner and the fusion, resorption activity (pit formation assay), and TRAP 5b synthesis of the cells were analyzed. Differences in the effect of the growth factors were seen depending on the differentiation state of the cells. The fusion of the monocytes to multinuclear osteoclasts was significantly enhanced by the application of TGF-beta1 both alone and in combination with IGF-I. No effect was seen after application of IGF-I alone or BMP-2. The resorption activity of the osteoclasts analyzed on dentine chips was significantly enhanced after application of TGF-beta1 or BMP-2. These results indicate a differentiation-dependent effect of growth factors on osteoclasts. TGF-beta1 affects both the osteoclastogenesis and the activity of osteoclasts, whereas BMP-2 had an effect only on the activity of mature osteoclasts but not on the fusion of the PBMNCs.

Acid Phosphatase↗
PubMed2004

Local and controlled release of growth factors (combination of IGF-I and TGF-beta I, and BMP-2 alone) from a polylactide coating of titanium implants does not lead to ectopic bone formation in sheep muscle.

The osteoinductive potential of growth factors leads not only to a stimulated bone formation in bony tissue but also in extra skeletal tissue. This potential depends on the dosage and potentially on the application method and may limit the clinical use. The aim of the present study was to investigate the potential of IGF-I, TGF-beta1 and BMP-2 released from a newly developed application systems of orthopaedic implants to induce ectopic bone formation in muscles. This bioactive coating showed a stimulating effect on fracture healing in several experimental studies before. Titanium discs were coated on one side with the drug carrier poly(d,l-lactide) (PDLLA), with the carrier plus IGF-I and TGF-beta1 or with the carrier plus BMP-2. The discs were implanted in the Musculus cleidomastoideus of sheep and followed up for 3 months. X-rays were taken after the operation and the day of sacrifice. The muscles plus implant were harvested and prepared for histology. Neither the radiology nor the histology revealed any signs of ectopic ossification in the implant/muscle interface or in a distance to the plate in any group. An influence of the locally applied growth factor, however, was seen in the formation of a soft tissue capsule. Histomorphometric analysis revealed a significantly larger capsule area over the growth factor coated side in comparison to the uncoated side or the pure titanium plate, indicating an effect of the applied growth factors on cells, however, not resulting in osteoinduction in muscle. The result showed that the local and controlled release of growth factors from PDLLA coated implants does not induce ectopic bone formation in sheep muscle and could be used in orthopaedic surgery to increase healing without the risk of ectopic bone formation in the surrounding soft tissue.

Animals↗
PubMed2004

[Accuracy of CT-based navitation of pedicle screws in the thoracic spine compared with conventional technique].

The goal of this study was to evaluate the accuracy of CT-based computer-assisted pedicle screw insertion in the thoracic spine in patients with fractures, metastases, and spondylodiscitis compared to a conventional technique. A total of 324 pedicle screws were inserted in the thoracic spines of 85 patients: 211 screws were placed using a CT-based optoelectronic navigation system assisted by an image intensifier and 113 screws were placed with a conventional technique. Screw positions were evaluated with postoperative CT scans by an independent radiologist. In the computer-assisted group, 174 (82.5%) screws were found completely within their pedicles compared with 77 (68.1%) correctly placed screws in the conventional group ( p<0.003). Despite use of the navigation system, 1.9% of the computer-assisted screws perforated the pedicle wall by more than 4 mm. The additional use of the image intensifier helped to identify the correct vertebral body and avoided cranial or caudal pedicle wall perforations.

Adolescent↗
PubMed2004

Quantification, localization, and expression of IGF-I and TGF-beta1 during growth factor-stimulated fracture healing.

Because of the increasing interest on stimulating fracture healing, knowledge about the role and chronology of growth factors during the healing process is important. The purpose of this study was to quantify the protein concentration of IGF-I and TGF-beta1 during rat tibial fracture healing 5, 10, and 15 days after fracture using ELISA methods and to analyze the distribution of the proteins and the related mRNA expression in the fracture callus by immunohistochemistry and in situ hybridization. The following three groups were analyzed: Fractured tibiae intramedullary stabilized with K-wires coated with IGF-I and TGF-beta1 compared with fractures stabilized with uncoated K-wires and unfractured tibiae. The weight of the callus increased during the healing process in both experimental groups. The protein concentration of IGF-I and TGF-beta1 in the fracture callus showed significant changes between the investigated time points and treatment groups compared with the unfractured tibia. IGF-I increased with healing time whereas TGF-beta1 revealed a constantly elevated level at the investigated time points. Mesenchymal cells, osteoblasts, osteocytes, proliferating and immature chondrocytes, and osteoclasts expressed both growth factors. No differences in the expression and localization pattern of the growth factors were detectable among the groups. Using the different methods for quantification and visualization of the growth factors, no differences (except the increased IGF-I concentration at day 15 in the growth factor group) were seen between the normal and the growth factor-stimulated fracture healing as an indication for physiological healing after exogenous growth factor treatment.

Absorbable Implants↗
PubMed2004

IGF-I and TGF-beta 1 incorporated in a poly(D,L-lactide) implant coating maintain their activity over long-term storage-cell culture studies on primary human osteoblast-like cells.

Biodegradable coating of osteosynthetic materials with poly(D,L-lactide) (PDLLA) and incorporated growth factors has been used successfully as drug carrier to stimulate fracture healing in several rat and porcine models. A cold coating technique was used to incorporate growth factors without loss of activity during the coating process. The aim of this study was to investigate the activity of incorporated insulin like growth factor-I and transforming growth factor-beta 1 (TGF-beta1) after long-time storage (5 and 14 months at -20 degrees C). Primary human osteoblast-like cells (HOB) were cultured in a non-contact manner with titanium wires coated with PDLLA and IGF-I (33 microg) and TGF-beta1 (6 microg) for 0, 5, 10 and 15 days. Osteoblast culture without wires, with titanium wires or wires with the PDLLA coating served as control ( n=3 each time point and group). Cell vitality, cell proliferation and the production of procollagen 1 were measured. No differences in cell count and vitality were accessed in the two growth factor treated groups compared to the control groups at the same time point. Independently from the storage duration, the incorporated growth factors significantly stimulated the production of osteoblast specific type I collagen (CICP) compared to the controls. The results indicate, that the growth factors stimulated osteoblast to an enhanced collagen 1 production and that the coating method meets a major requirement for clinical use of growth factor-coated implants: biological activity of the incorporated growth factors for at least 14 months.

Cell Division↗
PubMed2004

Local delivery of growth factors from coated titanium plates increases osteotomy healing in rats.

Different methods for the stabilization of long bone fractures are used in clinic. Besides the development of further stabilization devices, the use of new materials, the modification of the surfaces, and the local application of stimulating factors for enhancement of healing are from great interest. Previous studies successfully used a biodegradable poly(d,l-lactide) coating as a local drug delivery system of growth factors from intramedullary (IM) implants to enhance fracture healing. In this study, we developed a new rat model (n = 60) for plate osteosynthesis and used a plate for stabilization and as a local drug delivery system for the growth factors IGF-I and TGF-beta1. A four-hole titanium plate was used for stabilization of a 0.6-mm osteotomy gap of the femur. The space between the inner holes was coated with 50 microg IGF-I and 10 microg TGF-beta1 incorporated in the poly(d,l-lactide) coating or with the coating alone. After 42 days, biomechanical tests and histomorphological analyses were performed to investigate osteotomy healing. Radiologically small differences were detectable between the groups. The biomechanical torsional testing revealed a significantly higher maximum load of the osteotomized femura after treatment with growth factors compared to the uncoated group. In the histomorphometric analyses measuring the callus composition, a significantly higher percentage of mineralized tissue in the osteotomy callus was assessed in the growth factor treated group compared to the uncoated. In conclusion, the local application of IGF-I and TGF-beta1 from a biodegradable coating enhances the osteotomy healing as shown in the biomechanical testing and the histomorphometry. Bioactive plates could be used in clinic for fracture stabilization and for local and controlled application of growth factors to stimulate bone healing.

Animals↗
PubMed2003

A new model of implant-related osteomyelitis in rats.

Infection related to osteosynthesis often has dramatic consequences for the patient. Prolonged hospitalization with systemic antibiotic therapy, several revision procedures, possible amputation, and even death may occur. To investigate the pathology of infection in orthopedic surgery, a new rat model of implant related osteomyelitis was developed. Three different concentrations (10(6), 10(3), and 10(2) colony-forming units (CFU)/10 microl) of Staphylococcus aureus were inoculated into the tibial medullary cavity with simultaneous insertion of a titanium Kirschner wire. Controls received phosphate-buffered saline (PBS). Each group consisted of 10 animals. Animals were followed for 4 weeks until sacrifice. X-rays of the tibiae were taken weekly, blood counts were analyzed, and body temperature and weight were determined. After sacrifice, infection was evaluated by histological and microbiological investigations. All animals inoculated with Staph. aureus in either concentration developed microbiological, histological, and radiological signs of osteomyelitis in correlation to the amount of inoculated bacteria. X-rays clearly revealed osseous destruction after 14 days with progression of osteomyelitis during the following weeks. CFU/g bone and bone weight after sacrifice showed dependence on the amount of inoculated CFU. The histological results confirmed the radiological findings. No significant changes in blood counts, body weight, and body temperature between the groups could be observed. The results demonstrate that it is possible to develop a model of implant-related osteomyelitis in rats with dependence on the amount of inoculated bacteria. No other promoters of infection besides intramedullary insertion of titanium Kirschner wires were used in this model.

Animals↗
PubMed2003

Cell proliferation and differentiation during fracture healing are influenced by locally applied IGF-I and TGF-beta1: comparison of two proliferation markers, PCNA and BrdU.

Growth factors IGF-I and TGF-beta1 are known to stimulate fracture healing. The purpose of this study was to investigate the role of locally applied IGF-I and TGF-beta1 during the early phase of fracture healing (Days 5, 10, and 15 after fracture) on cellular processes like proliferation and differentiation in a rat model. Two different immunohistochemical markers were used to analyze cell proliferation: (1) injection of the thymidine analogue BrdU and subsequent immunohistochemical staining for BrdU-positive nuclei, and (2) the antibody against the "proliferating cell nuclear antigen" (PCNA). In comparison, both methods revealed similar results concerning the types of proliferating cells at the different time points and the two groups. Labeling indices of both methods showed very good correlation (e.g., r(s): 0.887 and p < 0.001 at day 10 in the control group without growth factors). Comparison of the callus morphology and the proliferation rate showed differences during fracture healing due to the local application of IGF-I and TGF-beta1 from coated implants. At Day 5 the callus of the group treated with growth factors displayed an earlier appearance of cartilage compared to the control group. This was accompanied by an onset of cell proliferation in chondrocytes. Likewise, at the later time points an enhanced maturation of the callus tissue and the proliferation pattern were detectable in the growth-factor group. These results indicate that local application of IGF-I and TGF-beta1 accelerates early cellular processes during fracture healing.

Animals↗
PubMed2003

IGF-I and TGF-beta 1 incorporated in a poly(D,L-lactide) implant coating stimulates osteoblast differentiation and collagen-1 production but reduces osteoblast proliferation in cell culture.

Previous in vivo studies revealed a stimulating effect of locally applied IGF-I and TGF-beta1 released from poly(D,L-lactide)-coated titanium implants on rat and porcine fracture healing. The purpose of the present study was to evaluate the effect of IGF-I (5% w/w) and TGF-beta1 (1% w/w) and the carrier PDLLA on osteoblasts in cell culture to improve the understanding of these growth factors. The well-characterized human osteoblast cell line hFOB 1.19 was used in the study. The implants and cells were cocultured in a noncontact manner. The cells were incubated for 10 days in total, and the implants (n = 6 each group and time point) were added for 1 h, 12 h, 24 h, 2 d, 4 d, or 10 d. To analyze a possible effect of the growth factors or the coating, cell proliferation, metabolism, and differentiation were investigated. As an indicator for differentiation the production of collagen I was chosen. All experimental groups showed comparable cell vitality. No change in the pH of the medium was detectable between the analyzed groups. When the effect of the titanium implant and the PDLLA coating were compared with the control culture, no differences in proliferation, metabolic activity, and collagen I production were detectable. The osteoblasts treated with IGF-I and TGF-beta1 released from PDLLA revealed a significantly enhanced collagen I production with a decrease in proliferation and metabolic activity compared to the other groups. No significant differences in collagen I production were seen due to the incubation time points. None of the experimental groups evoked an immunological response on mouse macrophages. In conclusion, the PDLLA-carrier showed no negative effect on osteoblasts, whereas the incorporated growth factors stimulated osteoblast differentiation.

Bone Substitutes↗
PubMed2003

Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats.

Antibiotic prophylaxis is a routine procedure in orthopedic surgery. Various local antibiotic delivery techniques are used to reduce bone- and soft tissue-related infection. The objective of this study was to evaluate the efficacy of a new biodegradable, gentamicin-loaded poly(D,L-lactide) (PDLLA) coating of orthopedic devices in preventing implant-related osteomyelitis. The medullary cavities of tibiae in 30 Sprague Dawley rats were contaminated with Staphylococcus aureus (10(3) colony forming units). Simultaneously titanium Kirschner wires, uncoated (group II), coated with PDLLA (group III), or coated with PDLLA + 10% gentamicin (group IV), were implanted. Ten animals that received phosphate-buffered saline and uncoated Kirschner wires served as controls (group I). Follow-up was 6 weeks. In weekly intervals X-rays of the tibiae were performed, blood counts were taken, and body temperature and weight were determined. After sacrifice infection was evaluated by histological and microbiological analysis. All animals of groups II and III developed microbiological, histological, and radiological signs of infection, including osseous destruction and soft tissue swelling. All animals of the control group remained sterile. Cultures of implants of group IV showed significantly reduced bacterial growth compared to cultures of groups II and III, and three implants of group IV remained sterile. Further radiological and histological signs of infection were significantly reduced in the gentamicin-coated group compared to groups II and III. No significant differences in body weight, body temperature, and blood parameters between all groups were observed. Local application of antibiotic-coated orthopedic devices containing PDLLA and 10% gentamicin significantly reduced implant-related infection in this animal model.

Animals↗
PubMed2003

Homologous growth hormone accelerates bone healing--a biomechanical and histological study.

The purpose of this study was to prove whether homologous growth hormone has a beneficial effect in the early phase of bone healing. Therefore the left tibias of 24 Yucatan micropigs were osteotomized and stabilized by plate fixation. The treatment group (12 animals) received 100 microg of recombinant porcine growth hormone (rpGH)/kg body w/day sc, whereas the control pigs (12 animals) received 1 ml sodium chloride as placebo. After a healing period of 4 weeks the animals were sacrificed and destructive torsional testing was performed. For histological evaluation 6 microm serial slices of the tibiae were stained with von Kossa. The total area of callus formation (CA) and the mineralized bone area (BA) were quantified by image analysis. The fraction of mineralized bone tissue within the callus area, the bone density (BD), was calculated as follows: BD = (BA/CA) x 100. Torsional failure load was 91% higher and torsional stiffness 61% higher in the treatment group than in the control group (P < 0.05). The histomorphometric measurements revealed an advance for the CA (GH: 127.6 +/- 38.9 mm(2); placebo: 75.9 +/- 50.7 mm(2); P < 0.005) as well as for the BA (GH: 89.3 +/- 25.8 mm(2); placebo: 55.9 +/- 38.5 mm(2); P < 0.001) for the GH-treated animals in comparison to the control animals. The BD was similar in both groups (GH: 70.6 +/- 8.4%; placebo: 74.0 +/- 6.24%; P = 0.28). These data indicate that administration of homologous GH stimulates callus formation and ossification in the early phase of bone healing, which consequently results in an increased mechanical strength and stiffness.

Animals↗
PubMed2003

Small volume hypertonic hydroxyethyl starch reduces acute microvascular dysfunction after closed soft-tissue trauma.

A major pathway of closed soft-tissue injury is failure of microvascular perfusion combined with a persistently enhanced inflammatory response. We therefore tested the hypothesis that hypertonic hydroxyethyl starch (HS/HES) effectively restores microcirculation and reduces leukocyte adherence after closed soft-tissue injury. We induced closed soft-tissue injury in the hindlimbs of 14 male isoflurane-anaesthetised rats. Seven traumatised animals received 7.5% sodium chloride-6% HS/HES and seven isovolaemic 0.9% saline (NS). Six non-injured animals did not receive any additional fluid and acted as a control group. The microcirculation of the extensor digitorum longus muscle (EDL) was quantitatively analysed two hours after trauma using intravital microscopy and laser Doppler flowmetry, i.e. erythrocyte flux. Oedema was assessed by the wet-to-dry-weight ratio of the EDL. In NS-treated animals closed soft-tissue injury resulted in massive reduction of functional capillary density (FCD) and a marked increase in microvascular permeability and leukocyte-endothelial cell interaction as compared with the control group. By contrast, HS/HES was effective in restoring the FCD to 94% of values found in the control group. In addition, leukocyte rolling decreased almost to control levels and leukocyte adherence was found to be reduced by approximately 50%. Erythrocyte flux in NS-treated animals decreased to 90 +/- 8% (mean SEM), whereas values in the HS/HES group significantly increased to 137 +/- 3% compared with the baseline flux. Oedema in the HS/HES group (1.06 +/- 0.02) was significantly decreased compared with the NS-group (1.12 +/- 0.01). HS/HES effectively restores nutritive perfusion, decreases leukocyte adherence, improves endothelial integrity and attenuates oedema, thereby restricting tissue damage evolving secondary to closed soft-tissue injury. It appears to be an effective intervention, supporting nutritional blood flow by reducing trauma-induced microvascular dysfunction.

Acute Disease↗
PubMed2002

Dose-dependent effects of combined IGF-I and TGF-beta1 application in a sheep cervical spine fusion model.

Combined IGF-I and TGF-beta1 application by a poly-(D,L-lactide) (PDLLA) coated interbody cage has proven to promote spine fusion. The purpose of this study was to determine whether there is a dose-dependent effect of combined IGF-I and TGF-beta1 application on intervertebral bone matrix formation in a sheep cervical spine fusion model. Thirty-two sheep underwent C3/4 discectomy and fusion. Stabilisation was performed using a titanium cage coated with a PDLLA carrier including no growth factors in group 1 ( n=8), 75 micro g IGF-I plus 15 micro g TGF-beta1 in group 2 ( n=8), 150 micro g IGF-I plus 30 micro g TGF-beta1 in group 3 ( n=8) and 300 micro g IGF-I plus 60 micro g TGF-beta1 in group 4 ( n=8). Blood samples, body weight and temperature were analysed. Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks. At the same time points, disc space height and intervertebral angle were measured. After 12 weeks, the animals were killed and fusion sites were evaluated using quantitative computed tomographic (CT) scans to assess bone mineral density, bone mineral content and bony callus volume. Biomechanical testing was performed and range of motion, and neutral and elastic zones were determined. Histomorphological and histomorphometrical analysis were carried out and polychrome sequential labelling was used to determine the time frame of new bone formation. In comparison to the group without growth factors (group 1), the medium- and high-dose growth factor groups (groups 3 and 4) demonstrated a significantly higher bony callus volume on CT scans, a higher biomechanical stability, an advanced interbody bone matrix formation in histomorphometrical analysis, and an earlier bone matrix formation on fluorochrome sequence labelling. Additionally, the medium- and high-dose growth factor groups (groups 3 and 4) demonstrated a significantly higher bony callus volume, a higher biomechanical stability in rotation, and an advanced interbody bone matrix formation in comparison to the low-dose growth factor group (group 2). No significant difference could be determined between the medium- and the high-dose growth factor groups (groups 3 and 4, respectively). The local application of IGF-I and TGF-beta1 by a PDLLA-coated cage significantly improved results of interbody bone matrix formation in a dose-dependent manner. The best dose-response relationship was achieved with the medium growth factor dose (150 micro g IGF-I and 30 micro g TGF-beta1). With an increasing dose of these growth factors, no further stimulation of bone matrix formation was observed. Although these results are encouraging, safety issues of combined IGF-I and TGF-beta1 application for spinal fusion still have to be addressed.

Animals↗
PubMed2002

Comparison of BMP-2 and combined IGF-I/TGF-ss1 application in a sheep cervical spine fusion model.

Growth factors have proven to promote spine fusion. However, no comparative evaluation of growth factors in spinal fusion has yet been performed. The purpose of this study was to compare the efficacy and safety of combined IGF-I and TGF-ss1 application with BMP-2 application and autologous cancellous bone graft at an early time point in a sheep cervical spine fusion model. Thirty-two sheep underwent C3/4 discectomy and fusion. They were divided into four groups, according to their treatment: group 1, titanium cage ( n=8); group 2, titanium cage filled with autologous cancellous iliac crest bone grafts ( n=8); group 3, titanium cage coated with a poly-(D,L-lactide) (PDLLA) carrier including BMP-2 (5% w/w) ( n=8); group 4, titanium cage coated with a PDLLA carrier including IGF-I (5% w/w) and TGF-ss1 (1% w/w) ( n=8). Blood samples, body weight and temperature were analysed. Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8 and 12 weeks. At the same time points, disc space height and intervertebral angle were measured. After 12 weeks, the animals were killed and fusion sites were evaluated using functional radiographic views in flexion and extension. Quantitative computed tomographic scans were performed to assess bone mineral density, bone mineral content and bony callus volume. Biomechanical testing was carried out and the values for range of motion, and neutral and elastic zone were determined. Histomorphological and histomorphometrical analysis were performed and polychrome sequential labelling was used to determine the time frame of new bone formation. The results showed that, in comparison to the group treated with the cage alone (group 1), the cage plus BMP-2 group (group 3) and the cage plus IGF-I and TGF-ss1 group (group 4) demonstrated a significantly higher fusion rate in radiographic findings, a higher biomechanical stability, a more advanced interbody fusion in histomorphometrical analysis, and an accelerated interbody fusion on fluorochrome sequence labelling. In comparison to the bone graft group (group 2), the BMP-2 (group 3) and IGF-I/TGF-ss1 group (group 4) showed significantly less residual motion on functional radiographic evaluation, higher bone mineral density of the callus and higher biomechanical stability in extension, rotation and bending. The BMP-2 group showed significantly less residual motion on functional radiographic evaluation and higher intervertebral bone matrix formation on fluorochrome sequence labelling at 9 weeks in comparison to the IGF-I/TGF-ss1 group. In contrast, the IGF-I/TGF-ss1 group showed a significantly higher bone mineral density of the callus than the BMP-2 group. In comparison to the autologous cancellous bone graft group, both growth factors (BMP-2 and combined IGF-I and TGF-ss1) significantly improved the biomechanical results of interbody fusion. No systemic side effects were observed for either growth factor. On the basis of these preliminary results, it would appear that combined IGF-I/TGF-ss1 application yields equivalent results to BMP-2 application at an early time point in anterior sheep cervical spine fusion.

Animals↗
PubMed2002

A new electrochemically graded hydroxyapatite coating for osteosynthetic implants promotes implant osteointegration in a rat model.

Hydroxyapatite (HAP) is widely used as an osteoconductive coating for orthopedic implants. So far standard coating methods like plasma spraying produce a relatively thick coating layer (>30 microm). In addition, the chemical structure of the HAP may be altered because of the heating throughout the coating process. This may have negative effects on the coating stability, implant fixation, and induction of bone formation. The relatively thick layer may detach from the implant with the risk of wear debris. In the present study the potential of a newly developed HAP coating of implants on osteointegration was investigated in a rat model. The coating method, based on an electrochemical process, is applied in a graded manner and results in a biodegradable HAP coating with a thickness of approximately 2 mum. Coated versus uncoated titanium Kirschner wires (1.4-mm diameter) were inserted into the medullary cavity of the right femora of 5-month old female Sprague Dawley rats (n=36) in a retrograde fashion. Throughout an experimental period of 2 months the osteointegration was traced radiologically. After this time the animals were sacrificed and the implant integration was tested biomechanically with the use of a push-out test. To analyze the bone-implant interface, histological sections (80 mum) were investigated with an image analyzing system. The biomechanical testing revealed a significantly higher implant fixation in the group treated with the HAP-coated implant (shear strength: 27.8 +/- 6.7 MPa) compared to control (shear strength: 8.08 +/- 3.4 MPa). The histological analyses demonstrated a better ingrowth of the implants in the HAP group with significantly more direct bone-implant contacts compared to the control group. The results demonstrate that the HAP coating promotes implant osteointegration in a rat model.

Animals↗