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M Raschke

Publications and source records attributed to M Raschke.

At least 37 records · Page 2Linked to original sources

[Experimental fusion of the sheep cervical spine. Part II: Effect of growth factors and carrier systems on interbody fusion].

INTRODUCTION: A sheep cervical spine interbody fusion model was used to determine the effect of different carriers and growth factors on interbody bone matrix formation. The purpose of this study was to compare the efficacy and safety of combined IGF-I and TGF-beta1 application with BMP-2 application in spinal fusion. Additionally, a new poly (D, L-lactide) carrier system was compared to a collagen sponge carrier. METHOD: Forty sheep underwent C3/4 discectomy and fusion: group 1: titanium cage ( n=8), group 2: titanium cage coated with a PDLLA carrier (n=8), group 3: titanium cage coated with a PDLLA carrier including BMP-2 ( n=8), group 4: titanium cage with a collagen carrier including BMP-2 ( n=8), and group 5: titanium cage coated with a PDLLA carrier including IGF-I and TGF-beta1 ( n=8). Blood samples, body weight, and temperature were analyzed. Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks, respectively. At the same time points, disc space height (DSH) and intervertebral angle (IVA) 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 (QCT) were performed to assess bone mineral density (BMD), bone mineral content (BMC), and bony callus volume (BCV). Biomechanical testing was carried out in flexion, extension, axial rotation, and lateral bending. Range of motion (ROM), neutral zone (NZ), and elastic zone (EZ) were determined. Histomorphological and histomorphometrical analyses were performed and polychrome sequential labeling was used to determine the time frame of new bone formation. RESULTS: In comparison to the non-coated cages, all PDLLA-coated cages showed significantly higher values for BMD of the callus and bone volume/total volume ratio. In comparison to the cage groups (groups 1 and 2), the cage plus BMP-2 (groups 3 and 4) and the cage plus IGF-I and TGF-beta1 group (group 5) demonstrated a significantly higher fusion rate in radiographic findings, a higher biomechanical stability, an advanced interbody fusion in histomorphometric analysis, and an accelerated interbody fusion on fluorochrome sequence labeling. BMP-2 application by the PDLLA carrier system (group 3) demonstrated significantly higher bony callus volume than BMP-2 application by a collagen sponge carrier (group 4). The BMP-2 group (group 3) showed significantly lower residual motion on functional radiographic evaluation and higher intervertebral bone matrix formation on fluorochrome sequence labeling at 9 weeks in comparison to the IGF-I/TGF-beta1 group (group 5). In contrast, the IGF-I/TGF-beta1 group (group 5) showed a significantly higher bone mineral density of the callus than the BMP-2 group (group 3). CONCLUSION: PDLLA coating of cervical spine interbody fusion cages as a delivery system for growth factors was effective and safe. In comparison to the collagen sponge carrier, the new PDLLA carrier system was able to improve results of interbody bone matrix formation. Both growth factors (BMP-2 and combined IGF-I and TGF-beta1) significantly accelerated results of interbody fusion. Based on these preliminary results, the combined IGF-I/TGF-beta1 application yields results equivalent to BMP-2 application at an early time in anterior sheep cervical spine fusion.

Animals↗

[Computer assisted pelvic and acetabular surgery. Clinical experiences and indications].

CT based navigation has been used in spine surgery since 1994. Several clinical studies could show an increase in precision compared to the conventional technique and thus nowadays the navigated pedicle screw placement is a routine procedure in many hospitals. Based upon the experience in spine surgery the CT based navigation module was used for percutaneous screw fixations in minimally displaced pelvic ring and acetabular fractures. After preclinical experimental trials the C-arm navigation was used for 19 screw fixations. The postoperative control of the screw position was performed with postop. X-ray and CT. Overall 23 of the 24 screws were placed correctly. In one SI screw the postoperative CT could reveal a ventral cortex perforation of the sacrum without any clinical symptoms. Based upon this limited clinical experience we see the indication for CT based navigation in minimally displaced acetabular fractures or in SI screw fixations in case of sacral dysplasia. The C-arm based navigation with adequate image quality is our method of choice for SI screw fixation in traumatic or degenerative instabilities, especially if reduction maneuvers are necessary.

Acetabulum↗

Insulin-like growth factor-1 and transforming growth factor-beta1 accelerates osteotomy healing using polylactide-coated implants as a delivery system: a biomechanical and histological study in minipigs.

Stimulation of bone healing and bone formation through local application of growth factors from implants may improve the clinical outcome in fracture treatment. Previous studies demonstrated a high mechanical stability of a thin poly(D,L-lactide) (PDLLA) coating on metallic implants that can withstand the process of intramedullary insertion. Following an initial peak, 80% of incorporated insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1) were released continuously, within 42 days. The goal of the present study is evaluation of the coated implants on fracture healing in a large animal model. A midshaft osteotomy (1 mm gap) of the right tibia of Yucatan minipigs was stabilized with uncoated vs. coated titanium interlocking nails (5 mm). X-ray examinations and blood analyses (including IGF-1 and IGF-binding proteins) were performed, and body weight and body temperature were taken throughout the experiment. After 28 days, both tibiae were dissected for mechanical torsional testing and histomorphometric analyses. No differences were found in the blood analyses, body weight, or temperature due to the coating or the incorporated growth factors between the groups. X-ray examinations revealed a faster consolidation of the osteotomy in the growth factor-treated group. Biomechanical testing showed a significantly higher torsional stiffness and maximum load. Progressive remodeling was observed in the histological and histomorphometric analyses with a larger callus volume in the growth factor group compared with the control groups. We conclude that local application of growth factors from a biodegradable PDLLA coating of intramedullary implants accelerates bone healing in a large animal model without systemic side effects.

Animals↗

Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: a biomechanical and histological study in rats.

Bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor (TGF)-beta superfamily, is known to be a very potent osteoinductive growth factor. The purpose of this study was to investigate the effect of BMP-2 (5% [w/w], 50 microg on each nail), locally released from poly(D,L-lactide) (PDLLA)-coated intramedullary implants, on fracture healing. A closed fracture of the right tibia of 5-month-old Sprague-Dawley rats (n = 64) was intramedullary stabilized with uncoated vs. BMP-2-coated titanium Kirschner wires. X-ray examinations (posteroanterior and lateral) were performed throughout the experiment. At 28 and 42 days after fracture, the animals were killed and both tibiae were dissected for biomechanical torsional testing. For histological and histomorphometric evaluation, 5 microm sections were obtained, stained with Safranin-O/light green and von Kossa, and examined using an image analysis system. The radiological results demonstrated progressed callus consolidation in the BMP-2-treated groups compared with the uncoated groups at both timepoints. Histomorphometric evaluation showed progressed callus remodeling with significantly increased mineralization and less cartilage of the periosteal callus. Due to the BMP-2 treatment, increased mineralization of the cortices was detected at 28 and 42 days after fracture. Biomechanical testing revealed significantly elevated maximum load and torsional stiffness in the BMP-2-treated groups compared with controls at both timepoints. The results clearly demonstrate that local application of BMP-2 from PDLLA-coated implants is feasible and significantly accelerates fracture healing. Local administration of growth factors from coated implants could reduce clinical problems in fracture treatment without opening of the fracture, implantation of further devices, or injection with the risk of infection or side effects caused by other carriers.

Animals↗

Improvement of fracture healing by systemic administration of growth hormone and local application of insulin-like growth factor-1 and transforming growth factor-beta1.

Fracture healing is influenced by numerous hormones, growth factors, and cytokines. The systemic administration of growth hormone (GH) has shown to accelerate bone regeneration. Local application of growth factors, such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta-1 (TGF-beta1), are known to stimulate bone metabolism. Until now, the exact local and systemic mechanisms that lead to improved bone regeneration remain unclear. In addition, the effect of systemic administration of GH as compared with locally delivered growth factors on fracture healing in rats is not known. A midshaft fracture of the right tibia of 5-month-old female Sprague-Dawley rats (n = 80) was intramedullary stabilized with IGF-1 and TGF-beta1 coated vs. uncoated titanium K-wires. The growth factors were incorporated in a poly(D,L-lactide) (PDLLA) coating and released continuously throughout the experiment. Recombinant species-specific (rat) GH was applied systemically (2 mg/kg body weight) by daily subcutaneous injection and compared with a placebo group. The healing process was radiologically monitored. Twenty-eight days after fracture biomechanical torsional testing was performed. The consolidation and callus composition, including quantification of cartilage and mineralized tissue, was traced in histomorphometrical investigations using an image analysis system. Both methods, the systemic administration of GH and the local application of growth factors, showed significant biomechanical and histological effects on fracture healing. The local growth factor application showed a stronger effect on fracture healing than the systemic GH injection. The combined application of both methods did not accelerate the effect on bone healing compared with the single application. It is therefore concluded that combining local and systemic stimulating methods does not provide further additive effects with regard to fracture healing.

Animals↗

Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients.

BACKGROUND: The treatment of open fractures of the tibial shaft is often complicated by delayed union and nonunion. The objective of this study was to evaluate the safety and efficacy of the use of recombinant human bone morphogenetic protein-2 (rhBMP-2; dibotermin alfa) to accelerate healing of open tibial shaft fractures and to reduce the need for secondary intervention. METHODS: In a prospective, randomized, controlled, single-blind study, 450 patients with an open tibial fracture were randomized to receive either the standard of care (intramedullary nail fixation and routine soft-tissue management [the control group]), the standard of care and an implant containing 0.75 mg/mL of rhBMP-2 (total dose of 6 mg), or the standard of care and an implant containing 1.50 mg/mL of rhBMP-2 (total dose of 12 mg). The rhBMP-2 implant (rhBMP-2 applied to an absorbable collagen sponge) was placed over the fracture at the time of definitive wound closure. Randomization was stratified by the severity of the open wound. The primary outcome measure was the proportion of patients requiring secondary intervention because of delayed union or nonunion within twelve months postoperatively. RESULTS: Four hundred and twenty-one (94%) of the patients were available for the twelve-month follow-up. The 1.50-mg/mL rhBMP-2 group had a 44% reduction in the risk of failure (i.e., secondary intervention because of delayed union; relative risk = 0.56; 95% confidence interval = 0.40 to 0.78; pairwise p = 0.0005), significantly fewer invasive interventions (e.g., bone-grafting and nail exchange; p = 0.0264), and significantly faster fracture-healing (p = 0.0022) than did the control patients. Significantly more patients treated with 1.50 mg/mL of rhBMP-2 had healing of the fracture at the postoperative visits from ten weeks through twelve months (p = 0.0008). Compared with the control patients, those treated with 1.50 mg/mL of rhBMP-2 also had significantly fewer hardware failures (p = 0.0174), fewer infections (in association with Gustilo-Anderson type-III injuries; p = 0.0219), and faster wound-healing (83% compared with 65% had wound-healing at six weeks; p =0.0010). CONCLUSIONS: The rhBMP-2 implant was safe and, when 1.50 mg/mL was used, significantly superior to the standard of care in reducing the frequency of secondary interventions and the overall invasiveness of the procedures, accelerating fracture and wound-healing, and reducing the infection rate in patients with an open fracture of the tibia.

Adolescent↗

Osseous integration of hydroxyapatite grafts in metaphyseal bone defects of the proximal tibia (CT-study).

PURPOSE OF THE STUDY: The purpose of the study was the examination of the osseous integration of hydroxyapatite grafts used for the filling of metaphyseal bone defects in tibia head fractures. MATERIAL: Four patients with lateral tibia plateau fractures AO-type B3 (12) were included in the study. Patients were treated by arthroscopically assisted reduction and percutaneous screw fixation. The metaphyseal bone defects were filled with prepared solid hydroxyapatite graft blocks (Endobon Fa. Merk Darmstadt, Germany). In all of the patients a CT study for the osseous integration of hydroxyapatite grafts used for the filling of metaphyseal bone defects in tibial head fractures was performed. Measurements of density were performed of the implant region, the periimplant region, the distant periimplant region and the fibula bone. Follow-up CT examinations of these specific regions were performed 6 and 12 months postoperative. RESULTS: In all cases an increase of density of the hydroxyapatite graft after 6 months and 12 months follow-up was detected. The periimplant region showed in all cases a decrease of density. A progressive decrease of the periimplant and the distant cancellous tibial bone region was also detectable after 6 and 12 months post-op. A similar decrease of density was visible in the region of the cancellous bone of the fibula. In the interface region a direct bone formation between the hydroxyapatite graft and the adjected cancellous bone was visible in all cases during follow-up. CONCLUSION: The increase of density of the hydroxyapatite grafts and the direct bone formation in the interface region between the hydroxyapatite graft and the adjacent cancellous bone are clear radiomorphological signs for an osteointegration of hydroxyapatite grafts in the metaphyseal region.

Adult↗

Biodegradable poly(D,L-lactide) coating of implants for continuous release of growth factors.

Local application of growth factors like insulin like growth factor-I (IGF-I) and transforming growth factor-beta 1 (TGF-beta1) from a biodegradable thin layer of poly(D,L-lactide) (PDLLA) coated implants could stimulate fracture healing. A new "cold coating technique" for metallic implants was established to produce a biodegradable coating with a high mechanical stability that provides a continuous release of incorporated growth factors. The properties of this bioactive coating were investigated in vitro and in vivo. Scanning electron microscope analysis revealed a coating thickness of in average 14.8 microm on titanium and 10.7 microm on steel wires. Intramedullary implantation and extraction experiments depicted a loss of PDLLA coating from titanium and steel implants of less than 5%. After explantation of the implants, the coating displayed a complete and regular layer without any defects of PDLLA uncovering the metallic surface. Smear tests demonstrate that the coating can be performed under sterile conditions. The PDLLA depicted a reduction of about 8% within 6 weeks in vitro and in vivo. The growth factors were incorporated in a stable form and demonstrated a loss of stability of less than 3% within 42 days and less than 5% within one year. In an elution experiment, 54% IGF-I and 48% TGF-beta1 were released within the first 48 h. After 42 days, 76% of IGF-I and 71% of TGF-beta1 were detected in the elution fluid by ELISA. Comparable results were obtained in the in vivo experiments after 42 days.

Animals↗

Three-dimensional ultrasonography of bone and soft tissue lesions.

BACKGROUND: The aim of this study was to investigate feasibility and potential applications of three-dimensional (3D) ultrasonography in the evaluation of musculoskeletal disorders. METHODS: 3D ultrasonography was performed in 83 patients with bone (n = 50) or soft tissue lesions (n = 33). Volume data were obtained using two volume probes (1-8.5 and 8.5-12 MHz) and a 3D ultrasound unit. The results of 3D ultrasonography were compared to two-dimensional ultrasound and radiological imaging. RESULTS: The system enabled acquisition of 3D ultrasound data in diagnostic quality. 3D image-processing permits to analyse ultrasound data interactively in three orthogonal planes (section mode) or in realistic 3D views (rendering mode). Compared to conventional ultrasonography 3D image analysis improved assessment of details, provided better spatial orientation and facilitated image interpretation in 23, 44 and 49 cases, respectively. Additional findings that had significant influence on patient management were obtained in 16 of 83 patients (19%). Multiplanar reformating provided additional scan planes and increased the comparability of follow up examinations by standardized display and measurement. 3D surface reconstructions were very helpful to understand the morphology of bone lesions e.g. tortuous fracture lines. CONCLUSION: Our preliminary experience shows that 3D ultrasonography of musculoskeletal disorders is feasible. The ability to assess previously unattainable scan planes and lifelike surface projections may be particularly valuable for imaging of bone lesions. Further studies will be required to assess the exact role of this new technique for the evaluation of musculoskeletal disorders.

Adult↗

Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-beta1) from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats.

In vitro and in vivo studies have demonstrated an osteoinductive effect of growth factors such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1). However, for therapeutic use in fracture treatment, questions remain with regard to the local application of these proteins. A controlled, local release of growth factors from a biodegradable polylactide coating of osteosynthetic implants may have a stimulating effect on fracture healing. Such implants could stabilize the fracture and their bioactive surface could function simultaneously as a local drug-delivery system. Previous studies have demonstrated the high mechanical stability of an approximately 10-14-microm-thick poly(D,L-lactide) (PDLLA) coating on metallic implants, which can even withstand the process of intramedullary insertion. Following an initial peak, 80% of incorporated growth factors IGF-1 and TGF-beta1 were continuously released within 42 days. The effect of locally applied IGF-1 and TGF-beta1 from a biodegradable PDLLA coating of intramedullary implants on fracture healing was investigated in a rat model. Midshaft fractures of the right tibia of 5-month-old female Sprague-Dawley rats (n = 127) were stabilized with coated vs. uncoated titanium Kirschner wires. X-ray examinations and blood analyses were performed, and body weight and body temperature measurements were taken throughout the experimental period. After 28 and 42 days, respectively, tibiae were dissected for mechanical torsional testing and histomorphometrical analyses. X-rays demonstrated an almost completely consolidated fracture, biomechanical testing showed a significantly higher maximum load and torsional stiffness, and histological and histomorphometric analyses demonstrated progressed remodeling after 28 and 42 days in the group treated with growth factors as compared with controls. Interestingly, the PDLLA coating itself revealed a positive effect on fracture healing even without incorporated growth factors. No systemic changes of serum parameters, including IGF-1 and IGF binding proteins, and no differences in body weight and body temperature were observed within and between groups. These findings suggest that the local application of growth factors from a biodegradable PDLLA coating of osteosynthetic implants accelerates fracture healing significantly without systemic side effects.

Animals↗

Homologous growth hormone accelerates healing of segmental bone defects.

The effect of homologous recombinant porcine growth hormone (r-pGH) on secondary fracture healing was investigated in a diaphyseal defect of the tibia in Yucatan micropigs. A 1 cm defect of the tibia was created surgically and stabilized with an AO 3.5 mm DCP plate. The treatment group (12 animals) received 100 microg of r-pGH per kilogram of body weight subcutaneously once per day, whereas the control pigs (12 animals) received 1 mL of sodium chloride as placebo. For evaluation of the GH-axis, serum levels of insulin-like growth factor-I (IGF-I) were sampled every fourth day. The animals were killed 6 weeks after surgery. Quantitative computed tomography (qCT) was performed to determine bone mineral density (BMD) and bone mineral content (BMC) of the defect zone. The torsional stiffness and the torsional failure load were measured by destructive torsional testing of the defect and contralateral tibiae. qCT measurements revealed a significant increase in the BMC of the defect zone in the treatment group compared with controls (GH BMC = 2833 +/- 679 mg, placebo BMC = 2215 +/- 636 mg; p < 0.05), whereas the BMD values were similar in both groups (GH BMD = 668 +/- 60 mg/mm(2), placebo BMD = 629 +/- 52 mg/mm(2), p = 0.12). Torsional failure load was 70% higher and torsional stiffness 83% higher in the treatment group than in the control group (p < 0.05). The mean serum level of IGF-I in the treatment group increased to 382% of the preoperative basal level and decreased to 69% in the control group, and this difference was highly significant (p < 0.001). Our data indicate that daily administration of recombinant GH leads to an increase of serum IGF-I levels and stimulates secondary fracture healing, resulting in increased mechanical strength and stiffness of the callus.

Animals↗

Studies on the nonmevalonate pathway of terpene biosynthesis. The role of 2C-methyl-D-erythritol 2,4-cyclodiphosphate in plants.

2C-methyl-D-erythritol 2,4-cyclodiphosphate was recently shown to be formed from 2C-methyl-D-erythritol 4-phosphate by the consecutive action of IspD, IspE, and IspF proteins in the nonmevalonate pathway of terpenoid biosynthesis. To complement previous work with radiolabelled precursors, we have now demonstrated that [U-13C5]2C-methyl-D-erythritol 4-phosphate affords [U-13C5]2C-methyl-D-erythritol 2,4-cyclodiphosphate in isolated chromoplasts of Capsicum annuum and Narcissus pseudonarcissus. Moreover, chromoplasts are shown to efficiently convert 2C-methyl-D-erythritol 4-phosphate as well as 2C-methyl-D-erythritol 2,4-cyclodiphosphate into the carotene precursor phytoene. The bulk of the kinetic data collected in competition experiments with radiolabeled substrates is consistent with the notion that the cyclodiphosphate is an obligatory intermediate in the nonmevalonate pathway to terpenes. Studies with [2,2'-13C2]2C-methyl-D-erythritol 2,4-cyclodiphosphate afforded phytoene characterized by pairs of jointly transferred 13C atoms in the positions 17/1, 18/5, 19/9, and 20/13 and, at a lower abundance, in positions 16/1, 4/5, 8/9, and 12/13. A detailed scheme is presented for correlating the observed partial scrambling of label with the known lack of fidelity of the isopentenyl diphosphate/dimethylethyl diphosphate isomerase.

Capsicum↗

[Evaluating the stability of fracture fixation systems: mechanical device for evaluation of 3-D stiffness in vitro].

Different fixation systems are used for fracture and defect treatment. A prerequisite for complication free healing is sufficient mechanical stability of the osteosynthesis. In vitro investigations offer the possibility of both analysing and assessing the pre-clinical fixation stability. Due to the complex loading environment in vivo, stiffness analysis should include a complete determination of the stiffness under standardised conditions. Based on a mathematical procedure to calculate the 3-D stiffness, a mechanical testing device for the 3-D loading of fixation systems was designed and integrated in the existing test set-up. The set-up consisted of a material testing machine to produce the necessary loads and an optical measurement device to detect the resulting inter-fragmentary movements. To validate the testing device, the 3-D stiffness matrices of different Ilizarov fixator configurations were determined and compared. The good reproducibility of the test was reflected in the small intra-individual variability of the stiffness components. A distinct direction dependence of the fixator stiffness was observed. Increasing the number of rings led to a stiffness increase of up to 50%, especially in bending. The presented testing device allows a complete standardised determination of the stiffness of different fixation systems. It considers the direction dependence of the stiffness and creates a prerequisite for a more direct implant comparison.

Biomechanical Phenomena↗

Quantitative assessment of in vivo bone regeneration consolidation in distraction osteogenesis.

We present a new method for quantitatively assessing the consolidation of bone regeneration by performing distraction osteogenesis in micropigs. We measured in vivo stiffness using a newly developed, revolving, bone-healing meter. After the micropigs were killed, we obtained maximum torsional moment data for the regenerated bones by destructive mechanical testing, and we then correlated these data with the data for stiffness. We found a highly significant regression between in vivo stiffness and maximum torsional moment (r2 = 0.80), suggesting that monitoring stiffness may be useful for the prediction of bone regeneration in distraction osteogenesis. Therefore, our method may be a reliable tool for future quantitative monitoring of healing progress in patients with healing bones or in animal studies addressing treatments to increase bone formation in long-bone defects.

Animals↗

[Local liberation of IGF-I and TGF-beta 1 from a biodegradable poly(D,L-lactide) coating of implants accelerates fracture healing].

In vitro and in vivo studies have demonstrated an osteoinductive effect of growth factors like IGF-I and TGF-beta 1. However, for therapeutic use in fracture treatment, the local application of these bioactive molecules is still an unsolved problem. The controlled release of growth factors from a biodegradable coating of osteosynthetic implants could stimulate fracture healing locally. Coated implants could stabilise the fracture and work as a local drug delivery system. Previous studies demonstrated a high mechanical stability of a thin 10 microns poly(D,L-lactide) (PDLLA) coating on metallic implants that withstands even an intramedullary insertion process. After an initial peak, 80% of incorporated growth factors IGF-I and TGF-beta 1 were continuously released within 42 days. The effect of locally applied IGF-I and TGF-beta 1 from a biodegradable PDLLA coating of intramedullary implants on fracture healing were investigated in a rat model. A fracture of the right tibia of 5-month-old female Sprague-Dawley rats was stabilised with coated versus uncoated titanium K-wires. X-ray examinations and blood analysis were performed, body weight and body temperature monitored throughout the experimental period. After 42 days both tibiae were dissected for mechanical torsional testing and histomorphometric analyses. The results demonstrate a nearly completely consolidated fracture in the X-ray examinations, a significant higher maximum load and torsional stiffness in the biomechanical tests and a progressed remodeling in the histological and histomorphometric analyses after 42 days in the group treated with growth factors compared to the controls. Interestingly, the PDLLA coating itself had a positive effect on fracture healing even without incorporated growth factors. No systemic change of serum parameters including IGF-I and IGF binding proteins and no differences in body weight and body temperature were seen in any group. These findings suggest that the local application of growth factors from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing significantly without systemic side effects.

Animals↗

[Mechanical behavior of Ilizarov ring fixators. Effect of frame parameters on stiffness and consequences for clinical use].

Using a mechanical testing procedure, various fixator constructs were tested in vitro. In addition, the influence of the passive soft tissue structures on the fixation stiffness was determined. An increased number of Schanz' screws or Kirschner wires led to a comparable increase in stiffness than that observed with an increasing screw or wire diameter. In consequence, larger diameters should be preferred over an additional screw or wire where clinically applicable. With diaphyseal telescoping rods only the axial stiffness decreased. As expected, large ring diameters as well as titanium wires reduced stiffness components. Bracing the outer rings caused a reduction of the overall stiffness. Asymmetric pre-tensioning of the K-wires resulted in a significant reduction of tension in the neighboring wire. Removal of the soft tissues reduced stiffness to a similar extend as experienced in a fibula defect situation. The study demonstrates the correlation between design parameters, passive soft tissues and fixation stiffness and presents guidelines for an optimized fixator design.

Biomechanical Phenomena↗

In vivo analysis of microcirculation following closed soft-tissue injury.

Major loss of tissue is an almost invariable consequence of severe closed soft-tissue injury. Clinically, the extent of soft-tissue trauma determines the outcome of complex injuries and significantly influences bone healing. With use of a new animal model, this study quantitatively analyzed microcirculation, i.e., nutritive perfusion and leukocyte-endothelial cell interaction, in skeletal muscle after standardized closed soft-tissue injury. By means of a computer-assisted controlled-impact technique, a severe standardized closed soft-tissue injury was induced in the left hindlimb of 28 rats. The rats were assigned to four experimental groups (n = 7 per group) that differed by time of analysis (1.5, 24, 72, and 120 hours after injury); rats that were not injured served as controls (n = 7). Intramuscular pressure was measured, and microcirculation in the rat extensor digitorum longus muscle was analyzed by in vivo fluorescence microscopy, which allowed assessment of microvascular diameters, functional capillary density, number of rolling and adherent leukocytes in venules, and microvascular permeability. Edema weight gain was quantified by the ratio of wet to dry weight of the extensor digitorum longus muscle. Microvascular perfusion of the skeletal muscle was characterized by a significant reduction in functional capillary density, which was paralleled by an increase in capillary diameter throughout the 120 hours of observation when compared with the controls. Trauma-induced inflammatory response was reflected by a markedly increased rolling and adherence of leukocytes, primarily restricted to the endothelium of postcapillary venules; this was accompanied by increased microvascular permeability, indicative of a substantial loss of endothelial integrity. The microcirculation surrounding the core of the damaged tissue area resembled that of ischemia-reperfusion injury in skeletal muscle, i.e., heterogeneous capillary perfusion, pronounced microvascular leakage, and adherence of leukocytes. Enhanced vascular leakage and leukocyte adherence (24-72 hours after injury) coincided with the maximum intramuscular pressure (which was not indicative of compartment syndrome) and edema formation. These results demonstrate that initial changes, leading to ultimate tissue death, after closed soft-tissue injury are caused on the microcirculatory level. This standardized model provides further insight into microvascular pathophysiology and cellular interactions following closed soft-tissue injury. Thus, it is an adequate tool for testing novel therapeutic interventions.

Animals↗