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Biomedical subjects

C Bünger

Publications and source records attributed to C Bünger.

At least 37 records · Page 2Linked to original sources

A review of ceramic coatings for implant fixation.

The present series of eight studies was performed in order to investigate the effect of various clinically relevant factors on bone ingrowth in relation to hydroxyapatite (HA) and titanium-alloy (Ti) coating when subjected to pathological and mechanical conditions mimicking the clinical situation. HA- and Ti-coated implants were inserted into the femoral condyles of mature dogs and one study was performed on humans. The observation period ranged from 4 to 52 weeks, and the results were evaluated by mechanical push-out testing, histomorphometric analysis, polarized light microscopy, UV fluorescence microscopy and collagen analysis. There were no complications related to the operative procedures, and all dogs were killed according to the original time schedule. Two studies focused on in vivo mechanisms and factors influencing resorption of HA coating. The overall conclusions from these studies are that HA coatings do resorb in vivo, that micromotion accelerates resorption, and that resorbed HA is partly replaced by newly formed bone, suggesting that implants fixation is durable. The other studies focused on the significance of mechanical stabilization and loading conditions of the implant immediately after surgery. From these studies, it can be concluded that HA-coating has a positive effect on bone-implant fixation in various situations, i.e., under stable loaded conditions and under unstable mechanical conditions. The most striking effect of HA coating was that it enhanced bone growth across a gap around the implant both during stable and unstable mechanical conditions; it even converted a motion-induced fibrous membrane to bony anchorage.

Animals↗

Mechanical and histological analysis of bone-pedicle screw interface in vivo: titanium versus stainless steel.

OBJECTIVE: To investigate the differences in bone interface between titanium and stainless steel pedicle screws in the lumbar spine. METHODS: Eighteen adult mini-pigs that underwent total laminectomy, posterolateral spinal fusion (L4-L5) were randomly selected to receive stainless steel (9) or titanium pedicle screw devices (9). In both groups, the devices were CCD (Sofamore Danek) type with the same size and shape. The postoperative observation time was 3 months. Screws from L4 were harvested along their long axis of pedicle for histomorphometric study. Bone-screw interface and bone volume from thread were examined using linear intercept techniques. Mechanical testing (torsional test and pull-out test) was performed on the screws from L5. RESULTS: The titanium screw group had a significantly higher maximum torque (P < 0.05) and angle related stiffness (P < 0.05) measured by torsional test. In the pull-out tests, no differences were found between the two groups in relation to the maximum load, stiffness and energy to failure. Direct bone contact with the screw in percentage was 29.4% for stainless steel and 43.8% for titanium (P < 0.05). No differences in the bone purchase between the vertebral body part and pedicle part were found. CONCLUSION: Pedicle screws made of titanium have a better bone-screw interface binding than screws made of stainless steel. Torsional tests are more informative for bone-screw interface study. Pull-out tests seem less valuable when comparing bone purchase of screws made from different materials.

Animals↗

Resorption of hydroxyapatite and fluorapatite ceramic coatings on weight-bearing implants: a quantitative and morphological study in dogs.

Resorption (defined as loss of ceramic coating because of cellular activity or dissolution) of ceramic coatings is a matter of concern for the long-term performance of ceramic-coated implants. A new fluorine-containing coating, fluorapatite (FA), has been shown to be more stable than hydroxyapatite (HA) in unloaded models. In a weight-bearing model in trabecular bone, we evaluated loss (defined as reduction of coating irrespective of type of mechanism) of HA and FA coatings during 25 weeks of implantation. Eight mature dogs had HA- or FA-coated implants inserted bilaterally into the weight-bearing region of the medial femoral condyle. Quantified loss of ceramic coating was estimated at the light microscopic level using stereological methods. The experiment showed significant loss of both types of coatings. However, no statistical difference in loss of ceramic coating was found regarding surface area implant coverage, volume, and thickness (p = 0.77, p = 0.13, p = 0.56, p = 0.23, respectively). Completely resorbed HA coating was replaced by 36 +/- 6.0% (range: 26-42) bone in direct contact with the implant surface compared with 29 +/- 16.0% (range: 12-59) for FA (p = 0.40), suggesting that the implant was firmly fixed despite loss of the ceramic coating. Transmission electron microscopy in combination with electron energy spectroscopy and electron spectroscopic imaging showed that osteclast-like cells, osteocytes, macrophage-like cells, and fibroblasts had phagocytosed calcium-containing fragments, indicating cell-mediated resorption of the ceramic coating.

Animals↗

Porous-coated versus grit-blasted surface texture of hydroxyapatite-coated implants during controlled micromotion: mechanical and histomorphometric results.

Hydroxyapatite (HA)-coated implants with porous-coated and grit-blasted surface textures were inserted bilaterally in a paired design into the medial femoral condyles of eight dogs for 16 weeks. The implants were weight-loaded and initially subjected to controlled micromotion of 500 microm during each gait cycle. Histology revealed that five implants in each group had bony anchorage, and the remaining implants were surrounded by fibrous tissue. Push-out testing showed no difference in shear stiffness and strength, while energy absorption for porous-coated implants was increased significantly by threefold. The HA coating delaminated on grit-blasted implants during push-out testing, whereas porous-coated implants predominantly failed at the HA-tissue interface. Coverage, surface area, volume, and thickness of the HA coating were significantly reduced in vivo for porous-coated and grit-blasted implants. In conclusion, a plasma-sprayed porous-coated implant surface seems to give better fixation not only of the HA-coating to the implant surface but also of the implant to the surrounding tissues in comparison to a grit-blasted implant surface. The HA coating was reduced more on fibrous-anchored than on bony-anchored implants, suggesting that micromotion accelerates resorption of HA. Resorbed HA coating was replaced by more bone on porous-coated implants than on grit-blasted implants, which suggests that fixation of porous-coated implants will be durable.

Animals↗

Spinal cord and nerve root blood flow in acute double level spinal stenosis.

STUDY DESIGN: Twenty-four pigs were randomized into three groups of eight pigs; a control group with 0% stenosis, a 25% stenosis group, and a 50% stenosis group. A fourth 75% stenosis group was added when results of the randomized experiment had been analyzed. Blood flow of the spinal cord and nerve roots and spinal evoked potentials were determined before and 1 hour after induction of the spinal stenoses. OBJECTIVES: To study the acute effects of different degrees of spinal stenosis on neural tissue blood flow and spinal evoked potentials. SUMMARY OF BACKGROUND DATA: Spinal cord dysfunction may be caused by vascular impairment or mechanical injury to neural tissue. Experimental double level compression of the cauda equina causes reversible nerve root edema, stasis, blood flow decrease, and compromised neural function. The vascular pathophysiology after spinal cord trauma was studied previously, and both increased and decreased neural tissue blood flow have been reported. METHODS: Two level spinal stenosis was introduced by placement of stenosing bands around the dural sac at L4 and L6. Neurologic function was monitored by sensory and motor evoked potentials. Regional blood flow (RBF) was measured in the stenotic segments between the bands and other regions of neural tissue by radioactive microspheres before and after induction of stenosis. RESULTS: Regional blood flow increased in the stenotic segments after 0% sham stenosis. Analysis of variance revealed no differences in RBF between the three randomized groups under comparable conditions of 0% stenosis. However, the RBF level of the added 75% group was lower than that of the other three groups. By comparison of RBF within groups before and after stenosis, no decrease in RBF was found between the stenosing bands in any of the groups. Fifty percent stenosis changed the amplitude of evoked potentials in half of the animals. Seventy-five percent stenosis caused severe changes in evoked potentials in 7 of 8 animals. CONCLUSIONS: Blood supply of the spinal cord and nerve roots in the segments between two central stenoses is preserved immediately after stenosis introduction by way of the segmental nerve pathway, even if nerve conduction is impaired.

Acute Disease↗

Hydroxyapatite and fluorapatite coatings for fixation of weight loaded implants.

Survivor analysis of total hip replacement recently has shown disappointing results in younger patients. To improve this, ceramic coatings have been applied to prostheses for cementless use. A new fluorine containing coating, fluorapatite, has been shown to increase bone ingrowth compared with hydroxyapatite in unloaded models. In a weight loaded model, the effects of hydroxyapatite and fluorapatite coated implants on implant fixation and bone ingrowth were evaluated. Eight hydroxyapatite and fluorapatite coated implants with porous surface were inserted into the medial femoral condyles of 8 mature dogs in a paired design. The implants initially were surrounded by a gap communicating with the joint space and were loaded during each gait cycle. After 25 weeks, no differences in pushout data or bone ingrowth between hydroxyapatite and fluorapatite coated implants were found. An important finding was the absence of foreign body reaction in the bone. Neither hydroxyapatite nor fluorapatite coatings delaminated during implantation or as a result of the pushout test. Bone repair activity remained in the initial gap zone, but most of the bone was of the lamellar type. No difference in bone remodeling between the hydroxyapatite and fluorapatite coated implants was found in the initial gap zone. Microprobe analysis showed no increase in fluorine content around the fluorapatite coated implants. The hydroxyapatite and fluorapatite coatings seem efficacious after a 25-week implantation period under weight loaded conditions.

Animals↗

Resorption of hydroxyapatite and fluorapatite coatings in man. An experimental study in trabecular bone.

The clinical use of hydroxyapatite (HA) coating is controversial especially in regard to the long-term performance of the coating and the effects of resorption. In each of 15 consenting patients we inserted two implants, coated with either HA or fluorapatite (FA) into the iliac crest. They were harvested at a mean of 13.6 +/- 0.6 months after surgery. Histological examination showed that bone ongrowth on the HA-coated implants was significantly greater (29%) than that on the FA-coated implants. When bone was present on the coating surface the HA coating was significantly thicker than the FA coating. When bone marrow was present, the HA coating was significantly thinner than the FA coating. The reduction in coating thickness when covered by bone or bone marrow was 23.1 +/- 9.7 microm for HA and 5.1 +/- 1.7 microm for FA (p < 0.01) suggesting that FA is more stable than HA against resorption by bone marrow. The findings suggest that in man the osteoconductive properties of HA coating are superior to those of FA. Resorption rates for both coatings were approximately 20% of the coating thickness per year. Bone ongrowth appears to protect against resorption whereas bone marrow seems to accelerate resorption. No adverse reaction was seen in the surrounding bone.

Apatites↗

Improved fixation of porous-coated versus grit-blasted surface texture of hydroxyapatite-coated implants in dogs.

We inserted, in 8 dogs, implants with either porous-coated or grit-blasted titanium surface and coated with hydroxyapatite (HA) into trabecular bone in the proximal humerus, using a 1 mm gap model. After 25 weeks, push-out tests showed that energy absorption for porous-coated implants was twice that of grit-blasted implants, whereas shear stiffness was reduced by one fifth, indicating a stronger fixation of porous-coated implants. Macroscopically, all grit-blasted implants had delamination of the HA coating, whereas porous implants failed mostly at the HA-tissue interface. Porous-coated implants had 47% bone ingrowth and grit-blasted implants 70% (p = 0.02), however, no difference in absolute surface area was found. Part of the HA coating was resorbed during the implantation period as regards volume and thickness. HA coverage was more reduced on porous-coated than on grit-blasted implants (p = 0.01). No foreign-body reaction or osteolysis was seen. An important finding was that one fifth of the surface with complete resorption of HA coating was replaced by newly formed bone.

Animals↗

Improved method for examination of microvascular structures in bone tissue.

Scanning electron microscopy of methylmethacrylate vascular corrosion casts was used for the morphologic examination of the microvascular system in bone. The methylmethacrylate used for vascular casting was prepared by prepolymerization with ultraviolet light. To approximate the viscosity of blood in the microcirculation, where the hematocrit of blood is lower than in the rest of the circulation, a viscosity between that of plasma and full blood was chosen for the casting material. Neither the ultraviolet prepolymerization of methylmethacrylate nor the choice of a viscosity this low has been used in microcorrosion casting in bone before. Further preparation of the tissue followed 2 directions: (1) complete maceration and decalcification of the specimens, thereby exposing all the vascular structures for detailed examination. By this procedure, it was possible to show detailed and sharp impressions of the vascular bed, and to show, for the first time, the vascular loop from a cutting cone; and (2) maceration without decalcification of the specimens, which is suitable for examination of relations between the microvascular system and the bone tissue. This technique enables studies of the role of the vascular system in bone remodeling and of the involvement of vascular structures in bone disorders. This improved technique for examination of microvascular structures in bone enables detailed studies of the vascular system and its relation to active remodeling sites in bone.

Animals↗

Transforming growth factor-beta 1 enhances bone healing to unloaded tricalcium phosphate coated implants: an experimental study in dogs.

Growth of bone into cementless prosthetic components is compromised after revision of failed joint prostheses and by osteoporosis, gaps, and micromotion. We studied the effects of recombinant human transforming growth factor-beta 1 adsorbed on ceramic coated implants on the improvement of mechanical fixation and bone growth on the implant. Unloaded cylindrical grit-blasted titanium alloy implants were inserted bilaterally into both the medial and lateral femoral condyles of 10 skeletally mature mongrel dogs. The implants measured 10 mm in length and 6 mm in diameter and were initially surrounded by a 2 mm gap. One implant had an uncoated titanium surface and three implants were coated with tricalcium phosphate and 0, 0.3, or 3.0 micrograms of recombinant human transforming growth factor-beta 1. The dogs were killed at 6 weeks. Mechanical testing showed a 3-fold increase in fixation for the 0.3 microgram dose of recombinant human transforming growth factor-beta 1 and a 2-fold increase for the 3.0 micrograms dose. Histological analysis of bone growth on the implant demonstrated that maximal stimulation occurred with the 0.3 microgram dose, but bone volume in the gap was maximally stimulated by the 3.0 micrograms dose and increased 2-fold over control values. The majority of tricalcium phosphate was resorbed after the 6-week observation period. This study suggests that recombinant human transforming growth factor-beta 1 adsorbed onto implants coated with tricalcium phosphate ceramic can enhance mechanical fixation and bone growth on the implant. The use of transforming growth factor-beta 1 on ceramic coated prosthetic components may help to improve the functional outcome of cementless total joint replacements.

Animals↗

Role of different loading conditions on resorption of hydroxyapatite coating evaluated by histomorphometric and stereological methods.

The role of different loading conditions on resorption of plasma-sprayed hydroxyapatite coating was investigated in an experimental study. Resorption of hydroxyapatite was quantified by histomorphometric and stereological methods on backscattered scanning electron images. Hydroxyapatite-coated titanium implants were inserted unilaterally into the medial femoral condyle of the knee in 14 mature dogs. Initially, all implants were subjected to controlled micromotion of 150 microns. After 4 weeks, the dogs were randomly assigned either to have the implant surgically immobilized to prevent further micromovement or to have a sham operation. Sixteen weeks after the first operation, the implants were analyzed. Six noninserted implants served as controls. The surface area and volume of the hydroxyapatite coating were reduced on the immobilized implants by 53 and 67% (p < 0.05), respectively, and were further significantly reduced on the continuously loaded implants by 83 and 87%, respectively, compared with the control implants. The hydroxyapatite coating was significantly thinner on immobilized (15 microns) and continuously loaded (15 microns) implants as compared with control implants (23 microns), but no difference between the inserted implants was found. Areas not covered with hydroxyapatite had 29 and 24% bone coverage on the immobilized and continuously loaded implants (not significant). Resorption of hydroxyapatite coating did occur in vivo. Continuous loading of the implants accelerated resorption significantly compared with immobilization of the implants. It is suggested that completely resorbed hydroxyapatite was partly replaced by bone in direct contact with the metal implant surface.

Animals↗

Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells.

Bone morphogenetic proteins (BMPs) have important functions for the differentiation of bone cells, but the exact role for bone remodeling and bone healing still needs to be defined. Migration of bone forming cells is an important physiological event both during bone healing and bone remodeling. The chemotatic properties of the bone morphogenetic protein family of growth factors have not been investigated. In this study the chemotactic effects of the bone morphogenetic proteins BMP-2, -4, and -6 have been quantitated toward human osteoblasts, human marrow stromal osteoblasts, and U2-OS human osteosarcoma cells. BMP-2 stimulated the migration of human stromal osteoblasts, human osteoblasts, and U2-OS cells with bell-shaped response curves in a dose-dependent manner with a 300% increase in cell migration at 1.0 ng/mL for human stromal osteoblasts and a 170-180% increase for human osteoblasts and U2-OS cells. At higher concentrations, migration decreased to background levels. BMP-4 and -6 did not show any effect on cellular migration. This study shows that BMP-2 can stimulate in vitro migration of human osteoblasts and human osteosarcoma cells. BMP-2 might play a role in the chemotactic recruitment of especially undifferentiated osteoblasts during bone remodeling and bone healing.

Bone Marrow↗

Transforming growth factor-beta stimulates bone ongrowth. Hydroxyapatite-coated implants studied in dogs.

Unloaded cylindrical grit-blasted titanium (Ti-6A-4V) implants (6 x 10 mm) coated with hydroxyapatite ceramic were inserted into the proximal part of the humerus of 20 skeletally mature Labrador dogs. The implants were initially surrounded by a 2 mm gap. In 10 dogs, HA-coated implants without growth factor were inserted in one humerus and implants with 0.3 microgram rhTGF-beta 1 adsorbed onto the HA coating were inserted in the contralateral humerus. In another group of 10 dogs, a dose of 3.0 micrograms rhTGF-beta 1 was tested in a similar design. All dogs were killed at 6 weeks after treatment. Results were evaluated by histomorphometry and mechanical push-out testing. Bone ongrowth was increased by one third, using the 0.3 mg rhTGF-beta 1 stimulation. Bone volume in the gap and mechanical testing showed no statistically significant differences between control and rhTGF-beta 1 stimulated implants. RhTGF-beta 1 only moderately enhanced bone ongrowth to hydroxyapatite-coated implants.

Alloys↗

Transforming growth factor-beta 1 stimulates bone ongrowth to weight-loaded tricalcium phosphate coated implants: an experimental study in dogs.

Bone growth into cementless prosthetic components is compromised by osteoporosis, by any gap between the implant and the bone, by micromotion, and after the revision of failed prostheses. Recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) has recently been shown to be a potent stimulator of bone healing and bone formation in various models in vivo. We have investigated the potential of rhTGF-beta 1, adsorbed on to weight-loaded tricalcium phosphate (TCP) coated implants, to enhance bone ongrowth and mechanical fixation. We inserted cylindrical grit-blasted titanium alloy implants bilaterally into the weight-bearing part of the medial femoral condyles of ten skeletally mature dogs. The implants were mounted on special devices which ensured stable weight-loading during each gait cycle. All implants were initially surrounded by a 0.75 mm gap and were coated with TCP ceramic. Each animal received two implants, one with 0.3 microgram rhTGF-beta 1 adsorbed on the ceramic surface and the other without growth factor. Histological analysis showed that bone ongrowth was significantly increased from 22 +/- 5.6% bone-implant contact in the control group to 36 +/- 2.9% in the rhTGF-beta 1 stimulated group, an increase of 59%. The volume of bone in the gap was increased by 16% in rhTGF-beta1-stimulated TCP-coated implants, but this difference was not significant. Mechanical push-out tests showed no difference in fixation of the implant between the two groups. Our study suggests that rhTGF-beta 1 adsorbed on TCP-ceramic-coated implants can enhance bone ongrowth.

Adsorption↗

Two-level spinal stenosis in minipigs. Hemodynamic effects of exercise.

STUDY DESIGN: Twenty-two Göttingen minipigs were trained to run on a treadmill. Two-level lumbar spinal stenosis was created in 12 pigs, 10 were unoperated control subjects. Blood flow of the spinal cord and nerve roots was determined with microspheres at rest, during exercise, and after exercise. OBJECTIVES: To study the effect of lumbar spinal stenosis and exercise on blood flow of spinal neural tissue. SUMMARY OF BACKGROUND DATA: Neurogenic claudication, the key symptom of lumbar spinal stenosis, may be caused by vascular impairment or mechanical distress of neural tissue during exercise. Experimental compression of the cauda equina causes reversible nerve root edema, stasis, blood flow decrease, and compromised neural function. The vascular pathophysiology of spinal stenosis during exercise has not been studied previously. METHODS: Pigs were trained daily for 3 months. Two-level 25% lumbar spinal stenosis was introduced by placement of stenosing bands around the dural sac. Neurologic function was monitored before surgery by evoked potentials and after surgery by the Tarlov score. Regional blood flow in lumbosacral neural tissue was measured 3 days after chronic catheterization using microspheres at rest, during exercise at 3 km/h for 15 minutes, and at rest 30 minutes after exercise. RESULTS: Blood flow of grey and white matter increased during exercise in both groups, with no differences between groups. slight hyperemia prevailed after exercise in white matter of the stenotic area but not in grey matter. Nerve root blood flow was largely unchanged in control subjects during exercise but was reduced in spinal stenosis at rest, further depressed during exercise, and normalized after exercise. Dural blood flow was elevated throughout. CONCLUSION: The study suggests that exercise-induced impairment of spinal nerve root blood flow plays a role in the pathophysiology of neurogenic claudication.

Animals↗

Polyethylene particles stimulate monocyte chemotactic and activating factor production in synovial mononuclear cells in vivo. An immunohistochemical study in rabbits.

We report that polyethylene particles can activate mononuclear cells within the joint to produce the monocyte chemotactic and activating factor (MCAF) and to a lesser degree interleukin 8 (IL-8) as judged by immunohistological staining. Polyethylene particles suspended in hyaluronic acid were injected weekly for 12 weeks into the right knee joint of New Zealand white rabbits. The average size of the particles was 7 (3-12) microns in diameter. The left knee joint was injected with hyaluronic acid as the control. The animals were killed after 13 weeks. On the control side, the synovial membrane was histologically normal, without signs of inflammation. In the knees that were injected with polyethylene particles, histological analysis showed a weak inflammatory response, consisting of mononuclear cells, multi-nucleated giant cells and polyethylene particles. In the vicinity of the particles, the presence of mononuclear cells that were highly positive for MCAF was noted, whereas IL-8 was present in endothelial cells and in the lining layer, but not in cells in the vicinity of polyethylene particles, suggesting that polyethylene particles are able to activate cytokine metabolism in a differentiated way in the synovial monocytes.

Animals↗

Chemotaxis of human osteoblasts. Effects of osteotropic growth factors.

The in vitro chemotactic response of human osteoblasts was investigated towards the following growth factors: TGF-beta, PDGFs, FGFs and IGFs. Human osteoblasts grown from trabecular bone after enzymatic digestion were studied. TGF-beta stimulated the migration of human osteoblasts in a dose-dependent manner with a four-fold increase in migrated cells at 100 pg/ml, which was the optimum concentration. PDGF-BB also stimulated migration four-fold in a dose-dependent manner with a maximum response at 10 ng/ml. PDGF-AA, IGF-I and IGF-II stimulated migration two-fold at 100 ng/ml. The results show that TGF-beta and PDGF-BB are important regulators of human osteoblast migration, but other growth factors IGF-I, IGF-II and PDGF-AA may also stimulate osteoblast migration. Our results additionally suggest that TGF-beta and PDGF-BB may participate in the recruitment of osteoblasts during bone remodeling since both TGF-beta and PDGF-BB are found in bone matrix and could be released during osteoclastic bone resorption. They furthermore support a possible use of TGF-beta and PDGF-BB in growth factor-induced osteogenesis.

Cells, Cultured↗