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Cody Bünger

Publications and source records attributed to Cody Bünger.

At least 19 recordsLinked to original sources

Experimental lumbar spine fusion with novel tantalum-coated carbon fiber implant.

Implants of carbon fiber composite have been widely used in orthopedic and spinal surgeries. However, studies using carbon fiber-reinforced cages demonstrate frequent appearance of fibrous layer interposed between the implant and the surrounding bone. The aim of the present study was to test the possibility of coating a biocompatible metal layer on top of the carbon fiber material, to improve its biological performance. Tantalum was chosen because of its bone compatibility, based on our previous studies. A novel spinal fusion cage was fabricated by applying a thin tantalum coating on the surface of carbon-carbon composite material through chemical vapor deposition. Mechanical and biological performance was tested in vitro and in vivo. Compress strength was found to be 4.9 kN (SD, 0.2). Fatigue test with 500,000 cycles was passed. In vitro radiological evaluation demonstrated good compatibility with X-ray and CT scan examinations. In vivo test employed eight pigs weighing 50 kg each. Instrumented lumbar spine fusion of L3/4 and L4/5 with these cages was performed on each pig. After 3 months, excellent bone integration property was demonstrated by direct contact of the cage with the host bone and newly formed bone. No inflammatory cells were found around the implant. Cages packed with two different graft materials (autograft and COLLOSS) achieved the same new bone formation. The present study proved that coating tantalum on top of the carbon-based implant is feasible, and good bone integration could be achieved.

Animals↗

Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds.

Culture of osteogenic cells on a porous scaffold could offer a new solution to bone grafting using autologous human mesenchymal stem cells (hMSC) from the patient. We compared coralline hydroxyapatite scaffolds with pore sizes of 200 and 500 microm for expansion and differentiation of hMSCs. We cultivated the hMSC statically or in spinner flasks for 1, 7, 14 and 21 days and found that the 200-microm pore scaffolds exhibited a faster rate of osteogenic differentiation than did the 500-microm pore scaffolds as shown by an alkaline phosphatase activity assay and real-time reverse transcriptase polymerase chain reaction for 10 osteogenic markers. The 500-microm scaffolds had increased proliferation rates and accommodated a higher number of cells (shown by DNA content, scanning electron microscopy and fluorescence microscopy). Thus the porosity of a 3D microporous biomaterial may be used to steer hMSC in a particular direction. We found that dynamic spinner flask cultivation of hMSC/scaffold constructs resulted in increased proliferation, differentiation and distribution of cells in scaffolds. Therefore, spinner flask cultivation is an easy-to-use inexpensive system for cultivating hMSCs on small to intermediate size 3D scaffolds.

Biocompatible Materials↗

Costs and effects in lumbar spinal fusion. A follow-up study in 136 consecutive patients with chronic low back pain.

Although cost-effectiveness is becoming the foremost evaluative criterion within health service management of spine surgery, scientific knowledge about cost-patterns and cost-effectiveness is limited. The aims of this study were (1) to establish an activity-based method for costing at the patient-level, (2) to investigate the correlation between costs and effects, (3) to investigate the influence of selected patient characteristics on cost-effectiveness and, (4) to investigate the incremental cost-effectiveness ratio of (a) posterior instrumentation and (b) intervertebral anterior support in lumbar spinal fusion. We hypothesized a positive correlation between costs and effects, that determinants of effects would also determine cost-effectiveness, and that posterolateral instrumentation and anterior intervertebral support are cost-effective adjuncts in posterolateral lumbar fusion. A cohort of 136 consecutive patients with chronic low back pain, who were surgically treated from January 2001 through January 2003, was followed until 2 years postoperatively. Operations took place at University Hospital of Aarhus and all patients had either (1) non-instrumented posterolateral lumbar spinal fusion, (2) instrumented posterolateral lumbar spinal fusion, or (3) instrumented posterolateral lumbar spinal fusion + anterior intervertebral support. Analysis of costs was performed at the patient-level, from an administrator's perspective, by means of Activity-Based-Costing. Clinical effects were measured by means of the Dallas Pain Questionnaire and the Low Back Pain Rating Scale at baseline and 2 years postoperatively. Regression models were used to reveal determinants for costs and effects. Costs and effects were analyzed as a net-benefit measure to reveal determinants for cost-effectiveness, and finally, adjusted analysis (for non-random allocation of patients) was performed in order to reveal the incremental cost-effectiveness ratios of (a) posterior instrumentation and (b) anterior support. The costs of non-instrumented posterolateral spinal fusion were estimated at DKK 88,285(95% CI 81,369;95,546), instrumented posterolateral spinal fusion at DKK 94,396(95% CI 89,865;99,574) and instrumented posterolateral lumbar spinal fusion + anterior intervertebral support at DKK 120,759(95% CI 111,981;133,738). The net-benefit of the regimens was significantly affected by smoking and functional disability in psychosocial life areas. Multi-level fusion and surgical technique significantly affected the net-benefit as well. Surprisingly, no correlation was found between treatment costs and treatment effects. Incremental analysis suggested that the probability of posterior instrumentation being cost-effective was limited, whereas the probability of anterior intervertebral support being cost-effective escalates as willingness-to-pay per effect unit increases. This study reveals useful and hitherto unknown information both about cost-patterns at the patient-level and determinants of cost-effectiveness. The overall conclusion of the present investigation is a recommendation to focus further on determinants of cost-effectiveness. For example, patient characteristics that are modifiable at a relatively low expense may have greater influence on cost-effectiveness than the surgical technique itself--at least from an administrator's perspective.

Activities of Daily Living↗

Nanostructure of the neurocentral growth plate: Insight from scanning small angle X-ray scattering, atomic force microscopy and scanning electron microscopy.

In this study, the experimental techniques scanning electron microscopy (SEM) including energy-dispersive X-ray analysis, atomic force microscopy (AFM) and scanning small angle X-ray scattering (SAXS) have been exploited to characterize the organization of large molecules and nanocrystallites in and around the neurocentral growth plate (NGP) of a pig vertebrae L4. The techniques offer unique complementary information on the nano- to micrometer length scale and provide new insight in the changes in the matrix structure during endochondral bone formation. AFM and SEM imaging of the NGP reveal a fibrous network likely to consist of collagen type II and proteoglycans. High-resolution AFM imaging shows that the fibers have a diameter of approximately 100 nm and periodic features along the fibers with a periodicity of 50-70 nm. This is consistent with the SAXS analysis that yields a cross-sectional diameter of the fibers in the range of 90 to 112 nm and a predominant orientation in the longitudinal direction of the NGP. Furthermore, we find inhomogeneities around 7 nm in the NGP by SAXS analysis. Moving towards the bone in the direction perpendicular to the growth plate, a systematic change in apparent thickness is observed, while the large-scale structural features remain constant. In the region of bone, the apparent thickness equals the mean mineral thickness and increases from 2 nm to approximately 3.5 nm as a function distance from the NGP. The mineral particles are organized as plates in a rather compact network structure. We have demonstrated that SEM, AFM and SAXS are valuable tools for the investigation of the organization of large molecules and nanocrystallites in the NGP and adjacent trabecular bone. Our findings will be an important basis for future work into identifying the defects on nanometer length scale responsible for idiopathic scoliosis and other growth-plate-related diseases.

Animals↗

Evaluation of a Dallas Pain Questionnaire classification in relation to outcome in lumbar spinal fusion.

Several studies have suggested that psychosocial distress is an important predictor of negative outcome in lumbar spine surgery. Ozguler et al. [Spine 27:1783-1789, 2002, 18] described a classification tool for low back pain patients using the Dallas Pain Questionnaire (DPQ) which included a measure of distress. We wanted to evaluate the ability of this classification tool to predict the outcome in spinal fusion patients. Five hundred and sixty-six patients (239 men, 327 women; mean age 46, range 18-81) operated between 1992 and 2002, with a complete DPQ preoperatively and after a minimum of 1-year follow-up, were included. They were classified preoperatively and at follow-up into four groups: group 1 (slight disability), group 2 (intermediate disability), group 3 (major disability) and group 4 (major disability and emotional distress). Using logistic regression, seven predictor variables were investigated: age (-39 years/40-59 years/60+ years), Gender (male/female), Indication (spondylolisthesis/primary degeneration/secondary degeneration), Work status (working/without work or on sick leave/retired or pensioned), Duration of pain (less than 1 year/1-2 years/more than 2 years), Presence of radiating pain (yes/no) and disability/distress [intermediate disability (group 1-2)/major disability (group 3)/major disability and distress (group 4)]. The outcome variable was disability at follow-up (low = group1 + 2/high = group 3 + 4). Preoperative classification was group 1, 1%; group 2, 14%; group 3, 37%; group 4, 48%. Variables found to predict high disability at follow-up were secondary degeneration Odds Ratio (OR) 1.61 (P=0.020), being retired/pensioned OR 3.48 (P<0.0005), age between 40-59 years OR 1.68 (P=0.011), belonging to group 3 OR 2.69 (P=0.003) or belonging to group 4 OR 5.53 (P<0.0005). The classification based on the DPQ were able to identify lumbar spinal fusion patients with a considerable amount of psychological distress in their symptomatology. Furthermore, the presence of distress, as determined by this classification, was a highly significant risk factor for inferior outcome.

Adolescent↗

Porous tantalum trabecular metal scaffolds in combination with a novel marrow processing technique to replace autograft.

INTRODUCTION: Interbody fusion requires a structural member to carry load while the autograft or osteoinductive agent stimulates bone formation. In the present study, we evaluated the potential use of extracted nucleated cells from bone marrow mixed in hyaluronic acid gel as an osteoinductive agent, in comparison to Collagraft loaded with nucleated cells or rhBMP-2 in the porous tantalum ring, in an anterior lumbar interbody fusion (ALIF) in pigs. METHODS: Four 3-month-old female Danish landrace pigs were employed in the current study. Bone marrow was collected by means of aspiration, from the medullary cavity of the proximal tibia. The nucleated cells were isolated with a Ficoll step gradient centrifugation. The cell adhered rate after 24 hours of cultivation and ALP activity in the osteogenic medium following 4 days of cultivation were measured. Cell numbers in the porous tantalum discs were assessed by CyQuant measurement, and fluorescent live/dead cell staining in the porous tantalum discs was performed after periods of 24 hours and 7 days of cultivation. The nucleated cells mixed in hyaluronic acid gel were cultivated on slides for 24 hours, 7 days and 21 days. The live/dead cell staining, ALP staining or osteocalcin staining, were performed. A porous tantalum ring was loaded with nucleated cells in hyaluronic acid gel or packed with Collagraft strips also with nucleated cells or rhBMP-2. Immediately after preparation, one of three implants was inserted into L2-3, L4-5 or L6-7 respectively. The pigs were killed 3 months postoperatively. The lumbar spine specimens were prepared for histological evaluation. RESULTS: The adhered rate, of the nucleated cells, was 2.26+/-0.56%. ALP activity was no different in the osteogenic culture compared to DMEM/10%FBS alone. Cell numbers and live/dead cells showed no difference in the porous tantalum discs. Histological appearance showed that nucleated cells mixed with hyaluronic acid gel, had more mature bone in the central hole of the porous tantalum ring, compared to Collagraft strips with nucleated cells or rhBMP-2. Bone volume fraction did not differ within the three porous tantalum rings; however, more marrow space in the central hole of the porous tantalum ring was present when nucleated cells mixed with hyaluronic acid gel (57.4%) compared to Collagraft strips with rhBMP-2 (29.7%). CONCLUSION: In the current study, we demonstrate that nucleated cells, which were isolated from bone marrow intraoperatively, could be used to replace autograft if nucleated cells mixed with hyaluronic acid gel or with Collagraft strips packed into the porous tantalum ring in the pig ALIF model.

Animals↗

Ectopic bone induction by equine bone protein extract.

Demineralized bone matrix from horse has been reported to be osteoinductive. However, its performance was inferior to autogenous bone graft in terms of new bone formation. In the present experiment, an equine bone protein extract-COLLOSS E was investigated for its osteoinductivity in a rat model. At the mean time, carboxymethyl-cellulose (CMC) was tested as a potential carrier for the protein extract. 18 male Wistar rats (8 weeks) were employed in the experiment. Each rat was implanted randomly with the 2 of the following implants, one on each side of the abdominal muscle. 1) COLLOSS E lyophilisate. 2) PEEK ring holder. 3) 3% or 10% CMC .in gel or lyophilized form 4) COLLOSS E lyophilisate with 3% CMC, implanted as gel or in lyophilized form. 5) COLLOSS E suspension with 10% CMC, implanted as gel or in lyophilized form. The rats were followed up for 21 days. After termination, samples were subjected to macroscopic examination, plain radiograph, micro-CT and histological evaluations. The results showed that PEEK ring or CMC alone could not induce ectopic bone formation. COLLOSS E lyophilisate has a slightly higher (6 out of 7) positive bone formation rate over COLLOSS E/3% CMC (3 out of 5, both gel and lyophilized form), however, the difference is non-significant (p=0.36, Fisher's exact test). 10% CMC with COLLOSS E did not show ectopic bone formation when implanted as gel form (0/8), while 1 positive bone formation was found when implanted as the lyophilized form (1/4). Bone tissue volume ranged from 0 mm(3) to 23.1mm(3) for COLLOSS-E lyophilisate alone and 0 to 29.7mm(3) for COLLOSS E/3%CMC (gel or lyophilized form). We concluded that equine bone protein extract has the ability to induce ectopic bone formation in the rat model. CMC could be a potential carrier, however, further studies are needed to verify the proportion and efficacy.

Animals↗

Molecular mechanism of osteochondroprogenitor fate determination during bone formation.

Osteoblasts and chondrocytes, which derive from a common mesenchymal precursor (osteochondroprogenitor), are involved in bone formation and remodeling in vivo. Determination of osteochondroprogenitor fate is under the control of complex hormonal and local factors converging onto a series of temporospatial dependent transcription regulators. Sox9, together with L-Sox5 and Sox6, of the Sox family is required for chondrogenic differentiation commitment, while Runx2/Cbfa 1, a member of runt family and Osterix/Osx, a novel zinc finger-containing transcription factor play a pivotal role in osteoblast differentiation decision and hypertrophic chondrocyte maturation. Recent in vitro and in vivo evidence suggests beta-catenin, a transcriptional activator in the canonical Wnt pathway, can act as a determinant factor for controlling chondrocyte and osteoblast differentiation. Here we focus on several intensively studied transcription factors and Wnt/beta-catenin signal molecules to illustrate the regulatory mechanism in directing commitment between osteoblast and chondrocyte, which will eventually allow us to properly manipulate the mesenchymal progenitor cell differentiation on bone and regeneration of cartilage tissue engineering.

Animals↗

Endothelin-1-induced femoral head epiphyseal artery constriction is enhanced by long-term corticosteroid treatment.

BACKGROUND: With regard to the pathogenesis of corticosteroid-associated femoral head osteonecrosis, only intravascular and extravascular factors have been discussed. Wall constriction of the lateral epiphyseal arteries, which are the main supplying arteries within the femoral head, has not previously been investigated. This study examined the effect of long-term corticosteroid treatment on vasoconstriction of the lateral epiphyseal arteries of the femoral head in a porcine model. METHODS: The immature female Danish Landrace pig was chosen as the model for our study because femoral head osteonecrosis can be induced in this animal and because the lateral epiphyseal arteries of the femoral heads are of the appropriate size for myographic investigation. Twenty-four female Danish Landrace pigs (two siblings from each of twelve litters for a total of twelve sibling pairs) were divided by randomly separating the sibling pairs into two groups, with a total of twelve pigs in each group. One group of twelve animals received a daily dose of 100 mg of methylprednisolone orally for three months. The other group of twelve pigs served as controls and received no corticosteroids. After the animals were killed with an intravenous injection of pentobarbital, the lateral epiphyseal arteries of the femoral head were isolated from the cancellous bone. These arteries were mounted as ring preparations on a small-vessel myograph for measurement of isometric force development. The effects on the resected vessels of the vasoactive agents endothelin-1, noradrenaline, bradykinin, substance P, and nitrous oxide were investigated. RESULTS: Vasoconstriction induced by increasing doses of endothelin-1 was increased after three months of methylprednisolone treatment compared with the vasoconstriction in vessels from control animals. Sensitivity to noradrenaline was not altered by this treatment. After submaximal precontraction by noradrenaline, vasorelaxation was elicited by substance P, nitrous oxide, and increasing doses of bradykinin without differences between the corticosteroid-treated and the control groups. CONCLUSIONS: Endothelin-1-induced vasoconstriction of the epiphyseal arteries of the femoral head was increased in this corticosteroid-treated pig model. Such vasoconstriction may lead to a reduction in femoral head blood flow and to local ischemia and thus may be a newly described factor in the multifactorial pathomechanism of osteonecrosis of the femoral head.

Animals↗

[Estimation of life expectancy for selecting surgical procedure and predicting prognosis of extradural spinal metastases].

BACKGROUND & OBJECTIVE: Clinically, whether and how to make a surgical interventional decision for the patients with spinal metastases is still controversial. Life expectancy is a significant determinant in the selection of surgical procedure for spinal metastases. This study was to evaluate Tomita and Tokuhashi scoring systems in selecting surgical procedure and predicting prognosis of extradural spinal metastases. METHODS: A total of 169 patients with spinal metastases, treated in the Spine Unit of Aarhus University Hospital, Denmark, from Jan. 2001 to Apr. 2004, were enrolled. The life expectancy was scored according to both Tomita system and Tokuhashi system before operation, the spinal metastases were classified according to Tomita system, and the patients underwent surgery accordingly. Follow-up was done 6, 12, and 24 months after operation. The precise of Tomita system and Tokuhashi system in estimating "death within 3 months", "death within 6 months", and "death within 12 months" was compared using Receiver Operating Characteristic curves (ROC curves). The mean survival time of the patients was calculated by Kaplan-Meier method. RESULTS: ROC curves of "death within 3 months", "death within 6 months", and "death within 12 months" showed no significant difference between Tomita score and Tokuhashi score in each group (P = 0.16, P = 0.47, and P = 0.38, respectively). Kaplan-Meier survival curves showed that Tomita system overestimated the prognosis in scores from 4 to 7, and Tokuhashi system underestimated the prognosis in scores from 0 to 8. CONCLUSIONS: Both Tomita and Tokuhashi scoring systems could be used to predict prognosis of spinal metastases after operation. Tokuhashi scoring system can predict early death more accurately, which can be used to avoid major operation for these patients.

Adult↗

Outcome in adolescent idiopathic scoliosis after brace treatment and surgery assessed by means of the Scoliosis Research Society Instrument 24.

A retrospectively designed long-term follow-up study of adolescent idiopathic scoliosis (AIS) patients who had completed treatment, of at least 2 years, by means of brace, surgery, or both brace and surgery. This study is to assess the outcome after treatment for AIS by means of the Scoliosis Research Society Outcome Instrument 24 (SRS 24). One hundred and eighteen AIS patients (99 females and 19 males), treated at the Aarhus University Hospital from January 1, 1987 to December 31, 1997, were investigated with at least 2 years follow-up at the time of receiving a posted self-administered questionnaire. Forty-four patients were treated with Boston brace (B) only, 41 patients had surgery (S), and 33 patients were treated both with brace and surgery (BS). The Cobb angles of the three treatment groups did not differ significantly after completed treatment. The outcome in terms of the total SRS 24 score was not significantly different among the three groups. B patients had a significantly better general (not treatment related) self-image and higher general activity level than the total group of surgically treated patients, while surgically treated patients scored significantly better in post-treatment self-image and satisfaction. Comparing B with BS we found a significantly higher general activity level in B patients, while the BS group had significantly higher satisfaction. There were no significant differences between BS and S patients in any of the domain scores. All treatment groups scored "fair or better" in all domain scores of the SRS 24 questionnaire, except in post-treatment function, where all groups scored worse than "fair". Improvement of appearance by means of surgical correction increases mean scores for post-treatment self-image and post-treatment satisfaction. Double-treatment by brace and surgery does not appear to jeopardize a good final outcome.

Adolescent↗

Pedicle screw fixation enhances anterior lumbar interbody fusion with porous tantalum cages: an experimental study in pigs.

STUDY DESIGN: A porous tantalum implant (Hedrocel, Implex Corp., Allendale, NJ), designed to assist interbody lumbar fusion, was tested biologically in an experimental model. A total of 11 female Danish landrace pigs received 3 levels of anterior lumbar interbody fusion at L2-L3, L4-L5, and L6-L7. Each level was randomly assigned one of the procedures: (1) implantation of PT-ring with pedicle screw fixation (PSF), (2) implantation of a porous tantalum ring (PT-ring) stabilized anteriorly with staples, or (3) implantation of carbon fiber cage (CF-cage) stabilized anteriorly with 2 staples. Each implant was filled with autogenous iliac crest bone graft. OBJECTIVES: To evaluate the effects of PSF on the incorporation of autologous bone in a porous tantalum interbody device and to compare healing in PT-rings to that in CF-cages of autologous bone. SUMMARY OF BACKGROUND DATA: Despite the promising results that early clinical trials have shown, interbody fusion cage technology is still under debate because of uncertainties that include indications for surgery, criteria for fusion, material, cage design, cage subsidence, and the effect of immediate stabilization. METHODS: Pigs were euthanized 6 months after surgery. Fusion segments were evaluated by plain radiography, conventional radiograph tomography, and histology. RESULTS: Fusion segments with PSF had significantly fewer radiolucencies than the other 2 levels (P = 0.002). Improved interface healing and fusion rate were observed in PT-rings when supplemented with PSF (P = 0.03). His tomorphometric results showed that the percentage of bone and bone marrow space in the center of a PT-ring was not significantly different from that of its adjacent vertebral body, but PSF increased bone marrow and decreased fibrous tissue formation in a tantalum cage. However, a CF-cage had higher bone volume and lower bone marrow space inside the cage compared with its adjacent vertebral body (P < 0.001). Fibrous tissue formation inside and around a CF-cage was more than that of a PT-ring (P < 0.05). CONCLUSION: Interbody fusion using a PT-ring cage packed with autologous bone achieved higher interface healing and more reliable fusion when fixated with supplementary pedicle screws than did fixated anteriorly with 2 staples. A lesser amount of bone graft was required, and bone remodeling was enhanced in the PT-ring when compared to the CF-cage.

Animals↗

Orthopaedic applications of gene therapy.

Gene therapy presents a novel approach to biological treatment. Several orthopaedic diseases can cause changes in biological signalling at the tissue level that potentially can be repaired or modified by inserting genes into the cells or tissues to modulate gene expression. Impaired bone healing, need for extensive bone formation, cartilage repair and metabolic bone diseases are all conditions where alterations of the signalling peptides involved may provide cure or improvement. In orthopaedic oncology, gene therapy may achieve induction of tumour necrosis and increased tumour sensitivity to chemotherapy. In the last decade, extensive improvements have been made to optimise gene therapy and have been tested on several orthopaedic conditions. How far this development has come in orthopaedics is highlighted in this paper.

Bone Diseases↗

The influence of alendronate treatment and bone graft volume on posterior lateral spine fusion in a porcine model.

STUDY DESIGN: An experimental animal study with randomized, paired control design was conducted using a porcine model. OBJECTIVES: The aim of this study was to evaluate the influence of alendronate treatment and the significance of different amounts of bone graft on posterior lateral spine fusion. SUMMARY OF BACKGROUND DATA: Treatment with bisphosphonates inhibits osteoclast-induced bone resorption and increases bone quality and density. It has been widely used clinically for treatment of osteoporosis. Bisphosphonates have been reported to elongate the callus remodeling process during fracture healing. Bisphosphonate treatment may modify bone graft healing and the remodeling process in spine fusion. The bone resorption phase exists during the healing process. Extensive bone graft resorption could reduce the basis for new bone formation, which could be an important factor for failure of spine fusion. Furthermore, different amounts of initially applied bone graft may influence spine fusion rate and bone graft incorporation process. METHODS: Twenty-two pigs were included in the study. Eleven pigs in the treatment group received alendronate 10 mg/day p.o. for 3 months after surgery. The other 11 pigs received no bisphosphonate and served as control group. Posterior lateral fusion with the CD Horizon system was performed on the lumbar spine using different amounts of autograft (4 g on one side and 8 g on the other side) in all animals. The fusion was evaluated using radiograph, CT scan, and histomorphometry at 3 months after operation. RESULTS: There was no statistical difference in either fusion rate or fusion mass volume between the two groups. The fusion rate based on radiograph was 75% on the 8-g autograft side and 45% on the 4-g side (P < 0.05). The mean volume of fusion mass was 2.36 cm3 on the 4-g side and 3.29 cm3 on the 8-g side (P < 0.01). No difference was found in either trabecular bone volume or fusion rate between treatment and control groups using histologic evaluation.The treatment group showed a higher fibrous tissue volume(P < 0.05), higher proportion of woven bone structure(P < 0.001), and lower bone marrow volume (P = 0.088) in the fusion mass. Different amounts of bone graft did not change the tissue composition of the fusion mass. CONCLUSIONS: Alendronate treatment in this study decreased fusion mass remodeling without inhibiting fusion rate. Increased amounts of autologous bone graft could improve the fusion rate in this experimental spine fusion study.

Administration, Oral↗

Experimental anterior lumbar interbody fusion with an osteoinductive bovine bone collagen extract.

STUDY DESIGN: A randomized experimental porcine anterior lumbar interbody fusion. OBJECTIVE: To determine the osteoinductive potential of a bovine bone derived collagen lyophilisate for anterior interbody spinal fusion in an animal model. SUMMARY OF BACKGROUND DATA: Complications associated with autologous bone graft harvesting are still major concerns when performing spinal fusion surgery. A new formulation of bovine bone collagen-protein extracts (Colloss) has been shown to be effective in animal studies as a bone graft enhancer. The present study further tested its osteogenic potential in the anterior spinal fusion cage in a controlled animal study. METHODS: Twelve normal Danish landrace pigs of 50 kg each were chosen as experimental animals. Lumbar spine interbody fusion of L3-L4, L4-L5 using titanium alloy cages was performed on each pig with pedicle screws instrumentation. Cages packed with either autograft or Colloss were randomly assigned to the two levels. Pigs were followed up to 3 months. After termination, the spine segments were evaluated by radiograph, micro-CT, and histomorphometry RESULTS: Ten pigs completed the study. Implant breakage, loosening, or spinal deformity was not observed after 12 weeks on radiograph examination. Micro-CT evaluations demonstrated that cages with Colloss had the same fusion rate (9 of 10) as those with autograft, further evaluation of bone volume (BV/TV), and trabecular thickness (Tb Th) also showed no different between them. Histologically, both autograft and Colloss levels had 80% (8 of 10) fusion rate. Histomorphometric results revealed that the only difference was the Colloss-filled cages had a higher cartilage tissue volume (P < 0.04). CONCLUSION: Colloss was effective as a bone graft substitute. It achieved the same fusion rate and the samepercentage of new bone formation as that of autologous iliac bone graft in this demanding porcine anterior spinal fusion model after 12 weeks.

Animals↗

Cytokine profiles in conditioned media from cultured human intervertebral disc tissue. Implications of their effect on bone marrow stem cell metabolism.

BACKGROUND: Cytokines released from intervertebral discs cultured in vitro have not been profiled, and the effect of these cytokines on human bone marrow stem cells is yet to be studied. MATERIALS AND METHODS: Intervertebral discs from 14 patients who had undergone spinal fusion surgery were cultured separately in vitro. Conditioned media were collected after 48 and 96 h of culture in serum-free Minimum Essential Medium (MEM). Profiling of the cytokines was conducted using pooled media. Conditioned medium from each patient was also tested in human bone marrow stem cell culture, and incorporation of alkaline phosphatase and 3H-thymidine incorporation was evaluated. RESULTS: Of the 18 cytokines screened, 12 were found to be positive, but only eotaxin, IP-10, Rantes IL-6 and IL-8 seemed to be present at high levels. There was a close correlation between IL-6 and IL-8 levels in the medium (R = 0.90, p < 0.001). When the conditioned media were added to human bone marrow stem cell cultures, cellular proliferation was stimulated (p = 0.02), but alkaline phosphatase activity remained unchanged. Cellular proliferation correlated negatively with IL-6 levels (R = -0.44, p = 0.04). INTERPRETATION: Intervertebral discs secrete certain cytokines into the medium when cultured in vitro, and conditioned media from cultured intervertebral discs stimulate proliferation of bone marrow stem cells.

Adolescent↗

Healing properties of allograft from alendronate-treated animal in lumbar spine interbody cage fusion.

This study investigated the healing potential of allograft from bisphosphonate-treated animals in anterior lumbar spine interbody fusion. Three levels of anterior lumbar interbody fusion with Brantigan cages were performed in two groups of five landrace pigs. Empty Brantigan cages or cages filled with either autograft or allograft were located randomly at different levels. The allograft materials for the treatment group were taken from the pigs that had been fed with alendronate, 10 mg daily for 3 months. The histological fusion rate was 2/5 in alendronate-treated allograft and 3/5 in non-treated allograft. The mean bone volume was 39% and 37.2% in alendronate-treated or non-treated allograft (NS), respectively. No statistical difference was found between the same grafted cage comparing two groups. The histological fusion rate was 7/10 in all autograft cage levels and 5/10 in combined allograft cage levels. No fusion was found at all in empty cage levels. With the numbers available, no statistically significant difference was found in histological fusion between autograft and allograft applications. There was a significant difference of mean bone volume between autograft (49.2%) and empty cage (27.5%) (P<0.01). In conclusion, this study did not demonstrate different healing properties of alendronate-treated and non-treated allograft for anterior lumbar interbody fusion in pigs.

Alendronate↗

Anterior lumbar interbody fusion with carbon fiber cage loaded with bioceramics and platelet-rich plasma. An experimental study on pigs.

Platelet-rich plasma (PRP) is an autogenous source of growth factor and has been shown to enhance bone healing both in clinical and experimental studies. PRP in combination with porous hydroxyapatite has been shown to increase the bone ingrowth in a bone chamber rat model. The present study investigated whether the combination of beta tricalcium phosphate (beta-TCP) and PRP may enhance spinal fusion in a controlled animal study. Ten Danish Landrace pigs were used as a spinal fusion model. Immediately prior to the surgery, 55 ml blood was collected from each pig for processing PRP. Three-level anterior lumbar interbody fusion was performed with carbon fiber cages and staples on each pig. Autogenous bone graft, beta-TCP, and beta-TCP loaded with PRP were randomly assigned to each level. Pigs were killed at the end of the third month. Fusion was evaluated by radiographs, CT scanning, and histomorphometric analysis. All ten pigs survived the surgery. Platelet concentration increased 4.4-fold after processing. Radiograph examination showed 70% (7/10) fusion rate in the autograft level. All the levels with beta-TCP+PRP showed partial fusion, while beta-TCP alone levels had six partial fusions and four non-fusions ( P=0.08). CT evaluation of fusion rate demonstrated fusion in 50% (5/10) of the autograft levels. Only partial fusion was seen at beta-TCP levels and beta-TCP+PRP levels. Histomorphometric evaluation found no difference between beta-TCP and beta-TCP+PRP levels on new bone volume, remaining beta-TCP particles, and bone marrow and fibrous tissue volume, while the same parameters differ significantly when compared with autogenous bone graft levels. We concluded from our results in pigs that the PRP of the concentration we used did not improve the bone-forming capacity of beta-TCP biomaterial in anterior spine fusion. Both beta-TCP and beta-TCP+PRP had poorer radiological and histological outcomes than that of autograft after 3 months.

Animals↗