PubMed Health⌕ Search

Biomedical subjects

Scott D Boden

Publications and source records attributed to Scott D Boden.

At least 37 records · Page 2Linked to original sources

Gene therapy applications for spine fusion.

OBJECTIVE: This article reviews the potential utilization of various growth factors to enhance spinal fusion and outlines the principles of gene therapy and its application to spinal fusion surgery. SUMMARY OF BACKGROUND DATA: Gene therapy offers an exciting new way to potentially deliver growth factors locally in a targeted fashion with physiologic doses. In its current definition, gene therapy is defined as the use of nucleic acid transfer, either RNA or DNA, to treat or prevent a disease. The scope of gene therapy has expanded beyond its initial application as a method of replacing genetic defects, and its potential to facilitate spinal fusions is currently being evaluated. CONCLUSIONS: Gene therapy strategies for spine fusion are appealing because the setting is uniquely suited for genetic manipulation. The intervention is locally applied. Only a short duration of transgene response by the cells is necessary to establish a spine fusion, and a variety of osteoinductive growth factors have been identified and are available for use. Attempts at spine fusion using gene therapy in the lower animals have been successful using both in vivo and ex vivo approaches. Before human clinical trials can be established, further testing is required in more challenging animal models of bone induction such as nonhuman primates. Should a successful clinical program of gene therapy for spine fusion be established, the use of autograft and its associated morbidities could be eliminated. In fact, gene therapy offers the potential for minimally invasive applications that could bypass the need for an open procedure altogether. It is likely that gene therapy will be a powerful therapeutic tool for the spine surgeon in the new millennium.

Animals↗

BMPs and gene therapy for spinal fusion: summary statement.

The use of biologic technologies to engender spinal fusion is at various stages of scientific and clinical development. Recombinant human bone morphogenetic protein 2 is now available for clinical use in anterior lumbar intervertebral fusion and has been extensively studied in other spinal fusion applications. Recombinant bone morphogenetic protein 7 is under examination in regulated clinical trials. Gene therapy technologies are in the preclinical stage of development. In time, biologic interventions will continue to capture greater roles in the treatment of spinal disease.

Animals↗

Biologic treatment for intervertebral disc degeneration: summary statement.

In past decades, the biomechanics of intervertebral disc degeneration have received much attention. More recent research efforts have focused on understanding the biology of the disc degenerative process. The ability to manipulate disc architecture and biology by direct application of growth factors or by gene therapy techniques may present an opportunity to halt or slow disc degeneration. Preliminary studies using these strategies have confirmed their ability to replenish essential disc matrix components that are known to decrease with disc degeneration.

Aging↗

A critical guide to case series reports.

OBJECTIVE: Provide guidance to investigators and authors regarding appropriate conduct and reporting of case-series studies. SUMMARY OF BACKGROUND DATA: Evidence-based practice has provided a substantial contribution to advancing clinical science. Many study designs have been critically examined, and the quality of the research literature has improved. A common study design in musculoskeletal medicine is the case series: a description of the course of patients over time. Case series can provide valuable information as to: case definition, trend analyses regarding outcomes, and clues as to causation. Case series cannot be used to draw inferences regarding treatment effect. METHODS: Examination of previous work on identification of characteristics of high quality study designs such as cohort studies; extending this work to case series. RESULTS: We identified draft characteristics that good case series studies should address: clearly defined study question; well- described study population; well-described intervention; use of validated outcome measures; appropriate statistical analyses; well-described results; discussion/conclusions supported by the data presented; funding sources acknowledged. CONCLUSIONS: We propose these measures to authors and journal editors as one mechanism to improve the quality of the case series study.

Case-Control Studies↗

Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion.

STUDY DESIGN: A nonhuman primate lumbar intertransverse process arthrodesis model was used to evaluate modifications to a plain collagen sponge to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2). OBJECTIVES: To evaluate the feasibility of enhancing the delivery of rhBMP-2 with the established collagen sponge carrier by adding biphasic ceramic phosphate (BCP) granules (15% hydroxyapatite, 85% tricalcium phosphate) or allograft chips to provide compression resistance for posterolateral spine arthrodesis. SUMMARY OF BACKGROUND DATA: Recombinant human bone morphogenetic protein-2 was successfully delivered with a resorbable collagen sponge in a rabbit intertransverse process fusion model. Success in nonhuman primates required a higher dose (6-9 mg) of rhBMP-2 and a more compression-resistant matrix (ceramic) than plain collagen. The limitation of the ceramic carrier was its radiopacity, which made radiographic detection of new bone formation difficult. METHODS: Nine adult rhesus monkeys underwent bilateral posterolateral intertransverse process arthrodesis at L4-L5. The animals were divided into three groups (n = 3 each) based on the graft material implanted: 1) autogenous iliac crest bone (5 cm3/side); 2) collagen sponge and 15:85 BCP granules loaded with rhBMP-2 (3 mg/side); and, 3) collagen sponge and allograft chips loaded with rhBMP-2 (3 mg/side). The monkeys were killed 24 weeks after surgery. Inspection, manual palpation, radiography, computed tomographic scans, and histology were used to assess fusion. RESULTS: All six monkeys with rhBMP-2 delivered in the collagen/15:85 BCP carrier and the collagen/allograft chips carrier achieved solid spine fusions, whereas only one of three animals fused with autogenous bone graft. Histologic analysis of the bone induced by rhBMP-2 showed normal trabecular bone and bone marrow elements. CONCLUSIONS: The addition of either 15:85 BCP granules or allograft bone chips to the existing resorbable collagen sponge matrix enhanced delivery of rhBMP-2 in the posterolateral spine. The combination matrices were more compression resistant and had improved radiographic resorption properties that permitted easy radiographic visualization of new bone. In addition, a lower dose of rhBMP-2 (3 mg/side) was successful compared with the dose previously used with the plain collagen sponge (6 mg/side).

Animals↗

Overcoming the immune response to permit ex vivo gene therapy for spine fusion with human type 5 adenoviral delivery of the LIM mineralization protein-1 cDNA.

STUDY DESIGN: An animal study in immune competent rabbits and athymic rats was conducted. OBJECTIVES: To develop an animal model for simulation of previous human Type 5 adenovirus (Ad5) exposure, to determine the impact of adenoviral pre-exposure on spine fusion induced with ex vivo Ad5-LMP-1, and to test strategies for overcoming any potential immune response. SUMMARY OF BACKGROUND DATA: Cells transduced with adenovirus containing the osteoinductive LMP-1 cDNA (Ad5-LMP-1) can induce spine fusion in rabbits. Because up to 80% of the human population has been exposed to adenovirus, immune responses to the vector may limit this strategy in humans. Few studies have modeled previous adenoviral exposure and tested strategies to circumvent it. METHODS: Adult New Zealand white rabbits were injected with 10 or 10 viral particles of Ad5-LacZ. At 4 or 16 weeks after Ad5 injection, autologous buffy coats were prepared from peripheral blood, and 4 million cells per side were infected ex vivo for 10 minutes with Ad5-LMP-1 (multiplicity of infection = 4). Cells were implanted on a collagen matrix instead of an autograft for posterolateral lumbar arthrodesis. Unimmunized rabbits served as control subjects. Additional immunized rabbits underwent arthrodesis at 4 weeks with increased cell number (10 million) and viral dose (multiplicity of infection = 10), or with both parameters increased. The rabbits were killed at 4 weeks, and the spines were assessed by palpation and radiograph. A parallel study was performed in athymic rats using immunized rabbits for the donor cells. RESULTS: All the unimmunized rabbits had solid spine fusions. None of the rabbits arthrodesed 4 weeks after Ad5 pre-exposure achieved fusion. At 4 weeks after Ad5 exposure, increasing the multiplicity of infection to 10 did not overcome the immune response (0/3 fused), but increasing the cell number to 10 million (2/3 fused) or increasing both cell number and multiplicity of infection (3/3 fused) did overcome the immune effects. Delaying arthrodesis until 16 weeks after Ad5 pre-exposure also overcame the immune response (3/3 fused). Similar results were seen in the athymic rat ectopic implant model, suggesting that the immune effect was mediated by humoral antibodies rather than a T-cell response. CONCLUSIONS: Two model systems were developed that simulate previous exposure to human Ad5 and could separate the cellular and humoral components of the response. There was a dose-dependent inhibition of ex vivo Ad5-LMP-1 gene transfer to cells from animals previously exposed to human Ad5. Data suggested that the inhibition of Ad5 infection was caused by humoral antibodies rather than a T-cell-based response. Minor modifications in the gene transfer protocol, such as doubling the viral dose or number of cells infected, or increasing the infection time, could overcome the immune response for an ex vivo approach.

Adaptor Proteins, Signal Transducing↗

Outcome research in patients with chronic low back pain.

Outcome research in chronic low-back pain is entering a new phase. In the past several years, several outcome measures have been evaluated for their psychometric properties, and databases for patients with low-back pain exist for some of them. A set of recommended and standardized outcome measures and questionnaires is now available for the different outcome domains. The use of computerized versions of these questionnaires will allow simplified data collection and analyses, which will not only help to formulate a more uniform design of research trials, but can be useful for clinicians interested in documenting multi-dimensional outcomes in their patient population.

Chronic Disease↗

Physical function measurements in neck pain.

The literature on physical and functional measurements for the cervical spine is more limited than for the lumbar spine. Most of the studies so far have dealt with the methods for range-of-motion measurements in the cervical spine. These studies indicate that newer computer-guided, three-dimensional measurements systems may provide more precise and reliable data than inclinometer-based techniques and visual estimation methods. The research available also shows a correlation between training and strength improvement in the cervical spine. In addition to physical measurements, several tests have been developed to measure pain level, psychologic factors, disability from neck pain, and generic health, which can assist the clinician in choosing the most appropriate treatment for patients with neck pain. Furthermore, functional measurement systems, such as FCEs, have been developed to describe the functional limitations that a patient may have as a result of a spinal injury. Except for the range-of-motion measurement methods, much more research is required to determine which measurement systems provide the optimal balance between reliability and validity and pragmatic considerations such as time and expense.

Cervical Vertebrae↗

Laboratory evaluation in neck pain.

Laboratory investigations for neck pain play a minor role in most cases. When clinical suspicion of infection or tumor arises, however, laboratory testing can provide definitive information to direct the patient's care. Specialized laboratory testing including autoantibody titers can be useful in confirming and categorizing inflammatory arthritides. Judicious use of laboratory tests greatly enhances the physician's ability to provide appropriate care.

Cervical Vertebrae↗

Mechanism of bone formation with gene transfer of the cDNA encoding for the intracellular protein LMP-1.

BACKGROUND: LIM mineralization protein-1 (LMP-1), an intracellular protein, is thought to induce secretion of soluble factors that convey its osteoinductive activity. Although evidence suggests that LMP-1 may be a critical regulator of osteoblast differentiation in vitro and in vivo, little is known about its mechanism of action. The purpose of the present study was to identify candidates for the induced secreted factors and to describe the time sequence of histological changes during bone formation induced by LMP-1. METHODS: Human lung carcinoma (A549) cells were used to determine if LMP-1 overexpression would induce expression of bone morphogenetic proteins (BMPs) in vitro. Cultured A549 cells were infected with recombinant replication-deficient human type-5 adenovirus containing the LMP-1 or LacZ cDNA. Cells were subjected to immunohistochemical analysis after forty-eight hours. Finally, sixteen athymic rats received subcutaneous implants consisting of collagen disks loaded with human buffy-coat cells that were infected with one of the above two viruses. Rats were killed at intervals, and explants were studied with histological and immunohistochemical analyses. RESULTS: In vitro experiments with A549 cells showed that AdLMP-1-infected cells express elevated levels of BMP-2, BMP-4, BMP-6, BMP-7, and TGF-beta1 (transforming growth factor-beta 1) protein. Human buffy-coat cells infected with AdLMP-1 also demonstrated increased levels of BMP-4 and BMP-7 protein seventy-two hours after ectopic implantation in athymic rats, confirming the in vitro hypothesis. CONCLUSIONS: The osteoinductive properties of LMP-1 involve synthesis of several BMPs and the recruitment of host cells that differentiate and participate in direct membranous bone formation.

Adaptor Proteins, Signal Transducing↗

Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies.

STUDY DESIGN: A prospective randomized clinical study was conducted. OBJECTIVE: To determine whether the dose and carrier that were successful in rhesus monkeys could induce consistent radiographic spine fusion in humans. SUMMARY OF BACKGROUND DATA: Preclinical studies have demonstrated that recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive bone morphogenetic protein, is successful at generating spine fusion in rabbits and rhesus monkeys. METHODS: For this study, 25 patients undergoing lumbar arthrodesis were randomized (1:2:2 ratio) based on the arthrodesis technique: autograft/Texas Scottish Rite Hospital (TSRH) pedicle screw instrumentation (n = 5), rhBMP-2/TSRH (n = 11), and rhBMP-2 only without internal fixation (n = 9). On each side, 20 mg of rhBMP-2 were delivered on a carrier consisting of 60% hydroxyapatite and 40% tricalcium phosphate granules (10 cm /side). The patients had single-level disc degeneration, Grade 1 or less spondylolisthesis, mechanical low back pain with or without leg pain, and at least 6 months failure of nonoperative treatment. RESULTS: All 25 patients were available for follow-up evaluation (mean, 17 months; range 12-27 months). The radiographic fusion rate was 40% (2/5) in the autograft/TSRH group and 100% (20/20) with rhBMP-2 group with or without TSRH internal fixation ( = 0.004). A statistically significant improvement in Oswestry score was seen at 6 weeks in the rhBMP-2 only group (-17.6; = 0.009), and at 3 months in the rhBMP-2/TSRH group (-17.0; = 0.003), but not until 6 months in the autograft/TSRH group (-17.3; = 0.041). At the final follow-up assessment, Oswestry improvement was greatest in the rhBMP-2 only group (-28.7, < 0.001). The SF-36 Pain Index and PCS subscales showed similar changes. DISCUSSION: This pilot study is the first with at least 1 year of follow-up evaluation to demonstrate successful posterolateral spine fusion using a BMP-based bone graft substitute, with radiographs and CT scans as the determinant. Consistently, rhBMP-2 was able to induce bone in the posterolateral lumbar spine when delivered at a dose of 20 mg per side with or without the use of internal fixation. Patients with spondylolisthesis classified higher than Meyerding Grade 1 or with more than 5 mm of translational motion may still require internal fixation. Some patients did smoke during the postoperative period, and all in the rhBMP-2 groups still obtained solid fusions. CONCLUSIONS: Consistently, rhBMP-2 with the biphasic calcium phosphate granules induced radiographic posterolateral lumbar spine fusion with or without internal fixation in patients whose spondylolisthesis did not exceed Grade 1. Statistically greater and quicker improvement in patient-derived clinical outcome was measured in the rhBMP-2 groups.

Awards and Prizes↗

Overview of the biology of lumbar spine fusion and principles for selecting a bone graft substitute.

STUDY DESIGN: Reviews were conducted. OBJECTIVES: To review the biology of spine fusion healing, and to outline several fundamental principles required for the selection of a bone graft substitute. SUMMARY OF BACKGROUND DATA: More than 200,000 spine fusions are performed each year in the United States. The success of this procedure is limited by morbidity from iliac crest bone graft harvest and a nonunion rate that ranges from 10% to 40%. In recent years, there has been an increased understanding of the biology of spine fusion healing. In addition, there has been a focus on finding suitable substitutes for autogenous iliac crest bone graft to promote spine fusion. The selection of a specific bone graft substitute can be a daunting task for the surgeon. METHODS: The available literature was reviewed and combined with the author's personal experience. RESULTS: A basic understanding of the biology of healing in different types of spine fusions and the differences between different categories of bone graft substitutes can help surgeons organize the graft selection process. CONCLUSIONS: In general, purely osteoconductive substitutes are less effective in adult posterolateral spine fusions, but may be suitable in the anterior spine when it is rigidly immobilized. Osteoinductive substitutes are more likely to be successful as extenders, enhancers, or substitutes for posterolateral spine fusion.

Animals↗

Purified bovine BMP extract and collagen for spine arthrodesis: preclinical safety and efficacy.

STUDY DESIGN: Rabbit and nonhuman primate posterolateral intertransverse process spinal fusions were performed. OBJECTIVES: To determine the preclinical safety and efficacy of bBMPx product (a composite of collagen and bovine bone morphogenetic protein extract) mixed with demineralized bone matrix for posterolateral intertransverse process spinal fusions. SUMMARY OF BACKGROUND DATA: A dose response of bovine BMP extract with collagen in demineralized bone matrix has demonstrated spinal fusion to a rate of 100% in a rabbit spinal fusion model. This study furthers the research to demonstrate safety in the rabbit and efficacy of bovine BMP extract for spinal fusion applications in nonhuman primates. Additionally, preliminary human clinical data are presented. METHODS: For the safety portion of the study, 45 New Zealand white rabbits underwent posterolateral intertransverse process spinal fusion after laminectomy. Nine additional rabbits served as nontreated control subjects. Graft material (autograft or bBMPx product) was placed in the gutters in 30 animals, and no material was used in 15 animals. The animals were observed for abnormal physical activity, then killed at 8, 29, or 57 days. Histologic evaluation was performed on explanted spines. In the nonhuman primate efficacy studies, 54 rhesus macaques also underwent bilateral posterolateral intertransverse process fusion. bBMPx product with varying bovine BMP extract doses was implanted bilaterally. The animals were killed at 4, 8, 12, 18, or 24 weeks. Plain radiograph, computed tomography scanning, and histology were performed. RESULTS: The rabbit safety study demonstrated that any spinal cord compression or degeneration was caused by the inflammatory response after surgery and was equivalent in all groups. These issues resolved over time. Efficacy data demonstrated an autograft fusion rate of only 21% in the rhesus macaques. The bovine BMP extract demonstrated a dose response in which 3 mg per side gave twice the fusion rate as autograft. CONCLUSIONS: bBMPx product is safe and effective as an autograft substitute for posterolateral intertransverse process spinal fusion. Clinical studies are underway.

Animals↗

Three-question depression screener used for lumbar disc herniations and spinal stenosis.

STUDY DESIGN: A depression screener was used to determine positive responses amongst patients with two disorders commonly treated with surgery. OBJECTIVE: To examine the relation between positive responses to the depression screener and pain characteristics, sociodemographic responses, and Short-Form 36-Item Health Survey subscale scores among patients with lumbar disc herniation or spinal stenosis. SUMMARY OF BACKGROUND DATA: Numerous studies have reported a correlation between depression and low back pain, but few have examined this relation among patients with a diagnosis of sciatica from lumbar disc herniation or spinal stenosis. The Health Status Questionnaire 2.0 includes both the Short-Form 36-Item Health Survey (a validated, multidimensional, generic instrument measuring health-related quality of life and functional status) and the three-question depression screener. METHODS: The database of the National Spine Network (a nonprofit collaboration of physicians caring for patients with back and neck problems that pools patient data) was queried for patients 18 to 65 years of age with a diagnosis of lumbar disc herniation (n = 2878) and patients 30 to 80 years of age with a diagnosis of spinal stenosis (n = 3801). Depression screeners scored positive when patients reported depressive symptoms within the year to any question about symptoms. RESULTS: The screener elicited positive responses from 36.4% of the patients with spinal stenosis and 38.4% of the patients with lumbar disc herniation. Among the patients with spinal stenosis or lumbar disc herniation, those with positive depression screener responses reported longer duration of symptoms (>7 weeks) and failure to improve. They were more likely to be obese, recipients of workers' compensation, unmarried, and less educated (below Grade 12). In multivariate analyses, positive depression screener responses were significantly associated with an attorney's services and a longer duration of symptoms. CONCLUSIONS: A positive depression screener response is strongly associated with poorer functional status and health-related quality of life, as measured by the Short-Form 36-Item Health Survey, among patients with lumbar disc herniation or spinal stenosis, and higher symptom intensity.

Adolescent↗

Delivery of recombinant human bone morphogenetic protein-2 using a compression-resistant matrix in posterolateral spine fusion in the rabbit and in the non-human primate.

STUDY DESIGN: A rabbit and rhesus monkey model of posterolateral intertransverse process spine arthrodesis was used. OBJECTIVE: To test two new soft tissue compression resistant ceramic/collagen sponge carriers for recombinant human bone morphogenetic protein-2. SUMMARY OF BACKGROUND DATA: After determining that a plain collagen sponge was too compressible for large animals in a posterolateral fusion application, the authors demonstrated good bone induction using biphasic ceramic phosphate granules (60% hydroxyapatite/40% tricalcium phosphate) as the carrier matrix for recombinant human bone morphogenetic protein 2 in rhesus monkeys. A limitation of 60:40 biphasic ceramic phosphate was its slow resorption time caused by the high hydroxyapatite content, making radiographic detection of new bone formation very difficult. METHODS: Adult New Zealand white rabbits (n = 14) underwent posterolateral spine arthrodesis at L5-L6 using 5:95 biphasic ceramic phosphate (5% hydroxyapatite/95% tricalcium phosphate) impregnated Type I collagen sponges (17 x 35 x 2.5 mm, two per side) loaded with 0.86 mg recombinant human bone morphogenetic protein 2. Additional rabbits (n = 14) received 60:40 hydroxyapatite-tricalcium phosphate granules as the carrier for bone morphogenetic protein 2. Adult rhesus monkeys (n = 6) underwent posterolateral arthrodesis at L4-L5 with ceramic/collagen sponge carrier loaded with 9 mg recombinant human bone morphogenetic protein 2 per side. Two monkeys received ceramic/collagen sponges containing 15:85 biphasic ceramic phosphate (15% hydroxyapatite/85% tricalcium phosphate) with two pieces per side; two received sponges containing 5:95 biphasic ceramic phosphate with two pieces per side, and two received sponges containing 5:95 biphasic ceramic phosphate with four pieces per side. The rabbits were killed after 5 weeks and the monkeys after 24 weeks; the spines were evaluated by manual palpation, radiographs, tensile mechanical testing (rabbits only), and histology. RESULTS: The recombinant human bone morphogenetic protein 2 delivered in the 5:95 biphasic ceramic phosphate/collagen sponge achieved fusion in 100% of rabbits and had improved handling properties compared with the biphasic ceramic phosphate granules. Biomechanical results with 5:95 biphasic ceramic phosphate/collagen carrier were comparable to those obtained with the 60:40 biphasic ceramic phosphate granules and superior to those of autogenous bone graft (P < 0.05). The recombinant human bone morphogenetic protein 2 delivered in the 15:85 or the 5:95 biphasic ceramic phosphate/collagen sponge carrier (two pieces per side) induced fusion in nonhuman primates with normal bone histology, less residual ceramic, and more bone in the center of the carrier matrix in comparison with BCO granules alone. The 15:85 biphasic ceramic phosphate/collagen sponge resulted in fusion mass sizes closer to the original size of the matrix implanted than did the 5:95 biphasic ceramic phosphate/collagen sponge, which was considered a desirable feature. The monkeys with 9 mg recombinant human bone morphogenetic protein 2 spread over four sponges per side instead of two had half the effective recombinant human bone morphogenetic protein 2 concentration per sponge and inferior results. CONCLUSIONS: The new compression-resistant biphasic ceramic phosphate/collagen sponge matrices were biologically compatible with recombinant human bone morphogenetic protein 2 bone formation, resulted in biomechanically stiffer fusion masses than autograft, better space maintenance than plain collagen sponges, and improved handling and radiographic resorption properties over the ceramic carriers previously tested.

Animals↗

Retention of 125I-labeled recombinant human bone morphogenetic protein-2 by biphasic calcium phosphate or a composite sponge in a rabbit posterolateral spine arthrodesis model.

The purpose of this study was to characterize the retention kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) applied to two calcium-based delivery matrices. Biphasic calcium phosphate (BCP) and a composite containing BCP in an absorbable collagen sponge (BCP/ACS) were evaluated using a spinal fusion model in rabbits. rhBMP-2 labeled with radioactive iodine (125I) was used as a tracer to assess in vivo retention of rhBMP-2 in the presence of these materials (nine animals per material studied). Over a 36 day study period, animals were assessed for the following: percent administered dose retained at the implant site as measured by scintigraphic imaging (counting) with a gamma camera (all animals), radiography of the implant site (all animals), radioactivity in blood and plasma (all animals), and radioactivity in the urine and feces (three animals for each material). Radioactivity data were corrected for the decay of 125I and the attenuation between the implant in vivo and the gamma camera. Differences observed between the two materials for the area under the retention vs. time profile (AUC; 988%*day for BCP vs. 1070%*day for BCP/ACS, p = 0.57) and the mean residence time (MRT; 10.2 days for BCP vs. 7.6 days for BCP/ACS, p = 0.06) were not statistically significant. Initial retention/incorporation of rhBMP-2 was slightly higher for rhBMP-2/BCP/ACS than for rhBMP-2/BCP (96.8% vs. 86.0%, p < 0.05). Animals receiving rhBMP-2/BCP showed a longer terminal retention half-life (t1/2) than did those receiving rhBMP-2/BCP/ACS (7.5 vs. 4.5 days, p < 0.05). The urinary radioactivity recovery data supported the data obtained by scintigraphy. Over the 36 day collection period, essentially complete recovery of radioactivity (dose) in urine was observed for rhBMP-2/BCP and rhBMP-2/BCP/ACS and the majority of the radioactivity (approximately 95%) was soluble in trichloroacetic acid, suggesting extensive catabolism of rhBMP-2 before renal excretion. Fecal recovery of radioactivity was low, approximately 2-3%. In conclusion, rhBMP-2 was retained at the implant site when delivered with either BCP or BCP/ACS based on mean residence time and area under the retention curve vs. time profile. Use of these matrices resulted in detectable rhBMP-2 levels at the surgical site for over a week in contrast to data reported with several other matrices that lasted less time. Systemic catabolism and elimination of the rhBMP-2 was extensive and systemic presence of the protein was negligible.

Animals↗