transforming-growth-factor-beta and Seroma

Case presentation and literature review.. To review the safety of using INFUSE bone graft (recombinant human bone morphogenetic protein-2 applied to an absorbable collagen sponge) in occipitocervical (OC) fusion.. Although INFUSE bone graft is currently approved for use in certain tibial fractures, oral maxillary procedures, and anterior lumbar interbody fusion, it has been extensively used "off-label" in posterolateral lumbar and anterior cervical fusions. INFUSE is highly effective in promoting cervical spine fusion via an anterior approach, but its potential role in promoting bony fusion in posterior cervical or OC fixation has not been studied.. A 53-year-old woman with basilar invagination underwent OC fixation using INFUSE bone graft. Three days after surgery she experienced neurologic decline associated with significant tissue swelling and a large postoperative seroma under significant pressure. She made excellent recovery after reoperation and drainage. An extensive review of the literature was performed to propose a modified approach to the use of INFUSE in OC fixation.. Proper dosing and delivery of INFUSE for posterior cervical/OC fixation is not currently known. Previously published experience with anterior cervical fusion suggests that INFUSE can have potent inflammatory effects on paraspinal soft tissue.. INFUSE should only be used for OC fixation in patients at elevated risk of nonunion. To prevent complications due to soft tissue swelling, consideration should be given to preventing direct exposure of INFUSE to paraspinal musculature, prolonged soft tissue drainage, and prophylactic treatment with perioperative steroid therapy.

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cervical Vertebrae; Female; Humans; Middle Aged; Occipital Bone; Postoperative Complications; Radiography; Recombinant Proteins; Seroma; Spinal Fusion; Transforming Growth Factor beta

This is a basic science, animal research study.. This study aims to explore, in rodent models, the effectiveness of systemic nonsteroidal anti-inflammatory drugs in reducing recombinant human bone morphogenetic protein-2 (rhBMP-2) induced neuroinflammation.. rhBMP-2 is increasingly used to augment fusion in lumbar interbody fusion surgeries, although it can cause complications including postoperative radiculitis.. Eighteen 8-week-old Sprague-Dawley rats underwent Hargreaves testing to measure the baseline thermal withdrawal threshold before undergoing surgical intervention. The L5 nerve root was exposed and wrapped with an Absorbable Collagen Sponge containing rhBMP-2. Rats were randomized into 3 groups: (1) Low dose (LD), (2) high dose (HD) diclofenac sodium, and (3) saline, receiving daily injection treatment. Hargreaves testing was performed postoperatively on days 5 and 7. Seroma volumes were measured by aspiration and the nerve root was then harvested for hematoxylin and eosin, immunohistochemistry, Luxol Fast Blue staining, and real-time quantitative polymerase chain reaction. The Student t test was used to evaluate the statistical significance among groups.. The intervention groups showed reduced seroma volume, and a general reduction of inflammatory markers (MMP12, MAPK6, GFAP, CD68, and IL18) compared with controls, with the reduction in MMP12 being statistically significant ( P = 0.02). Hematoxylin and eosin and immunohistochemistry of the nerve roots showed the highest macrophage density in the saline controls and the lowest in the HD group. Luxol Fast Blue staining showed the greatest extent of demyelination in the LD and saline groups. Lastly, Hargreaves testing, a functional measure of neuroinflammation, of the HD group demonstrated a minimal change in thermal withdrawal latency. In contrast, the thermal withdrawal latency of the LD and saline groups showed a statistically significant decrease of 35.2% and 28.0%, respectively ( P < 0.05).. This is the first proof-of-concept study indicating that diclofenac sodium is effective in alleviating rhBMP-2-induced neuroinflammation. This can potentially impact the clinical management of rhBMP-2-induced radiculitis. It also presents a viable rodent model for evaluating the effectiveness of analgesics in reducing rhBMP-2-induced inflammation.

Topics: Animals; Bone Morphogenetic Protein 2; Diclofenac; Eosine Yellowish-(YS); Hematoxylin; Humans; Lumbar Vertebrae; Matrix Metalloproteinase 12; Neuroinflammatory Diseases; Radiculopathy; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Rodentia; Seroma; Spinal Fusion; Transforming Growth Factor beta

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used in spine fusion surgery. However, high doses of rhBMP-2 delivered with absorbable collagen sponge (ACS) have led to inflammation-related adverse conditions. Polyelectrolyte complex (PEC) control release carrier can substantially reduce the rhBMP-2 dose and complication without compromising fusion. The molecular events underlying controlled release and their effects on spinal fusion remain unknown. In this study, a rabbit interbody spinal fusion chamber was designed to provide a controlled environment for profiling molecular events during the fusion process. Study groups included Group 1, PEC with 100 μg rhBMP-2; Group 2, ACS with 100 μg rhBMP-2; Group 3, ACS with 300 μg rhBMP-2; Group 4, autologous bone graft; and Group 5, empty chamber. Manual palpation, microcomputed tomography, and histological analysis showed that Group 1 and 3 achieved bone fusion, while the other groups showed no signs of fusion. Gene expression profiling showed robust induction of osteogenic markers in Groups 1 and 3, with modulated early induction of inflammatory genes in the PEC group. Delivery of 100 μg rhBMP-2 with ACS (Group 2) resulted in less upregulation of osteogenic genes, increased inflammatory genes expression, and upregulation of osteoclastic genes compared to Group 1. These results suggest that the manner of BMP-2 release at the interbody spinal defect site could dictate the balance of

Topics: Animals; Biomarkers; Bone Morphogenetic Protein 2; Bone Regeneration; Delayed-Action Preparations; Gene Expression Regulation; Humans; Implants, Experimental; Inflammation; Osteoclasts; Osteogenesis; Polyelectrolytes; Rabbits; Recombinant Proteins; Seroma; Spinal Cord; Spinal Fusion; Transforming Growth Factor beta; X-Ray Microtomography

Topics: Bone Morphogenetic Protein 2; Humans; Male; Middle Aged; Recombinant Proteins; Seroma; Spinal Fusion; Transforming Growth Factor beta

Previous studies document the therapeutic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier for indications in the axial and appendicular skeleton. Nevertheless, the ACS does not comprise structural integrity to adequately support bone formation for onlay indications. The objective of this study was to evaluate local bone formation and osseointegration following surgical implantation of rhBMP-2 soak-loaded onto a compression resistant matrix (CRM).. Routine, contralateral, critical-size, supraalveolar, peri-implant defects in five adult male Hound Labrador mongrel dogs received 0.8 mg rhBMP-2 soak-loaded onto either the ACS (benchmark control) or a CRM (collagen/β-TCP/hydroxyapatite) followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histologic/histometric evaluation.. Healing was uneventful albeit considerable initial swelling was observed for either treatment. Sites receiving rhBMP-2/CRM showed significantly increased bone area (20.0 ± 0.9 versus 12.3 ± 2.6 mm(2) , p = 0.03) and bone density (24.1 ± 1.4% versus 14.6 ± 2.0%, p = 0.04) compared with those receiving rhBMP-2/ACS. There were no significant differences between treatments for new bone height and osseointegration. Woven and lamellar trabecular bone lined with abundant osteoid was observed for all sites. Inconsistent cortex formation confirmed the immature nature of the newly formed bone. Seroma formation was observed for both treatments (80-100% of the animals/implants). Sites receiving rhBMP-2/CRM showed residual ceramic granules undergoing biodegradation, including accumulation of foamy macrophages.. rhBMP-2/CRM supports bone formation of clinically relevant geometry. Longer observation intervals as well as dose variations appear necessary to capture maturation of the newly formed bone, elimination of residual ceramic granules and resolution of seroma formation(s).

Topics: Absorbable Implants; Alveolar Bone Loss; Animals; Bone Density; Bone Matrix; Bone Morphogenetic Protein 2; Bone Regeneration; Bone Remodeling; Collagen Type I; Dental Implantation, Endosseous; Dogs; Drug Carriers; Drug Delivery Systems; Foam Cells; Humans; Hydroxyapatites; Male; Materials Testing; Osseointegration; Osteogenesis; Recombinant Proteins; Seroma; Tissue Scaffolds; Tooth Extraction; Tooth Socket; Transforming Growth Factor beta

Seroma formation following posterior cervical laminectomy and fusion is now recognized as a rare but significant risk. Previous reports have attributed the development of postoperative seromas to the use of recombinant bone morphogenetic protein-2 (rhBMP-2). Here the authors present the case of a 78-year-old female with a history of osteoporosis who developed delayed postoperative neck and shoulder pain following posterior cervical laminectomy and fusion utilizing only autograft bone and demineralized bone matrix (DBM) allograft. Postoperative MRI demonstrated normal hardware placement and a large epidural fluid collection that extended from C-4 to C-6. The patient underwent decompression and drainage of her sterile postoperative seroma. To the authors' knowledge, no case of seroma formation with the use of DBM has been previously reported. This case suggests that although rhBMP-2 is involved in the majority of postoperative seroma developments, other osteoinductive agents such as DBM can contribute to the development of a symptomatic seroma. This report presents an illustrative case study and reviews the current understanding of the development of and treatment for cervical seroma following posterior cervical laminectomy and fusion.

Topics: Aged; Bone Demineralization, Pathologic; Bone Morphogenetic Protein 2; Bone Transplantation; Cervical Vertebrae; Female; Humans; Laminectomy; Postoperative Complications; Recombinant Proteins; Seroma; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Topics: Bone Morphogenetic Protein 2; Bone Transplantation; Female; Humans; Laminectomy; Seroma; Spinal Fusion; Transforming Growth Factor beta

Dendritic cells (DCs) migrate from peripheral tissues to secondary lymphoid organs (SLOs) through the afferent lymph. Owing to limitations in investigating human lymph, DCs flowing in afferent lymph have not been properly characterized in humans until now. In this study, DCs present in seroma, an accrual of human afferent lymph occurring after lymph node surgical dissection, were isolated and analyzed in detail. Two main DC subsets were identified in seroma that corresponded to the migratory DC subsets present in lymph nodes, that is, CD14(+) and CD1a(+). The latter also included CD1a(bright) Langerhans cells. The two DC subsets appeared to share the same monocytic precursor and to be developmentally related; both of them spontaneously released high levels of TGF-β and displayed similar T cell-activating and -polarizing properties. In contrast, they differed in the expression of surface molecules, including TLRs; in their phagocytic activity; and in the expression of proteins involved in Ag processing and presentation. It is worth noting that although both subsets were detected in seroma in the postsurgical inflammatory phase, only CD1a(+) DCs migrated via afferent lymph under steady-state conditions. In conclusion, the high numbers of DCs contained in seroma fluids allowed a proper characterization of human DCs migrating via afferent lymph, revealing a continuous stream of DCs from peripheral regions toward SLOs under normal conditions. Moreover, we showed that, in inflammatory conditions, distinct subsets of DCs can migrate to SLOs via afferent lymph.

Topics: Aged; Aged, 80 and over; Antigens, CD1; Cell Movement; Dendritic Cells; Female; Humans; Lipopolysaccharide Receptors; Lymph; Lymph Nodes; Lymphocyte Activation; Male; Middle Aged; Seroma; Transforming Growth Factor beta

Chinese hamster ovary (CHO) cell-derived recombinant human bone morphogenetic protein-2 (rhBMP-2) has been introduced for spine, long bone, and craniofacial indications. Escherichia coli- (E. coli) derived rhBMP-2 displays comparable efficacy to CHO cell-derived rhBMP-2 in vitro and in small-animal models. The objective of this study is to evaluate the efficacy of E. coli-derived rhBMP-2 compared to the benchmark CHO cell-derived rhBMP-2 using an established large-animal model.. Contralateral, critical-size supraalveolar peri-implant defects in six adult male Hound Labrador mongrel dogs received CHO cell- or E. coli-derived rhBMP-2 (0.2 mg/mL) in an absorbable collagen sponge (ACS) carrier. In each quadrant, three dental implants were placed. A titanium mesh device was used to support space provision. The animals received fluorescent bone markers for qualitative evaluations. Animals were euthanized at 8 weeks for histopathologic and histometric evaluation.. Clinical healing included significant swelling, but none of the animals experienced wound dehiscences. CHO cell- and E. coli-derived rhBMP-2 supported comparable bone formation (new bone area, 35.8 ± 3.6 versus 30.1 ± 2.2 mm(2); bone density, 31.8% ± 1.6% versus 35.6% ± 2.5%; and osseointegration, 32.9% ± 7.4% versus 33.7% ± 8.1%) without statistically significant differences between treatments. Newly formed immature delicate trabecular bone in fibrovascular marrow filled the space underneath the titanium mesh and extended coronally above the mesh. Seroma formation was frequently observed. There were no discernable qualitative histologic differences between treatments.. CHO cell- and E. coli-derived rhBMP-2 in an ACS carrier appear equally effective at inducing local bone formation in support of dental implant osseointegration.

Topics: Alveolar Bone Loss; Alveolar Process; Animals; Bone Morphogenetic Protein 2; CHO Cells; Cricetinae; Cricetulus; Dental Implants; Dogs; Escherichia coli; Female; Male; Models, Animal; Oral Surgical Procedures; Osseointegration; Recombinant Proteins; Seroma; Surgical Mesh; Transforming Growth Factor beta

Retrospective cohort study of 1430 patients undergoing lumbar spinal fusion from 2002 - 2009.. The goal of this study was to compare and evaluate the number of complications requiring reoperation in elderly versus younger patients.. rhBMP-2 has been utilized off label for instrumented lumbar posterolateral fusions for many years. Many series have demonstrated predictable healing rates and reoperations. Varying complication rates in elderly patients have been reported.. All patients undergoing instrumented lumbar posterolateral fusion of ≤ 3 levels consenting to utilization of rhBMP-2 were retrospectively evaluated. Patient demographics, body mass index, comorbidities, number of levels, associated interbody fusion, and types of bone void filler were analyzed. The age of patients were divided into less than 65 and greater than or equal to 65 years. Complications related to the performed procedure were recorded.. After exclusions, 482 consecutive patients were evaluated with 42.1% males and 57.9% females. Average age was 62 years with 250 (51.9%) < 65 and 232 (48.1%) ≥ 65 years. Patients ≥ 65 years of age stayed longer (5.0 days) in the hospital than younger patients (4.5 days) (p=0.005).Complications requiring reoperation were: acute seroma formation requiring decompression 15/482, 3.1%, bone overgrowth 4/482, 0.8%, infection requiring debridement 11/482, 2.3%, and revision fusion for symptomatic nonunion 18/482, 3.7%. No significant differences in complications were diagnosed between the two age groups. Statistical differences were noted between the age groups for medical comorbidities and surgical procedures. Patients older than 65 years underwent longer fusions (2.1 versus 1.7 levels, p=0.001).. Despite being older and having more comorbidities, elderly patients have similar complication and reoperation rates compared to younger healthier patients undergoing instrumented lumbar decompression fusions with rhBMP-2.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Decompression, Surgical; Female; Humans; Length of Stay; Lumbar Vertebrae; Male; Middle Aged; Recombinant Proteins; Reoperation; Retrospective Studies; Risk Factors; Seroma; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome; Young Adult

A rodent model of posterior spinal fusion.. The aim of this study was to evaluate the efficacy of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered with a heparin based polylectrolyte complex (PEC) carrier in facilitating posterior spinal fusion while concurrently minimizing seroma and heterotopic ossification.. rhBMP-2 is being used to augment spinal fusion. However, complications such as heterotopic ossification and local soft tissue swellings have been reported. These are attributed to supraphysiological amount of rhBMP-2 and the poor modulation capacity of absorbable collagen sponge.. Forty rats were randomized into 6 groups as follows. Group I: absorbable collagen sponge without rhBMP-2 (n = 4); group II: positive control, absorbable collagen sponge + 10 μg rhBMP-2 (n = 4); group III: alginate-(poly-L-lysine)-heparin (PEC) without rhBMP-2 (n = 8); group IV: PEC + 4.5 μg rhBMP-2 (n = 8); group V: PEC + 1.5 μg rhBMP-2 (n = 8); group VI: PEC + 0.5 μg rhBMP-2 (n = 8).. Between postoperative days 5 and 7, seroma was observed in all rhBMP-2 implanted groups irrespective of carrier and dose. However, the rate and size of seroma differed considerably. Although all animals (100%) in positive control group showed seroma, only one animal (12.5%) in group VI developed seroma at the implant site. The size of seroma in group VI was significantly smaller than that in positive control group. Micro-computed tomography evaluation revealed comparable mean fusion scores in all rhBMP-2 implanted groups. More importantly, although new bone was well contained within the cage in group VI, heterotopic ossification beyond the cage was observed in positive control group.. A new carrier has demonstrated capacity to minimize seroma formation as well as heterotopic ossification associated with rhBMP-2 by reducing the efficacious dose needed for consistent fusion. The results of this study indicate that PEC alginate microbeads may represent a new opportunity to define an efficient rhBMP-2 carrier.

Topics: Alginates; Animals; Anticoagulants; Bone Morphogenetic Protein 2; Drug Carriers; Heparin; Humans; Inflammation; Microspheres; Ossification, Heterotopic; Polylysine; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Seroma; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome; X-Ray Microtomography

Case report.. Two cases are presented in which the use of recombinant bone morphogenetic protein-2 (rh-BMP-2) in a posterior cervical decompression and instrumented arthrodesis may have contributed to seroma formation and cord compression.. The use of rh-BMP-2 has been proven effective in promoting bone formation in anterior lumbar spine arthrodesis. Whether rh-BMP-2 is safe and/or effective in the cervical spine has not been determined. Adverse effects when it is used for anterior cervical fusion procedures have been reported but its role in posterior cervical decompression and instrumented fusions has yet to be determined.. We report on two cases. The first is a 68-year-old man presenting with a substantial decline in his neurologic status approximately 2 weeks after surgery. The second is a 44-year-old man presenting with a substantial decline in his neurologic status approximately 5 days after surgery. Both complications occurred after a posterior cervical laminectomy and instrumented arthrodesis when rh-BMP-2 was used as a bone graft substitute.. Both patients were found to have a moderate-to-large seroma causing severe compression on the spinal cord and were urgently taken to an operating room for evacuation of the seromas. Both showed improvement of their neurologic status immediately after surgery. As rh-BMP-2 is known to occasionally cause seroma formation it is postulated that it may have been the cause of the seromas.. Caution should be exercised with rh-BMP-2 use in posterior cervical applications when a laminectomy has been performed. The safe and effective dose and technique for application have yet to be determined. Seroma formation is possible, which can cause acute stenosis with cord compression and neurologic compromise.

Topics: Adult; Aged; Arthrodesis; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cervical Vertebrae; Decompression, Surgical; Humans; Male; Postoperative Complications; Recombinant Proteins; Seroma; Spinal Cord Compression; Spinal Stenosis; Spondylosis; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome

In vivo and in vitro model.. Investigate soft-tissue inflammation caused by rhBMP-2.. Although rhBMP-2 produces excellent rates of fusion in the spine, dysphagia and respiratory compromise have occurred when used in the neck. The mechanism of the swelling and inflammatory response has yet to be fully elucidated.. ELISA kits (IL-6, IL-10, TNF-α) were used to measure cytokine levels at different concentrations of rhBMP-2. Absorbable collagen sponges were implanted with or without different concentrations of rhBMP-2 into the backs of rats subcutaneously (SC) and intramuscularly (IM). Magnetic resonance imaging was used to measure inflammation at 3 hours and 2, 4, and 7 days. The inflammatory volumes were measured and compared using MIPAV software. Rats were killed after 7 days and studied.. IL-6, IL-10, and TNF-α release was dose-dependent. Soft-tissue edema after rhBMP-2 implantation was also dose-dependent, peaking at 3 hours SC, after SC and IM implantations, and on day 2 IM after IM implantation. All formed a granuloma-type mass after SC insertion. The mass was much larger in the 10 and 20 μg/10 μL (high-concentration) groups. The inflammatory response did not diffuse across physiologic barriers (subcutaneous fascia). Both high-dose groups were associated with encapsulated hematomas and a significant increase in the inflammatory zone.. Swelling and inflammation after rhBMP-2 use are dose-dependent. Swelling may be due to direct contact as well as spread in the plane of access. The causes are a robust inflammatory reaction as well as sterile seroma and encapsulated hematoma formation.

Topics: Animals; Bone Morphogenetic Protein 2; Disease Models, Animal; Dose-Response Relationship, Drug; Hematoma; Inflammation; Neck; Rats; Rats, Inbred Lew; Recombinant Proteins; Rodentia; Seroma; Transforming Growth Factor beta

Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling.. To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling.. Twelve, male, adult, Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load/six animals) or by immersion of the entire implant in an rhBMP-2 solution (soak-load/six animals) for a total of 30 mug rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation.. Clinical healing was uneventful. Supraalveolar bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (+/- SE) 3.4 +/- 0.2 versus 3.5 +/- 0.4 mm and 2.6 +/- 0.4 versus 2.5 +/- 0.7 mm(2) for coronal-load and soak-load implants, respectively (p>0.05). The corresponding bone density and bone-implant contact (BIC) recordings averaged 38.0 +/- 3.8%versus 34.4 +/- 5.6% and 25.0 +/- 3.8%versus 31.2 +/- 3.3% (p>0.05). In contrast, resident bone remodelling was significantly influenced by the rhBMP-2 application protocol. Bone density outside the implants threads averaged 74.7 +/- 3.8% and 50.8 +/- 4.1% for coronal-load and soak-load implants, respectively (p<0.05); bone density within the thread area averaged 51.8 +/- 1.2% and 37.8 +/- 2.9%, and BIC 70.1 +/- 6.7% and 43.3 +/- 3.9% (p<0.05).. Local application of rhBMP-2 appears to be a viable technology to support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodelling without compromising new bone formation.

Topics: Alveolar Bone Loss; Animals; Bone Density; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Remodeling; Coated Materials, Biocompatible; Dental Implants; Dental Materials; Dental Prosthesis Design; Dogs; Fluorescent Dyes; Humans; Male; Mandibular Diseases; Microscopy, Electron, Scanning; Osseointegration; Osteogenesis; Oxytetracycline; Porosity; Postoperative Complications; Recombinant Proteins; Seroma; Surface Properties; Titanium; Transforming Growth Factor beta; Wound Healing

Topics: Adult; Aged; Aged, 80 and over; Benzophenones; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Cervical Vertebrae; Collagen Type I; Deglutition Disorders; Diskectomy; Drug Carriers; Female; Hematoma; Humans; Ketones; Male; Middle Aged; Orthopedic Fixation Devices; Polyethylene Glycols; Polymers; Postoperative Complications; Range of Motion, Articular; Recombinant Proteins; Safety; Seroma; Spinal Fusion; Titanium; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome

The goal in this study was to demonstrate the safety and efficacy of anterior cervical discectomy and fusion ([ACDF]; single- or multilevel procedure) performed using titanium plates and polyetheretherketone (PEEK) spacers filled with recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated in a type I collagen sponge to achieve fusion.. The authors retrospectively reviewed 200 patients who underwent a single- or multilevel ACDF with titanium plate fixation and PEEK spacer filled with a collagen sponge impregnated with low-dose rhBMP-2. Clinical outcomes were assessed using pre- and postoperative Nurick grades and the Odom criteria. Radiographic outcomes were assessed using dynamic radiographs and computed tomography (CT) scans.. The follow-up period ranged from 8 to 36 months (mean 16.7 months). A single-level ACDF was performed in 96 patients, 2-level ACDF in 62 patients, 3-level ACDF in 36 patients, and 4-level ACDF in 6 patients. Long-term follow-up was available for 193 patients. The Odom outcomes were rated as good to excellent in 165 patients (85%), fair in 24 (12.4%), and poor in 4 (2%). Among patients with myelopathy, Nurick grades improved from a preoperative mean of 1.42 to a postoperative mean of 0.26. All patients (100%) achieved solid radiographic fusion on dynamic radiographs and CT scans. Fourteen patients (7%) in this series experienced clinically significant dysphagia, and 4 (2%) required repeated operation for hematoma or seroma.. An ACDF performed using a PEEK spacer filled with rhBMP-2 leads to good to excellent clinical outcomes and solid fusion, even in multilevel cases and in patients who are smokers. The incidence of symptomatic dysphagia may be decreased with a lower dose of rhBMP-2 that is placed only within the PEEK spacer.

Topics: Adult; Aged; Aged, 80 and over; Benzophenones; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Cervical Vertebrae; Collagen Type I; Deglutition Disorders; Diskectomy; Drug Carriers; Female; Follow-Up Studies; Hematoma; Humans; Ketones; Longitudinal Studies; Male; Middle Aged; Orthopedic Fixation Devices; Polyethylene Glycols; Polymers; Postoperative Complications; Range of Motion, Articular; Recombinant Proteins; Retrospective Studies; Safety; Seroma; Spinal Fusion; Titanium; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome

Studies using ectopic rodent, orthotopic canine, and non-human primate models show that bone morphogenetic proteins (BMPs) coated onto titanium surfaces induce local bone formation. The objective of this study was to examine the ability of recombinant human BMP-2 (rhBMP-2) coated onto a titanium porous oxide implant surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge.. Bilateral, critical-size, 5 mm, supra-alveolar, peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml, and six animals received implants coated with rhBMP-2 at 3.0 mg/ml or uncoated control. Treatments were randomized between jaw quadrants. The mucoperiosteal flaps were advanced, adapted and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7 and 8 post-surgery when they were euthanized for histologic evaluation.. Jaw quadrants receiving implants coated with rhBMP-2 exhibited gradually regressing swelling that became hard to palpate disguising the contours of the implants. The histologic evaluation showed robust bone formation reaching or exceeding the implant platform. The newly formed bone exhibited characteristics of the adjoining resident Type II bone including cortex formation for sites receiving implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml. Sites receiving implants coated with rhBMP-2 at 3.0 mg/ml exhibited more immature trabecular bone formation, seroma formation and peri-implant bone remodelling resulting in undesirable implant displacement. Control implants exhibited minimal, if any, bone formation. Thus, implants coated with rhBMP-2 at 0.75, 1.5 and 3.0 mg/ml exhibited significant bone formation (height and area) compared with the sham-surgery control averaging (+/-SD) 4.4+/-0.4, 4.2+/-0.7 and 4.2+/-1.2 versus 0.8+/-0.3 mm; and 5.0+/-2.2, 5.6+/-2.2 and 7.4+/-3.5 versus 0.7+/-0.3 mm(2), respectively (p<0.01). All the treatment groups exhibited clinically relevant osseointegration.. rhBMP-2 coated onto titanium porous oxide implant surfaces induced clinically relevant local bone formation including vertical augmentation of the alveolar ridge and osseointegration. Higher concentrations/doses were associated with untoward effects.

Topics: Alveolar Bone Loss; Alveolar Ridge Augmentation; Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Coated Materials, Biocompatible; Dental Implants; Dogs; Dose-Response Relationship, Drug; Humans; Implants, Experimental; Male; Osseointegration; Random Allocation; Recombinant Proteins; Seroma; Surface Properties; Titanium; Transforming Growth Factor beta

Alveolar ridge aberrations commonly require bone augmentation procedures for optimal placement of endosseous dental implants. The objective of this study was to evaluate local bone formation following implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier with or without provisions for guided bone regeneration (GBR) as potential treatment modalities for alveolar augmentation.. Surgically induced, large, mandibular alveolar ridge saddle-type defects (2 defects/jaw quadrant) in seven young adult Hound dogs were assigned to receive rhBMP-2/ACS, rhBMP-2/ACS combined with GBR (rhBMP-2/GBR), GBR, and surgery controls. The animals were euthanized at 12 weeks post-surgery when block sections of the defect sites were collected for histologic analysis.. Clinical complications included swelling for sites receiving rhBMP-2 and wound failure with exposure of the barrier device for sites receiving GBR (4/6) or rhBMP-2/GBR (3/7). The radiographic evaluation showed substantial bone fill for sites receiving rhBMP-2/ACS, rhBMP-2/GBR, and GBR. In particular, sites receiving rhBMP-2/GBR presented with seroma-like radiolucencies. The surgery control exhibited moderate bone fill. To evaluate the biologic potential of the specific protocols, sites exhibiting wound failure were excluded from the histometric analysis. Sites receiving rhBMP-2/ACS or rhBMP-2/GBR exhibited bone fill averaging 101%. Bone fill averaged 92% and 60%, respectively, for sites receiving GBR and surgery controls. Bone density ranged from 50% to 57% for sites receiving rhBMP-2/ACS, GBR, or surgery controls. Bone density for sites receiving rhBMP-2/GBR averaged 34% largely due to seroma formation encompassing 13% to 97% of the sites.. rhBMP-2/ACS appears to be an effective alternative to GBR in the reconstruction of advanced alveolar ridge defects. Combining rhBMP-2/ACS with GBR appears to be of limited value due to the potential for wound failure or persistent seromas.

Topics: Alveolar Bone Loss; Alveolar Process; Alveolar Ridge Augmentation; Animals; Bone Density; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Dogs; Drug Carriers; Gelatin Sponge, Absorbable; Guided Tissue Regeneration, Periodontal; Humans; Mandible; Membranes, Artificial; Osteogenesis; Postoperative Complications; Radiography; Recombinant Proteins; Seroma; Surgical Wound Dehiscence; Transforming Growth Factor beta