Cyst-Like Osteolytic Formations in Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Augmented Sheep Spinal Fusion.

Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro-computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2-affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone.

Cervical stabilization with polyaxial pedicle screw and rod construct in horses: A proof of concept study.

OBJECTIVE: To evaluate safety and efficacy of a novel technique for cervical stabilization. STUDY DESIGN: In vivo experimental. ANIMALS: Four normal adult quarterhorse crossbreed horses (2-4 years of age, > 250 kg). METHODS: One mid-cervical spinal unit (C3-C4) was distracted with a porous metal interbody fusion device (IFD) and stabilized with a polyaxial pedicle screw and rod construct. Neurologic examinations were performed preoperatively and postoperatively. Radiographs of the fusion site and adjoining vertebrae were obtained preoperatively and monthly. Horses were euthanized at 8 months and spinal units were evaluated for osseointegration and implant safety via micro-computed tomography (CT), histology, and histomorphometry. RESULTS: The procedure was performed safely in all horses, without severe postoperative complications. Evaluation of radiographs revealed no implant failure, implant migration, or spinal unit instability in any of the horses. The presence of new bone formation around the screw and rod constructs was confirmed via micro-CT. No evidence of inflammation or iatrogenic damage was noted from histology. New bone was present within the IFD in all horses, with variable osseointegration on the cranial and caudal surfaces of the implant in 3 horses. CONCLUSION: The novel technique reported in the present study was safely applied to stabilize the C3-C4 spinal unit in the horses tested here and led to variable osseointegration within 8 months. CLINICAL SIGNIFICANCE: The results of this study justify evaluation of this technique in horses with a diagnosis of cervical vertebral compressive myelopathy.

An analysis of spine fusion outcomes in sheep pre-clinical models.

PURPOSE: The ovine model is often used to evaluate new spine fusion technologies prior to clinical testing. An important aspect of designing sheep surgery protocols is to select the appropriate postoperative time period for comparing fusion outcomes. Unfortunately, determining the ideal study endpoint is complicated by the fact that prior published studies have not used consistent timeframes. Thus, the primary aim of this study was to provide a reference for investigators as to the expected fusion outcomes of control groups at varying timepoints in sheep spine surgery models. METHODS: We identified published sheep fusion studies using autograft, interbody cages, and/or instrumentation. Fusion data were extracted, converted to a common scale, and analyzed across studied timepoints. RESULTS: Overall, 29 studies of 360 fusion levels were identified: 11 ALIF (158 levels), 3 PLIF/TLIF (28 levels), 8 PLF (90 levels), and 7 ACDF (84 levels). Studied timepoints ranged from 4 to 48 weeks postoperative. In general, fusion rates varied across techniques and instrumentation. The time to reach solid fusion differed by as many as 20 weeks between control groups. CONCLUSIONS: Recommended timeframes for future studies designed to show either superiority over controls or equivalent outcomes with controls were developed based on aggregate results. Designating ideal study endpoints for sheep fusion models has both ethical implications associated with responsible use of animals in research, and economic implications given the cost of animal research. The current results can guide the development of future research methods and help investigators choose appropriate study timelines for various control groups.

Comparison of a Thiolated Demineralized Bone Matrix Hydrogel to a Clinical Product Control for Regeneration of Large Sheep Cranial Defects.

Regeneration of calvarial bone remains a major challenge in the clinic as available options do not sufficiently regenerate bone in larger defect sizes. Calvarial bone regeneration cases involving secondary medical conditions, such as brain herniation during traumatic brain injury (TBI) treatment, further exacerbate treatment options. Hydrogels are well-positioned for severe TBI treatment, given their innate flexibility and potential for bone regeneration to treat TBI in a single-stage surgery. The current study evaluated a photocrosslinking pentenoate-modified hyaluronic acid polymer with thiolated demineralized bone matrix (i.e., TDBM hydrogel) capable of forming a completely interconnected hydrogel matrix for calvarial bone regeneration. The TDBM hydrogel demonstrated a setting time of 120 s, working time of 3 to 7 days, negligible change in setting temperature, physiological setting pH, and negligible cytotoxicity, illustrating suitable performance for in vivo application. Side-by-side ovine calvarial bone defects (19 mm diameter) were employed to compare the TDBM hydrogel to the standard-of-care control material DBX®. After 16 weeks, the TDBM hydrogel had comparable healing to DBX® as demonstrated by mechanical push-out testing (~800 N) and histology. Although DBX® had 59% greater new bone volume compared to the TDBM hydrogel via micro-computed tomography, both demonstrated minimal bone regeneration overall (15 to 25% of defect volume). The current work presents a method for comparing the regenerative potential of new materials to clinical products using a side-by-side cranial bone defect model. Comparison of novel biomaterials to a clinical product control (i.e., standard-of-care) provides an important baseline for successful regeneration and potential for clinical translation.

Bone Mineralization and Spinal Fusion Evaluation of a Truss-based Interbody Fusion Device: Ovine Finite Element Analysis with Confirmatory In Vivo Outcomes.

STUDY DESIGN: Finite element analysis (FEA) and in vivo ovine spinal interbody fusion study. OBJECTIVE: To determine comparative load-induced strain amplitudes, bone mineralization and fusion outcomes associated with different diameter struts in a truss-based interbody fusion device. SUMMARY OF BACKGROUND DATA: Additive manufacturing technology has been employed to develop implants that actively participate in the fusion process. The truss device enables the optimal transfer of compressive and tensile stresses via the struts. Mechanobiologic principles postulate that strut diameter can be regulated to allow different magnitudes of strain distribution within the struts which may affect fusion rates. METHODS: Modeling of strain distributions as a function of strut diameter (0.75, 1.0, 1.25, and 1.5 mm) employed FEA that simulated physiologic loading conditions. A confirmatory in vivo ovine lumbar spinal interbody fusion study compared fusion scores and bone histomorphometric variables for cages with 0.75 and 1.5 mm strut diameters. Outcomes were compared at 3-, 6-, and 12-month follow-up intervals. RESULTS: FEA showed an inverse association between strut diameter and peak strain amplitude. Cages with 1.0, 1.25, and 1.5 mm struts had peak strain values that were 36%, 60%, and 73% lower than the 0.75 mm strut strain value. In vivo results showed the mean fusion score for the 0.75 mm diameter strut cage was significantly greater by 3-months versus the 1.5 mm strut cage, and remained significantly higher at each subsequent interval (P < 0.001 for all comparisons). Fusion rates were 95%, 100%, and 100% (0.75 mm) and 72.7%, 86.4%, and 95.8% (1.5 mm) at 3, 6, and 12 months. Thinner struts had greater mineralized bone tissue and less fibrous/chondral tissue than the thicker struts at each follow-up. CONCLUSION: Validating FEA estimates, cages with smaller diameter struts exhibited more rapid fusion consolidation and more aggressive osseointegration compared with cages with larger diameters struts.Level of Evidence: 4.

Outcomes after cervical vertebral interbody fusion using an interbody fusion device and polyaxial pedicle screw and rod construct in 10 horses (2015-2019).

BACKGROUND: Further development of surgical techniques for equine cervical stabilisation is necessary to make the procedure less technically demanding, reduce complications and improve outcomes. OBJECTIVE: To describe clinical outcomes and owner reports in horses undergoing placement of an interbody fusion device and polyaxial pedicle screw and rod construct for cervical vertebral fusion in horses with cervical vertebral compressive myelopathy. STUDY DESIGN: Retrospective case series. METHODS: Data were retrieved from medical records of 10 horses undergoing cervical vertebral fusion (2015-2019). Records were evaluated for signalment, duration of clinical signs, number and location of compression sites, grade of ataxia, duration of hospitalisation and complications. Long-term follow-up was obtained through clinical re-evaluation, postoperative radiographs and owner contact. RESULTS: Breeds were mixed. Median age was 24 (range 12-168) months. There were 2/10 mares, 4/10 geldings and 4/10 stallions. Preoperative grade of ataxia ranged from 1-3/5. Fusion was performed at one (n = 3) or two (n = 7) sites. Two horses were euthanised within the first year. In 6 of 8 horses with ≥1-year follow-up, ataxia improved by 1-3 grades, with an average improvement of 1.25 grades. In four horses, ataxia improved to grade 0-1. In two horses the gait was unaffected, but neck comfort improved. Complications included seroma formation (n = 9), pain (n = 5), fever (n = 4), upper respiratory tract obstruction (n = 2), azotemia (n = 2), screw breakage (n = 2), progression of neurological signs (n = 1), Horner's Syndrome (n = 1), dysphagia (n = 1), hives (n = 1), implant infection (n = 1) and nondisplaced fracture (n = 1). MAIN LIMITATIONS: Small case series, heterogeneous patient population. CONCLUSIONS: This technique resulted in ≥1 grade gait improvement in 6/10 cases operated and 6/8 cases for which ≥1-year follow-up was available, similar to other methods. Fatal complications related to implant placement did not occur. This technique may represent a safer alternative to current techniques of ventral interbody fusion with similar outcomes.

Outcomes of cats undergoing surgical attenuation of congenital extrahepatic portosystemic shunts through cellophane banding: 9 cases (2000-2007).

OBJECTIVE: To evaluate the long-term prognosis of cats with a congenital extrahepatic portosystemic shunt (CEPSS) attenuated through gradual occlusion with cellophane banding (CB). DESIGN: Retrospective case series. ANIMALS: 9 cats with a CEPSS that was attenuated with CB. PROCEDURES: Medical records of cats surgically treated for CEPSS by means of CB from January 2000 through March 2007 were reviewed. Extracted data included preoperative clinical signs, medications, diagnostic results including serum bile acids concentrations, surgical technique, intraoperative and postoperative complications, and long-term follow-up information. RESULTS: 2 cats that developed refractory seizures were euthanized within 3 days after the CB procedure. Seven of the 9 cats survived to 15 days after surgery. Four cats did not have any clinical signs of CEPSS at long-term follow up. At that time, 5 cats had a postprandial SBA concentration within reference limits and 1 cat had persistent ptyalism. One cat had biurate ammonium stones removed > 2 years after surgery. One cat was euthanized 105 days after surgery because of uncontrolled seizures. The 3-year survival rate was 66%. CONCLUSIONS AND CLINICAL RELEVANCE: Uncontrolled seizure activity was the most common cause of death after CB. Long-term outcome for cats with CEPSS was fair to good after the procedure. Cats with a CEPSS surviving the immediate postoperative period had a fair to good long-term outcome. Cellophane banding without intraoperative attenuation appears to be an acceptable technique for gradual occlusion of a CEPSS in cats. Cats should be monitored closely for development of neurologic disorders in the postoperative period.

Evaluation of lumbar spinal fusion utilizing recombinant human platelet derived growth factor-B chain homodimer (rhPDGF-BB) combined with a bovine collagen/ß-tricalcium phosphate (ß-TCP) matrix in an ovine model.

BACKGROUND CONTEXT: While the clinical effectiveness of recombinant human Platelet Derived Growth Factor-B chain homodimer combined with collagen and ß-tricalcium phosphate (rhPDGF-BB + collagen/ß-TCP) treatment for indications involving hindfoot and ankle is well-established, it is not approved for use in spinal interbody fusion, and the use of autograft remains the gold standard. PURPOSE: The purpose of this study was to compare the effects of rhPDGF-BB + collagen/ß-TCP treatment on lumbar spine interbody fusion in an ovine model to those of autograft bone and collagen/ß-TCP treatments using biomechanical, radiographic, and histological assessment techniques. STUDY DESIGN: Thirty-two skeletally mature Columbian Rambouillet sheep were used to evaluate the safety and effectiveness of rhPDGF-BB + collagen/ß-TCP matrix in a lumbar spinal fusion model. Interbody polyetheretherketone (PEEK) cages contained either autograft, rhPDGF-BB + collagen/ß-TCP, collagen/ß-TCP matrix, or left empty. METHODS: Animals were sacrificed 8- or 16-weeks post-surgery. Spinal fusion was evaluated via post-sacrifice biomechanical, micro-computed tomography (µCT), and histological analysis. Outcomes were statistically compared using a two-way analysis of variance (ANOVA) with an alpha value of 0.05 and a Tukey post-hoc test. RESULTS: There were no statistically significant differences between groups within treatment timepoints for flexion-extension, lateral bending, or axial rotation range of motion, neutral zone, neutral zone stiffness, or elastic zone stiffness. µCT bone volume fraction was significantly greater between treatment groups independent of timepoint where Autograft and rhPDGF-BB + collagen/ß-TCP treatments demonstrated significantly greater bone volume fraction as compared to collagen/ß-TCP (P = .026 and P = .038, respectively) and Empty cage treatments (P = .002 and P = .003, respectively). µCT mean bone density fraction was most improved in rhPDGF-BB + collagen/ß-TCP specimens at the 8 week and 16-week timepoints as compared to all other treatment groups. There were no statistically significant differences in histomorphometric measurements of bone, soft tissue, or empty space between rhPDGF-BB + collagen/ß-TCP and autograft treatments. CONCLUSIONS: The results of this study indicate that the use of rhPDGF-BB combined with collagen/ß-TCP promotes spinal fusion comparable to that of autograft bone. CLINICAL SIGNIFICANCE: The data indicate that rhPDGF-BB combined with collagen/ß-TCP promotes spinal fusion comparably to autograft bone treatment and may offer a viable alternative in large animal spinal fusion. Future prospective clinical studies are necessary to fully understand the role of rhPDGF-BB combined with collagen/ß-TCP in human spinal fusion healing.

Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model.

A prospective, randomized study was performed in an ovine model to compare the efficacy of an anorganic bovine-derived hydroxyapatite matrix combined with a synthetic 15 amino acid residue (ABM/P-15) in facilitating lumbar interbody fusion when compared with autogenous bone harvested from the iliac crest. P-15 is a biomimetic to the cell-binding site of Type-I collagen for bone-forming cells. When combined with ABM, it creates the necessary scaffold to initiate cell invasion, binding, and subsequent osteogenesis. In this study, six adult ewes underwent anterior-lateral interbody fusion at L3/L4 and L4/L5 using PEEK interbody rings filled with autogenous bone at one level and ABM/P-15 at the other level and no additional instrumentation. Clinical CT scans were obtained at 3 and 6 months; micro-CT scans and histomorphometry analyses were performed after euthanization at 6 months. Clinical CT scan analysis showed that all autograft and ABM/P-15 treated levels had radiographically fused outside of the rings at the 3-month study time point. Although the clinical CT scans of the autograft treatment group showed significantly better fusion within the PEEK rings than ABM/P-15 at 3 months, micro-CT scans, clinical CT scans, and histomorphometric analyses showed there were no statistical differences between the two treatment groups at 6 months. Thus, ABM/P-15 was as successful as autogenous bone graft in producing lumbar spinal fusion in an ovine model, and it should be further evaluated in clinical studies.

Long-term outcome of domestic ferrets treated surgically for hyperadrenocorticism: 130 cases (1995-2004).

OBJECTIVE: To determine the long-term survival rate and factors that affect survival time of domestic ferrets treated surgically for hyperadrenocorticism. STUDY DESIGN: Retrospective case series. ANIMALS: 130 ferrets with hyperadrenocorticism that were treated surgically. PROCEDURES: Medical records of ferrets surgically treated for hyperadrenocorticism were reviewed. Data recorded included signalment, duration of clinical signs prior to hospital admission, CBC values, serum biochemical analysis results, anesthetic time, surgical time, concurrent diseases, adrenal gland affected (right, left, or both [bilateral]), histopathologic diagnosis, surgical procedure, caudal vena caval involvement (yes or no), postoperative melena (yes or no), days in hospital after surgery, and whether clinical signs of hyperadrenocorticism developed after surgery. RESULTS: 130 ferrets were entered in the study (11 of 130 ferrets were admitted and underwent surgery twice). The 1- and 2-year survival rates were 98% and 88%, respectively. A 50% survival rate was never reached. Combined partial adrenal gland resection with cryosurgery had a significantly negative effect on survival time. No other risk factors were identified. Survival time was not significantly affected by either histopathologic diagnosis or specific affected adrenal gland (right, left, or bilateral). CONCLUSIONS AND CLINICAL RELEVANCE: Ferrets with adrenal gland masses that were treated surgically had a good prognosis. Survival time of ferrets with hyperadrenocorticism undergoing surgery was not affected by the histologic characteristic of the tumor, the adrenal glands affected (right, left, or bilateral), or complete versus partial adrenal gland resection. Debulking was a sufficient surgical technique to allow a favorable long-term outcome when complete excision was not possible.

Bony ingrowth potential of 3D-printed porous titanium alloy: a direct comparison of interbody cage materials in an in vivo ovine lumbar fusion model.

BACKGROUND CONTEXT: There is significant variability in the materials commonly used for interbody cages in spine surgery. It is theorized that three-dimensional (3D)-printed interbody cages using porous titanium material can provide more consistent bone ingrowth and biological fixation. PURPOSE: The purpose of this study was to provide an evidence-based approach to decision-making regarding interbody materials for spinal fusion. STUDY DESIGN: A comparative animal study was performed. METHODS: A skeletally mature ovine lumbar fusion model was used for this study. Interbody fusions were performed at L2-L3 and L4-L5 in 27 mature sheep using three different interbody cages (ie, polyetheretherketone [PEEK], plasma sprayed porous titanium-coated PEEK [PSP], and 3D-printed porous titanium alloy cage [PTA]). Non-destructive kinematic testing was performed in the three primary directions of motion. The specimens were then analyzed using micro-computed tomography (µ-CT); quantitative measures of the bony fusion were performed. Histomorphometric analyses were also performed in the sagittal plane through the interbody device. Outcome parameters were compared between cage designs and time points. RESULTS: Flexion-extension range of motion (ROM) was statistically reduced for the PTA group compared with the PEEK cages at 16 weeks (p-value=.02). Only the PTA cages demonstrated a statistically significant decrease in ROM and increase in stiffness across all three loading directions between the 8-week and 16-week sacrifice time points (p-value≤.01). Micro-CT data demonstrated significantly greater total bone volume within the graft window for the PTA cages at both 8 weeks and 16 weeks compared with the PEEK cages (p-value<.01). CONCLUSIONS: A direct comparison of interbody implants demonstrates significant and measurable differences in biomechanical, µ-CT, and histologic performance in an ovine model. The 3D-printed porous titanium interbody cage resulted in statistically significant reductions in ROM, increases in the bone ingrowth profile, as well as average construct stiffness compared with PEEK and PSP.

Reinforced Electrospun Polycaprolactone Nanofibers for Tracheal Repair in an In Vivo Ovine Model.

Tracheal stenosis caused by congenital anomalies, tumors, trauma, or intubation-related damage can cause severe breathing issues, diminishing the quality of life, and potentially becoming fatal. Current treatment methods include laryngotracheal reconstruction or slide tracheoplasty. Laryngotracheal reconstruction utilizes rib cartilage harvested from the patient, requiring a second surgical site. Slide tracheoplasty involves a complex surgical procedure to splay open the trachea and reconnect both segments to widen the lumen. A clear need exists for new and innovative approaches that can be easily adopted by surgeons, and to avoid harvesting autologous tissue from the patient. This study evaluated the use of an electrospun patch, consisting of randomly layered polycaprolactone (PCL) nanofibers enveloping 3D-printed PCL rings, to create a mechanically robust, suturable, air-tight, and bioresorbable graft for the treatment of tracheal defects. The study design incorporated two distinct uses of PCL: electrospun fibers to promote tissue integration, while remaining air-tight when wet, and 3D-printed rings to hold the airway open and provide external support and protection during the healing process. Electrospun, reinforced tracheal patches were evaluated in an ovine model, in which all sheep survived for 10 weeks, although an overgrowth of fibrous tissue surrounding the patch was observed to significantly narrow the airway. Minimal tissue integration of the surrounding tissue and the electrospun fibers suggested the need for further improvement. Potential areas for further improvement include a faster degradation rate, agents to increase cellular adhesion, and/or an antibacterial coating to reduce the initial bacterial load.

Histological evaluation of an impacted bone graft substitute composed of a combination of mineralized and demineralized allograft in a sheep vertebral bone defect.

Demineralized bone matrix (DBMs) preparations are a potential alternative or supplement to autogenous bone graft, but many DBMs have not been adequately tested in clinically relevant animal models. The aim of current study was to compare the efficacy of a new bone graft substitute composed of a combination of mineralized and demineralized allograft, along with hyaluronic acid (AFT Bone Void Filler) with several other bone graft materials in a sheep vertebral bone void model. A drilled defect in the sheep vertebral body was filled with either the new DBM preparation, calcium sulfate (OsteoSet), autologous bone graft, or left empty. The sheep were euthanized after 6 or 12 weeks, and the defects were examined by histology and quantitative histomorphometry. The morphometry data were analyzed by one-way analysis of variance with the post hoc Tukey-Kramer test or the Student's t-test. All of the bone defects in the AFT DBM preparation group showed good new bone formation with variable amounts of residual DBM and mineralized bone graft. The DBM preparation group at 12 weeks contained significantly more new bone than the defects treated with calcium sulfate or left empty (respectively, p < 0.05, p < 0.01). There was no significant difference between the DBM and autograft groups. No adverse inflammatory reactions were associated with any of the three graft materials. The AFT preparation of a mixture of mineralized and demineralized allograft appears to be an effective autograft substitute as tested in this sheep vertebral bone void model.

Histological and mechanical evaluation of self-setting calcium phosphate cements in a sheep vertebral bone void model.

We investigated the histological and compressive properties of three different calcium phosphate cements (CPCs) using a sheep vertebral bone void model. One of the CPCs contained barium sulfate to enhance its radiopacity. Bone voids were surgically created in the lumbar region of 23 ovine spines - L3, L4, and L5 (n = 69 total vertebral bodies) - and the voids were filled with one of the three CPCs. A fourth group consisted of whole intact vertebrae. Histologic evaluation was performed for 30 of the 69 vertebrae 2 or 4 months after surgery along with radiographic evaluation. Compressive testing was performed on 39 vertebrae 4 months after surgery along with micro-CT analysis. All three CPCs were biocompatible and extremely osteoconductive. Osteoclasts associated with adjacent bone formation suggest that each cement can undergo slow resorption and replacement by bone and bone marrow. Compressive testing did not reveal a significant difference in the ultimate strength, ultimate strain, and structural modulus, among the three CPCs and intact whole vertebrae. Micro-CT analysis revealed good osseointegration between all three CPCs and adjacent bone. The barium sulfate did not affect the CPCs biocompatibility or mechanical properties. These results suggest that CPC might be a good alternative to polymethylmethacrylate for selected indications.

Is lumbar facet fusion biomechanically equivalent to lumbar posterolateral onlay fusion?

OBJECTIVE This study was designed with the following research objectives: 1) to determine the efficacy of facet fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS) in an ovine lumbar facet fusion model; 2) to radiographically and histologically compare the efficacy of lumbar facet fusion with rhBMP-2/ACS to facet fusion with an iliac crest bone graft (ICBG); and 3) to biomechanically compare lumbar facet fusion with rhBMP-2/ACS to lumbar posterolateral fusion (PLF) with ICBG. METHODS The efficacies of the 3 treatments to induce fusion were evaluated in an instrumented ovine lumbar fusion model. Eight sheep had 10 cm3/side ICBG placed as an onlay graft for PLF at L2-3. At the adjacent L3-4 level, 0.5 cm3/side ICBG was placed for facet fusion. Finally, 0.5 cm3/side rhBMP-2/ACS (0.43 mg/ml) was placed for facet fusion at L4-5. CT scans were obtained at 2, 4, and 6 months postoperatively with 2 reviewers conducting an evaluation of the 6-month results for all treated spinal levels. All 8 sheep were killed at 6 months, and all posterolateral instrumentation was removed at this time. The spines were then sectioned through L3-4 to allow for nondestructive unconstrained biomechanical testing of the L2-3 and L4-5 segments. All treated spinal levels were analyzed using undecalcified histology with corresponding microradiography. Statistical comparisons were made between the treatment groups. RESULTS The PLF with ICBG (ICBG PLF group) and the rhBMP-2 facet fusion (rhBMP-2 Facet group) treatment groups demonstrated similar levels of stiffness, with the rhBMP-2 Facet group having on average slightly higher stiffness in all 6 loading directions. All 8 levels in the autograft facet fusion treatment group demonstrated CT radiographic and histological fusion. All 8 levels in the rhBMP-2 Facet group showed bilateral CT radiographic and histological fusion. Six of 16 rhBMP-2/ACS-treated facet defects demonstrated small intraosseous hematomas or seromas. Four of the 8 levels (50%) in the ICBG PLF treatment group demonstrated bilateral histological fusion. Three of 8 levels in the ICBG PLF treatment group showed unilateral fusion. One of the 8 levels in the ICBG PLF treatment group demonstrated bilateral histological nonfusion. CONCLUSIONS Both rhBMP-2/ACS and autograft demonstrated 100% efficacy when used for facet fusion in the instrumented ovine model. However, the ICBG PLF treatment group only demonstrated a 50% bilateral fusion rate. Biomechanically, the ICBG PLF and rhBMP-2 Facet groups demonstrated similar stiffness in all 6 loading directions, with the rhBMP-2 Facet group having on average slightly higher stiffness in all directions.

Evaluation of a polyetheretherketone (PEEK) titanium composite interbody spacer in an ovine lumbar interbody fusion model: biomechanical, microcomputed tomographic, and histologic analyses.

BACKGROUND CONTEXT: The most commonly used materials used for interbody cages are titanium metal and polymer polyetheretherketone (PEEK). Both of these materials have demonstrated good biocompatibility. A major disadvantage associated with solid titanium cages is their radiopacity, limiting the postoperative monitoring of spinal fusion via standard imaging modalities. However, PEEK is radiolucent, allowing for a temporal assessment of the fusion mass by clinicians. On the other hand, PEEK is hydrophobic, which can limit bony ingrowth. Although both PEEK and titanium have demonstrated clinical success in obtaining a solid spinal fusion, innovations are being developed to improve fusion rates and to create stronger constructs using hybrid additive manufacturing approaches by incorporating both materials into a single interbody device. PURPOSE: The purpose of this study was to examine the interbody fusion characteristic of a PEEK Titanium Composite (PTC) cage for use in lumbar fusion. STUDY DESIGN/SETTING: Thirty-four mature female sheep underwent two-level (L2-L3 and L4-L5) interbody fusion using either a PEEK or a PTC cage (one of each per animal). Animals were sacrificed at 0, 8, 12, and 18 weeks post surgery. MATERIALS AND METHODS: Post sacrifice, each surgically treated functional spinal unit underwent non-destructive kinematic testing, microcomputed tomography scanning, and histomorphometric analyses. RESULTS: Relative to the standard PEEK cages, the PTC constructs demonstrated significant reductions in ranges of motion and a significant increase in stiffness. These biomechanical findings were reinforced by the presence of significantly more bone at the fusion site as well as ingrowth into the porous end plates. CONCLUSIONS: Overall, the results indicate that PTC interbody devices could potentially lead to a more robust intervertebral fusion relative to a standard PEEK device in a clinical setting.

Polyetheretherketone as a biomaterial for spinal applications.

Threaded lumbar interbody spinal fusion devices (TIBFD) made from titanium have been reported to be 90% effective for single-level lumbar interbody fusion, although radiographic determination of fusion has been intensely debated in the literature. Using blinded radiographic, biomechanic, histologic, and statistical measures, we evaluated a radiolucent polyetheretherketone (PEEK)-threaded interbody fusion device packed with autograft or rhBMP-2 on an absorbable collagen sponge in 13 sheep at 6 months. Radiographic fusion, increased spinal level biomechanical stiffness, and histologic fusion were demonstrated for the PEEK cages filled with autograft or rhBMP-2 on a collagen sponge. No device degradation or wear debris was observed. Only mild chronic inflammation consisting of a few macrophages was observed in peri-implant tissues. Based on these results, the polymeric biomaterial PEEK may be a useful biomaterial for interbody fusion cages due to the polymer's increased radiolucency and decreased stiffness.

Long-term survival and risk factors associated with biliary surgery in dogs: 34 cases (1994-2004).

OBJECTIVE: To determine factors associated with long-term survival after biliary surgery in dogs. DESIGN: Retrospective case series. ANIMALS: 34 dogs that underwent biliary surgery. PROCEDURES: Data extracted from medical records included sex, breed, body weight, age at surgery, history and clinical examination findings, preoperative and postoperative CBC, serum biochemical panel and coagulation profiles results, abdominal ultrasonographic findings, results of bacteriologic culture and histologic examination, surgical findings, postoperative complications, and survival time. Follow-up information was obtained from medical records or phone conversations with owners and referring veterinarians. RESULTS: Primary biliary findings included gallbladder mucocele (n = 20 dogs), inflammatory diseases (4), trauma (3), and neoplasia (1). Secondary biliary diseases included pancreatitis (n = 4), pancreatic neoplasia (1), and duodenal perforation (1). One- and 2-year survival rates were both 66%. Increasing age; gamma-glutamyltransferase activity; preanesthetic heart rate; BUN, phosphorus, and bilirubin concentrations; and the use of biliary diversion procedures were risk factors for death, although pancreatitis was not. However, poor long-term survival was associated with pancreatitis. CONCLUSIONS AND CLINICAL RELEVANCE: Long-term prognosis was guarded after biliary surgery in dogs. However, dogs that survived the early postoperative period had good long-term prognosis. Dogs with pancreatitis had poor prognosis. Overall, the prognosis was worse for dogs that underwent a biliary diversion, compared with dogs that did not.

Risk factors associated with short-term outcome and development of perioperative complications in dogs undergoing surgery because of gastric dilatation-volvulus: 166 cases (1992-2003).

OBJECTIVE: To evaluate risk factors associated with death and development of perioperative complications in dogs undergoing surgery for treatment of gastric dilatation-volvulus (GDV). DESIGN: Retrospective case series. ANIMALS: 166 dogs. PROCEDURES: Records of dogs with confirmed GDV that underwent surgery were reviewed. Logistic regression was performed to identify factors associated with development of complications (ie, hypotension, arrhythmias, gastric necrosis necessitating gastrectomy, disseminated intravascular coagulation, peritonitis, sepsis, postoperative dilatation, postoperative vomiting, and incisional problems) and with short-term outcome (ie, died vs survived to the time of suture removal). RESULTS: Short-term mortality rate was 16.2% (27/166). Risk factors significantly associated with death prior to suture removal were clinical signs for > 6 hours prior to examination, combined splenectomy and partial gastrectomy, hypotension at any time during hospitalization, peritonitis, sepsis, and disseminated intravascular coagulation. Partial gastrectomy was not a significant risk factor for death but was for peritonitis, disseminated intravascular coagulation, sepsis, and arrhythmias. Age, gastrectomy, and disseminated intravascular coagulation were risk factors for development of hypotension. Use of a synthetic colloid or hypertonic saline solution was associated with a significantly decreased risk of hypotension. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the prognosis for dogs undergoing surgery because of GDV is good but that certain factors are associated with an increased risk that dogs will develop perioperative complications or die.

Transient Local Bone Remodeling Effects of rhBMP-2 in an Ovine Interbody Spine Fusion Model.

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a powerful osteoinductive morphogen capable of stimulating the migration of mesenchymal stem cells (MSCs) to the site of implantation and inducing the proliferation and differentiation of these MSCs into osteoblasts. Vertebral end-plate and vertebral body resorption has been reported after interbody fusion with high doses of rhBMP-2. In this study, we investigated the effects of 2 rhBMP-2 doses on peri-implant bone resorption and bone remodeling at 7 time points in an end-plate-sparing ovine interbody fusion model. METHODS: Twenty-one female sheep underwent an end-plate-sparing discectomy followed by interbody fusion at L2-L3 and L4-L5 using a custom polyetheretherketone (PEEK) interbody fusion device. The PEEK interbody device was filled with 1 of 2 different doses of rhBMP-2 on an absorbable collagen sponge (ACS): 0.13 mg (1×) or 0.90 mg (7×). Bone remodeling and interbody fusion were assessed via high-resolution radiography and histological analyses at 1, 2, 3, 4, 8, 12, and 20 weeks postoperatively. RESULTS: Peri-implant bone resorption peaked between 3 and 8 weeks in both the 1× and the 7× rhBMP-2/ACS-dose group. Osteoclastic activity and corresponding peri-implant bone resorption was dose-dependent, with moderate-to-marked resorption at the 7×-dose level and less resorption at the 1×-dose level. Both dose (p < 0.0007) and time (p < 0.0025) affected bone resorption significantly. Transient bone-resorption areas were fully healed by 12 weeks. Osseous bridging was seen at all but 1 spinal level at 12 and at 20 weeks. CONCLUSIONS: In the ovine end-plate-sparing interbody fusion model, rhBMP-2 dose-dependent osteoclastic resorption is a transient phenomenon that peaks at 4 weeks postoperatively. CLINICAL RELEVANCE: Using the U.S. Food and Drug Administration (FDA)-approved rhBMP-2 concentration and matching the volume of rhBMP-2/ACS with the volume of desired bone formation within the interbody construct may limit the occurrence of transient bone resorption.