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Department of Orthopedic Surgery, Laboratory for Experimental Orthopedics, CAPHRI, Maastricht University Medical Center, Maastricht, the NetherlandsDepartment of Biomedical Engineering, Orthopedic Biomechanics, Eindhoven University of Technology, Eindhoven, the Netherlands
Department of Orthopedic Surgery, Laboratory for Experimental Orthopedics, CAPHRI, Maastricht University Medical Center, Maastricht, the NetherlandsDepartment of Biomedical Engineering, Orthopedic Biomechanics, Eindhoven University of Technology, Eindhoven, the Netherlands
Corresponding author: Department of Orthopedic Surgery, Laboratory for Experimental Orthopedics, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands, P. Debyelaan 25, HX 6229 Maastricht, the Netherlands, Tel.: +31 43 388 1272.
Department of Orthopedic Surgery, Laboratory for Experimental Orthopedics, CAPHRI, Maastricht University Medical Center, Maastricht, the NetherlandsDepartment of Biomedical Engineering, Orthopedic Biomechanics, Eindhoven University of Technology, Eindhoven, the Netherlands
Lumbar interbody fusion is an effective treatment for unstable spinal segments. However, the time needed to establish a solid bony interbody fusion between the two vertebrae may be longer than twelve months after surgery. During this time window, the instrumented spinal segment is assumed to be at increased risk for instability related complications such as cage migration or subsidence. It is hypothesized that the design of new interbody cages that enable direct osseointegration of the cage at the vertebral endplates, without requiring full bony fusion between the two vertebral endplates, might shorten the time window that the instrumented spinal segment is susceptible to failure.
PURPOSE
To quantify the bone ingrowth and resulting segmental stability during consolidation of lumbar interbody fusion using two different cage types.
STUDY DESIGN
Preclinical ovine model.
METHODS
Seven skeletally mature sheep underwent bi-segmental lumbar interbody fusion surgery with one conventional polyether ether ketone (PEEK) cage, and one newly developed trussed titanium (TT) cage. After a postoperative time period of 13 weeks, non–destructive range of motion testing, and histologic analysis was performed. Additionally, sample specific finite element (FE) analysis was performed to predict the stability of the interbody fusion region alone.
RESULTS
Physiological movement of complete spinal motion segments did not reveal significant differences between the segments operated with PEEK and TT cages. The onset of creeping substitution within the cage seemed to be sooner for PEEK cages, which led to significantly higher bone volume over total volume (BV/TV) compared with the TT cages. TT cages showed significantly more direct bone to implant contact (BIC). Although the mean stability of the interbody fusion region alone was not statistically different between the PEEK and TT cages, the variation within the cage types illustrated an all-or-nothing response for the PEEK cages while a more gradual increase in stability was found for the TT cages.
CONCLUSIONS
Spinal segments operated with conventional PEEK cages were not different from those operated with newly developed TT cages in terms of segmental stability but did show a different mechanism of bone ingrowth and attachment. Based on the differences in development of bony fusion, we hypothesize that TT cages might facilitate increased early segmental stability by direct osseointegration of the cage at the vertebral endplates without requiring complete bony bridging through the cage.
CLINICAL SIGNIFICANCE
Interbody cage type affects the consolidation process of spinal interbody fusion. Whether different consolidation processes of spinal interbody fusion result in clinically significant differences requires further investigation.
The influence of subgroup diagnosis on radiographic and clinical outcomes after lumbar fusion for degenerative disc disorders revisited: a systematic review of the literature.
]. This surgery relies on restoring the segmental stability by implanting a cage into the intervertebral disc space which facilitates bony union of the two adjacent vertebrae. Polyether ether ketone (PEEK) and titanium remain the most commonly used cage materials with both materials having their own strengths and shortcomings [
]. Since bone can only adhere to the implant surface and cannot grow into non–porous materials, both PEEK and titanium cages typically contain a central cavity to enable graft placement and to facilitate bony bridging between vertebral endplates through the cage [
]. During this healing period, the interbody cage is not yet physically constrained by new bony tissue. It has been suggested before that, during this time window, the instrumented spinal segment is at increased risk for complications such as migration or subsidence of the cage [
Fusion rates and subsidence of morselized local bone grafted in titanium cages in posterior lumbar interbody fusion using quantitative three-dimensional computed tomography scans.
]. The usage of supplemental osteobiologics, like bone morphogenetic proteins (BMPs), has previously been evaluated for their ability to shorten this vulnerable healing period [
]. Although BMPs accelerate bone formation, BMPs also demonstrate an initial resorptive response, which may actually lead to an increased incidence of cage migration and subsidence [
]. Another strategy to shorten the time window that a cage is susceptible for migration and subsidence would be the design of new interbody cages that enable quick osseointegration at the vertebral endplates without requiring full consolidation of fusion through the cage.
The emergence of titanium three-dimensional (3D) printing has enabled the production of novel, complex implant geometries, which reduce the apparent stiffness of the total construct and simultaneously provide an open architecture for bone ingrowth [
Metallic powder-bed based 3D printing of cellular scaffolds for orthopaedic implants: A state-of-the-art review on manufacturing, topological design, mechanical properties and biocompatibility.
Mater Sci Eng C Mater Biol Appl.2017; 76: 1328-1343
]. Using 3D printing to manufacture newly designed titanium interbody cages, the osteoconductive material property of titanium can be retained, while eliminating the mismatch in apparent stiffness between cage and native bone. One such novel cage is the trussed titanium (TT) interbody fusion cage (4WEB Medical, Frisco, TX, USA). This design is tailored to distribute the load more evenly throughout the implant and to accommodate ample space for bone ingrowth [
]. Compared with conventional, non–porous, ringed and boxed cages, the TT open cage architecture is hypothesized to facilitate increased early segmental stability during consolidation of fusion, as new bony structures emerging from the vertebral endplates can directly integrate with the interbody cage to establish early osseointegration of the cage at the endplates.
The aim of this study was to quantify the bone ingrowth and segmental stability during consolidation of fusion following lumbar interbody fusion surgery using a novel TT cage compared with a conventional boxed PEEK cage. An ovine lumbar interbody fusion model with a short postoperative time period was used to monitor the development of bone ingrowth histologically and biomechanically before full consolidation of fusion was achieved. Non–destructive range of motion testing was used to evaluate the segmental stability of the complete spinal motion segment and segment specific finite element (FE) analysis was conducted to predict the stability of the interbody fusion region only.
Materials and methods
Cage types
The TT cage used in this research originates from the Posterior Spine Truss System (PSTS) portfolio of interbody fusion devices (4WEB Medical, Frisco, TX, USA). Based on cadaver analysis, the 22×9×6 mm cage without lordosis angle (PSTS-SM0006-22-SP) was selected to be implemented in this ovine study. The open space available for bone graft throughout this TT cage is approximately 0.5 mL. Custom-made, boxed, PEEK cages with the same outer dimensions and a central graft window of about 0.5 mL were designed and manufactured (Instrument Development, Engineering and Evaluation, Maastricht University, Maastricht, the Netherlands).
Animal model and study design
All procedures were in compliance with the European directive 2010/63/EU. Study protocols were approved by local animal welfare committees at the involved institutions in Belgium (Medanex Clinic, Diest) and in the Netherlands (Maastricht University, Maastricht). Seven skeletally mature female Zwartbles sheep (age 2–4 years, weight 76–112 kg) underwent interbody fusion surgery at two non–contiguous levels (L2–L3 and L4–L5). Each sheep was assigned a PEEK cage at one level and a TT cage at the other level using block randomization.
Surgical technique and postoperative course
All surgeries were performed by an experienced spine surgeon (PW). Animals were sedated by intravenous (IV) administration of xylazine (0.1 mg/kg) and anesthesia was induced by injection of ketamine (4 mg/kg, IV) and midazolam (0.2 mg/kg, IV). The animal was placed on the operating table in a right lateral recumbent position and a cuffed endotracheal tube was inserted to provide mechanical ventilation. General anesthesia was maintained with isoflurane (2%). The surgical site was shaved, scrubbed with chlorhexidine gluconate, disinfected with ethanol, and sterilely draped. Then, the lower lumbar spine was retroperitoneally approached following left sided lumbotomy. The spinal column was reached after careful dissection of the iliopsoas muscle and the L2–L3 and L4–L5 disc spaces were identified using fluoroscopy. Next, discectomy was performed. Customized rasp tools that gradually increased in height up to 5 mm allowed the surgeon to induce revascularization of the endplates and to prepare the intervertebral disc space for proper cage impaction without requiring distraction of the vertebrae. At the caudal side of the lumbotomy incision, the iliac crest was exposed, and its cortical shell was opened to harvest chips of trabecular bone. Both cage types were filled with the autologous iliac crest bone graft (ICBG) before impaction. As the 6 mm high cages were hammered into the prepared disc space and were tightly compressed by the two adjacent vertebrae, supplemental fixation could be avoided. The wound was routinely closed in layers (polyglactin 910 braided absorbable suture, size 1) after which the skin was closed (polydioxanone monofilament absorbable suture, size 2/0) and disinfected with chlortetracycline spray. Antibiotics (ceftiofur, 2.2 mg/kg, IV) and analgesia (meloxicam, 0.5 mg/kg, IV; buprenorphine, 6 µg/kg, IV) were administered during surgery.
Sheep were group housed after 2 weeks, were free to move throughout the follow-up period, and had ad libitum access to hay and water. Routine welfare monitoring was performed while paying extra attention to ambulatory function. Daily administration of ceftiofur (2.2 mg/kg, IV) for antibiotic prophylaxis was continued until five days after surgery. The sheep received meloxicam (0.5 mg/kg IV, once a day) for analgesia up to three days after surgery and additional analgesia was given intramuscularly (IM) with buprenorphine (6 µg/kg, twice a day) if deemed necessary by the veterinarian. Red (30 mg/kg alizarin complexone, IV; Sigma #A3882), green (10 mg/kg calcein green, IV; Sigma #C0875), blue (30 mg/kg calcein blue, IV; Sigma #M1255), and orange (90 mg/kg xylenol orange, IV; Sigma #398187) fluorochrome markers were administered to the sheep at 3, 6, 9, and 12 weeks after surgery respectively. Fluorochrome solutions were freshly prepared one day before administration. Each fluorochrome powder was dissolved in 1.4 % (vol/vol) NaHCO3, pH adjusted, sterile filtered, and protected from light. After 13 weeks, the sheep were euthanized by administering an overdose of pentobarbital (200 mg/kg, IV).
Ex vivo non–destructive range of motion testing
Immediately after euthanasia, the lumbar spine L1-L6 was resected en bloc. Excessive soft tissue and musculature were removed from the spine, while retaining ligamentous structures, vertebral bodies, intervertebral discs, and joint capsules. The spine was wrapped in saline soaked gauzes, vacuum sealed in plastic bags, and stored at -20°C. Before testing, spines were slowly thawed to 4°C overnight. Following insertion of wood screws at the distant endplates of the spine, both ends were embedded in Technovit 3040 (Heraeus Kulzer, Dromagen, Germany) using customized potting frames. Next, the spine was mounted on a ST21 Biomechanical Spine Test System (Applied Test Systems, Butler, PA, USA). This system is capable of applying pure moments along each of the anatomical axes of the spine simulating flexion-extension (FE), lateral bending (LB), and axial rotation (AR) [
]. In parallel, an Optotrak (Northern Digital Inc, Waterloo, ON, Canada) optoelectronic measurement device captured the 3D motion of infrared light-emitting diode markers which were rigidly attached to each single vertebral body. All test procedures were performed at room temperature and spines were regularly moistened with saline spray.
Five loading and unloading cycles of continuous moment (±6 Nm) were applied along each of the anatomical axes to simulate FE, LB, and AR. The relative vertebral rotation of each spinal motion segment was determined [
], and the rotation in the loaded direction was expressed versus applied moment. Data of the fourth cycle was used for biomechanical analysis. Range of motion (ROM) was defined as the difference in rotation at maximum and minimum load, neutral zone (NZ) as the difference in rotation between the unloading and loading curve at zero applied moment, and the compliances as the steepest slope of the loading and unloading curve (cloading and cunloading respectively). Data analysis was performed by means of a customized MATLAB (MathWorks, Natick, MA, USA) script.
Histologic analysis
Following non–destructive biomechanical testing, intervertebral segments L2–L3, and L4–L5 were isolated. Undecalcified specimens were trimmed, fixed in 10% neutral buffered formalin, dehydrated through an ascending series of ethanol, infiltrated with methyl methacrylate, and polymerized. Two inner circular sawing microtomes (SP1600, Leica microsystems, Wetzlar, Germany and RMS-16G3, RHA-tech Engineering, Oostzaan, the Netherlands) were used to obtain one 40 µm and three 20 µm thick midsagittal sections per segment. The sections were approximately 300 µm distance from each other as a result of the thickness of the diamond blade [
The 40 µm thick sections were left unstained for epifluorescence microscopy (Eclipse Ti-E, Nikon, Tokyo, Japan). This system was equipped with a quadruple filter block (DAPI/FITC/TRITC/Cy5) and images were digitalized with a color camera (DS-Ri2, Nikon, Tokyo, Japan). Sections were completely digitalized at 4x magnification, and stitched to give a complete image of the histologic section. Per section, the presence of each fluorochrome marker around and within the cage was registered to gain insight into the timing of new bone formation [
The 20 µm thick sections were stained with basic fuchsin and methylene blue solutions to visualize mineralized tissue in and around the cage. A digital image of the entire intervertebral space was captured using bright light microscopy (M8, Precipoint, Freising, Germany). Following segmentation of the image in three regions (cage, bone, soft tissue), bone volume over total volume (BV/TV), and bone to implant contact (BIC) were calculated via a customized MATLAB (MathWorks, Natick, MA, USA) script. BV/TV was defined as the percentage of mineralized tissue area within the available void space of the cage. BIC was expressed as the percentage of the cage interface which was in direct contact with mineralized tissue.
FE analysis
Following segmentation of the three-consecutive histologic sections per spinal segment, the sections were further prepared to establish segment specific FE models. First, the three sections were aligned, cropped to a 15×15 mm region surrounding the cage, and downscaled to a resolution of 20 microns. Second, a semi 3D mesh was generated consisting of 750×750×3 brick elements, each 20×20×300 µm in size. As the size of these elements resembled the spatial resolution of the stacked consecutive sections, segment specific morphologies could be integrated into the model by defining the material of each element based on the pixel values of the prepared sections (Fig. 1).
Fig. 1The FE models were 15×15×0.9 mm in size. A general semi 3D mesh template consisting of 750×750×3 brick elements (each 20×20×300 µm in size) was used. Segment specific morphologies were integrated into the model based on the histologic sections.
]. Poisson's ratio was set to 0.3 for both materials. The cage was implemented as rigid body and compressive axial strain boundary conditions were prescribed [
]. With these boundary conditions, a compressive displacement of 0.075 mm was prescribed to the top surface of the segment to induce 0.5% compressive strain in the longitudinal direction of the segment while the displacement in the other directions at the top face and in all directions at the bottom face were constrained. Models were solved using the FE solver ABAQUS and/or Standard (Simulia, Inc, Providence, RI, USA) version 2018. Per segment, the required stress to achieve 0.5% compressive strain was calculated as the reaction force over the total cross-sectional area of the top surface. In addition, the local maximum (in an absolute sense) principal strains, and stresses were visualized in contour plots.
Statistical analysis
Paired 2-tailed t tests were employed to evaluate differences between PEEK and TT segments for biomechanical parameters, bone histomorphometric parameters (BV/TV and BIC), and reaction stress as predicted by the FE model. In case the difference between paired data did not follow a normal distribution, Wilcoxon signed-rank test was performed. Tests were evaluated using SPSS (IBM Corp., Armonk, NY, USA) version 25.0 and differences were considered to be significant when p<.05.
Results
One sheep expressed signs of paralysis postoperatively and was therefore euthanized prematurely and excluded from the study. Post-mortem micro computed tomography and tissue examination of the operated segments revealed presence of a small piece of loose bone (mm scale) in the vertebral foramen, comprising the spinal cord. Most likely, this small piece of bone was dislodged from the vertebral endplate and pushed forward during endplate rasping or cage impaction. The remaining six animals all completed the study according to protocol. Gross examination of the explanted lumbar spines revealed the presence of anterolateral bony bridges outside the cage at all operated segments.
The derived biomechanical parameters that resulted from non–destructive range of motion testing are displayed in Table 1. For AR loading, only the ROM was reported, as the loading and unloading curves were noisy and overlapping each other impeding reliable evaluation of NZ, cloading,and cunloading. No significant differences were found between the PEEK and TT segments for any of the evaluated biomechanical parameters.
Table 1Biomechanical parameters derived from ex vivo non–destructive range of motion testing. Values expressed as mean ± standard deviation.
PEEK
TT
Flexion Extension
ROM (°)
1.3 ± 0.5
1.3 ± 0.6
NZ (°)
0.6 ± 0.3
0.5 ± 0.2
cextension (°/Nm)
0.4 ± 0.2
0.4 ± 0.4
cflexion (°/Nm)
0.3 ± 0.1
0.3 ± 0.2
Lateral Bending
ROM (°)
1.0 ± 0.4
1.2 ± 0.6
NZ (°)
0.4 ± 0.2
0.5 ± 0.2
cleft (°/Nm)
0.2 ± 0.1
0.2 ± 0.1
cright (°/Nm)
0.3 ± 0.1
0.3 ± 0.2
Axial Rotation
ROM (°)
0.6 ± 0.2
0.5 ± 0.2
Abbreviations: PEEK, polyether ether ketone; TT, trussed titanium; ROM, range of motion; NZ, neutral zone; cx, compliance in the indicated direction x.
The presence of fluorochrome markers is summarized in Table 2. The marker administered at 9 weeks after surgery (calcein blue) showed a diffuse signal which could not be properly distinguished from background signal. Therefore, the 9 week time point has been omitted from the analysis. All other markers were found around both cage types, while marker presence within the cages depended on timing and cage type. There was no sign of bone formation within the cages 3 weeks after surgery. At 6 weeks after surgery, bone formation was found in all PEEK cages, whereas this was found in only four out of six of the TT cages. Active bone formation within the cage was found for all operated segments after 12 weeks, independent of cage type.
Table 2Overview of the presence of the 3-, 6-, and 12-week fluorochrome markers. Per cage type, the number indicates the number of fusion segments in which the marker was present around or within the cage.
Fig. 2 shows the cropped segmented histologic sections for all six segments per cage type. Additionally, the calculated BV/TV and BIC are reported per segment. A significantly higher BV/TV was found for the PEEK cages whereas a significantly higher BIC value was revealed for the TT cages. As noticeable on the segmented sections, BV/TV, and BIC varied widely between segments within both cage types. Despite the presence of substantial bony tissue (BV/TV 22%–42%), there was no direct bone to cage contact for five out of six PEEK segments. Only the segment with the highest BV/TV showed direct bone contact to the PEEK cage. In contrast, direct bone to cage contact was found for every TT segment, also for those having a low BV/TV. The relation between BIC and BV/TV is plotted in Fig. 3 and labeled per cage type. Increasing BV/TV within the TT cage was accompanied by an exponential increase in BIC.
Fig. 2Polyether ether ketone (PEEK) and trussed titanium (TT) segmented histologic sections (c, cage; b, bone; st, soft tissue) as well as corresponding bone volume over total volume (BV/TV) and bone to implant contact (BIC) are displayed. Additionally, the reaction stress (σ) required for inducing a 0.5% compressive strain in the longitudinal direction of the segment is shown. Resulting local maximum absolute principal strains (Max|εprinc|) and stresses (Max|σprinc|) are visualized for each segment. Fusion segments are ordered on BV/TV within both groups. Mean values for BV/TV, BIC, and σ can be found below the double bottom line. # and $ indicate a significant difference between the PEEK and TT group (p<.05). Orientation of sections: top, cranial; bottom, caudal; left, anterior; right, posterior.
Fig. 3Bone to implant contact (BIC) versus bone volume over total volume (BV/TV) for the polyether ether ketone (PEEK) and trussed titanium (TT) segments. Color fill of the markers indicate the reaction stress (σ) required for inducing a 0.5% compressive strain in the longitudinal direction of the segment.
The local maximum absolute principal strains and stresses under 0.5% compressive strain are visualized for every segment in Fig. 2. In addition, the longitudinal reaction stress to realize 0.5% compressive strain is presented per segment. As long as soft tissue separated bony structures from each other and from the cage in the longitudinal direction of the segment (PEEK segments on row 1–5 and TT segments on row 1–2), high local principal strains could be observed in these soft tissue areas. Consequently, the predicted reaction stress and local principal stresses were found to be low for these segments. Reaction stress and local principal stresses increased strongly for segments in which the bony structures were bridged, either directly or indirectly via the cage, in the longitudinal direction of the segment. The mean reaction stress was not significantly different between the PEEK and TT segments. In Fig. 3, the fill of the markers relates to the reaction stress as derived from the FE analysis. For PEEK segments an all-or-nothing response could be observed, whereas for TT segments a more gradual increase in segmental stability was found.
Discussion
The objective of this study was to evaluate the early bone ingrowth and corresponding segmental stability during consolidation of interbody fusion in two different cage types. Differences in interbody fusion development were confirmed between conventional PEEK and newly developed TT cages as demonstrated by bone histomorphometric quantifications. Segment specific FE analysis suggested that bony structures emerging from the vertebral endplate could directly attach and integrate with the TT structure potentially providing early stability, whereas complete bony bridging was required for the PEEK cage in order to provide stability. These trends on cage level were not apparent during non–destructive range of motion testing of the complete spinal motion segment.
Consistent presence of the fluorochrome markers around the cage indicates continuous bone remodeling of the host bone [
]. Generally, several weeks are required to realize vascular ingrowth into the cage before collagen matrix is actively deposited and ossified within the cage [
]. This explains the absence of the 3 week fluorochrome marker within all cages. The difference found between PEEK and TT cages for the 6-week fluorochrome marker within the cage confirms a difference in timing of new bone formation in the cages predicting higher BV/TV within PEEK cages.
Bone histomorphometry indeed revealed that significantly more mineralized tissue was formed within the PEEK cages. This difference potentially arose from the decision to graft both cages as intended clinically, i.e. cages were manually packed with as much ICBG as possible, ignoring standardization of graft quantities. The central cuboid graft window in the PEEK cages could be completely filled with ease, whereas it was more complex to pack the TT cages with graft material throughout the cage. As a result, graft material distribution throughout the TT cages was potentially suboptimal at the onset of impaction, which might have affected the development of bone fusion [
Fusion rate according to mixture ratio and volumes of bone graft in minimally invasive transforaminal lumbar interbody fusion: minimum 2-year follow-up.
]. The TT cage used in this research was the smallest cage commercially available from the PSTS portfolio. Difficulties concerning graft placement will doubtlessly diminish with the use of larger cages, as these contain larger open spaces. Furthermore, the expected difference in graft quantities between cages raises the question whether TT cages can reduce or even obviate the use of graft material. In fact, Wu et al. showed that bone graft could be completely eliminated using 3D printed, porous, titanium cages in the cervical spine in an ovine model [
Porous titanium-6 aluminum-4 vanadium cage has better osseointegration and less micromotion than a poly-ether-ether-ketone cage in sheep vertebral fusion.
]. Future research on the TT cage used in this study should be pursued in order to provide definite conclusions about the necessity to enrich TT cages with graft material.
Although the onset of creeping substitution within PEEK cages appeared to be sooner and led to higher BV/TV, the BIC was higher for the TT cages. Extrapolating the results, it can be suggested that even TT cages without any bone in the cage will have some BIC, i.e. bone emerging from the endplates might firmly attach to the outer interface of the cage before there is any bone present within the cage. As a consequence, early osseointegration of the TT cage at the endplates can be established without requiring full consolidation of fusion through the cage. As soon as the bone growth into the TT cages starts, BIC increases tremendously. On the contrary, PEEK cages only showed direct bone to implant contact in case of complete bony bridging through the cage. It is noteworthy to highlight that the BIC is expressed relatively to the total available interface of the implemented cage. The TT cages have both a larger total interface and a significantly larger BIC, meaning the absolute difference in bone to implant contact between PEEK and TT cage is even higher.
The three local consecutive histologic sections, used to calculate bone morphometric parameters and to establish segment specific FE analysis of the interbody fusion region alone, were assumed to be representative for the overall bone growth throughout the entire cage. Although this assumption may have caused modest over- or underestimations of the total bone structure, there are other factors precluding a direct comparison between the stability results of the interbody fusion region alone and the stability results of the corresponding total spinal segment. The non–destructive range of motion testing presented stability characteristics of the complete motion segment involving ligamentous structures and joint capsules, whilst the segment specific FE models solely focused on the stability of the fusion region surrounding the cage. Moreover, the anterolateral bony bridges found at the operated segments obscured the potential mechanical changes in the interbody region. Although anterolateral bony bridges have been recognized before in ovine interbody fusion models [
], we hypothesize that these bridges were prominently present in the current study as a consequence of the surgical rasping which was performed in order to prepare the intervertebral space for cage impaction. The rasping proceedings presumably irritated the periosteum surrounding the vertebrae, which might have elicited rapid new bone formation outside the interbody area [
Wu S Lin Z Yamaguchi A Kasugai S The effects of periosteum removal on the osteocytes in mouse calvaria. 5th. Volume 1. Dent Oral Craniofac Res 1,
2015: 146-149
Therefore, this study mainly focused on the results of the FE analysis to evaluate the influence of cage type on the interbody segmental stability during consolidation of fusion. Although the mean reaction stress required for inducing a 0.5% compressive strain did not significantly differ between PEEK and TT segments, the distribution of the stress values within each group presents insight into the progression of interbody segmental stability. PEEK segments require direct fusion of the adjacent vertebrae by an uninterrupted bone bridge through the cage in order to provide increased interbody segmental stability. In contrast, TT segments can also provide increased interbody segmental stability by indirect fusion of the adjacent vertebrae, i.e. both adjacent vertebrae firmly attach to the cage without being uninterruptedly bridged through the cage. As a consequence, TT cages can provide a more gradual increase in interbody segmental stability as fusion progresses. This finding is consistent with previous preclinical and clinical literature, describing that PEEK cages require bone to grow around and through the cage to achieve successful fusion, while porous titanium cages have the benefit to accelerate consolidation of fusion by promoting direct osseointegration of the cage at the vertebral endplates [
Porous titanium cervical interbody fusion device in the treatment of degenerative cervical radiculopathy; 1-year results of a prospective controlled trial.
]. Results of the current study also reconfirm that higher BV/TV and BIC alone do not per definition result in higher segmental stability. In fact, proper connectivity in conjunction with decent BV/TV and BIC is essential to attain segmental stability.
A point of improvement for the FE analysis would be the inclusion of more than three histologic sections in order to comprise a larger 3D portion of the total fusion region. This would not only ensure higher representability of the total fusion region, but would also allow for incorporation of the exact 3D connectivity of the cages. In current models, this connectivity was implemented by assuming the cage to be a rigid body. This rigidity may construct an artificially shielded environment for the central part of the interbody fusion region in case this tissue was totally surrounded by cage material. This phenomenon is expressed in the sample on the fourth row of the TT segments (Fig. 2) in which there is hardly any strain or stress observed in the center of the fusion region. Implementation of the exact 3D geometry of the cage would resolve these issues and yield more accurate FE analyses. The distance between consecutive histologic sections (300 µm) was considered suitable for characterizing the 3D structure of trabecular bone since it is in the same order of magnitude as the trabecular thickness and separation of bone from an interbody fusion zone [
Peptide enhanced bone graft substitute presents improved short-term increase in bone volume and construct stiffness compared to iliac crest autologous bone in an ovine lumbar interbody fusion model.
A long postoperative recovery period in an ovine interbody fusion model (>6 months) results in complete fusion of all operated segments, reduces variability within experimental groups, but also conceals potential short-term differences between and within experimental groups [
]. A relatively short postoperative time period was therefore adopted in the current study in order to prevent full completion of interbody fusion in all operated segments upon termination of the experiment. Significant differences emerged between the PEEK and TT group in terms of mean BV/TV and BIC. Since considerable variability in BV/TV and BIC were observed between segments within each group, segments were ordered on BV/TV to gain more insight into the bone ingrowth and segmental stability during consolidation of fusion. Although this method is not a direct longitudinal examination of the progression of fusion within subjects, it is believed to provide reliable information on the progression of the interbody fusion over time. For future research it could be interesting to include multiple postoperative time periods in order to verify these findings.
Current study showed no differences between conventional PEEK and newly developed TT cages in terms of segmental stability of the complete spinal motion segment, but did reveal differences between cages in the mechanism of bone ingrowth and attachment. Based on the differences in development of bony fusion, we hypothesize that TT cages might facilitate increased early segmental stability by direct osseointegration of the cage at the vertebral endplates without requiring complete bony bridging through the cage. When increased stabilization of the interbody segment can be attained before achieving full consolidation of fusion, the time window that a segment is vulnerable to instability related complications might be shortened. Clinical trials involving TT cages should assess whether these local effects indeed develop, and result in lower cage related complication rates.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research for this paper was financially supported by the Prosperos project, funded by the Interreg VA Flanders – the Netherlands program, CCI grant no. 2014TC16RFCB046.
Acknowledgments
The authors would like to thank the Medanex Clinic team and all personnel of the Maastricht University animal facility for their expertise and assistance in performing the animal protocols. Additionally, the authors would like to acknowledge Remco Doodkorte for assistance with biomechanical testing.
Declaration of conflicting interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AL reports investigator salary from 4WEB EU, CS is chief operating officer of 4WEB EU.
References
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The influence of subgroup diagnosis on radiographic and clinical outcomes after lumbar fusion for degenerative disc disorders revisited: a systematic review of the literature.
Fusion rates and subsidence of morselized local bone grafted in titanium cages in posterior lumbar interbody fusion using quantitative three-dimensional computed tomography scans.
Metallic powder-bed based 3D printing of cellular scaffolds for orthopaedic implants: A state-of-the-art review on manufacturing, topological design, mechanical properties and biocompatibility.
Mater Sci Eng C Mater Biol Appl.2017; 76: 1328-1343
Fusion rate according to mixture ratio and volumes of bone graft in minimally invasive transforaminal lumbar interbody fusion: minimum 2-year follow-up.
Porous titanium-6 aluminum-4 vanadium cage has better osseointegration and less micromotion than a poly-ether-ether-ketone cage in sheep vertebral fusion.
Wu S Lin Z Yamaguchi A Kasugai S The effects of periosteum removal on the osteocytes in mouse calvaria. 5th. Volume 1. Dent Oral Craniofac Res 1,
2015: 146-149
Porous titanium cervical interbody fusion device in the treatment of degenerative cervical radiculopathy; 1-year results of a prospective controlled trial.
Peptide enhanced bone graft substitute presents improved short-term increase in bone volume and construct stiffness compared to iliac crest autologous bone in an ovine lumbar interbody fusion model.
FDA device/drug status: Approved (Trussed Titanium (TT) cage from 4WEB Medical [PSTS-SM0006-22-SP])
Author disclosures: ACYL: Nothing to disclose. MJMP: Nothing to disclose. RTJB: Grant: Interreg VA Flanders - The Netherlands (G, Paid directly to institution/employer). CS: Nothing to disclose. EVH: Support for travel to meetings for the study or other purposes: EU grant (A, Paid directly to institution/employer); Payment for writing or reviewing the manuscript: EU grant (A, Paid directly to institution/employer); Research Support (Investigator Salary, Staff/Materials); EU grant (A, Paid directly to institution/employer). VMJIC: Nothing to disclose. TR: Nothing to disclose. BVR: Nothing to disclose. PCW: Nothing to disclose. JJA: Grant: European Union Interreg V Flanders-The Netherlands (l, Paid directly to institution/employer); Consulting: DSM Biomedical (B, Paid directly to institution/employer), Bonalive (B, Paid directly to institution/employer); Research Support (Investigator Salary, Staff/Materials)^: Bonalive (B, Paid directly to institution/employer), DSM biomedical (B, Paid directly to institution/employer), Cerapedics (B, Paid directly to institution/employer); Grants: NWA-DARTBAC (I, Paid directly to institution/employer).
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