Percutaneous thoraco-lumbar-sacral pedicle screw placement accuracy results from a multi-center, prospective clinical study using a skin marker-based optical navigation system.

STUDY DESIGN: Prospective multi-center study. OBJECTIVE: The study aimed to evaluate the accuracy of pedicle screw placement using a skin marker-based optical surgical navigation system for minimal invasive thoraco-lumbar-sacral pedicle screw placement. METHODS: The study was performed in a hybrid Operating Room with a video camera-based navigation system integrated in the imaging hardware. The patient was tracked with non-invasive skin markers while the instrument tracking was via an on-shaft optical marker pattern. The screw placement accuracy assessment was performed by three independent reviewers, using the Gertzbein grading. The screw placement time as well as the staff and patient radiation doses was also measured. RESULTS: In total, 211 screws in 39 patients were analyzed for screw placement accuracy. Of these 32.7% were in the thoracic region, 59.7% were in the lumbar region, and 7.6% were in the sacral region. An overall accuracy of 98.1% was achieved. No screws were deemed severely misplaced (Gertzbein grading 3). The average time for screw placement was 6 min and 25 secs (± 3 min 33 secs). The average operator radiation dose per subject was 40.3 µSv. The mean patient effective dose (ED) was 11.94 mSv. CONCLUSION: Skin marker-based ON can be used to achieve very accurate thoracolumbarsacral pedicle screw placements.

Suppression of the immune system as a critical step for bone formation from allogeneic osteoprogenitors implanted in rats.

The surface marker profile of mesenchymal stromal cells (MSCs) suggests that they can escape detection by the immune system of an allogeneic host. This could be an optimal strategy for bone regeneration applications, where off-the-shelf cells could be implanted to heal bone defects. However, it is unknown how pre-differentiation of MSCs to an osteogenic lineage, a means of improving bone formation, affects their immunogenicity. Using immunohistological techniques in a rat ectopic implantation model, we demonstrate that allogeneic osteoprogenitors mount a T cell- and B cell-mediated immune response resulting in an absence of in vivo bone formation. Suppression of the host immune response with daily administration of an immunosuppressant, FK506, is effective in preventing the immune attack on the allogeneic osteoprogenitors. In the immunosuppressed environment, the allogeneic osteoprogenitors are capable of generating bone in amounts similar to those of syngeneic cells. However, using osteoprogenitors from one of the allogeneic donors led to newly deposited bone that was attacked by the host immune system, despite the continued administration of the immunosuppressant. This suggests that, although using an immunosuppressant can potentially suppress the immune attack on the allogeneic cells, optimizing the dose of the immunosuppressant may be crucial to ensure bone formation within the allogeneic environment. Overall, allografts comprising osteoprogenitors derived from allogeneic MSCs have the potential to be used in bone regeneration applications.

Image quality and radiation dose in spinal surgery: a comparison of three imaging systems in phantom.

Purpose: Using optimal settings for x-ray scans is crucial for obtaining three-dimensional images of high quality while keeping the patient dose low. Our work compares dose and image quality (IQ) of three intraoperative imaging systems [O-arm cone-beam computed tomography (CBCT), ClarifEye C-arm CBCT, and Airo computed tomography] used for spinal surgery. Approach: Patients of 70, 90, and 110 kg were simulated with an anthropomorphic phantom by adding tissue-equivalent material. Titanium inserts were placed in the phantom spine for reproducing metal artifacts in the images. Organ dose was measured with thermo-luminescent dosimeters for effective dose (E) calculation. Subjective IQ was assessed by ranking the images acquired with the manufacturer-defined imaging protocols. Objective IQ was assessed with a customized Catphan phantom. Results: The ClarifEye protocols resulted in the lowest E ranging from 1.4 to 5.1 mSv according to phantom size and protocol. The highest E was measured for the high-definition protocol of O-arm (E 2.2 to 9 mSv) providing the best subjective IQ for imaging of the spine without titanium inserts. For the images with metal, the best IQ was obtained with ClarifEye. Airo (E 5.5 to 8.4 mSv) was ranked with the lowest IQ for images without metal while the rank improved for images with metal. Airo images had better uniformity, noise, and contrast sensitivity compared with CBCTs but worse high-contrast resolution. The values of these parameters were comparable between the CBCT systems. Conclusions: Both CBCT systems provided better IQ compared with Airo for navigation of lumbar spinal surgery for the original phantom. Metal artifacts particularly affect O-arm images decreasing the subjective IQ. The high spatial resolution of CBCT systems resulted in a relevant parameter for the visibility of anatomical features important for spine navigation. Low dose protocols were enough to obtain a clinically acceptable contrast-to-noise ratio in the bones.

Minimally Invasive Transforaminal Lumbar Interbody Fusion Using Augmented Reality Surgical Navigation for Percutaneous Pedicle Screw Placement.

STUDY DESIGN: This was a retrospective observational study. OBJECTIVE: The aim of this study was to evaluate the accuracy of percutaneous pedicle screw placement using augmented reality surgical navigation during minimally invasive transforaminal lumbar interbody fusion (TLIF). SUMMARY OF BACKGROUND DATA: Augmented reality-based navigation is a new type of computer-assisted navigation where video cameras are used instead of infrared cameras to track the operated patients and surgical instruments. This technology has not so far been clinically evaluated for percutaneous pedicle screw placement. MATERIALS AND METHODS: The study assessed percutaneous pedicle screw placement in 20 consecutive patients who underwent single-level minimally invasive TLIF using augmented reality surgical navigation. Facet joint violation and depression by the inserted pedicle screws were evaluated. Secondary outcome such as radiation dose exposure, fluoroscopy time, and operative time were collected for 3 phases of surgery: preparation phase, pedicle screw placement, and decompression with cage placement. RESULTS: A clinical accuracy for screw placement within the pedicle (Gertzbein 0 or 1) of 94% was achieved. One screw violated the facet joint with a transarticular pathway. The screw head did not depress the facet in 54%. The use of fluoroscopy during navigation correlated with patient body-mass index (r=0.68, P<0.0001). The pedicle screw placement time corresponded to 36±5% of the total operative time of 117±11 minutes. A statistically significant decrease of 10 minutes in operative time was observed between the first and last 10 procedures which corresponded to the pedicle screw placement time decrease (48±9 vs. 38±7 min, P=0.0142). The learning curve model suggests an ultimate operative time decrease to 97 minutes. CONCLUSION: Augmented reality surgical navigation can be clinically used to place percutaneous screws during minimally invasive TLIF. However, the lack of tracking of the location of the device requires intraoperative fluoroscopy to monitor screw insertion depth especially in obese patients. LEVEL OF EVIDENCE: Level III.

Accuracy of augmented reality surgical navigation for minimally invasive pedicle screw insertion in the thoracic and lumbar spine with a new tracking device.

BACKGROUND CONTEXT: Minimally invasive approaches are increasingly used in spine surgery. The purpose of navigation systems is to guide the surgeon and to reduce intraoperative x-ray exposure. PURPOSE: This study aimed to determine the feasibility and clinical accuracy of a navigation technology based on augmented reality surgical navigation (ARSN) for minimally invasive thoracic and lumbar pedicle screw instrumentation compared with standard fluoroscopy-guided minimally invasive technique. STUDY DESIGN/SETTING: Cadaveric laboratory study. METHODS: ARSN was installed in a hybrid operating room, consisting of a flat panel detector c-arm with two dimensional/three dimensional imaging capabilities and four integrated cameras in its frame. The surface-referenced navigation device does not require a bony reference but uses video cameras and optical markers applied to the patient's skin for tracking. In four cadavers, a total of 136 pedicle screws were inserted in thoracic and lumbar vertebrae. The accuracy was assessed by three independent raters in postoperative conventional computed tomography. RESULTS: The overall accuracy of ARSN was 94% compared with an accuracy of 88% for fluoroscopy. The difference was not statistically significant. In the thoracic region, accuracy with ARSN was 92% compared with 83% with fluoroscopy. With fluoroscopy, unsafe screws were observed in three normal cadavers and one with scoliosis. Using ARSN, unsafe screws were only observed in the scoliotic spine. No significant difference in the median of time for K-wire placement was recorded. As no intraoperative fluoroscopy was necessary in ARSN, the performing surgeon was not exposed to radiation. CONCLUSIONS: In this limited cadaveric study minimally invasive screw placement using ARSN was demonstrated to be feasible and as accurate as fluoroscopy. It did not require any additional navigation time or use of any intraoperative x-ray imaging, thereby potentially permitting surgery in a protective lead garment-free environment. A well-powered clinical study is needed to demonstrate a significant difference in the accuracy between the two methods. CLINICAL SIGNIFICANCE: ARSN offers real-time imaging of planned insertion paths, instrument tracking, and overlay of three dimensional bony anatomy and surface topography. The referencing procedure, by optical recognition of several skin markers is easy and does not require a solid bony reference as necessary for conventional navigation which saves time. Additionally, ARSN may foster the reduction of intraoperative x-ray exposure to spinal surgeons.

Fabrication of polycaprolactone-silanated ß-tricalcium phosphate-heparan sulfate scaffolds for spinal fusion applications.

BACKGROUND CONTEXT: Interbody spinal fusion relies on the use of external fixation and the placement of a fusion cage filled with graft materials (scaffolds) without regard for their mechanical performance. Stability at the fusion site is instead reliant on fixation hardware combined with a selected cage. Ideally, scaffolds placed into the cage should both support the formation of new bone and contribute to the mechanical stability at the fusion site. PURPOSE: We recently developed a scaffold consisting of silane-modified PCL-TCP (PCL-siTCP) with mechanical properties that can withstand the higher loads generated in the spine. To ensure the scaffold more closely mimicked the bone matrix, we incorporated collagen (Col) and a heparan sulfate glycosaminoglycan sugar (HS3) with increased affinity for heparin-binding proteins such as bone morphogenetic protein-2 (BMP-2). The osteostimulatory characteristic of this novel device delivering exogenous BMP2 was assessed in vitro and in vivo as a prelude to future spinal fusion studies with this device. STUDY DESIGN/SETTING: A combination of cell-free assays (BMP2 release), progenitor cell-based assays (BMP2 bioactivity, cell proliferation and differentiation), and rodent ectopic bone formation assays was used to assess the osteostimulatory characteristics of the PCL-siTCP-based scaffolds. MATERIALS AND METHODS: Freshly prepared rat mesenchymal stem cells were used to determine reparative cell proliferation and differentiation on the PCL-siTCP-based scaffolds over a 28-day period in vitro. The bioactivity of BMP2 released from the scaffolds was assessed on progenitor cells over a 28-day period using ALP activity assays and release kinetics as determined by enzyme-linked immunosorbent assay. For ectopic bone formation, intramuscular placement of scaffolds into Sprague Dawley rats (female, 4 weeks old, 120-150 g) was achieved in five animals, each receiving four treatments randomized for location along the limb. The four groups tested were (1) PCL-siTCP/Col (5-mm diameter×1-mm thickness), PCL-siTCP/Col/BMP2 (5 µg), (3) PCL-siTCP/Col/HS3 (25 µg), and (4) PCL-siTCP/Col/HS3/BMP2 (25 and 5 µg, respectively). Bone formation was evaluated at 8 weeks post implantation by microcomputed tomography (µCT) and histology. RESULTS: Progenitor cell-based assays (proliferation, mRNA transcripts, and ALP activity) confirmed that BMP2 released from PCL-siTCP/Col/HS3 scaffolds increased ALP expression and mRNA levels of the osteogenic biomarkers Runx2, Col1a2, ALP, and bone gla protein-osteocalcin compared with devices without HS3. When the PCL-siTCP/Col/HS3/BMP2 scaffolds were implanted into rat hamstring muscle, increased bone formation (as determined by two-dimensional and three-dimensional µCTs and histologic analyses) was observed compared with scaffolds lacking BMP2. More consistent increases in the amount of ectopic bone were observed for the PCL-siTCP/Col/HS3/BMP2 implants compared with PCL-siTCP/Col/BMP2. Also, increased mineralizing tissue within the pores of the scaffold was seen with modified-tetrachrome histology, a result confirmed by µCT, and a modest but detectable increase in both the number and the thickness of ectopic bone structures were observed with the PCL-siTCP/Col/HS3/BMP2 implants. CONCLUSIONS: The combination of PCL-siTCP/Col/HS3/BMP2 thus represents a promising avenue for further development as a bone graft alternative for spinal fusion surgery.

Inflammatory response and bone healing capacity of two porous calcium phosphate ceramics in critical size cortical bone defects.

In the present study, two open porous calcium phosphate ceramics, ß-tricalcium phosphate (ß-TCP), and hydroxyapatite (HA) were compared in a critical-sized femoral defect in rats. Previous comparisons of these two ceramics showed significantly greater osteoinductive potential of ß-TCP upon intramuscular implantation and a better performance in a spinal fusion model in dogs. Results of the current study also showed significantly more bone formation in defects grafted with ß-TCP compared to HA; however, both the ceramics were not capable of increasing bone formation to such extend that it bridges the defect. Furthermore, a more pronounced degradation of ß-TCP was observed as compared to HA. Progression of inflammation and initiation of new bone formation were assessed for both materials at multiple time points by histological and fluorochrome-based analyses. Until 12 days postimplantation, a strong inflammatory response in absence of new bone formation was observed in both ceramics, without obvious differences between the two materials. Four weeks postimplantation, signs of new bone formation were found in both ß-TCP and HA. At 6 weeks, inflammation had subsided in both ceramics while bone deposition continued. In conclusion, the two ceramics differed in the amount of bone formed after 8 weeks of implantation, whereas no differences were found in the duration of the inflammatory phase after implantation or initiation of new bone formation.

Engineering new bone via a minimally invasive route using human bone marrow-derived stromal cell aggregates, microceramic particles, and human platelet-rich plasma gel.

There is a rise in the popularity of arthroscopic procedures in orthopedics. However, the majority of cell-based bone tissue-engineered constructs (TECs) rely on solid preformed scaffolding materials, which require large incisions and extensive dissections for placement at the defect site. Thus, they are not suitable for minimally invasive techniques. The aim of this study was to develop a clinically relevant, easily moldable, bone TEC, amenable to minimally invasive techniques, using human mesenchymal stromal cells (hMSCs) and calcium phosphate microparticles in combination with an in situ forming platelet-rich plasma gel obtained from human platelets. Most conventional TECs rely on seeding and culturing single-cell suspensions of hMSCs on scaffolds. However, for generating TECs amenable to the minimally invasive approach, it was essential to aggregate the hMSCs in vitro before seeding them on the scaffolds as unaggregated MSCs did not generate any bone. Twenty four hours of in vitro aggregation was determined to be optimal for maintaining cell viability in vitro and bone formation in vivo. Moreover, no statistically significant difference was observed in the amount of bone formed when the TECs were implanted via an open approach or a minimally invasive route. TECs generated using MSCs from three different human donors generated new bone through the minimally invasive route in a reproducible manner, suggesting that these TECs could be a viable alternative to preformed scaffolds employed through an open surgery for treating bone defects.

Streamlining the generation of an osteogenic graft by 3D culture of unprocessed bone marrow on ceramic scaffolds.

Mesenchymal stromal cells are present in very low numbers in the bone marrow, necessitating their selective expansion on tissue culture plastic prior to their use in tissue-engineering applications. MSC expansion is laborious, time consuming, unphysiological and not economical, thus calling for automated bioreactor-based strategies. We and others have shown that osteogenic grafts can be cultured in bioreactors by seeding either 2D-expanded cells or by direct seeding of the mononuclear fraction of bone marrow. To further streamline this protocol, we assessed in this study the possibility of seeding the cells onto porous calcium phosphate ceramics directly from unprocessed bone marrow. Using predetermined volumes of bone marrow from multiple human donors with different nucleated cell counts, we were able to grow a confluent cell sheath on the scaffold surface in 3 weeks. Cells of stromal, endothelial and haematopoietic origin were detected, in contrast to grafts grown from 2D expanded cells, where only stromal cells could be seen. Upon implantation in nude mice, similar quantities of bone tissue were generated as compared to that obtained by using the conventional number of culture expanded cells from the same donor. We conclude that human osteogenic grafts can be efficiently prepared by direct seeding of cells from unprocessed bone marrow.

The effect of platelet lysate supplementation of a dextran-based hydrogel on cartilage formation.

In situ gelating dextran-tyramine (Dex-TA) injectable hydrogels have previously shown promising features for cartilage repair. Yet, despite suitable mechanical properties, this system lacks intrinsic biological signals. In contrast, platelet lysate-derived hydrogels are rich in growth factors and anti-inflammatory cytokines, but mechanically unstable. We hypothesized that the advantages of these systems may be combined in one hydrogel, which can be easily translated into clinical settings. Platelet lysate was successfully incorporated into Dex-TA polymer solution prior to gelation. After enzymatic crosslinking, rheological and morphological evaluations were performed. Subsequently, the effect of platelet lysate on cell migration, adhesion, proliferation and multi-lineage differentiation was determined. Finally, we evaluated the integration potential of this gel onto osteoarthritis-affected cartilage. The mechanical properties and covalent attachment of Dex-TA to cartilage tissue during in situ gel formation were successfully combined with the advantages of platelet lysate, revealing the potential of this enhanced hydrogel as a cell-free approach. The addition of platelet lysate did not affect the mechanical properties and porosity of Dex-TA hydrogels. Furthermore, platelet lysate derived anabolic growth factors promoted proliferation and triggered chondrogenic differentiation of mesenchymal stromal cells.

Clinical application of human mesenchymal stromal cells for bone tissue engineering.

The gold standard in the repair of bony defects is autologous bone grafting, even though it has drawbacks in terms of availability and morbidity at the harvesting site. Bone-tissue engineering, in which osteogenic cells and scaffolds are combined, is considered as a potential bone graft substitute strategy. Proof-of-principle for bone tissue engineering using mesenchymal stromal cells (MSCs) has been demonstrated in various animal models. In addition, 7 human clinical studies have so far been conducted. Because the experimental design and evaluation parameters of the studies are rather heterogeneous, it is difficult to draw conclusive evidence on the performance of one approach over the other. However, it seems that bone apposition by the grafted MSCs in these studies is observed but not sufficient to bridge large bone defects. In this paper, we discuss the published human clinical studies performed so far for bone-tissue regeneration, using culture-expanded, nongenetically modified MSCs from various sources and extract from it points of consideration for future clinical studies.