In Vitro Biomechanical Testing and Computational: Modeling in Spine

Two separate in vitro biomechanical studies were conducted on human cadaveric spines (Lumbar) to evaluate the stability following the implantation of two different spinal fixation devices interspinous fixation device (ISD) and Hybrid dynamic stabilizers. ISD was evaluated as a stand-alone and in combination with unilateral pedicle rod system. The results were compared against the gold standard, spinal fusion (bilateral pedicle rod system). The second study involving the hybrid dynamic system, evaluated the effect on adjacent levels using a hybrid testing protocol. A robotic spine testing system was used to conduct the biomechanical tests. This system has the ability to apply continuous unconstrained pure moments while dynamically optimizing the motion path to minimize off-axis loads during testing. Thus enabling precise control over the loading and boundary conditions of the test. This ensures test reliability and reproducibility. We found that in flexion-extension, the ISD can provide lumbar stability comparable to spinal fusion. However, it provides minimal rigidity in lateral bending and axial rotation when used as a stand-alone. The ISD with a unilateral pedicle rod system when compared to the spinal fusion construct were shown to provide similar levels of stability in all directions, though the spinal fusion construct showed a trend toward improved stiffness overall. The results for the dynamic stabilization system showed stability characteristics similar to a solid all metal construct. Its addition to the supra adjacent level (L3- L4) to the fusion (L4- L5) indeed protected the adjacent level from excessive motion. However, it essentially transformed a 1 level into a 2 level lumbar fusion with exponential transfer of motion to the fewer remaining discs (excessive adjacent level motion). The computational aspect of the study involved the development of a spine model (single segment). The kinematic data from these biomechanical studies (ISD study) was then used to validate a finite element model

DESIGN AND DEVELOPMENT OF IN VITRO TOOLS TO ASSESS FIXATION AND MOTION IN THE SPINE

In vitro biomechanical testing of the spine is an important method for evaluating new surgical methods and components, prior to in vivo implementation. This relies upon special laboratory tools and techniques to create spinal motion and loading similar to those experienced in the body. In this thesis, two different studies were performed to evaluate the effects of spinal fixation and motion. The first study compared the fixation of a novel hollow screw and a conventional solid screw in an in vitro sacral model. Screws were tested in seven cadaveric sacra and subjected to stair-cased cyclic flexion- extension loading to simulate the clinical loading scenario. The hollow screw was less resistant to loosening compared to the solid screw in this model. In the second part of this thesis, a spinal loading simulator was developed as a modification to an existing Instron® materials testing machine to produce motion in a multi-segment spine using applied pure bending moments (i.e. flexibility protocol). A custom-designed 2D optical tracking system was used to record the planar motion achieved. An experimental validation study was performed using the developed apparatus, and showed the device was capable of independently producing repeatable and reproducible spine motions (i.e. flexion-extension, lateral bending, and axial rotation) in a single cadaveric specimen. Future work will focus on the continued development of the simulator for use in the assessment of spinal orthopaedic interventions

DESIGN AND DEVELOPMENT OF IN VITRO TOOLS TO ASSESS FIXATION AND MOTION IN THE SPINE

In vitro biomechanical testing of the spine is an important method for evaluating new surgical methods and components, prior to in vivo implementation. This relies upon special laboratory tools and techniques to create spinal motion and loading similar to those experienced in the body. In this thesis, two different studies were performed to evaluate the effects of spinal fixation and motion. The first study compared the fixation of a novel hollow screw and a conventional solid screw in an in vitro sacral model. Screws were tested in seven cadaveric sacra and subjected to stair-cased cyclic flexion­ extension loading to simulate the clinical loading scenario. The hollow screw was less resistant to loosening compared to the solid screw in this model. In the second part of this thesis, a spinal loading simulator was developed as a modification to an existing Instron® materials testing machine to produce motion in a multi-segment spine using applied pure bending moments (i.e. flexibility protocol). A custom-designed 2D optical tracking system was used to record the planar motion achieved. An experimental validation study was performed using the developed apparatus, and showed the device was capable of independently producing repeatable and reproducible spine motions (i.e. flexion-extension, lateral bending, and axial rotation) in a single cadaveric specimen. Future work will focus on the continued development of the simulator for use in the assessment of spinal orthopaedic interventions

ADVANCED INTRAOPERATIVE IMAGE REGISTRATION FOR PLANNING AND GUIDANCE OF ROBOT-ASSISTED SURGERY

Robot-assisted surgery offers improved accuracy, precision, safety, and workflow for a variety of surgical procedures spanning different surgical contexts (e.g., neurosurgery, pulmonary interventions, orthopaedics). These systems can assist with implant placement, drilling, bone resection, and biopsy while reducing human errors (e.g., hand tremors and limited dexterity) and easing the workflow of such tasks. Furthermore, such systems can reduce radiation dose to the clinician in fluoroscopically-guided procedures since many robots can perform their task in the imaging field-of-view (FOV) without the surgeon. Robot-assisted surgery requires (1) a preoperative plan defined relative to the patient that instructs the robot to perform a task, (2) intraoperative registration of the patient to transform the planning data into the intraoperative space, and (3) intraoperative registration of the robot to the patient to guide the robot to execute the plan. However, despite the operational improvements achieved using robot-assisted surgery, there are geometric inaccuracies and significant challenges to workflow associated with (1-3) that impact widespread adoption. This thesis aims to address these challenges by using image registration to plan and guide robot- assisted surgical (RAS) systems to encourage greater adoption of robotic-assistance across surgical contexts (in this work, spinal neurosurgery, pulmonary interventions, and orthopaedic trauma). The proposed methods will also be compatible with diverse imaging and robotic platforms (including low-cost systems) to improve the accessibility of RAS systems for a wide range of hospital and use settings. This dissertation advances important components of image-guided, robot-assisted surgery, including: (1) automatic target planning using statistical models and surgeon-specific atlases for application in spinal neurosurgery; (2) intraoperative registration and guidance of a robot to the planning data using 3D-2D image registration (i.e., an “image-guided robot”) for assisting pelvic orthopaedic trauma; (3) advanced methods for intraoperative registration of planning data in deformable anatomy for guiding pulmonary interventions; and (4) extension of image-guided robotics in a piecewise rigid, multi-body context in which the robot directly manipulates anatomy for assisting ankle orthopaedic trauma

The safety and efficacy of mesenchymal stem cells for prevention or regeneration of intervertebral disc degeneration: a systematic review

General Posters: abstract no. GP86INTRODUCTION: Mesenchymal stem cells (MSCs) have been used to halt the progression or regenerate the disc with hopes to prevent or treat discogenic back pain. However, the safety and efficacy of the use of MSCs for such treatment in animal and human models at short and long term assessment (i.e. greater than 48 weeks) have not been systematically addressed. This study addressed a systematic review of comparative controlled studies addressing the use of MSCs to that of no treatment/saline for the treatment of disc degeneration. METHODS: Online databases were extensively searched. Controlled trials in animal models and humans were eligible for inclusion. Trial design, MSC characteristics, injection method, disc assessment, outcome intervals, and complication events were assessed. Validity of each study was assessed addressing trial design. Two individuals independently addressed the aforementioned. RESULTS: Twenty-two animal studies were included. No human comparative controlled trials were reported. All three types of MSCs (i.e. derived from bone marrow, synovial and adipose tissue) showed successful inhibition of disc degeneration progression. From three included studies, bone marrow derived MSC showed superior quality of disc repair when compared to other treatments, including TGF-β1, NP bilaminar co-culture and axial distraction regimen. However, osteophyte development was reported in two studies as potential complication of MSC transplantation. CONCLUSIONS: Based on animal models, the current evidence suggests that in the short-term MSC transplantation is safe and effective in halting disc degeneration; however, additional and larger studies are needed to assess the long-term regenerative effects and potential complications. Inconsistency in methodological design and outcome parameters prevent any robust conclusions. In addition, randomized controlled trials in humans are needed to assess the safety and efficacy of such therapy.published_or_final_versio

Factors affecting accuracy and fusion rate in lumbosacral fusion surgery - a preclinical and clinical study

Lumbosacral fusion surgery is indicated in symptomatic degenerative lumbosacral disorder, when the origin of pain is demonstrated to lie within the restricted number of functional spinal units and when the pain is refractory to the conservative treatment, to eliminate painful motion of the spinal units. Inaccurate placement of pedicle screws may cause neurological symptoms, and result in early hardware failure and return of spinal instability symptoms. All spinal instrumentation eventually fails without solid bony fusion, and the presence of symptomatic bony non-union at least a year after fusion surgery is defined as pseudoarthrosis. Bioactive glasses (BAGs) are synthetic, biocompatible, osteoconductive and osteostimulative materials with angiogenic and antibacterial properties, able to bond to bone. In a study of 147 patients and 837 pedicle screws placed due to degenerative lumbosacral spine disorder, 14.3 % breached the pedicle. New neurological symptoms corresponding to the breach were observed in 25.9 % of patients with pedicle breach, and 89.2 % of the symptomatic breaches were either medially or inferiorly. A preclinical controlled study of novel BAG S53P4 putty showed good biocompatibility, slightly higher intramedullary ossification of putty group compared to the control group, and that the binder agent did not disturb formation of new bone in vivo. The interbody fusion rate was 95.8 % with BAG S53P4 putty as bone graft expander with autograft in clinical lumbosacral interbody fusion, indicating at least as good interbody fusion results as the presently used materials. One early operative subsidence remaining unchanged over the study period was observed with putty.Lannerangan luudutusleikkausten tarkkuuteen ja luutumiseen vaikuttavat tekijät Lannerangan luudutusleikkaus voidaan tehdä oireisessa lannerangan rappeumasairaudessa, kun kivun syyn on osoitettu sijaitsevan rajallisessa määrässä selkärangan toiminnallisia yksikköjä ja kun kipu ei vähene leikkauksettomilla hoidoilla. Leikkauksella voidaan poistaa kipua tuottava selkärangan toiminnallisten yksikköjen liike. Epätarkka pedikkeliruuvien asettaminen voi aiheuttaa neurologisia oireita ja johtaa nopeaan kiinnitysosien irtoamiseen ja rangan epätukevuusoireiden palaamiseen. Suuri osa selkärangan kiinnityslaitteista irtoaa lopulta, jollei luutumista kiinnitettyjen kohtien välillä tapahdu. Vuoden kuluttua luudutusleikkauksesta oireista luutumatonta kiinnityskohtaa nimitetään pseudoartroosiksi. Bioaktiiviset lasit ovat synteettisiä, bioyhteensopivia, osteokonduktiivisia ja osteostimulatiivisia materiaaleja, joilla on angiogeenisiä ja antibakteerisia ominaisuuksia, ja ne voivat sitoutua suoraan luuhun. 147 potilaalle lannerangan rappeumasairauden vuoksi asetetut 837 pedikkeliruuvia käsittävän tutkimuksen mukaan 14.3 % ruuveista rikkoi luisen pedikkelin seinämän. 25.9 %:lla potilaista, joilla ruuvi läpäisi pedikkelin seinämän, ilmeni uusia neurologisia oireita, ja 89.2 %:lla oireisista potilaista pedikkeliruuvi läpäisi pedikkelin seinämän mediaalisesti tai inferiorisesti. Prekliinisessä kontrolloidussa tutkimuksessa uudenlainen bioaktiivisesta lasista valmistettu S53P4 luunkorviketahna todettiin bioyhteensopivaksi, ja sen avulla saavutettiin hieman vertailuryhmää parempi luutuminen luuydinontelossa. Tahnan sidosaineen ei eläinkokeessa todettu häiritsevän luun muodostumista. Kliinisessä tutkimuksessa saavutettiin 95.8 %:n luutuminen käytettäessä S53P4 biolasitahnaa yhdessä oman luun kanssa lannerangan nikamasolmujen välisessä luudutuksessa. Siten yhdessä oman luun kanssa käytettäessä S53P4 biolasitahnalla saadaan aikaan vähintään yhtä hyvä nikamasolmujen välinen luutuminen kuin nykyisin käytettävillä synteettisillä luunkorvikkeilla. Tutkimuksessa todettiin yksi leikkauksen yhteydessä tapahtunut nikamasolmujen välisen implantin päätelevyyn painuminen, jonka suuruus ei muuttunut seurantakuvantamisissa

The Development and Application of a Custom Robotic Biomechanical Testing Platform Employing Real-time Load-control to Compare Spinal Biomechanical Testing Protocols: Pure Moment, Ideal Follower Load, and a Novel Trunk Weight Protocol

The human lumbar spine has been the subject of biomechanical study for many decades owing to the numerous medical cases resulting in the development of various corrective surgical procedures and medical devices intended to relieve patient discomfort. Spinal biomechanics is a broad field containing but not limited to the in vitro study of cadaveric tissue utilizing testing platforms used to apply motion- or load-profiles to tissue in the investigation of the various kinetic or kinematic responses, respectively. The particular arena field of this research concerns the field of robotics as it applies to testing platforms and how they are applied to lumbar spine biomechanical testing. The in vivo spine is subject to six degrees of freedom (DOF) of motion as a consequence of the applied loads of surrounding musculature which apply component loads in 6 DOF. However current in vitro standard protocols apply isolated loads primarily in the anatomical planes. Although the primary goal of in vitro testing may not be the simulation of in vivo circumstances, the accurate recreation of the in vivo loading environment would reveal much regarding the passive biomechanics of the spine. To accomplish such a goal, it would be ideal to utilize a platform capable of providing 6 DOF of controlled mobility as well as capable of apply controlled load in those 6 DOF. The Musculoskeletal Research Laboratory has developed such a system. The system’s load-control capabilities were validated by simulating two standard biomechanical protocols, the pure moment and the ideal follower load on 6 L4-L5 single motion segment units. The robotic performance of the system was evaluated by measuring the tracking errors during testing, or the difference between experimental forces being applied and the forces commanded by the custom motion programs executed during protocol simulation. The biomechanical data that was recorded and compared to the literature for validation was rotational range of motion in the sagittal plane and anatomical point translation. Translation data proved to be difficult to compare effectively to the literature due to the sparseness of comparable numbers. There was also interest in the platform’s ability to control protocols. To test this hypothesis, three different biomechanical protocols were simulated and there biomechanical results were compared: pure moment, ideal follower load, and trunk weight. The system provided stable, good load-control in during combined motions involving all 6 DOF. The tracking errors observed were low compared to other published robotic biomechanical platforms. The mean combined flexion-extension rotational range of motion in the sagittal plane for the pure moment protocol, the ideal follower load, and the trunk weight protocols were 8.2°(±2.5°), 7.6°(±2.9°), and 7.4°(±2.8°), respectively. There were statistically significant differences in the absolute translational data across the protocols but when comparing relative changes due to flexion and extension only, there are no significant differences across protocols. In conclusion to this research the platform developed and validated in the current study adequately provides the capabilities of 6 DOF coordinated motion and 5 DOF coordinated load-control. It is sufficient to simulate the standard spine biomechanical test protocols of pure moment and ideal follower load on single segments. It is also a good tool for comparing the effects of particular protocols on the passive biomechanics of human cadaveric tissue. To the author’s knowledge, this is the first publication of a fully robotic system adequately controlling a non-zero dynamic force vector while a bending protocol was being applied to a human spinal segment. This research is limited to the sagittal plane and single lumbar spine motion segment units

Short and Long Term Immobilization on the Lumbar Spinal Joints: An Experimental Study Using Large Animal Model

Low back pain (LBP) is a common, widespread social and economic problem. Degenerative disc disease has been considered as a main risk factor for the LBP. In order to develop safe, effective and cost-efficient treatments, it is important to explore the pathomechanisms of this disease. In vivo animal models have an irreplaceable role in detecting long-term reactions to environmental factors, biology or biomechanical risk factors, and preclinical evaluation of therapeutics. Large animal models, due to their similarity in cellular populations, anatomy and biomechanics, are more closely comparable to the human intervertebral disc than smaller animal models. The major goal of current thesis was characterizing the effect of short and long term immobilization on the magnetic resonance imaging, radiological, histological and biomechanical characteristics of the in vivo ovine lumbar spine joints. To achieve this target, four experimental projects were performed. In the first experimental portion, a three-dimension motion capture system was set up and validated. A reliable method of the spinal kinematic analysis was established. The second experimental portion evaluated the biomechanical aspect of a synthetic biomimetic spine model with a validated spinal biomechanical test system combined with the motion capture system set up in the first study. This established the whole system applicability to the specific goal of examining spinal biomechanics. The third experimental chapter is an in vitro ovine biomechanical study. The purpose of this study was to characterize the effect of loading and soaking conditions on the spinal segment biomechanical property. Results indicated the biomechanics of spinal samples with hydration and dehydration discs differ considerably. Thus, the suitable pretest conditions need to be considered during in vitro spinal biomechanical test. The fourth experimental portion was the in vivo ovine model study. The aim of this chapter was evaluate the effect of the short and long term immobilization on the ovine lumbar spinal joints. The posterior pedicle screw instrumentation was applied on skeletally mature sheep lumbar spine. The immobilized level and adjacent levels spinal joints were evaluated at 0, 6 and 26 weeks. Results demonstrated the both short and long term immobilization can induce spinal joint degeneration on sheep model. This work presents a novel degenerative disc model without the need for annulus violation or chemical treatmen

Next generation of growth-sparing techniques: preliminary clinical results of a magnetically controlled growing rod in 14 patients

Session 3A - Early Onset Scoliosis: Paper no. 33SUMMARY: Growth-sparing techniques are commonly used for the treatment of progressive EOS. The standard growing rod (GR) technique requires multiple surgeries for lengthening. The preliminary results of MCGR has shown the comparable outcomes to standard GR without the need for repeated surgery which can be expected to reduce the overall complication rate in GR surgery. INTRODUCTION: The growing rod (GR) technique for management of progressive Early-Onset Scoliosis (EOS) is a viable alternative but with a high complication rate attributed to frequent surgical lengthenings. The safety and efficacy of a non-invasive Magnetically Controlled Growing Rod (MCGR) has been previously reported in a porcine model. We are reporting the preliminary results of this technique in EOS. METHODS: Retrospective review of prospectively collected multi-center data. Only patients who underwent MCGR surgery and at least 3 subsequent spinal distractions were included in this preliminary review. Distractions were performed in clinic without anesthesia or analgesics. T1-T12 and T1-S1 height and the distraction distance inside the actuator were analyzed in addition to conventional clinical and radiographic data. RESULTS: Patients (N=14; 7 F and 7 M) had a mean age of 8y+10m (3y+6m to 12y+7m) and underwent a total of 14 index surgeries (SR: index single rod in 5 and DR: dual rod in 9) and 91 distractions. There were 5 idiopathic, 4 neuromuscular, 2 congenital, 2 syndromic and one NF. Mean follow-up (FU) was 10 months (5.8-18.2). Mean Cobb changed from 57° pre-op to 35° post-op and correction was maintained (35°) at latest FU. T1-T12 increased by 4 mm for SR and 10 mm for DR with mean monthly gain of 0.5 and 1.39, respectively. T1-S1 gain was 4 mm for SR and 17 mm for DR with mean monthly gain of 0.5 mm for SR and 2.35 mm for DR. The mean interval between index surgery and the first distraction was 66 days and thereafter was 43 days. Complications included one superficial infection in (SR), one prominent implant (DR) and minimal loss of initial distraction in three after index MCGR (all SR). Overall, partial loss of distraction was observed following 14 of the 91 distractions (one DR and 13 SR). This loss was regained in subsequent distractions. There was no neurologic deficit or implant failure. CONCLUSION: MCGR appears to be safe and provided adequate distraction similar to the standard GR technique without the need for repeated surgeries. DR patients had better initial curve correction and greater spinal height. No major complications were observed during the short follow-up period. The FDA has not cleared the drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an ‘off label’ use).postprin