Aims

Tissue adhesives (TAs) are a commonly used adjunct to traditional surgical wound closures. However, TAs must be allowed to dry before application of a surgical dressing, increasing operating time and reducing intraoperative efficiency. The goal of this study is to identify a practical method for decreasing the curing time for TAs.

Introduction. Offset femoral broach handles have become more common as the anterior approach in total hip arthroplasty has increased in popularity. The difference in access to the femur compared to a posterior approach necessitates anterior and, in some cases, lateral offsets incorporated into the design of the broach handle to avoid interference with the patient's body and to ensure accessibility of the strike plate. Using a straight broach handle with a primary stem, impaction force is typically directed along the axis of the femoral broach. However, the addition of one or more offsets to facilitate an anterior approach results in force transmission in the transverse plane, which is unnecessary for eating the femoral broach. The direction of forces transmitted to the broach via strike plate impaction can introduce a large moment. A negative consequence of this moment is the amplification of stresses/strains at the bone/broach interface, which increases the likelihood of femoral fracture during impaction. It was proposed that optimizing the angle of the strike plate could minimize the moment to reduce the unintended stresses/strains at the bone/broach interface. Objectives. The objective was to minimize the stresses/strains imparted to the proximal aspect of the bone femur when broaching with a given dual offset broach handle design. Methods. Trigonometric calculations were used to optimize the strike plate angle for a given dual offset broach handle design. The point of intersection of the stem axis and transverse plane that intersects the medial calcar of the smallest size broach was assumed to be the ideal location of zero moment, given that intraoperative fractures related to this issue tend to occur in the proximal region of the femur. The strike plate was angled anteriorly and laterally such that the impaction force vector is directed at this point of intersection, thus negating the moment at this point. A prototype broach handle body was fabricated to accept different strike plates. Of the two strike plates tested, one strike plate was made such that the impaction surface followed the optimized angle, while the other simulated the strike plate angle of a previous, non-optimized design. Each broach handle configuration was connected to an identical broach and implanted into one of two identical Sawbones® femoral models. Equal loads were placed on the strike plates of each handle perpendicular to the strike plate angles. Digital image correlation was used to compare the resultant strains in both samples. Results. Testing demonstrated a 30% reduction in maximum strain on the proximal aspect of the bone using the broach handle with the optimized strike plate. Conclusions. While the optimal strike plate angle is dependent on the individual broach handle design, this method of optimization can be applied to the design of any offset broach handle. Optimization of offset broach handle strike plate angles could reduce the incidence of intraoperative femoral fractures when broaching by reducing the stresses/strains on the proximal aspect of the femur

The main reasons of aseptic loosening of the cemented hip stem are three: Bone cement fracture, bone cement debonding, and rupture of cement/bone interface. These are caused by normal/shear stress in the cement mantle. In past studies, there are introduced some optimum design of the hip prosthesis. But all there are not considered enough design objectives. The purpose of this study is to design the optimum stem geometry, which reduces the many stress in the cement mantle at the same time. We reserched the relationship between stem design and cement mantle stresses for this purpose. The cemented THA proximal femur FEM model was created on CAD and FEM software. Harris Precoat Design was used for stem model. Seven design parameters were defined on this model. Optimization calculation was performed by changing the design parameters. Four objective functions were defined; largest maximum principal stress in the cement mantle, stem/cement interface shear stress, bone/cement interface shear stress, and tensile stress between stem and cement mantle on proximal lateral section. Genetic algorithm was used to change the design parameters. Pareto map was created from results of calculation to reserach the realtionship of each objective functions. From Pareto maps, we can know that Principal stress and Tensile stress are trade-off relation; the geometry decreasing Princpal stress is increasing Tensile stress. However, stem/cement shear and bone/cement shear are similar. Principal stress and shear stress are also similar. Multicriteria design optimization of the hip prosthes is was performed based on the HARRIS Precoat stem. In the results, we got many Pareto solutions and relationship between each objective function. And with general methods of development, analysis of trade-off relationship is very useful method for Hip prosthesis development

Background. The evaluation and management of outcomes risk has become an essential element of a modern total joint replacement program. Our multidisciplinary team designed an evidence-based tool to address modifiable risk factors for adverse outcomes after primary hip and knee arthroplasty surgery. Methods. Our protocols were designed to identify, intervene, and mitigate risk through evidence-based patient optimization. Nurse navigators screened patients preoperatively, identified and treated risk factors, and followed patients for 90 days postoperatively. We compared patients participating in our optimization program (N=104) to both a historical cohort (N=193) and a contemporary cohort (N=166). Results. Risk factor identification and optimization resulted in lower hospital length of stay and post-operative emergency department visits. Patients in the optimization cohort had a statistically significant decrease in mean LOS as compared to both the historical cohort (2.55 vs 1.81 days, P<0.001) and contemporary cohort (2.56 vs 1.81 days, p<0.001). Patients in the optimization cohort had a statistically significant decrease in 30- and 90-day ED visits compared to the historical cohort (P. 30-day. =0.042, P. 90-day. =0.003). When compared with the contemporary cohort, the optimization cohort had a statistically significant decrease in 90-day ED visits (21.08% vs. 10.58%, P=0.025). The optimization cohort had a statistically significant increase in the percentage of patients discharged home. We noted nonsignificant reductions in readmission rate, transfusion rate, and surgical site infections. Conclusion. Optimization of patients prior to elective primary THA and TKA reduced average LOS, ED visits, and drove tele-rehabilitation use. Our results add to the limited body of literature supporting this patient-centered approach

INTRODUCTION. Understanding the relationship between knee specific tissue behavior and joint contact mechanics remains an area of focus. Seminal work from 1990's established the possibility to optimize tissue properties for recreation of laxity driven kinematics (Mommersteeg et al., 1996). Yet, the uniqueness and validity of such predictions could be strengthened, especially as they relate to joint contact conditions. Understanding this interplay has implications for the long term performance of joint replacements. Development of instrumented knee implants, highlighted by a single use tibial insert trial with embedded sensor technology (VERASENSE, Orthosensor Inc.), may offer an avenue to establish the relationship between tissue state and joint mechanics. Utilization of related data also has the potential to confirm computational predictions, where both rigid body motions and associated reactions are explicitly accounted for. Hence, the goal of this work was to evaluate an approach for optimization of ligament properties using joint mechanics data from an instrumented implant during laxity style testing. Such a framework could be used to inform joint balancing techniques, improve long term implant performance, and alternatively, qualify factors that may lead to poor outcomes. METHODS. Experimentation was performed on a 52 year old male, left, cadaveric specimen. Joint arthroplasty was performed using standard practice by an experienced orthopedic surgeon. To mimic passive intraoperative loading, laxity loading at 10°, 45° and 90° flexion, which consisted of discrete application of anterior-posterior (± 100N), varus-valgus (± 5 Nm) and internal-external (± 3 Nm) loads at each angle, was performed using a simVITROTM robotic musculoskeletal simulator (Cleveland Clinic, Cleveland, OH). Experimental results included relative tibiofemoral kinematics and sensor measured metrics (Fig 1). The finite element model was developed from specimen-specific MRIs and solved using Abaqus/Explicit. The model included the rigid bones, appropriately placed implants and relevant soft-tissue structures (Fig. 1). Ligament stiffness values were adopted from the literature and included a 6% strain toe region. Sets of nonlinear springs, defined using MR imaging, comprised each ligament/bundle. Optimization was performed, which minimized the root mean squared difference between VERASENSE measured tibiofemoral mechanics and the model predicted values. Ligament slack lengths were the control variables and the objective included each loading state and all contact metrics (θ, AFD, ML, and LL). RESULTS AND DISCUSSION. The model successfully recreated joint kinematics with average errors of 4° for rotations and 3 mm for translations, across all flexion angles (Fig 2). Though a systematic offset in θ was observed, model versus experiment contact locations were also in good agreement. Reaction forces were generally over-predicted by the model, but retained the overall trend (Fig 2). Sensitivity analysis also supported this finding. In light of the larger focus of this project, testing also included systematic removal of key tissues followed by repeat testing, as evaluated across numerous specimens. Overall, the presented framework represents a promising step towards establishing simulation based tools able to support exploratory studies as well as the clinical decision making process. Future work will evaluate efficacy across numerous specimens and assess sensitivity to key modeling and experimental parameters. To view tables/figures, please contact authors directly

Total knee and hip arthroplasty (TKA and THA) are the most commonly performed surgical procedures, the costs of which constitute a significant healthcare burden. Improving access to care for THA/TKA requires better efficiency. It is hypothesized that this may be possible through a two-stage approach that utilizes prediction of surgical time to enable optimization of operating room (OR) schedules.

Data from 499,432 elective unilateral arthroplasty procedures, including 302,490 TKAs, and 196,942 THAs, performed from 2014-2019 was extracted from the American College of Surgeons (ACS) National Surgical and Quality Improvement (NSQIP) database. A deep multilayer perceptron model was trained to predict duration of surgery (DOS) based on pre-operative clinical and biochemical patient factors. A two-stage approach, utilizing predicted DOS from a held out “test” dataset, was utilized to inform the daily OR schedule. The objective function of the optimization was the total OR utilization, with a penalty for overtime. The scheduling problem and constraints were simulated based on a high-volume elective arthroplasty centre in Canada. This approach was compared to current patient scheduling based on mean procedure DOS. Approaches were compared by performing 1000 simulated OR schedules.

The predict then optimize approach achieved an 18% increase in OR utilization over the mean regressor. The two-stage approach reduced overtime by 25-minutes per OR day, however it created a 7-minute increase in underutilization. Better objective value was seen in 85.1% of the simulations.

With deep learning prediction and mathematical optimization of patient scheduling it is possible to improve overall OR utilization compared to typical scheduling practices. Maximizing utilization of existing healthcare resources can, in limited resource environments, improve patient's access to arthritis care by increasing patient throughput, reducing surgical wait times and in the immediate future, help clear the backlog associated with the COVID-19 pandemic.

Abstract

Many factors have been reported to affect the functional survival of OCA transplants, including chondrocyte viability at time of transplantation, rate and extent of allograft bone integration, transplantation techniques, and postoperative rehabilitation protocols and adherence. The objective of this study was to determine the optimal subchondral bone drilling technique by evaluating the effects of hole diameter on the material properties of OCAs while also considering total surface area for potential biologic benefits for cell and vascular ingrowth.

Using allograft tissues that would be otherwise discarded in combination with deidentified diagnostic imaging (MRI and CT), a model of a large shell osteochondral allograft was recreated using LS-PrePost and FEBio based on clinically relevant elastic material properties for cortical bone, trabecular bone, cartilage, and hole ingrowth tissue. The 0.8 mesh size model consisted of 4 mm trabecular bone, 4 mm cortical bone, and 3 mm cartilage sections that summed to a cross-sectional area of 1600 mm2 (40 mm x 40 mm). Holes were modeled to be 4mm deep in relation to clinical practice where holes are drilled from the deep margin of subchondral trabecular bone to the cortical subchondral bone plate. To test the biomechanic variations between drill hole sizes, models with hole sizes pertinent to standard-of-care commercially available orthopaedic drill sizes of 1.1mm, 2.4 mm, or 4.0 mm holes were loaded across the top surface over a one second duration and evaluated for effective stress, effective strain, 1st principal strain, and 3rd principal strain in compressive conditions.

Results measured effective stress and strain and 1st and 3rd principal strain increased with hole depth.

The results of the present FEA modeling study indicate that the larger 4.0 mm diameter holes were associated with greater stresses and strains within OCA shell graft, which may render the allograft at higher risk for mechanical failure. Based on these initial results, the smaller diameter 2.4 mm and 1.1 mm holes will be further investigated to determine optimal number, configuration, and depth of subchondral drilling for OCA preparation for transplantation

In the current healthcare environment, cost containment has become more important than ever. Perioperative services are often scrutinized as they consume more than 30% of North American hospitals’ budgets. The procurement, processing, and use of sterile surgical inventory is a major component of the perioperative care budget and has been recognized as an area of operational inefficiency. Although a recent systematic review supported the optimization of surgical inventory reprocessing as a means to increase efficiency and eliminate waste, there is a paucity of data on how to actually implement this change. A well-studied and established approach to implementing organizational change is Kotter's Change Model (KCM). The KCM process posits that organizational change can be facilitated by a dynamic 8-step approach and has been increasingly applied to the healthcare setting to facilitate the implementation of quality improvement (QI) interventions. We performed an inventory optimization (IO) to improve inventory and instrument reprocessing efficiency for the purpose of cost containment using the KCM framework. The purpose of this quality improvement (QI) project was to implement the IO using KCM, overcome organizational barriers to change, and measure key outcome metrics related to surgical inventory and corresponding clinician satisfaction. We hypothesized that the KCM would be an effective method of implementing the IO.

This study was conducted at a tertiary academic hospital across the four highest-volume surgical services - Orthopedics, Otolaryngology, General Surgery, and Gynecology. The IO was implemented using the steps outlined by KCM (Figure 1): 1) create coalition, 2) create vision for change, 3) establish urgency, 4) communicate the vision, 5) empower broad based action, 6) generate general short term wins, 7) consolidate gains, and 8) anchor change. This process was evaluated using inventory metrics - total inventory reduction and depreciation cost savings; operational efficiency metrics - reprocessing labor efficiency and case cancellation rate; and clinician satisfaction.

The implementation of KCM is described in Table 1. Total inventory was reduced by 37.7% with an average tray size reduction of 18.0%. This led to a total reprocessing time savings of 1333 hours per annum and labour cost savings of $39 995 per annum. Depreciation cost savings was $64 320 per annum. Case cancellation rate due to instrument-related errors decreased from 3.9% to 0.2%. The proportion of staff completely satisfied with the inventory was 1.7% pre-IO and 80% post-IO.

This was the first study to show the success of applying KCM to facilitate change in the perioperative setting with respect to surgical inventory. We have outlined the important organizational obstacles faced when making changes to surgical inventory. The same KCM protocol can be followed for optimization processes for disposable versus reusable surgical device purchasing or perioperative scheduling. Although increasing efforts are being dedicated to quality improvement and efficiency, institutions will need an organized and systematic approach such as the KCM to successfully enact changes.

For any figures or tables, please contact the authors directly.

Neurological complications in oncological and degenerative spine surgery represent one of the most feared risks of these procedures. Multimodal intraoperative neurophysiological monitoring (IONM) mainly uses methods to detect changes in the patient's neurological status in a timely manner, thus allowing actions that can reverse neurological deficits before they become irreversible. The utopian goal of spinal surgery is the absence of neurological complications while the realistic goal is to optimize the responses to changes in neuromonitoring such that permanent deficits occur less frequently as possible. In 2014, an algorithm was proposed in response to changes in neuromonitoring for deformity corrections in spinal surgery. There are several studies that confirm the positive impact that a checklist has on care. The proposed checklist has been specifically designed for interventions on stable columns which is significantly different from oncological and degenerative surgery. The goal of this project is to provide a checklist for oncological and degenerative spine surgery to improve the quality of care and minimize the risk of neurological deficit through the optimization of clinical decision-making during periods of intraoperative stress or uncertainty.

After a literature review on risk factors and recommendations for responding to IONM changes, 3 surveys were administered to 8 surgeons with experience in oncological and degenerative spine surgery from 5 hospitals in Italy. In addition, anesthesiologists, intraoperative neuro-monitoring teams, operating room nurses participated. The members participated in the optimization and final drafting of the checklist. The authors reassessed and modified the checklist during 3 meetings over 9 months, including a clinical validation period using a modified Delphi process.

A checklist containing 28 items to be considered in responding to the changes of the IONM was created. The checklist was submitted for inclusion in the new recommendations of the Italian Society of Clinical Neurophysiology (SINC) for intraoperative neurophysiological monitoring. The final checklist represents the consensus of a group of experienced spine surgeons. The checklist includes the most important and high-performance items to consider when responding to IONM changes in patients with an unstable spine. The implementation of this checklist has the potential to improve surgical outcomes and patient safety in the field of spinal surgery.

Scoliosis correction surgery is one of the longest and most complex procedures of all orthopedic surgery. The complication rate is therefore not negligible and is particularly high when the surgery is performed in patients with neuromuscular or connective tissue disease or complex genetic syndromes. In fact, these patients have various comorbidities and organ deficits (respiratory capacity, swallowing / nutrition, heart function, etc.), which can compromise the outcome of the surgery. In these cases, an accurate assessment and preparation for surgery is essential, also making use of external consultants. To make this phase simpler, more effective and homogeneous, a multidisciplinary path of peri-operative optimization is being developed in our Institute, which also includes the possibility of post-operative hospitalization for rehabilitation and recovery. The goal is to improve the basic functional status as much as possible, in order to ensure faster functional recovery and minimize the incidence of peri-operative complications, to be assessed by clinical audit. The path model and the preliminary results on the first patients managed according to the new modality are presented here.

The multidisciplinary path involves the execution of the following assessments / interventions: • Pediatric visit with particular attention to the state of the upper airways and the evaluation of chronic or frequent inflammatory states • Cardiological Consultation with Echocardiogram. • Respiratory Function Tests, Blood Gas Analysis and Pneumological Consultation to evaluate indications for preoperative respiratory physiotherapy cycles, Non-Invasive Ventilation (NIV) cycles, Cough Machine. Possible Polysomnography. • Nutrition consultancy to assess the need for nutritional preparation in order to improve muscle trophism. • Consultation of the speech therapist in cases of dysphagia for liquids and / or solids. • Electroencephalogram and Neurological Consultation in epileptic patients. • Physiological consultation in patients already being treated with a cough machine and / or NIV. • Availability of postoperative hospitalization in the rehabilitation center (with skills in respiratory and neurological rehabilitation) for the most complex cases. When all the appropriate assessments have been completed, the anesthetist in charge at our Institute examines the clinical documentation and establishes whether the path can be considered complete and whether the patient is ready for surgery. At the end of the surgery, the patient is admitted to the Post-operative Intensive Care Unit of the Institute. If necessary, a new program of postoperative rehabilitation (respiratory, neuromotor, etc.) is programmed in a specialist reference center.

To date, two patients have been referred to the preoperative optimization path: one with Ullrich Congenital Muscular Dystrophy, and one with 6q25 Microdeletion Syndrome. In the first case, the surgery was performed successfully, and the patient was discharged at home. In the second case, after completing the optimization process, the surgery was postponed due to the finding of urethral malformation with the impossibility of bladder catheterization, which made it necessary to proceed with urological surgery first.

The preliminary case series presented here is still very limited and does not allow evaluations on the impact of the program on the clinical practice and the complication rate. However, these first experiences made it possible to demonstrate the feasibility of this complex multidisciplinary path in which a network of specialists takes part.

Thermal sensors have been used in bracing research as self-reported diaries are inaccurate. Little is known about new low-profile sensors, optimal location within a brace, locational thermal micro-climate and effect of brace lining. Our objective is to Determine an optimal temperature threshold for sensor-measured and true wear time agreement. Identify optimal sensor location. Assess all factors to determine the best sensor option for the Bracing AdoleScent Idiopathic Scoliosis (BASIS) multicentre RCT.

Seven Orthotimer and five iButton (DS1925L) sensors were synchronised to record temperature at five-minute intervals. Three healthy participants donned a rigid spinal brace, embedded with both sensors across four anatomical locations (abdomen/axilla/lateral-gluteal/sacral). Universal-coordinated-time wear protocols were performed in/out-doors. Intraclass correlation coefficient (ICC) assessed sensor-measured and true wear time agreement at thresholds 15–36oC.

Optimal thresholds, determined by largest ICC estimate: Orthotimer: Abdomen=26oC, axilla=27oC, lateral-gluteal=24.5oC, sacral=22.5oC. iButton: Abdomen=26oC, axilla=27oC, lateral-gluteal=23.5oC, sacral=23.5oC. Warm-up time and error at optimal thresholds increased for moulded sensors covered with 6mm lining.

Location: anterior abdominal wall. Excellent reliability and higher optimal thresholds, less likely to be exceeded by ambient temperature; not a pressure area. Sensor: iButton, longer battery life and larger memory than Orthotimer; allows recording at 10 min intervals for life of brace. Orthotimer only able to record every 30 mins, increasing error between true and measured wear time; Orthotimer needs 6-monthly data download. Threshold: 26oC is optimal threshold to balance warm-up and cool-down times for accurately measuring wear time. Sensor should not be covered by lining foam as this significantly prolongs warm-up time.

3D-printed orthopedic implants have been gaining popularity in recent years due to the control this manufacturing technique gives the designer over the different design aspects of the implant. This technique allows us to manufacture implants with material properties similar to bone, giving the implant designer the opportunity to address one of the main complications experienced after total hip arthroplasty (THA), i.e. aseptic loosening of the implant. To restore proper function after implant loosening, the implant needs to be replaced. During these revision surgeries, some extra bone is removed along with the implant, further increasing the already present defects, and making it harder to achieve proper mechanical stability with the revision implant. A possible way to limit the increasing loss of bone is the use of biodegradable orthopedic implants that optimize long-term implant stability. These implants need to both optimize the implant such that stress shielding is minimized, and tune the implant degradation rate such that newly formed bone is able to replace the degrading metal in order to maintain a proper bone-implant contact. The hope is that such (partly) degradable implants will lead to a reduction in the size of the bone defects over time, making possible future revisions less likely and less complex.

We focused on improving the long-term implant stability of patient-specific acetabular implants for large bone defects and the modeling of their biodegradable behavior. To improve long-term implant stability we implemented a topology optimization approach. A patient-specific finite element model of the hip joint with and without implant was derived from CT-scans to evaluate the performance of the designs during the optimization routine. To evaluate the biodegradation behavior, a quantitative mathematical model was developed to assess the degradation rates of the biodegradable part of the implant. Currently, the biodegradation model has been implemented for magnesium (Mg) implants as a first proof of concept.

For a first test case, an optimized implant was found with stress shielding levels below 20% in most regions. The highest stress shielding levels were found at the bone implant interface. The biodegradation model has been validated using experimental data, which includes immersion tests of simple scaffolds created from Commercial Pure Mg. The mass loss of the scaffold is about 0.8 mg/cm² for the first day of immersion in simulated body fluid (SBF) solution. After the formation of a protective film on the surface of the simple scaffold, the degradation rate starts to slow down.

Initial results presented serve as a proof of concept of the developed computational framework for the implant optimization and the implant biodegradation behavior. Currently, timing calibration, benchmarking and validation are taking place.

Reducing implant-induced stress shielding, obtaining a better implant integration and reduction of bone defects, by allowing for bone to partially replace the implant over time, are crucial design factors for large bone defect implants. In this research, we have developed in-silico models to investigate these factors. Once validated and coupled, the models will serve as an important tool to find the appropriate biodegradable implant designs and biodegradable metal properties for THA applications, that improve current implant lifetime while ensuring proper mechanical functioning.

Aim

The aim of the present work was (i) to survey the situation of healthcare regarding the use of antibiotics in orthopaedics and trauma surgery in Germany, (ii) to determine which empiric antibiotic regimens are preferred in the treatment of periprosthethic joint infections (PJI) and (iii) to evaluate the hypothetical antibiotic adequacy of the applied empirical antibiotic therapy regimens based on a patient collective of a German university hospital.

Neuromuscular scoliosis patients face rates of major complications of up to 49%. Along with pre-operative risk reduction strategies (including nutritional and bone health optimization), intra-operative strategies to decrease blood loss and decrease surgical time may help mitigate these risks. A major contributor to blood loss and surgical time is the insertion of instrumentation which is challenging in neuromuscular patient given their abnormal vertebral and pelvic anatomy. Standard pre-operative radiographs provide minimal information regarding pedicle diameter, length, blocks to pedicle entry (e.g. iliac crest overhang), or iliac crest orientation. To minimize blood loss and surgical time, we developed an “ultra-low dose” CT protocol without sedation for neuromuscular patients.

Our prospective quality improvement study aimed to determine: if ultra-low dose CT without sedation was feasible given the movement disorders in this population; what the radiation exposure was compared to standard pre-operative imaging; whether the images allowed accurate assessment of the anatomy and intra-operative navigation given the ultra-low dose and potential movement during the scan.

Fifteen non-ambulatory surgical patients with neuromuscular scoliosis received the standard spine XR and an ultra-low dose CT scan. Charts were reviewed for etiology of neuromuscular scoliosis and medical co-morbidities. The CT protocol was a high-speed, high-pitch, tube-current modulated acquisition at a fixed tube voltage. Adaptive statistical iterative reconstruction was applied to soft-tissue and bone kernels to mitigate noise. Radiation dose was quantified using reported dose indices (computed tomography dose index (CTDIvol) and dose-length product (DLP)) and effective dose (E), calculated through Monte-Carlo simulation. Statistical analysis was completed using a paired student's T-test (α = 0.05). CT image quality was assessed for its use in preoperative planning and intraoperative navigation using 7D Surgical System Spine Module (7D Surgical, Toronto, Canada).

Eight males and seven females were included in the study. Their average age (14±2 years old), preoperative Cobb angle (95±21 degrees), and kyphosis (60±18 degrees) were recorded. One patient was unable to undergo the ultra-low dose CT protocol without sedation due to a co-diagnosis of severe autism. The average XR radiation dose was 0.5±0.3 mSv. Variability in radiographic dose was due to a wide range in patient size, positioning (supine, sitting), number of views, imaging technique and body habitus. Associated CT radiation metrics were CTDIvol = 0.46±0.14 mGy, DLP = 26.2±8.1 mGy.cm and E = 0.6±0.2 mSv. CT radiation variability was due to body habitus and arm orientation. The radiation dose differences between radiographic and CT imaging were not statistically significant. All CT scans had adequate quality for preoperative assessment of pedicle diameter and orientation, obstacles impeding pedicle entry, S2-Alar screw orientation, and intra-operative navigation.

“Ultra-low dose” CT scans without sedation were feasible in paediatric patients with neuromuscular scoliosis. The effective dose was similar between the standard preoperative spinal XR and “ultra-low dose” CT scans. The “ultra-low dose” CT scan allowed accurate assessment of the anatomy, aided in pre-operative planning, and allowed intra-operative navigation despite the movement disorders in this patient population.

Neuromuscular scoliosis patients face rates of major complications of up to 49%. Along with pre-operative risk reduction strategies (including nutritional and bone health optimization), intra-operative strategies to decrease blood loss and decrease surgical time may help mitigate these risks. A major contributor to blood loss and surgical time is the insertion of instrumentation which is challenging in neuromuscular patient given their abnormal vertebral and pelvic anatomy. Standard pre-operative radiographs provide minimal information regarding pedicle diameter, length, blocks to pedicle entry (e.g. iliac crest overhang), or iliac crest orientation. To minimize blood loss and surgical time, we developed an “ultra-low dose” CT protocol without sedation for neuromuscular patients.

Our prospective quality improvement study aimed to determine:

Fifteen non-ambulatory surgical patients with neuromuscular scoliosis received the standard spine XR and an ultra-low dose CT scan. Charts were reviewed for etiology of neuromuscular scoliosis and medical co-morbidities. The CT protocol was a high-speed, high-pitch, tube-current modulated acquisition at a fixed tube voltage. Adaptive statistical iterative reconstruction was applied to soft-tissue and bone kernels to mitigate noise. Radiation dose was quantified using reported dose indices (computed tomography dose index (CTDIvol) and dose-length product (DLP)) and effective dose (E), calculated through Monte-Carlo simulation. Statistical analysis was completed using a paired student's T-test (α= 0.05). CT image quality was assessed for its use in preoperative planning and intraoperative navigation using 7D Surgical System Spine Module (7D Surgical, Toronto, Canada).

Eight males and seven females were included in the study. Their average age (14±2 years old), preoperative Cobb angle (95±21 degrees), and kyphosis (60±18 degrees) were recorded. One patient was unable to undergo the ultra-low dose CT protocol without sedation due to a co-diagnosis of severe autism. The average XR radiation dose was 0.5±0.3 mSv. Variability in radiographic dose was due to a wide range in patient size, positioning (supine, sitting), number of views, imaging technique and body habitus. Associated CT radiation metrics were CTDIvol = 0.46±0.14 mGy, DLP = 26.2±8.1 mGy.cm and E = 0.6±0.2 mSv. CT radiation variability was due to body habitus and arm orientation. The radiation dose differences between radiographic and CT imaging were not statistically significant. All CT scans had adequate quality for preoperative assessment of pedicle diameter and orientation, obstacles impeding pedicle entry, S2-Alar screw orientation, and intra-operative navigation.

“Ultra-low dose” CT scans without sedation were feasible in paediatric patients with neuromuscular scoliosis. The effective dose was similar between the standard preoperative spinal XR and “ultra-low dose” CT scans. The “ultra-low dose” CT scan allowed accurate assessment of the anatomy, aided in pre-operative planning, and allowed intra-operative navigation despite the movement disorders in this patient population.

Many navigation (Image Guided Surgery or IGS) systems are keyed to safely and accurately placing implants into complex anatomy. In spine surgery such as disc arthroplasty and fusion surgery this can be extremely helpful. Likewise, in joint arthroplasty the accurate placement with respect to the operative plan is widely recognized to be of benefit to long term results.

However, where realignment of anatomy is desired following implant placement, such as in high tibial osteotomy, spinal fusion with correction of deformity, and spinal disc arthroplasty, navigation systems can tell you where you are, but not where you would like to be.

We have developed specific software modification technology, applicable to all current navigation systems that addresses this need for assistance in surgical correction of anatomy to a desired alignment without the requirement for further imaging or irradiation. The benefits of our software allow image free re-referencing of image guided surgery, accommodation of intra-operative changes in anatomy, and intra-operative accountability and adjustment to allow errors of image guidance to be identifiable and correctible, at any stage of image guided surgery.

This software allows accurate pre-operative planning, intra-operative verification and assessment of the operative plan, and actual outcomes of the surgery to be assessed as the surgery is performed. It allows the surgeon to subsequently verify if the operative planning has been adequately achieved, and if not can verify if continued surgery has then achieved the planning goals. This verification and image guidance does not require further imaging during surgery, relying upon the original data set and software enhancements.

Evaluation of different biomaterials is being performed with various methods trying to simulate the closest hostile-like in vitro environments. However the complexity of the conditions usually limits practically feasible combination of most relevant chemical, biological, biomechanical parameters in one single test. Many biomaterials and tissue engineering developments rely on high-throughput screening to multiply number of specimens and thus to gather sufficient data. The price to be paid for these methods is limited number of physical readouts, increased inter-specimens scatter, and unavoidable spatial constrains driving the conditions away of the clinical scenarios. For orthopaedic biomaterials this is of a particular concern, as implantation site conditions cannot be squeezed too much without lost of natural-mimicking stimuli.

Here we are presenting another approach based on high-output screening of biomaterials, which is based on the strategy of raising the number of readouts obtainable from every specimen at more clinically-relevant conditions. On the contrary to common methods like ISO 10993 or simplified biomechanical tests, the biomaterials enhanced simulation testing (BEST) evaluates specimens without pre-selected biomaterial model, assessing the whole specimen as would happen in the implantation site. Besides reducing the risk of improper conclusions caused by wrong material model choice, the data processing with non-local method intrinsically includes the test history bypassing common challenges usually seen with hereditary integration. For properly designed experiment, readouts might include invariant moduli, viscous stiffness, fluidity, fluid permittivity and diffusivity (without need for pressure-driven separate tests), fluid source, effective channel size, and swelling pressure (if swelling is present) in addition to conventional biomechanical parameters.

New solutions in advanced and consistent evaluations for biomaterials allow better risks control, shorten lead development time and costs, and compliant with 3R-strategy (2010/63/EC) and new regulatory requirements (2012/0266/COD in EU and FY2017 regulatory priorities by FDA). The approach shown is able to combine scientifically based tests with multi-purpose protocols to secure patient safety by screening of biomaterials under proper conditions.

The authors thank Finnish Agency for Innovations (Tekes) for providing partial financial support.

Low back pain (LBP), caused by intervertebral disc (IVD) degeneration represents one of the most significant socioeconomic conditions facing Western economies. Novel regenerative therapies, however, have the potential to restore function and relieve pain. We have previously shown that stimulation of adipose-derived stem cells (ASCs) with growth differentiation factor-6 (GDF6) promotes differentiation to nucleus pulposus (NP) cells of the IVD, offering a potential treatment for LBP. The aims of this study were to i) elucidate GDF6 cell surface receptor profile and signalling pathways to better understand mechanism of action; and (ii) develop a microparticle (MP) delivery system for GDF6 stimulation of ASCs. GDF6 receptor expression by ASCs (N=6) was profiled through western blot, immunofluorescence (IF) and flow cytometry. Signal transduction through Smad1/5/9 and non-Smad pathways following GDF6 (100ng/ml) stimulation was assessed using western blotting and confirmed using pathway specific blockers and type II receptor sub-unit knockdown using CRISPR. Release kinetics of GDF6 from MPs was calculated (BCA assay, ELISAs) and ASC differentiation to NP cells was assessed. BMPR profiling revealed high BMPR2 expression on ASCs. GDF6 stimulation of ASCs resulted in significant increases in Smad1/5/9 and Erk phosphorylation, but not p38 signalling. Blocking GDF6 signalling confirmed differentiation to NP cells required Smad phosphorylation, but not Erk. GDF6 release from MPs was controlled over 14days in vitro and demonstrated comparable NP-like differentiation to exogenous GDF6 delivery. This study elucidates the signalling mechanisms responsible for GDF6-induced ASC differentiation to NP cells and also demonstrates an effective and controllable release vehicle for GDF6.

Tendon detachment from its bony insertion is one of the most frequent injuries occurring in the musculoskeletal interface, constituting an unmet challenge in orthopaedics. Tendon-to-bone integration occurs at the enthesis, which is characterized by a complex structure organized in a gradient of cells and microenvironments. Hence, the maintenance of a heterotypic cellular niche is critical for tissue functionality and homeostasis. Replicating this unique complexity constitutes a challenge when addressing tendon-to-bone regeneration and interfacial tissue engineering strategies. Currently, mechanisms presiding to tendon-to-bone interface healing are not yet fully understood, particularly the interactions between tendon and bone cells in the orchestration of interfacial repair versus regeneration. Therefore, this study focused on the hypothesis that interactions between human tendon-derived cells (hTDCs) and pre-osteoblasts (pre-OB) can initiate a cascade of events, potentially leading to interfacial regeneration. Thus, hTDCs and pre-OB (pre-differentiated human adipose-derived stem cells) were used. Herein, five different ratios between basal and osteogenic media (100:0,75:25,50:50,25:75,0:100) were assessed to estimate their influence on cell behaviour and identify the ideal parameters for simultaneously supporting tenogenic and osteogenic differentiation before establishing a co-culture. Tenogenic and osteogenic differentiation were assessed through the expression of tendon and bone markers, mineralization (alizarin red, AZ) and alkaline phosphatase (ALP) quantification. Results showed that hTDCs exhibited osteogenic differentiation potential when cultured in the presence of osteogenic media, as demonstrated by an increase in ALP activity and mineralization. Pre-OB expressed osteogenic markers (OCN, OPN) in all media conditions confirming osteogenic commitment, which was simultaneously confirmed by ALP levels and AZ staining. Thus, three different conditions (100:0, 50:50, 0:100) were chosen for further studies in a direct contact co-culture system. Similarly to single cultures, a significant proliferation was observed in all conditions and mineralization was increased as soon as 7 days of culture. Additionally, osteogenic, tenogenic and interface-relevant markers will be assessed to study the effect of co-culture on phenotype maintenance. In summary, the present work addresses major limitations to clinical translation of cell-based therapies aiming at promoting interfacial regeneration. Particularly, we explored the influence of culture media on the maintenance of tenogenic and osteogenic niches, taking a basic and critical step towards the establishment of more complex cell-based systems.

Acknowledgements

Authors thank Fundação para a Ciência e Tecnologia in the framework of FCT-POPH-FSE, SFRH/BD/96593/2013 (RCA) and IF/00593/2015 (MEG); and to FCT/MCTES and the FSE/POCH, PD/59/2013 for PD/BD/128088/2016 (IC).