2016-17 CDMI Projects
Immune responses associated with development of spine deformity
The hypothesis is that in the process of development of spinal deformity, cytokine levels in circulation or in tissue may be up regulated leading to lymphocyte development. We aim to utilize a nonsurgical mouse model mimicking scoliosis in vivo to assess cytokines and lymphocytes present in the blood and in the spine bone marrow.
Principal Investigator: Anand Agarwal, MD
Trainee: Boren Lin
Integrated in vivo and in vitro high-throughput analyses of osteocyte-mediated bone remodeling
Aim 1: Develop in vitro measures of PLR function for high throughput screening,
Based on PLR-dependent changes in osteocyte pH and bone matrix resorption, we will develop and validate in vitro fluorescent PLR assays that can be used in high-throughput screens to identify novel PLR-regulatory compounds.
Aim 2: Establish the Osteocyte-Mediated Bone Remodeling ECM (OMBRE) Core.
The OMBRE Core will provide novel, streamlined in vitro and in vivo analysis of PLR for basic, pre-clinical, or clinical studies.
When implemented, the OMBRE Core will support scientists, including those affiliated with the CDMI, by providing PLR analyses as they seek to identify new therapies to improve bone quality systemically or locally near orthopaedic devices.
Principal Investigator: Tamara Alliston, PhD
Trainees: Claire Acevedo, PhD, David Monteiro, Justin Lopez, Neha Dole, PhD, JJ Woo, Cristal Yee, Courtney Mazur, Tristan Fowler, PhD
Basic Science
Biomechanical Studies
Biomechanics of topping off the fused segment
Despite its success, spinal fusion has a huge effect on unfused segments [1, 2]. This is attributed to the post-surgical differences in stiffness between the spinal levels, which result in abnormal forces, stress shielding, and hypermobility at the adjacent levels [3, 4]. Recently there has been a general consensus among the surgeons to curb this steep transition from a rigid construct to mobile unfused segments, by providing an interface of semi-rigid fixation such as DYNESIS (ZIMMER), ISOBAR® TTL DynamicCompression Rod (ALPHATEC from Scient´X), CD HORIZON BalanC™ Rod(MEDTRONIC), HPS (PARADIGM SPINE), CD HORIZON PEEK RODS (MEDTRONIC) etc.; the list of devices that are being provided by industry is exhausting. Although this technique, known as “topping off”, has picked up wide acceptance in Europe and is bound to reach the practitioners in United states, there is a lack to biomechanical data showing the kinematic and kinetic response of the spine this “topping off“technique. Therefore, there is a need to assess this alternative method of spinal fusion. The results of this study will allow all industries involved to have a fair and unbiased assessment of this methodology for Spinal fusion. Furthermore, highlights from this study will allow them to plan and conduct more proprietary research at their facilities.
Principal Investigator: Anand Agarwal, MD
Trainees: Aakash Agarwal, Anoli Shah
Development of juvenile scoliosis spine FE models to understand growth rod failure mechanisms
Growth rods provide the opportunity for the spine to grow in juvenile patients alongside preventing the progression of deformity. For this reason, the growth rods are becoming more popular for the juvenile patients as compared to traditional rods. In spite of its undisputed acceptance, a higher rate of mechanical complication involving 15% rod fracture has emerged. This project’s overall goal is to identify the biomechanical parameters that contribute to this failure mode. This will be achieved through three aims described in the next section, using the finite element models of multiple juvenile scoliotic spines and F1717 type simulation of various designs; it will also involve upgrading our FE platform technology to include scoliotic spine models. All of the input data and clinical failure mode of various growth rod designs will be provided by the collaborators fromFDA (SN and AD). This project should lead to better understanding of growth rods failure mechanism and provide a more relevant testing methodology for standardization. It may also lead to newer robust concepts.
Principal Investigator: Vijay Goel, PhD
Trainees: Aakash Agarwal, Ardalan Vosoughi
How lumbar disc geometries effect the risk for rod fracture in patients undergoing adult spine deformity surgery
Rod fracture (RF) has significant consequences for patients, including pain, loss of correction, and revision surgery. Risk factors associated with RF includes age, previous surgery, insufficient sagittal plane correction, rod material and bending, and pedicle subtraction osteotomy (PSO). Lumbar disc geometries may also be a risk factor affecting RF rates. Increased stress can occur at the PSO site, which is also the weakest part of the rod due to the acute bend placed to accommodate the PSO. Increased disc heights allow for more motion in the anterior column resulting in increased risk of rod failure. Lumbar inter body support in those “discs at risk” may improve stability and decrease RF rates. Due to higher rates of RF with PSO, alternative instrumentation including interbody support in those “discs at risk” adjacent to a PSO may improve stability and decrease RFrates. With a substantial range in the rate of RF with PSO across centers, suggesting potential variations in technique that warrants future investigation.Our objective is to evaluate disc geometries as a risk factor for RF in patients undergoing surgical correction for adult spinal deformity using a Finite Element (FE) model, since it is not practical to under take construct testing with different disc heights in a controlled manner. We will upgrade our platform FE technology for this project.
Principal Investigator: Vijay Goel, PhD
Trainee: Ardalan Vosoughi
Lumbar-sacral destruction fixation biomechanics
Tuning fork plates based fixation system is an innovative concept that has been custom made fort reatment of sacral agenesis and neuro-fibromatosis type II with an extensive destruction of the lumbar spine and the sacrum. Clinical results in 4 cases, thus far, have been encouraging. However, it is essential that its design be evaluated biomechanically and compared with the S2AI pelvic fixation, golds tandard treatment. This unique concept may lead to other design concepts. Finite element models of the whole lumbar spine and pelvis, already developed as a platform technology, will be further improved to extend the applications of the platform in this area.
Principal Investigator: Jwalant Mehta, MD
Trainee: Amin Joukar
Vertebral cage subsidence is a function of the cage design, besides the variation in vertebral bone mineral density
There are several parameters which may affect the subsidence of an interbody device (cage) at least when used as a standalone device for spinal fixation. Cages may provide stronger fixation when extended over the ring apophysis of the vertebral endplate. Damaged vertebral end plates, and the BMD of the underlying/exposed cancellous bone may also negatively affect the strength of the bone-device interface. Another parameter that is likely to play a major role is the contact-characteristics of the cage-endplate interface. This parameter is a function of the cage design (solid vs a ring cage, for example). This study is designed to assess the effects of different cage designs, cage lengths, BMD, etc. on the construct stiffness and vertebra-device interface failure. We will measure failure loads and construct stiffness in an in vitro experiment using isolated vertebrae,and foams of varying BMD and PCF respectively for at least cages of two radically different designs.This study may lead to an innovative cage design.
Principal Investigator: Vijay Goel, PhD
Trainee: Sushil Sudershan
Clinical Outcomes
Analysis of the cause of pseudarthrosis in multilevel spinal fusions
Infection and pseudoarthrosis are widely understood to be commoncauses of revision surgery for the treatment of spinal pathologies. While patients who require revisionsurgery can still gain statistically relevant and clinically important improvements in their health status,it has been demonstrated in the literature that achieve worse outcomes than the subset of patientswho do not require revision surgery. Furthermore, the financial impact of revision surgery can beburdensome – with the potential to meet or exceed the cost of a patient’s index operation. An articlepublished by Theologis et al. demonstrated a 3.2 million dollar total direct cost for the revision of 57consecutive thoracolumbar fusion surgeries.
In light of this, much of clinical research in spine surgery has been focused on mitigating the needforearly revision surgery. While infection and pseudoarthrosis rates are frequently discussed in outcomesbased spine surgery literature, the role of infection as anetiology of pseudoarthrosis has not yet beendescribed. The purpose of this study is to identify the prevalence of occult and overt infection as anetiology of pseudoarthrosis, and to define approaches to avoid infection-related pseudoarthrosis.
Principal Investigator: Sigurd Berven, MD
Trainee: Daniel Beckerman
Digital Health
Wearable activity sensors and patient reportes outcomes in total hip arthropasty: a nested RCT
Decreasing the cost of care while improving the quality of care through digitally enabled technology is a majoraim of the digital health movement. Within the area of orthopedics, improving patient outcomes by focusing onupstream patient optimization has been shown to decrease complication rates. Further, monitoring qualitythrough the collection of Patient Reported Outcomes (PROs) has become a cornerstone of the move towardsvalue purchasing by payers. However, collecting PROs either at the POC or at home has been quite challenging asfew patients have the desire to answer numerous questions.In this study we aim to address both opportunities by collecting data both passively and actively through a sensorworn by patients before and after surgery and by using apps to support patient pre-operative rehabilitation andpostoperative recovery. To this data set we couple our existing PRO data collection database collected by theUCSF department of orthopedics. These three data sets (1) PRO data collected actively, 2) our passively collectedsensor data and 3) data collected through iPhone apps) will provide insight in two particular areas of interest: A)what impact on post-operative outcome does a course of pre-habilitation have on patient’s activity level aftersurgery, and B) how accurately does passively collected sensor data correlate with PRO scores? Our hypothesis isthat patients undergoing pre-habilitation would register a lower Length of Stay and higher overall satisfactionwith their hospital stay than non-pre-habilitated patients. In the context of bundled payments, such a correlationcould be easily turned into a risk mitigation tool for hospitals and providers keen on improving quality andlowering costs. Further, if it can be shown that a combination of data points gleaned passively through sensors orwearable devices would correlate with and be predictive of PROs, there would be a large market opportunity forimplant manufacturers, providers and insurers alike. For example, sensors build into implants could passivelycollect outcomes data that currently patients are unlikely to provide, and wearable devices could be engineeredto specifically focus on data collection and feedback loops to help patients recover quicker or identify patientswho need greater attention. There are many more potential applications.
Principal Investigator: Stefano Bini, MD
Trainees: Jeffrey Mulvihill, MD, Eli Kamara, MD, Ilya Bendich, MD,MBA, Kaitlin Vitek, Justin Krogue, MD, Kurt Yusi, MD, Austin Pitcher, MD, Kevin Choo, MD, Paul Yi,MD, Kevin Hwang, MD, Krishn Khanna, Joseph Patterson, MD
Innovative Devices and Materials
Development of Novel Impedance Sensor to Monitor Fracture Healing
10-20% of fractures result in delayed or non-union, but while radiography remains the standard technique to monitor healing, it can only diagnose delayed healing at the late stages of fracture repair (months following injury) due to its reliance on detection of mineralized tissue. Our goal is to develop a system that utilizes impedance spectroscopy to monitor progression of fracture healing and detect delays in union at an early stage and thus enable earlier intervention. We have shown that impedance spectroscopy can track fracture progression in cadaver and mouse models, and are currently building a prototype for a larger preclinical animal model.
Principal Investigator: Meir Marmor, MD, Chelsea Bahney, PhD, Safa Herfat, PhD, Michael Maharbiz
Trainees: Diane Hu, MD, Frank Yan, Monica Lin