2017-18 CDMI Projects

High-throughput screening for osteocyte-mediated bone remodeling (OMBRE) regulatory compounds.

This project promotes the development of new therapies to improve bone quality and prevent bone fragility and other common musculoskeletal diseases by targeting osteocyte-mediated bone remodeling (OMBRE) or perilacunar remodeling. This project objective is to screen a library of FDA-approved small molecule compounds to identify agents that regulate OMBRE in vitro. In partnership with M. Arkin, PhD, the Director of the UCSF Small Molecule Development Center (SMDC),
we have developed two in vitro assays to quantify functional OMBRE outcomes that are suitable for high through put screening (HTS).

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Principal Investigator: Tamara Alliston, PhD

Trainee: Cristal Yee, PhD

Nerve/Bone crosstalk: PEMF control of cAMP-sensitive TGFb signaling.

As illustrated in Figure 1, we will test the hypothesis that adrenergic receptor signaling epistatically regulates
TGFβ-inducible SOST expression in an osteocyte-intrinsic and cAMP-dependent manner. Furthermore, we will test the hypothesis that physical cues, such as PEMF or fluid flow shear stress, interfere with these regulatory relationships.

Principal Investigator: Tamara Alliston, PhD

Trainee: Courtney Mazur

Mechanisms of post-discectomy vertebral endplate changes

Principal Investigator: Jeffrey Lotz, PhD

Trainee: Alexander Ballatori

Animal Model to Characterize Natural History of Intracept Basivertebral Nerve Ablation

Principal Investigator: Jeffrey Lotz, PhD

Trainee: Alexander Ballatori

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Basic Science

 

Biomaterials

Development of hard antibacterial (TiN/Ag) coatings on orthopedic instruments fabricated from Ti-alloys.

The main hypothesis here is to render the hard coating of TiN antibacterial by incorporating Ag in them. While we are aware of only one study in the literature (Moseke et al.), it is not clear, what is the state of Ag in the coating that facilitates the slow release of Ag. It is of great significance to understand the “Structure-Property-Processing” correlations in these coatings. Since the coatings will be deposited using magnetron sputtering, it will important to correlate the sputtering conditions to the structure of TiN/Ag coatings. The structures of the coatings can be subsequently correlated to the Ag release kinetics and antibacterial properties data.

The deposition parameters will be optimized by evaluating the silver content and uniformity in coatings, their adhesion, morphology, micro/nano-hardness, as well as Agrelease kinetics, and antibacterial properties using standard protocols.

Principal Investigator: Sarit Bhaduri, PhD

Co-Principal Investigator: Ahalapitiya H. Jayatissa, PhD

Trainee: Lufei Liu

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Clinical Outcomes

A validation study using gait analysis to test the accuracy of wearable sensor data in postsurgical patients

We aim to partner with the Human Performance Lab to test the accuracy and reproducibility of the signal obtained from patient worn sensors (“wearables”) during commonly performed activities 3 months following surgery when compared to a gold standard gait analysis lab data. We hypothesize that in combination with our earlier study, we will be able to identify 1) the optimal combination of data points (which data points, how many of them and over what time frame-prior study and 2) the most accurate and reproducible way to collect those data points (proposed study) that will provide an accurate picture of an individual’s clinical outcome that is predictive of standardized PRO results.

Principal Investigator: Stefano Bini, MD

Trainees: A Pitcher, MD; I Bendich, MD; K Hwang, MD; E Kamara, MD; J Patterson, MD

Predictive modeling for clinical outcomes and cost-effectiveness of surgery for lumbar degenerative pathologies and spinal deformity.

The purpose of this study is to follow on our previous work regarding the cost-effectiveness of surgery for

degenerative pathology and deformity, and to identify predictor variables for the outcomes of clinical improvement, readmission, revision surgery, cost-effectiveness, and appropriateness of surgery. A predictive model will be based upon patient specific and diagnosis specific variables. This model and other established models (SPORT calculator, Spine Sage, NSQIP Calculator) will then be compared. In parallel, we will apply a multidisciplinary conference prediction of complications to determine the accuracy of computerized predictive models with the wisdom of a crowd of clinicians.

The specific outcomes for the predictive model include expected complications, readmission, reoperation, and appropriateness of surgery based upon observed outcomes and complications.

Principal Investigator: Sigurd Berven, MD

Trainee: Paramjit Singh, MD

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Innovative Devices/Tools/Equipment or  Surgical Technique Evaluation

Biomechanical evaluation of the newly developed decompression surgery: Transforaminal ventral facetectomy

To elucidate the biomechanical effects of the PEVF using the finite element model. Figure 2 demonstrates the CT scans before and after the PEVF. Please note that the ventral aspect of the facet joint is removed.

Principal Investigators: Koichi Sairyo, MD and Vijay Goel, PhD

Trainee: Koji Matsumoto, PhD

Development of an innovative posterior pedicle-based screw device for multilevel semi-dynamic stabilization

A project is proposed to develop and evaluate a novel pedicle screw design, double-head pedicle screw, to be used as a component of multilevel posterior stabilization system for various scenarios, as listed above. We will developed the sytem using finite element analysis (FEA), mechanical and In vitro testing.

Principal Investigator: Deniz Erbulut, PhD

Effect of Talotarsal Joint Instability on Lower Extremity Alignment and the Role of Extra-osseous Talotarsal Joint Stabilization

Talotarsal joint (TTJ) instability leads to chronic "wear-and-tear" and misalignment of proximal musculoskeletal structures. Extra-osseous talotarsal stabilization (EOTTS), the insertion of a titanium stent in to the sinus tarsi, has been proven to realign and stabilize the TTJ, yet there is little evidence published on the positive effects to proximal musculoskeletal structures. This research will show the negative effects, if any, to the lower extremity alignment from TTJ instability and if a positive correlation can be made by realigning the TTJ with an EOTTS stent.

Principal Investigator: Vijay Goel, PhD

Trainee: Koji Matsumoto, PhD

Tapered reduction of cement volume in the proximal vertebrae adjacent to the fused segment may translate into a decreased rate of Proximal Junctional Kyphosis (PJK) using Calcium phosphate cement - A biomechanical investigation

Principal Investigator: Anand Agarwal, MD

Trainee: Anoli Shah

Transporter Table System

1) Design a system to safely move patients between a gurney and OR table using wheels

2) Build such a system and demonstrate its efficacy.

Principal Investigator: Anand Agarwal, MD

Trainee: David Dick

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