Medicine and Health Sciences Commons^™

Improving Motor Neuron-Like Cell Differentiation Of Henscs By The Combination Of Epothilone B Loaded Pcl Microspheres In Optimized 3d Collagen Hydrogel, Narges Mahmoodi, Jafar Ai, Zahra Hassannejad, Somayeh Ebrahimi-Barough, Elham Hasanzadeh, Houra Nekounam, Alex R. Vaccaro, Vafa Rahimi-Movaghar

Department of Orthopaedic Surgery Faculty Papers

Spinal cord regeneration is limited due to various obstacles and complex pathophysiological events after injury. Combination therapy is one approach that recently garnered attention for spinal cord injury (SCI) recovery. A composite of three-dimensional (3D) collagen hydrogel containing epothilone B (EpoB)-loaded polycaprolactone (PCL) microspheres (2.5 ng/mg, 10 ng/mg, and 40 ng/mg EpoB/PCL) were fabricated and optimized to improve motor neuron (MN) differentiation efficacy of human endometrial stem cells (hEnSCs). The microspheres were characterized using liquid chromatography-mass/mass spectrometry (LC-mas/mas) to assess the drug release and scanning electron microscope (SEM) for morphological assessment. hEnSCs were isolated, then characterized by flow cytometry, and …

Spinal Cord Signal Change On Magnetic Resonance Imaging May Predict Worse Clinical In- And Outpatient Outcomes In Patients With Spinal Cord Injury: A Prospective Multicenter Study In 459 Patients., Thorsten Jentzsch, David W Cadotte, Jefferson R Wilson, Fan Jiang, Jetan H Badhiwala, Muhammad A Akbar, Brett Rocos, Robert G Grossman, Bizhan Aarabi, James Harrop, Michael G Fehlings

Department of Orthopaedic Surgery Faculty Papers

Prognostic factors for clinical outcome after spinal cord (SC) injury (SCI) are limited but important in patient management and education. There is a lack of evidence regarding magnetic resonance imaging (MRI) and clinical outcomes in SCI patients. Therefore, we aimed to investigate whether baseline MRI features predicted the clinical course of the disease. This study is an ancillary to the prospective North American Clinical Trials Network (NACTN) registry. Patients were enrolled from 2005-2017. MRI within 72 h of injury and a minimum follow-up of one year were available for 459 patients. Patients with American Spinal Injury Association impairment scale (AIS) …

Bassini Inguinal Hernia Repair: Obsolete Or Still A Viable Surgical Option? A Single Center Cohort Study, Wayne Tse, William Johns, James Maher, Jeannie Rivers, Thomas Miller

Department of Orthopaedic Surgery Faculty Papers

Background: Most inguinal hernias are presently repaired using some type of mesh technique. This mesh can be placed through an inguinal incision or positioned through a laparoscopic approach. Either way, results have been impressive including a low recurrence rate, minimal pain and a rapid return to work and normal activity compared to tissue based approaches. Notwithstanding these results, there is still a subset of patients who, for various reasons, are strongly opposed to having a mesh repair. This study summarizes our 13 year experience with such patients and why the Bassini hernia repair is a viable surgical option in these …

Current Evidence On Potential Of Adipose Derived Stem Cells To Enhance Bone Regeneration And Future Projection, Quang Le, Vedavathi Madhu, Joseph M Hart, Charles R Farber, Eli R Zunder, Abhijit S Dighe, Quanjun Cui

Department of Orthopaedic Surgery Faculty Papers

Injuries to the postnatal skeleton are naturally repaired through successive steps involving specific cell types in a process collectively termed “bone regeneration”. Although complex, bone regeneration occurs through a series of well-orchestrated stages wherein endogenous bone stem cells play a central role. In most situations, bone regeneration is successful; however, there are instances when it fails and creates non-healing injuries or fracture nonunion requiring surgical or therapeutic interventions. Transplantation of adult or mesenchymal stem cells (MSCs) defined by the International Society for Cell and Gene Therapy (ISCT) as CD105+-CD90+CD73+CD45-CD34-CD14orCD11b-CD79αorCD19-HLA-DR-is being investigated as an attractive therapy for bone regeneration throughout the …

Mechanisms Of Reducing Joint Stiffness By Blocking Collagen Fibrillogenesis In A Rabbit Model Of Posttraumatic Arthrofibrosis, Andrzej Steplewski, Jolanta Fertala, Ryan Tomlinson, Mark L. Wang, Allison Donahue, William V Arnold, Michael Rivlin, Pedro K Beredjiklian, Joseph A Abboud, Surena Namdari, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on antiinflammatory and anti-proliferative agents with broad intracellular targets. As a result, their use is not fully effective and may cause unwanted side effects. Our group previously demonstrated that extracellular collagen fibrillogenesis is a valid and specific target to reduce collagen- rich scar buildup. Our previous studies showed that a rationally designed antibody that binds the C-terminal telopeptide of the α2(I) chain involved in the aggregation of collagen molecules limits fibril assembly in vitro and reduces scar …

Long-Term Treatment With Senolytic Drugs Dasatinib And Quercetin Ameliorates Age-Dependent Intervertebral Disc Degeneration In Mice, Emanuel J Novais, Victoria Tran, Shira N Johnston, Kayla R Darris, Alex J Roupas, Garrett A Sessions, Irving Shapiro, Brian O Diekman, Makarand V Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence, we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts show lower incidences of degeneration, and the treatment results in a significant decrease in senescence markers p16INK4a, …

Multicenter Outcomes After Hip Arthroscopy: Comparative Analysis Of Patients Undergoing Concomitant Labral Repair And Ligamentum Teres Debridement Versus Isolated Labral Repair, Blake Bodendorfer, Thomas Alter, Steven Defroda, Andrew Wolff, Dominic Carreira, John Cristoforetti, Dean Matsuda, John Salvo, Benjamin Kivlan, Shane Nho

Department of Orthopaedic Surgery Faculty Papers

Background: Increased attention has been directed toward the ligamentum teres (LT) and its association with acetabular coverage, labral pathology, and hip microinstability; however, few studies have evaluated whether LT pathology influences the rate of clinically significant outcome improvement after hip arthroscopy. Purpose: To determine if patients with femoroacetabular impingement syndrome (FAIS) undergoing labral repair and concomitant LT debridement achieve outcomes similar to patients without LT pathology undergoing labral repair. Study Design: Cohort study; Level of evidence, 3. Methods: We conducted a retrospective review of a prospectively maintained multicenter database for hip arthroscopy. Included were patients with FAIS who underwent primary …

The Utility Of Continuous Passive Motion After Anterior Cruciate Ligament Reconstruction: A Systematic Review Of Comparative Studies, Taylor D'Amore, Somnath Rao, John Corvi, Robert Jack Ii, Fotios Tjoumakaris, Michael G. Ciccotti, Kevin Freedman

Department of Orthopaedic Surgery Faculty Papers

Background: The application of continuous passive motion (CPM) after anterior cruciate ligament reconstruction (ACLR) was popularized in the 1990s, but advancements in the understanding of ACLR rehabilitation have made the application of CPM controversial. Many sports medicine fellowship–trained surgeons report using CPM machines postoperatively. Purpose: To determine the efficacy of CPM use for recovery after ACLR with respect to knee range of motion (ROM), knee swelling, postoperative pain, and postoperative complications. Study Design: Systematic review; Level of evidence, 3. Methods: The PubMed (MEDLINE), EMBASE, Cochrane, Cumulative Index of Nursing, and Allied Health Literature databases were searched from inception to January …

Trends In Leadership At Orthopaedic Surgery Sports Medicine Fellowships, Nicholas C. Schiller, Andrew J. Sama, Amanda F. Spielman, Chester J. Donnally, Benjamin I. Schachner, Dhanur M. Damodar, Christopher C. Dodson, Michael G. Ciccotti

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Fellowship directors (FDs) in sports medicine influence the future of trainees in the field of orthopaedics. Understanding the characteristics these leaders share must be brought into focus. For all current sports medicine FDs, our group analyzed their demographic background, institutional training, and academic experience.

AIM: To serve as a framework for those aspiring to achieve this position in orthopaedics and also identify opportunities to improve the position.

METHODS: Fellowship programs were identified using both the American Orthopaedic Society for Sports Medicine and the Arthroscopy Association of North America Sports Medicine Fellowship Directories. The demographic and educational background data for …

Leveraging Advancements In Tissue Engineering For Bioprinting Dental Tissues, Devin Grace Morrison, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

3D bioprinting allows biocompatible materials and cells to be deposited in precise locations in three-dimensional space, enabling researchers to surpass the limitations of traditional 2D cell culture and to create innovative therapies. 3D bioprinting is one of the newest tools developed in the field of tissue engineering, which has traditionally utilized a paradigm revolving around scaffolds, cells, and signals. In this review, we discuss how new developments in each of these three research areas relates to bioprinting dental tissues – specifically teeth, periodontal ligament, and alveolar bone. Important considerations include how scaffold materials and geometry affect regeneration of dental tissues, …

Development Of A Standardized Histopathology Scoring System Using Machine Learning Algorithms For Intervertebral Disc Degeneration In The Mouse Model-An Ors Spine Section Initiative., Itzel Paola Melgoza, Srish S Chenna, Steven Tessier, Yejia Zhang, Simon Y Tang, Takashi Ohnishi, Emanuel José Novais, Geoffrey J Kerr, Sarthak Mohanty, Vivian Tam, Wilson C W Chan, Chao-Ming Zhou, Ying Zhang, Victor Y Leung, Angela K Brice, Cheryle A Séguin, Danny Chan, Nam Vo, Makarand V Risbud, Chitra L Dahia

Department of Orthopaedic Surgery Faculty Papers

Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several intervertebral disc (IVD) histological scoring systems have been proposed, but none exists that reliably quantitate mouse disc pathologies. Here, we report a new robust quantitative mouse IVD histopathological scoring system developed by building consensus from the spine community analyses of previous scoring systems and features noted on different mouse models of IDD. The new scoring system analyzes 14 key histopathological features from nucleus pulposus (NP), annulus fibrosus (AF), endplate (EP), and AF/NP/EP interface regions. Each feature is categorized and …

Staphylococcus Aureus Floating Biofilm Formation And Phenotype In Synovial Fluid Depends On Albumin, Fibrinogen, And Hyaluronic Acid, Samantha Knott, Dylan Curry, Neil Zhao, Pallavi Metgud, Sana Dastgheyb, Caroline Purtill, Marc I. Harwood, Md, Antonia F Chen, Thomas P Schaer, Michael Otto, Noreen J. Hickok

Department of Orthopaedic Surgery Faculty Papers

Biofilms are typically studied in bacterial media that allow the study of important properties such as bacterial growth. However, the results obtained in such media cannot take into account the bacterial localization/clustering caused by bacteria–protein interactions in vivo and the accompanying alterations in phenotype, virulence factor production, and ultimately antibiotic tolerance. We and others have reported that methicillin-resistant or methicillin-susceptible Staphylococcus aureus (MRSA or MSSA, respectively) and other pathogens assemble a proteinaceous matrix in synovial fluid. This proteinaceous bacterial aggregate is coated by a polysaccharide matrix as is characteristic of biofilms. In this study, we identify proteins important for this …

Commentary On "A Prospective, Single-Blinded, Bicentric Study, And Literature Review To Assess The Need Of C2-Ganglion Preservation - Saviour's Criteria"., James Harrop

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

Neurological Manifestations As The Predictors Of Severity And Mortality In Hospitalized Individuals With Covid-19: A Multicenter Prospective Clinical Study, Man Amanat, Nima Rezaei, Mehrdad Roozbeh, Maziar Shojaei, Abbas Tafakhori, Anahita Zoghi, Ilad Alavi Darazam, Mona Salehi, Ehsan Karimialavijeh, Behnam Safarpour Lima, Amir Garakani, Alex R. Vaccaro, Mahtab Ramezani

Department of Orthopaedic Surgery Faculty Papers

BACKGROUNDS: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death.

METHODS: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements.

RESULTS: We included 873 participants. Of eligible cases, 122 …

The Trka Agonist Gambogic Amide Augments Skeletal Adaptation To Mechanical Loading., Gabriella Fioravanti, Phuong Q. Hua, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

The periosteal and endosteal surfaces of mature bone are densely innervated by sensory nerves expressing TrkA, the high-affinity receptor for nerve growth factor (NGF). In previous work, we demonstrated that administration of exogenous NGF significantly increased load-induced bone formation through the activation of Wnt signaling. However, the translational potential of NGF is limited by the induction of substantial mechanical and thermal hyperalgesia in mice and humans. Here, we tested the effect of gambogic amide (GA), a recently identified robust small molecule agonist for TrkA, on hyperalgesia and load-induced bone formation. Behavioral analysis was used to assess pain up to one …

Tonebp Regulates The Hyperosmotic Expression Of Aquaporin 1 And 5 In The Intervertebral Disc., Joseph Snuggs, Steven Tessier, R A B Bunning, Irving Shapiro, Makarand V Risbud, Christine Lyn Le Maitre

Department of Orthopaedic Surgery Faculty Papers

The central region of the intervertebral disc (IVD) is rich in proteoglycans, leading to a hyperosmotic environment, which fluctuates with daily loading. The cells of the nucleus pulposus (NP cells) have adapted to this environment via the function of tonicity enhancer binding protein (TonEBP), and NP cells have been shown to express several water channels known as aquaporins (AQP). We have previously shown that AQP1 and 5 decrease during IVD degeneration. Here, the regulation of AQP1 and 5 by hyperosmotic conditions and the role of TonEBP in this regulation was investigated. AQP1 and 5 gene expression was upregulated by hyperosmotic …

Genetic Murine Models Of Spinal Development And Degeneration Provide Valuable Insights Into Intervertebral Disc Pathobiology., J. Melrose, S. Tessier, M. V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Disc degeneration and associated back and neck pain elicits a substantial burden on healthcare systems and the individuals affected, necessitating the development of novel therapeutic strategies. This goal can only be achieved by a better understanding of intervertebral disc development, homeostasis and pathogenesis. A number of genetic and in-bred murine models are reviewed to underscore the importance of the mouse as an animal model of choice for the assessment of intervertebral disc pathobiology. Appraisals of the differences between mouse and human musculoskeletal systems and proteoglycan structures are also included. A number of important target pathways and molecules have been identified, …

Collagen Structure-Function Mapping Informs Applications For Regenerative Medicine., James D San Antonio, Olena Jacenko, Andrzej Fertala, Joseph P R O Orgel

Department of Orthopaedic Surgery Faculty Papers

Type I collagen, the predominant protein of vertebrates, assembles into fibrils that orchestrate the form and function of bone, tendon, skin, and other tissues. Collagen plays roles in hemostasis, wound healing, angiogenesis, and biomineralization, and its dysfunction contributes to fibrosis, atherosclerosis, cancer metastasis, and brittle bone disease. To elucidate the type I collagen structure-function relationship, we constructed a type I collagen fibril interactome, including its functional sites and disease-associated mutations. When projected onto an X-ray diffraction model of the native collagen microfibril, data revealed a matrix interaction domain that assumes structural roles including collagen assembly, crosslinking, proteoglycan (PG) binding, and …