Medicine and Health Sciences Commons^™

Evaluation Of Perioperative Care And Drivers Of Cost In Geriatric Thoracolumbar Trauma, Omar Tarawneh, Rajkishen Narayanan, Michael Mccurdy, Tariq Issa, Yunsoo Lee, Olivia Opara, Nicholas Pohl, Alexa Tomlak, Matthew Sherman, Jose Canseco, Alan Hilibrand, Alex Vaccaro, Gregory Schroeder, Christopher Kepler

Department of Orthopaedic Surgery Faculty Papers

INTRODUCTION: As the population of elderly patients continues to rise, the number of these individuals presenting with thoracolumbar trauma is expected to increase.

RESEARCH QUESTION: To investigate thoracolumbar fusion outcomes for patients with vertebral fractures as stratified by decade. Secondarily, we examined the variability of cost across age groups by identifying drivers of cost of care.

MATERIALS AND METHODS: We queried the United States Nationwide Inpatient Sample(NIS) for adult patients undergoing spinal fusion for thoracolumbar fractures between 2012 and 2017. Patients were stratified by decade 60-69(sexagenarians), 70-79(septuagenarians) and 80-89(octogenarians). Bivariable analysis followed by multivariable regression was performed to assess independent …

Increased Hif-2Α Activity In The Nucleus Pulposus Causes Intervertebral Disc Degeneration In The Aging Mouse Spine, Shira N Johnston, Maria Tsingas, Rahatul Ain, Ruteja A Barve, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Hypoxia-inducible factors (HIFs) are essential to the homeostasis of hypoxic tissues. Although HIF-2α, is expressed in nucleus pulposus (NP) cells, consequences of elevated HIF-2 activity on disc health remains unknown. We expressed HIF-2α with proline to alanine substitutions (P405A; P531A) in the Oxygen-dependent degradation domain (HIF-2αdPA) in the NP tissue using an inducible, nucleus pulposus-specific K19^CreERT allele to study HIF-2α function in the adult intervertebral disc. Expression of HIF-2α in NP impacted disc morphology, as evident from small but significantly higher scores of degeneration in NP of 24-month-old K19^CreERT; HIF-2α^dPA (K19-dPA) mice. Noteworthy, comparisons of grades …

In-Hospital Mortality Trends After Surgery For Traumatic Thoracolumbar Injury: A National Inpatient Sample Database Study, Michael Mccurdy, Rajkishen Narayanan, Omar Tarawneh, Yunsoo Lee, Matthew Sherman, Teeto Ezeonu, Michael Carter, Jose A. Canseco, Alan S. Hilibrand, Alex R. Vaccaro, Christopher K. Kepler, Gregory D. Schroeder

Department of Orthopaedic Surgery Faculty Papers

INTRODUCTION: Given the increasing incidence of traumatic thoracolumbar injuries in recent years, studies have sought to investigate potential risk factors for outcomes in these patients.

RESEARCH QUESTION: The aim of this study was to investigate trends and risk factors for in-hospital mortality after fusion for traumatic thoracolumbar injury.

MATERIALS AND METHODS: Patients undergoing thoracolumbar fusion after traumatic injury were queried from the National Inpatient Sample (NIS) from 2012 to 2017. Analysis was performed to identify risk factors for inpatient mortality after surgery.

RESULTS: Patients in 2017 were on average older (51.0 vs. 48.5, P = 0.004), had more admitting diagnoses …

Predictive Algorithm For Surgery Recommendation In Thoracolumbar Burst Fractures Without Neurological Deficits, Charlotte Dandurand, Nader Fallah, Cumhur F. Öner, Richard J. Bransford, Klaus Schnake, Alex R. Vaccaro, Lorin M. Benneker, Emiliano Vialle, Gregory D. Schroeder, Shanmuganathan Rajasekaran, Mohammad El-Skarkawi, Rishi M. Kanna, Mohamed Aly, Martin Holas, Jose A. Canseco, Sander Muijs, Eugen Cezar Popescu, Jin Wee Tee, Gaston Camino-Willhuber, Andrei Fernandes Joaquim, Ory Keynan, Harvinder Singh Chhabra, Sebastian Bigdon, Ulrich Spiegel, Marcel F. Dvorak

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: Predictive algorithm via decision tree.

OBJECTIVES: Artificial intelligence (AI) remain an emerging field and have not previously been used to guide therapeutic decision making in thoracolumbar burst fractures. Building such models may reduce the variability in treatment recommendations. The goal of this study was to build a mathematical prediction rule based upon radiographic variables to guide treatment decisions.

METHODS: Twenty-two surgeons from the AO Knowledge Forum Trauma reviewed 183 cases from the Spine TL A3/A4 prospective study (classification, degree of certainty of posterior ligamentous complex (PLC) injury, use of M1 modifier, degree of comminution, treatment recommendation). Reviewers' regions …

Significance Of Facet Fluid Index In Anterior Cervical Degenerative Spondylolisthesis, Yunsoo Lee, Jeremy Heard, Mark J Lambrechts, Nathaniel Kern, Bright Wiafe, Perry Goodman, John J. Mangan, Jose A. Canseco, Mark F. Kurd, Ian D. Kaye, Alan S. Hilibrand, Alex R. Vaccaro, Christopher K. Kepler, Gregory D. Schroeder, Jeffrey A. Rihn

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: Retrospective cohort study.

PURPOSE: To correlate cervical facet fluid characteristics to radiographic spondylolisthesis, determine if facet fluid is associated with instability in cervical degenerative spondylolisthesis, and examine whether vertebral levels with certain facet fluid characteristics and spondylolisthesis are more likely to be operated on.

OVERVIEW OF LITERATURE: The relationship between facet fluid and lumbar spondylolisthesis is well-documented; however, there is a paucity of literature investigating facet fluid in degenerative cervical spondylolisthesis.

METHODS: Patients diagnosed with cervical degenerative spondylolisthesis were identified from a hospital's medical records. Demographic and surgical characteristics were collected through a structured query language search and …

A New Perspective On Intervertebral Disc Calcification-From Bench To Bedside, Emanuel Novais, Rajkishen Narayanan, Jose Canseco, Koen Van De Wetering, Christopher Kepler, Alan Hilibrand, Alex Vaccaro, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular …

Evaluating The Efficacy Of A Thermoresponsive Hydrogel For Delivering Anti-Collagen Antibodies To Reduce Posttraumatic Scarring In Orthopedic Tissues., Andrzej Steplewski, Jolanta Fertala, Lan Cheng, Mark Wang, Michael Rivlin, Pedro K Beredjiklian, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical removal of fibrotic tissue, which can aggravate the problem. The primary component of orthopedic scars is collagen I-rich fibrils. Our research team has developed a monoclonal anti-collagen antibody (ACA) that alleviates posttraumatic scarring by inhibiting collagen fibril formation. We previously established the safety and efficacy of ACA in a rabbit-based arthrofibrosis model. In this study, we evaluate …

Sirtuin 6 Activation Rescues The Age-Related Decline In Dna Damage Repair In Primary Human Chondrocytes, Michaela E. Copp, Jacqueline Shine, Hannon L. Brown, Kirti R. Nimmala, Oliver B. Hansen, Susan Chubinskaya, John A. Collins, Richard F. Loeser, Brian O. Diekman

Department of Orthopaedic Surgery Faculty Papers

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from …

Finite Element Analysis Comparing A Peek Posterior Fixation Device Versus Pedicle Screws For Lumbar Fusion, Robert Eastlack, Pierce Nunley, Kornelis Poelstra, Alex Vaccaro, Marcus Stone, Larry Miller, Pierre Legay, Julien Clin, Aakash Agarwal

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Pedicle screw loosening and breakage are common causes of revision surgery after lumbar fusion. Thus, there remains a continued need for supplemental fixation options that offer immediate stability without the associated failure modes. This finite element analysis compared the biomechanical properties of a novel cortico-pedicular posterior fixation (CPPF) device with those of a conventional pedicle screw system (PSS).

METHODS: The CPPF device is a polyetheretherketone strap providing circumferential cortical fixation for lumbar fusion procedures via an arcuate tunnel. Using a validated finite element model, we compared the stability and load transfer characteristics of CPPF to intact conditions under a …

Role Of Preoperative Nerve Conduction Studies For Penetrating Hand Injuries Involving The Median Palmar Cutaneous Nerve, Saral Patel, David Hutchinson, Sebastian D. Arango, Andrew J. Miller, Rowena Mcbeath

Department of Orthopaedic Surgery Faculty Papers

Penetrating lacerations to the hand are a common cause of nerve injury and can lead to debilitating pain and numbness in the distribution of the nerve affected. Owing to an overlap in the cutaneous innervation from different sensory nerves, clinically identifying the injured nerve can be difficult. We present a novel case of isolated injury to the palmar cutaneous nerve from a penetrating knife injury which was detected using 'comparison waveform' nerve conduction studies. Using this technique, we can isolate injuries to the palmar cutaneous branch of the median nerve (PCBmdn) from the median nerve, dorsal radial sensory nerve, and …

Lateral Approach To The Lumbar Spine: The Utility Of An Access Surgeon, Matthew Meade, Yunsoo Lee, Parker Brush, Mark Lambrechts, Eleanor Jenkins, Cristian Desimone, Michael Mccurdy, John Mangan, Jose Canseco, Mark Kurd, Alan Hilibrand, Alexander Vaccaro, Christopher Kepler, Gregory Schroeder

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Lateral lumbar interbody fusions (LLIFs) utilize a retroperitoneal approach that avoids the intraperitoneal organs and manipulation of the anterior vasculature encountered in anterior approaches to the lumbar spine. The approach was championed by spinal surgeons; however, general/vasculature surgeons may be more comfortable with the approach.

OBJECTIVE: The objective of this study was to compare short-term outcomes following LLIF procedures based on whether a spine surgeon or access surgeon performed the approach.

MATERIALS AND METHODS: We retrospectively identified all one- to two-level LLIFs at a tertiary care center from 2011 to 2021 for degenerative spine disease. Patients were divided into …

Multilevel Ossification Of The Posterior Longitudinal Ligament Causing Cervical Myelopathy: An Observational Series Of North American Patients, Jonathan A. Ledesma, Tariq Z. Issa, Mark J. Lambrechts, Cannon Greco Hiranaka, Khoa Tran, Patrick O'Connor, Jose A. Canseco, Alan S. Hilibrand, Christopher K. Kepler, Todd J. Albert, Alex R. Vaccaro, Gregory D. Schroeder, David Greg Anderson

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Few studies regarding ossification of the posterior longitudinal ligament (OPLL) outside of Asia currently exist in the literature. A set of patients with multilevel cervical OPLL causing symptomatic myelopathy or radiculopathy from a North American sample is analyzed.

OBJECTIVE: The objective of this study was to describe the demographics, radiographic findings, and surgical outcomes of a cohort of North American patients with degenerative spondylosis presenting for operative management of multilevel (>3 segments) cervical OPLL.

MATERIALS AND METHODS: Forty-three patients diagnosed with multilevel cervical OPLL and degenerative spondylosis presenting with symptomatic cervical myelopathy or radiculopathy were surgically treated over …

Atmospheric Pressure Plasma Treatment Of Skin: Penetration Into Hair Follicles, Kseniia Konina, Theresa A. Freeman, Mark J. Kushner

Department of Orthopaedic Surgery Faculty Papers

Sterilization of skin prior to surgery is challenged by the reservoir of bacteria that resides in hair follicles. Atmospheric pressure plasma jets (APPJs) have been proposed as a method to treat and deactivate these bacteria as atmospheric plasmas are able to penetrate into structures and crevices with dimensions similar to those found in hair follicles. In this paper, we discuss results from a computational investigation of an APPJ sustained in helium flowing into ambient air, and incident onto a layered dielectric similar to human skin in which there are idealized hair follicles. We found that, depending on the location of …

Corneal Wound Healing In The Presence Of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study, Zeba A. Syed, Tatyana Milman, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Highly organized collagen fibrils interlacing with proteoglycans form the crucial architecture of the cornea and facilitate its transparency. Corneal scarring from accidental injury, surgery, or infection alters this highly organized tissue, causing severe consequences, including blindness. There are no pharmacological or surgical methods to effectively and safely treat excessive corneal scarring. Thus, we tested the anticorneal scarring utility of a rationally designed anticollagen antibody (ACA) whose antifibrotic effects have already been demonstrated in nonocular models. Utilizing a rabbit model with an incisional corneal wound, we analyzed ACA’s effects on forming collagen and proteoglycan-rich extracellular matrices in scar neotissue. We used …

Successful Return To Sport And Daily Activities After Suture Augmentation Of Both The Anterior Talofibular Ligament And Calcaneofibular Ligament, S Ali Ghasemi, Jetha Tallapaneni, Benjamin C Murray, Clark Yin, James Raphael, Zachary Vaupel, Allan Grant, Paul Fortin

Department of Orthopaedic Surgery Faculty Papers

PURPOSE: To evaluate the return to sport and daily activities in addition to clinical outcomes after modification of the Brostöm repair, specifically using suture augmentation for concomitant fixation of both the anterior talofibular ligament and calcaneofibular ligament.

METHODS: Patients who had grade III ankle sprains and lateral ankle instability, all of whom failed supervised conservative management, were included. Patients underwent a modified Broström procedure consisting of suture augmentation for both the anterior talofibular ligament and calcaneofibular ligament. For clinical outcome evaluation, Foot and Ankle Ability Measure (FAAM) and Karlsson-Peterson Scoring System for Ankle Function questionnaires coupled with questions regarding time …

Editorial: Intervertebral Disc Degeneration And Osteoarthritis: Mechanisms Of Disease And Functional Repair., Graciosa Q Teixeira, Jana Riegger, Raquel M Gonçalves, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

Republication Of “Open Repair Of Acute Achilles Tendon Ruptures: Is The Incidence Of Clinically Significant Wound Complications Overestimated?”, Meghan E. Bishop, Carly D. Comer, Justin M. Kane, Mitchell G. Maltenfort, Steven M. Raikin

Department of Orthopaedic Surgery Faculty Papers

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Loss Of Function Mutation In Ank Causes Aberrant Mineralization And Acquisition Of Osteoblast-Like-Phenotype By The Cells Of The Intervertebral Disc, Takashi Ohnishi, Victoria Tran, Kimheak Sao, Pranay Ramteke, William Querido, Ruteja A. Barve, Koen Van De Wetering, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Pathological mineralization of intervertebral disc is debilitating and painful and linked to disc degeneration in a subset of human patients. An adenosine triphosphate efflux transporter, progressive ankylosis (ANK) is a regulator of extracellular inorganic pyrophosphate levels and plays an important role in tissue mineralization. However, the function of ANK in intervertebral disc has not been fully explored. Herein we analyzed the spinal phenotype of Ank mutant mice (ank/ank) with attenuated ANK function. Micro-computed tomography and histological analysis showed that loss of ANK function results in the aberrant annulus fibrosus mineralization and peripheral disc fusions with cranial to caudal progression in …

Multiple Sterile Withdrawals From Iohexol Bottles Does Not Increase Contamination Risk, Caroline Purtill, Manraj Dhesi, Daniel Haber, Nicholas D'Antonio, Noreen J. Hickok, Jeremy I. Simon

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: There is a global shortage of iohexol contrast media, commonly used in epidural injections, as a result of lockdown and decreased production due to COVID-19. Iohexol bottles are designated for single use, which, depending on the vials available, often leads to wasting up to 95% of this limited resource. However, avoiding multiple withdrawals may be unnecessary if withdrawing multiple times using sterile technique does not increase the risk for contamination.

OBJECTIVES: The purpose of our study is to determine whether multiple withdrawals from iohexol injection bottles using a sterile technique poses a greater risk of introducing contaminants than a …

Postoperative Considerations Based On Graft Type After Anterior Cruciate Ligament Reconstruction A Narrative Review, Anne Leung, Bridget Desandis, Luke O'Brien, Sommer Hammoud, Ryan Zarzycki

Department of Orthopaedic Surgery Faculty Papers

Background and Objective: Graft selection for anterior cruciate ligament reconstruction (ACLR) affects rehabilitation throughout the course of postoperative care. Methods: A search of PubMed and EBSCO was performed and abstracts independently reviewed by two authors. This search was also supplemented with additional evidence relevant to each phase of ACLR rehabilitation.

Key Content and Findings: Direct implications of graft type on clinical decisions vary throughout treatment phases, transitioning from potential differences in acute postoperative pain management immediately after surgery to facilitating sufficient and appropriate lower extremity loading in subsequent weeks. Regardless of graft type, surgical limb weakness persists throughout the course …

Observations On The Present And The Future Of Hip Surgery, Alberto Di Martino

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

Extracellular Targets To Reduce Excessive Scarring In Response To Tissue Injury, Jolanta Fertala, Mark L. Wang, Michael Rivlin, Pedro K. Beredjiklian, Joseph Abboud, William V. Arnold, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Excessive scar formation is a hallmark of localized and systemic fibrotic disorders. Despite extensive studies to define valid anti-fibrotic targets and develop effective therapeutics, progressive fibrosis remains a significant medical problem. Regardless of the injury type or location of wounded tissue, excessive production and accumulation of collagen-rich extracellular matrix is the common denominator of all fibrotic disorders. A long-standing dogma was that anti-fibrotic approaches should focus on overall intracellular processes that drive fibrotic scarring. Because of the poor outcomes of these approaches, scientific efforts now focus on regulating the extracellular components of fibrotic tissues. Crucial extracellular players include cellular receptors …

Microbubble Cavitation Restores Staphylococcus Aureus Antibiotic Susceptibility In Vitro And In A Septic Arthritis Model, Neil Zhao, Dylan Curry, Rachel E Evans, Selin Isguven, Theresa A. Freeman, John R. Eisenbrey, Flemming Forsberg, Jessica M Gilbertie, Sophie Boorman, Rachel Hilliard, Sana S. Dastgheyb, Priscilla Machado, Maria Stanczak, Marc I. Harwood, Antonia F Chen, Javad Parvizi, Irving Shapiro, Noreen J. Hickok, Thomas P Schaer

Department of Orthopaedic Surgery Faculty Papers

Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using ultrasound-triggered microbubble destruction (UTMD), in vitro and in a porcine model of septic arthritis. In vitro, when bacterially laden SynF is diluted, akin to the dilution achieved clinically with lavage and local injection of antibiotics, amikacin and ultrasound application result in increased bacterial metabolism, aggregate permeabilization, and a 4-5 log decrease in colony forming units, independent of microbubble destruction. Without SynF dilution, amikacin + UTMD does …

Cold Atmospheric Pressure Plasma-Antibiotic Synergy In Pseudomonas Aeruginosa Biofilms Is Mediated Via Oxidative Stress Response, Jordanne-Amee Maybin, Thomas P. Thompson, Padrig B. Flynn, Timofey Skvortsov, Noreen J. Hickok, Theresa A. Freeman, Brendan F. Gilmore

Department of Orthopaedic Surgery Faculty Papers

Cold atmospheric-pressure plasma (CAP) has emerged as a potential alternative or adjuvant to conventional antibiotics for the treatment of bacterial infections, including those caused by antibiotic-resistant pathogens. The potential of sub-lethal CAP exposures to synergise conventional antimicrobials for the eradication of Pseudomonas aeruginosa biofilms is investigated in this study. The efficacy of antimicrobials following or in the absence of sub-lethal CAP pre-treatment in P. aeruginosa biofilms was assessed. CAP pre-treatment resulted in an increase in both planktonic and biofilm antimicrobial sensitivity for all three strains tested (PAO1, PA14, and PA10548), with both minimum inhibitory concentrations (MICs) and minimum biofilm eradication …

Berberine Disrupts Staphylococcal Proton Motive Force To Cause Potent Anti-Staphylococcal Effects, Neil Zhao, Selin Isguven, Rachel Evans, Thomas P Schaer, Noreen J. Hickok

Department of Orthopaedic Surgery Faculty Papers

The presence of antibiotic resistance has increased the urgency for more effective treatments of bacterial infections. Biofilm formation has complicated this issue as biofilm bacteria become tolerant to antibiotics due to environmental factors such as nutrient deprivation and adhesion. In septic arthritis, a disease with an 11% mortality rate, bacteria in synovial fluid organize into floating, protein-rich, bacterial aggregates (mm-cm) that display depressed metabolism and antibiotic tolerance. In this study, Staphylococcus aureus (S. aureus), which is the most common pathogen in septic arthritis, was tested against different inhibitors that modulate bacterial surface protein availability and that should decrease bacterial aggregation. …

Systematic Assessment Of The Quality And Comprehensibility Of Youtube Content On Ulnar Collateral Ligament Injury And Management, Sohil S. Desai, Matthew J. Anderson, Connor R. Crutchfield, Anastasia Gazgalis, Frank J. Alexander, Charles A. Popkin, Christopher S. Ahmad

Department of Orthopaedic Surgery Faculty Papers

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Magnetized Chitosan Hydrogel And Silk Fibroin, Reinforced With Pva: A Novel Nanobiocomposite For Biomedical And Hyperthermia Applications, Reza Eivazzadeh-Keihan, Zeinab Pajoum, Hooman Aghamirza Moghim Aliabadi, Adibeh Mohammadi, Amir Kashtiaray, Milad Salimi Bani, Banafshe Pishva, Ali Maleki, Majid M Heravi, Mohammad Mahdavi, Elaheh Ziaei Ziabari

Department of Orthopaedic Surgery Faculty Papers

Herein, a multifunctional nanobiocomposite was designed for biological application, amongst which hyperthermia cancer therapy application was specifically investigated. This nanobiocomposite was fabricated based on chitosan hydrogel (CS), silk fibroin (SF), water-soluble polymer polyvinyl alcohol (PVA) and iron oxide magnetic nanoparticles (Fe₃O₄ MNPs). CS and SF as natural compounds were used to improve the biocompatibility, biodegradability, adhesion and cell growth properties of the nanobiocomposite that can prepare this nanocomposite for the other biological applications such as wound healing and tissue engineering. Since the mechanical properties are very important in biological applications, PVA polymer was used to increase the …

Glut1 Is Redundant In Hypoxic And Glycolytic Nucleus Pulposus Cells Of The Intervertebral Disc, Shira N. Johnston, Elizabeth S. Silagi, Vedavathi Madhu, Duc H. Nguyen, Irving M. Shapiro, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Glycolysis is central to homeostasis of nucleus pulposus (NP) cells in the avascular intervertebral disc. Since the glucose transporter, GLUT1, is a highly enriched phenotypic marker of NP cells, we hypothesized that it is vital for the development and postnatal maintenance of the disc. Surprisingly, primary NP cells treated with 2 well-characterized GLUT1 inhibitors maintained normal rates of glycolysis and ATP production, indicating intrinsic compensatory mechanisms. We showed in vitro that NP cells mitigated GLUT1 loss by rewiring glucose import through GLUT3. Of note, we demonstrated that substrates, such as glutamine and palmitate, did not compensate for glucose restriction resulting …

Approximating Scaffold Printability Utilizing Computational Methods, Ashkan Sedigh, Pejman Ghelich, Jacob Quint, Evelyn C Mollocana-Lara, Mohamadmahdi Samandari, Ali Tamayol, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Bioprinting facilitates the generation of complex, three-dimensional (3D), cell-based constructs for various applications. Although multiple bioprinting technologies have been developed, extrusion-based systems have become the dominant technology due to the diversity of materials (bioinks) that can be utilized, either individually or in combination. However, each bioink has unique material properties and extrusion characteristics that affect bioprinting utility, accuracy, and precision. Here, we have extended our previous work to achieve high precision (i.e. repeatability) and printability across samples by optimizing bioink-specific printing parameters. Specifically, we hypothesized that a fuzzy inference system (FIS) could be used as a computational method to address …

Toll-Like Receptor 4 Signaling In Osteoblasts Is Required For Load-Induced Bone Formation In Mice, Ibtesam Rajpar, Gaurav Kumar, Paolo Fortina, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

In mature bone, NGF is produced by osteoblasts following mechanical loading and signals through resident sensory nerves expressing its high affinity receptor, neurotrophic tyrosine kinase receptor type 1 (TrkA), to support bone formation. Here, we investigated whether osteoblastic expression of Toll-like receptor 4 (TLR4), a key receptor in the NF-κB signaling pathway, is required to initiate NGF-TrkA signaling required for load-induced bone formation. Although Tlr4 conditional knockout mice have normal skeletal mass and strength in adulthood, the loss of TLR4 signaling significantly reduced lamellar bone formation following loading. Inhibition of TLR4 signaling reduced Ngf expression in primary osteoblasts and RNA …