John L Esterhai

University of Pennsylvania, Filadelfia, Pennsylvania, United States

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Publications (27)69.35 Total impact

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    ABSTRACT: Objectives: We hypothesized that the method of stress external rotation more accurately reproduces the mechanism of injury, and therefore this diagnostic method more likely detects ankle instability than the fibular stress examination. Design: Prospective cohort comparison study. Setting: Level 1 trauma center. Patients: Twenty-eight consecutive patients with unstable ankle fractures presenting within 7 days from the time of injury. Previous ankle surgical history or age younger than 18 years was excluded. Intervention: Stress external rotation and lateral fibular stress examination was performed intraoperatively. Main Outcome Measure: Radiographic measurement of the tibiofibular clear space, tibiofibular overlap, and medial clear space were recorded. Results: After normalization of the fluoroscopic measurements, there was no difference in detecting changes in tibiofibular clear space or tibiofibular overlap. However, there was a significant difference in detecting medial clear space widening with stress external rotation. Compared with lateral fibular stress, stress external rotation demonstrated a 35% increase (P < 0.05) in medial clear space widening. This difference correlates with the 1-2-mm difference of additional widening with stress external rotation. Conclusions: Untreated instability impacts patient outcomes. The difference in widening with stress external rotation was significantly greater than lateral fibular stress and appreciable on standard fluoroscopic views. Stress external rotation radiographs are a more reliable indicator of mortise instability than traditional lateral fibular stress.
    No preview · Article · Apr 2015 · Journal of Orthopaedic Trauma
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    ABSTRACT: Despite advances in tissue engineering for the knee meniscus, it remains a challenge to match the complex macroscopic and microscopic structural features of native tissue, including the circumferentially and radially aligned collagen bundles essential for mechanical function. To mimic this structural hierarchy, this study developed multi-lamellar mesenchymal stem cell (MSC)-seeded nanofibrous constructs. Bovine MSCs were seeded onto nanofibrous scaffolds comprised of poly(ε-caprolactone) with fibers aligned in a single direction (0° or 90° to the scaffold long axis) or circumferentially aligned (C). Multi-layer groups (0°/0°/0°, 90°/90°/90°, 0°/90°/0°, 90°/0°/90°, and C/C/C) were created and cultured for a total of 6 weeks under conditions favoring fibrocartilaginous tissue formation. Tensile testing showed that 0° and C single layer constructs had stiffness values several fold higher than 90° constructs. For multi-layer groups, the stiffness of 0°/0°/0° constructs was higher than all other groups, while 90°/90°/90° constructs had the lowest values. Data for collagen content showed a general positive interactive effect for multi-layers relative to single layer constructs, while a positive interaction for stiffness was found only for the C/C/C group. Collagen content and cell infiltration occurred independent of scaffold alignment, and newly formed collagenous matrix followed the scaffold fiber direction. Structural hierarchies within multi-lamellar constructs dictated biomechanical properties, and only the C/C/C constructs with non-orthogonal alignment within layers featured positive mechanical reinforcement as a consequence of the layered construction. These multi-layer constructs may serve as functional substitutes for the meniscus as well as test beds to understand the complex mechanical principles that enable meniscus function. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Feb 2015 · Journal of Biomechanics
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    ABSTRACT: Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues.
    No preview · Article · Nov 2014 · Biomaterials
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    ABSTRACT: Objectives: We hypothesized that the method of stress external rotation more accurately reproduces the mechanism of injury and therefore this diagnostic method more likely detects ankle instability than the fibular stress examination. Design: Prospective cohort comparison study Setting: Level 1 trauma center Patients/Participants: Twenty-eight consecutive patients with unstable ankle fractures presenting within seven days from the time of injury. Prior ankle surgical history or age < 18 years were excluded. Intervention: Stress external rotation and lateral fibular stress examination was performed intraoperatively. Main Outcome Measure: Radiographic measurement of the tibiofibular clear space, tibiofibular overlap and medial clear space were recorded. Results: After normalization of the fluoroscopic measurements, there was no difference in detecting changes in tibiofibular clear space or tibiofibular overlap. However, there was a significant difference in detecting medial clear space widening with stress external rotation. Compared to lateral fibular stress, stress external rotation demonstrated a 37% increase (p<0.05) in medial clear space widening. This difference correlates to between one to two millimeters difference of additional widening with stress external rotation. Conclusions: Untreated instability impacts patient outcomes. The difference in widening with stress external rotation was significantly greater than lateral fibular stress and appreciable on standard fluoroscopic views. Stress external rotation radiographs are a more reliable indicator of mortise instability than traditional lateral fibular stress. Copyright
    No preview · Article · Nov 2014 · Journal of Orthopaedic Trauma
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    Full-text · Article · Oct 2013 · The Journal of arthroplasty
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    ABSTRACT: The menisci are crescent-shaped fibrocartilaginous tissues which function to transmit and distribute complex loading patterns between the femur and tibia of the knee joint. Meniscus function in tension arises from highly aligned collagen fibers which run in a circumferential manner between insertion sites on the tibial plateau (1,2). However, the meniscus is often injured, and partial removal of the meniscus represents the most commonly performed orthopaedic surgery, despite the fact that its removal increases the likelihood of osteoarthritis in the long-term (3). Tissue engineered scaffolds have emerged as a promising alternative to replace portions of the damaged meniscus (4). Toward replacement, we have developed aligned nanofibrous scaffolds that can recapitulate the mechanical anisotropy of the meniscus (5,6). More recently, we have developed an approach to replicate the circumferential macroscopic orientation of fibers using a novel electrospinning method (7). However, these organized scaffolds are relatively thin (
    No preview · Conference Paper · Jun 2013
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    ABSTRACT: Endogenous repair of fibrous connective tissues is limited, and there exist few successful strategies to improve healing after injury. As such, new methods that advance repair by promoting cell growth, extracellular matrix (ECM) production, and tissue integration would represent a marked clinical advance. Using the meniscus as a test platform, we sought to develop an enzyme-releasing scaffold that enhances integrative repair. We hypothesized that the high ECM density and low cellularity present physical and biologic barriers to endogenous healing, and that localized collagenase treatment might expedite cell migration to the wound edge and tissue remodeling. To test this hypothesis, we fabricated a delivery system in which collagenase was stored inside electrospun poly(ethylene oxide) (PEO) nanofibers and released upon hydration. In vitro results showed that partial digestion of the wound interface improved repair by creating a microenvironment that facilitated cell migration, proliferation, and matrix deposition. Specifically, treatment with high-dose collagenase led to a 2-fold increase in cell density at the wound margin and a 2-fold increase in integrative tissue compared to untreated controls at 4 weeks (p⩽0.05). Furthermore, when composite scaffolds containing both collagenase-releasing and structural fiber fractions were placed inside meniscal tears in vitro, enzyme release acted locally and resulted in a positive cellular response similar to that of global treatment with aqueous collagenase. This innovative approach of targeted enzyme delivery may aid the many patients that exhibit meniscal tears by promoting integration of the defect, thereby circumventing the pathologic consequences of partial meniscus removal, and may find widespread application in the treatment of injuries to a variety of dense connective tissues.
    No preview · Article · Jan 2013 · Acta biomaterialia
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    ABSTRACT: The menisci are crescent-shaped fibrocartilaginous tissues whose structural organization consists of dense collagen bundles that are locally aligned, but show a continuous change in macroscopic directionality. This circumferential patterning is necessary for load transmission across the knee joint and is a key design parameter for tissue engineered constructs. To address this issue, we developed a novel electrospinning method to produce scaffolds composed of circumferentially aligned (CircAl) nanofibers, quantified their structure and mechanics, and compared them to traditional linearly aligned (LinAl) scaffolds. Fibers were locally oriented in CircAl scaffolds, but their orientation varied considerably as a function of position (p<0.05). LinAl fibers did not change in orientation over a similar length scale (p>0.05). Cell seeding of CircAl scaffolds resulted in a similar cellular directionality. Mechanical analysis of CircAl scaffolds revealed significant interactions between scaffold length and region (p<0.05), where the tensile modulus near the edge of the scaffolds decreased with increasing scaffold length. No differences were detected in LinAl specimens (p>0.05). Simulation of the fiber deposition process produced "theoretical" fiber populations that matched the fiber organization and mechanical properties observed experimentally. These novel scaffolds, with spatially varying local orientation and mechanics, will enable the formation of functional anatomic meniscus constructs.
    No preview · Article · Oct 2012 · Acta biomaterialia
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    ABSTRACT: The fibrous tissues prevalent throughout the body possess an ordered structure that underlies their refined and robust mechanical properties. Engineered replacements will require recapitulation of this exquisite architecture in three dimensions. Aligned nanofibrous scaffolds can dictate cell and matrix organization; however, their widespread application has been hindered by poor cell infiltration due to the tight packing of fibers during fabrication. Here, we develop and validate an enabling technology in which tunable composite nanofibrous scaffolds are produced to provide instruction without impediment. Composites were formed containing two distinct fiber fractions: slow-degrading poly(ε-caprolactone) and water-soluble, sacrificial poly(ethylene oxide), which can be selectively removed to increase pore size. Increasing the initial fraction of sacrificial poly(ethylene oxide) fibers enhanced cell infiltration and improved matrix distribution. Despite the removal of >50% of the initial fibers, the remaining scaffold provided sufficient instruction to align cells and direct the formation of a highly organized ECM across multiple length scales, which in turn led to pronounced increases in the tensile properties of the engineered constructs (nearly matching native tissue). This approach transforms what is an interesting surface phenomenon (cells on top of nanofibrous mats) into a method by which functional, 3D tissues (>1 mm thick) can be formed, both in vitro and in vivo. As such, this work represents a marked advance in the engineering of load-bearing fibrous tissues, and will find widespread applications in regenerative medicine.
    Full-text · Article · Aug 2012 · Proceedings of the National Academy of Sciences
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    ABSTRACT: The menisci are crescent-shaped fibrocartilaginous tissues which function to transmit and distribute loads between the femur and tibia of the knee joint. As such, the meniscus experiences complex loads, including tension, compression, and shear. Meniscus function in tension arises from an organized microstructure — bundles of highly aligned collagen circumnavigate the tissue between insertion sites on the tibial plateau (1). These aligned collagen bundles endow the tissue with mechanical properties that are highly anisotropic, and highest in the primary collagen orientation (2). Commercial products to replace the meniscus lack this unique structure and organization (3,4). To address engineering the knee meniscus, we have developed aligned nanofibrous scaffolds that can recapitulate this mechanical anisotropy (5,6). However promising, fibers within these scaffolds are unidirectional, while the fibers within the native tissue have a pronounced c-shaped macroscopic organization. To mimic this macroscopic orientation, we developed a new electrospinning method to collect organized fibers on a planar spinning disc (7). The objective of this study was to quantify the structure and mechanics of nanofibrous scaffolds collected using this novel technique and compare the data to aligned scaffolds obtained from a traditional electrospinning approach. We hypothesized that these circumferentially aligned (CircAl) scaffolds would behave similarly to linearly aligned (LinAl) scaffolds on short length scales, but exhibit marked differences in mechanics as the length scale increased.
    No preview · Conference Paper · Jun 2012
  • M.B. Fisher · E.A. Henning · J.L. Esterhai · R.L. Mauck
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    ABSTRACT: The menisci are crescent-shaped fibrocartilaginous tissues featuring highly aligned collagen arranged in a circumferential fashion to allow transmission of loads across the knee joint. To mimic this macroscopic orientation, we developed a novel electrospinning method to collect circumferentially aligned (CircAl) fibers, quantified their structure and mechanics, and compared them to linearly aligned (LinAl) scaffolds. Fiber orientation of CircAl scaffolds varied considerably as a function of position (p;0.05). Alterations in cellular alignment on a macroscopic scale were observed on the CircAl scaffolds. Mechanical analysis of the CircAl scaffolds revealed significant interactions between scaffold length and region (p;0.05). In conclusion, we developed electrospun nanofibrous scaffolds with a spatially varying macroscopic fiber orientation, creating a gradient in fiber alignment and differences in tensile properties over a macroscopic scale. These organized nanofibrous scaffolds can potentially direct the formation of an anatomic meniscus construct with structure and function that vary across a large anatomic expanse.
    No preview · Conference Paper · Mar 2012
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    ABSTRACT: Electrospun scaffolds hold promise for the regeneration of dense connective tissues, given their nanoscale topographies, provision of directional cues for infiltrating cells and versatile composition. Synthetic slow-degrading scaffolds provide long-term mechanical support and nanoscale instructional cues; however, these scaffolds suffer from a poor infiltration rate. Alternatively, nanofibrous constructs formed from natural biomimetic materials (such as collagen) rapidly infiltrate but provide little mechanical support. To take advantage of the positive features of these constructs, we have developed a composite scaffold consisting in both a biomimetic fiber fraction (i.e., Type I collagen nanofibers) together with a traditional synthetic (i.e., poly-[ε-caprolactone], PCL) fiber fraction. We hypothesize that inclusion of biomimetic elements will improve initial cell adhesion and eventual scaffold infiltration, whereas the synthetic elements will provide controlled and long-term mechanical support. We have developed a method of forming and crosslinking collagen nanofibers by using the natural crosslinking agent genipin (GP). Further, we have formed composites from collagen and PCL and evaluated the long-term performance of these scaffolds when seeded with mesenchymal stem cells. Our results demonstrate that GP crosslinking is cytocompatible and generates stable nanofibrous type I collagen constructs. Composites with varying fractions of the biomimetic and synthetic fiber families are formed and retain their collagen fiber fractions during in vitro culture. However, at the maximum collagen fiber fractions (20%), cell ingress is limited compared with pure PCL scaffolds. These results provide a new foundation for the development and optimization of biomimetic/synthetic nanofibrous composites for in vivo tissue engineering.
    Full-text · Article · Jan 2012 · Cell and Tissue Research
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    ABSTRACT: Diagnosis of periprosthetic joint infection (PJI) remains a real challenge to the orthopedic community. Currently, there is no single standard definition for PJI. This communication presents the diagnostic criteria that have been proposed by a workgroup convened by the Musculoskeletal Infection Society. The diagnostic criteria were developed after the evaluation of available evidence. The role of every diagnostic test was examined, and the literature was reviewed in detail to determine the threshold for each test. It is hoped that the proposed definition for PJI will be adopted universally, bringing standardization into a field that has suffered extensive variability and heterogeneity.
    No preview · Article · Dec 2011 · The Journal of Arthroplasty
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    ABSTRACT: Open fractures occur at a rate of 250,000 per year in the United States. Medical and surgical management of each injury poses a unique challenge to the orthopaedic surgeon in terms of antibiotic therapy, timing of surgery, wound irrigation and debridement techniques, soft tissue management, and wound closure. This chapter addresses five of the more common questions regarding the above variables in the management of open fractures.
    No preview · Article · Oct 2011
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    ABSTRACT: Wound infections present a difficult challenge to the practicing orthopedist. The burden of infection creates significant morbidity for the patient and requires time-intensive and more complicated treatment algorithms. Furthermore, the economic impact of orthopaedic infections is immense. This chapter focuses on key questions in the management of wound infections in orthopaedics. It is an evidence-based review of the best available literature on a number of topics, including prophylactic antibiotics in elective surgery, diagnostic workup of a suspected wound infection, and management of infected hardware. An evidence-based review of the literature points to the need for continued well-designed clinical trials to better establish guidelines for prevention, diagnosis, and treatment of orthopaedic wound infections.
    No preview · Article · Oct 2011
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    Keith Baldwin · Surena Namdari · John L Esterhai · Samir Mehta
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    ABSTRACT: This study was designed to determine the outcome of implemented guidelines for venous thromboembolism (VTE) prophylaxis. This study was a retrospective review of a series of consecutive blunt orthopaedic trauma patients with thromboembolic complications. The patients were compared to control subjects over the same 10-year period. Univariate and multivariate statistical methods were used to determine the odds of VTE in the setting of this management guideline and risk factors for thromboembolic complications that may be refractory to this strategy. In the 10 years following institution of clinical management guidelines at our institution, the rate of VTE events was 3.2%, and the rate of pulmonary embolus was 0.3%. Risk factors for VTE that were refractory to our clinical management guidelines were pelvic fractures, major lower extremity injury, greater than 3 days of mechanical ventilation, increasing injury severity, and spinal cord injury. The implementation of a clinical management strategy for decreasing the incidence of VTE in blunt trauma patients and other potentially preventable complications is essential. Our data suggest that patients with certain injuries are particularly at risk for VTE and warrant special attention in clinical management and risk stratification, despite effective clinical management guidelines.
    Preview · Article · May 2011 · American journal of orthopedics (Belle Mead, N.J.)
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    ABSTRACT: Débridement and irrigation (D&I) of open tibia fractures less than 6 hours from the time of injury has been promoted as orthopaedic dogma despite limited evidence. The goal of this study was to determine the duration between emergency room presentation and D&I in open tibia fractures and to examine factors associated with delay in treatment. The National Trauma Data Bank Version 3.0 identified 6099 blunt trauma patients with open tibia fractures. Time was calculated from emergency room arrival to first D&I. Risk factors associated with delay in treatment greater than 6 hours and greater than 24 hours were then calculated using univariate and multivariate statistical methods. Median time to D&I was 4.9 hours. Forty-two percent of patients with open tibia fractures experienced a delay in treatment of greater than 6 hours and 24% of patients experienced a delay to treatment of greater than 24 hours. Risk factors associated with greater than 6- and 24-hour delay on univariate and multivariate logistic regression were age, head or thoracic injury with Abbreviated Injury Score greater than 2, and presentation between 6 pm and 2 am. Level I and university hospitals carry a greater risk of delay that was independent of injury severity in multivariate analysis. A significant percentage of patients with open tibia fractures undergo their first surgical intervention of D&I greater than 6 hours after presentation to the emergency room. Patients with delayed D&I have more severe injuries, are treated at university or Level I centers, and present later in the day.
    No preview · Article · Mar 2011 · Journal of orthopaedic trauma
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    ABSTRACT: Obesity is prevalent in the developed world and is associated with significant costs to the health care system. The effect of morbid obesity in patients operatively treated for long-bone fractures of the lower extremity is largely unknown. The National Trauma Data Bank was accessed to determine if morbidly obese patients (body mass index >40) with lower extremity fractures have longer length of hospital stay, higher cost, greater rehabilitation admission rates, and more complications than nonobese patients. We identified patients with operatively treated diaphyseal femur (6920) and tibia (5190) fractures. Polytrauma patients and patients younger than 16 years were excluded. Morbidly obese patients were identified by ICD-9 and database comorbidity designation (femur, 131 morbidly obese; tibia, 75 morbidly obese). Patients meeting these criteria who were not morbidly obese were used as controls. Sensitivity analyses were performed to analyze patients with isolated trauma to the tibia or femur. Morbidly obese patients were more likely to be admitted to a subacute facility. Length of stay trended higher in morbidly obese patients. There was no significant relationship between obesity and inpatient mortality or inpatient complications. These trends held true when considering patients with multiple injuries and patients who had isolated long-bone injuries. Our study showed that morbidly obese patients may have greater rehabilitation needs following long-bone fractures in the lower extremity. Our study showed no difference in mortality or complications, although further studies are needed to confirm these findings.
    No preview · Article · Jan 2011 · Orthopedics
  • Jesse T. Torbert · John L. Esterhai
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    ABSTRACT: Fragility fractures of the distal femur pose a challenge for stable internal fixation and good functional outcomes. Among those challenges are frailty of the elderly patient, high degree of osteoporosis, instability of the fracture patterns, short distal femur segment, and amount of comminution. Mortality at 1 year has been reported as high as 30%. Morbidity includes significant decreases in function, quality of life as well as medical and surgical complications. Medical stabilization and optimization are extremely important in this frail population. Non-surgical management is reserved for minimally displaced fractures in the patient who will likely not tolerate the risks of anesthesia or surgical intervention. Surgical treatment, which is the favored treatment, is necessary to prevent prolonged immobilization and its sequelae. Surgical treatment options include antegrade or retrograde intramedullary nailing, standard lateral plating, the use of fixed angle devices, and total knee arthroplasty. Rehabilitation is necessary and includes early range of motion, strengthening, mobilization, gait training if possible, and prevention of common medical complications. KeywordsFracture-Supracondylar-Distal femur-Elderly-Fragility-Osteoporotic-Internal fixation-Arthroplasty-Outcomes
    No preview · Chapter · Dec 2010
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    John L Esterhai · Montri D Wongworawat

    Preview · Article · Aug 2010 · Clinical Orthopaedics and Related Research

Publication Stats

321 Citations
69.35 Total Impact Points

Institutions

  • 2008-2015
    • University of Pennsylvania
      • • McKay Orthopaedic Research Laboratory
      • • Department of Orthopaedic Surgery
      Filadelfia, Pennsylvania, United States
  • 2010-2014
    • Hospital of the University of Pennsylvania
      • Department of Orthopaedic Surgery
      Filadelfia, Pennsylvania, United States
  • 2009-2012
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2011
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
    • Philadelphia University
      Philadelphia, Pennsylvania, United States