John L Esterhai

University of Pennsylvania, Philadelphia, PA, United States

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Publications (17)44.9 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Acta biomaterialia 01/2013; · 5.09 Impact Factor
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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.
    Acta biomaterialia 10/2012; · 5.09 Impact Factor
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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.
    Proceedings of the National Academy of Sciences 08/2012; 109(35):14176-81. · 9.74 Impact Factor
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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.
    Cell and Tissue Research 01/2012; 347(3):803-13. · 3.68 Impact Factor
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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.
    Bioengineering Conference (NEBEC), 2012 38th Annual Northeast; 01/2012
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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.
    American journal of orthopedics (Belle Mead, N.J.) 05/2011; 40(5):E83-7.
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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.
    Journal of orthopaedic trauma 03/2011; 25(3):140-4. · 1.78 Impact Factor
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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.
    Orthopedics 01/2011; 34(1):18. · 1.05 Impact Factor
  • 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
    12/2010: pages 257-268;
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    John L Esterhai, Montri D Wongworawat
    Clinical Orthopaedics and Related Research 08/2010; 468(8):2007-8. · 2.79 Impact Factor
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    ABSTRACT: Venous thromboembolism (VTE) is an important problem in orthopedic trauma patients. An association between VTE and upper extremity injury has not been reported. The purpose of this investigation was to determine whether upper extremity trauma is an independent risk factor for lower extremity VTE. This study also attempted to identify associations between VTEs and demographic and injury variables in patients that sustained upper extremity trauma. Eleven years of data from the trauma registry at our Level I trauma center was retrospectively reviewed in an injury-matched cohort study. From an initial pool of 646 patients who sustained upper extremity trauma, 32 subjects (4.95%) were identified as having major upper extremity injuries as well as thromboembolic complications. Thirty-two injury-matched controls were randomly selected from the 646 patients with major upper extremity injuries. Regression analysis was performed to determine variables that were significantly associated with lower extremity thromboembolic complications. Overall incidence of VTE in patients sustaining upper extremity injury was 4.95% (deep vein thrombus 4.64%, pulmonary embolism 0.31%) and was similar to the 4.95% VTE rate in patients without upper extremity injury. Major head injury (p = 0.022) occurred at increased frequency in the VTE group. Patients with increased length of hospital stay (p < 0.001) and length of time on a ventilator (p = 0.002) were at significantly higher risk for thromboembolic complications. No patient with isolated upper extremity trauma had complications from VTE. Lower extremity VTE occurs at similar rates in patients sustaining upper extremity injury compared to those patients that do not. Major upper extremity orthopedic trauma is not an independent risk factor for lower extremity VTE, and current clinical management guidelines for VTE prophylaxis are adequate for patients sustaining major upper extremity trauma.
    Archives of Orthopaedic and Trauma Surgery 04/2010; 131(1):27-32. · 1.36 Impact Factor
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    ABSTRACT: Comorbidities before and complications following hip fracture surgery can impact the return of function. We hypothesized that the American Society of Anesthesiologists (ASA) classification of medical comorbidities is a useful surrogate variable for the patient's general medical condition and would be a strong predictor of perioperative medical complications following hip fracture surgery. A retrospective review of the cases of 197 elderly patients who had undergone operative management of a hip fracture was performed. The ASA class, data regarding perioperative medical and surgical complications, and demographic data were obtained. Medical complications were defined as those requiring intervention by an internist or medical specialist. Differences in complication rates among the ASA classes were determined. Medical complications were more common in patients in ASA class 3 (p < 0.001) and those in class 4 (p = 0.001) than in those in class 2. Patients in ASA class 3 had a 3.78 times greater chance of having a medical complication than did those in class 2 (p < 0.001). Patients in ASA class 4 had a 7.39 times greater chance of having medical complications than did those in class 2 (p = 0.001). No significant relationship was identified between the ASA class and surgical complications. The ASA class is strongly associated with medical problems in the perioperative period following hip fracture surgery in the elderly. Patients identified as being at higher risk (in ASA class 3 or 4) preoperatively should be closely managed medically so that perioperative medical complications can be managed and evolving medical issues can be addressed in a timely fashion.
    The Journal of Bone and Joint Surgery 04/2010; 92(4):807-13. · 3.23 Impact Factor
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    ABSTRACT: Definitive treatment of open fractures of the tibial diaphysis is challenging. The high-energy nature of these fractures, as well as the contamination of the fracture site and devitalization of the soft-tissue envelope, greatly increases the risk of infection, nonunion, and wound complications. The goals of definitive treatment include wound coverage or closure; prevention of infection; restoration of length, alignment, rotation, and stability; fracture healing; and return of function. Advances in orthobiologics, modern plastic surgical techniques, and fracture stabilization methods, most notably locked intramedullary nailing, have led to improved prognosis for functional recovery and limb salvage. Despite improved union and limb salvage rates, the prognosis for severe type III open fracture of the tibial shaft remains guarded, and outcomes are often determined by patient psychosocial variables.
    The Journal of the American Academy of Orthopaedic Surgeons 02/2010; 18(2):108-17. · 2.46 Impact Factor
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    ABSTRACT: Open fractures of the tibial diaphysis are often associated with severe bone and soft-tissue injury. Contamination of the fracture site and devitalization of the soft-tissue envelope greatly increase the risk of infection, nonunion, and wound complications. Management of open tibial shaft fractures begins with a thorough patient evaluation, including assessment of the bone and soft tissue surrounding the tibial injury. Classification of these injuries according to the system of Gustilo and Anderson at the time of surgical débridement is useful in guiding treatment and predicting outcomes. Administration of antibiotic prophylaxis as soon as possible after injury as well as urgent and thorough débridement, irrigation, and bony stabilization are done to minimize the risk of infection and improve outcomes. The use of antibiotic bead pouches and negative-pressure wound therapy has proved to be efficacious for the acute, temporary management of severe bone and soft-tissue defects.
    The Journal of the American Academy of Orthopaedic Surgeons 01/2010; 18(1):10-9. · 2.46 Impact Factor
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    ABSTRACT: Compartment syndrome is a devastating complication of tibial fractures. The purpose of this study was to investigate the rate of clinically determined compartment syndrome requiring surgical intervention in tibial fractures by anatomical region and to identify the associated patient and injury factors. Retrospective cohort. University level I trauma center. Acute tibial fractures in 414 patients from January 1, 2004 through October 31, 2006. Tibial fractures in 414 patients met the inclusion and exclusion criteria. The fractures were classified into 3 groups (proximal, diaphyseal, and distal) based on the anatomic location of the fractures (AO/OTA fractures 41, 42, and 43, respectively). To determine the patient and injury factors associated with the development of compartment syndrome in tibial fractures, the following data were obtained: patient age and sex, mechanism of injury, presence of associated fractures, presence of concomitant head/chest/abdominal/pelvic injury, blood pressure upon admission, open versus closed fracture (Gustilo-Anderson classification if open), status of the fibula, and AO/OTA classification of the tibial fracture. Rate of clinically determined compartment syndrome requiring fasciotomy by anatomical region of the tibia. The rate of compartment syndrome was highest in the diaphyseal group (8.1%, P < 0.05) followed by proximal (1.6%) and distal (1.4%) groups. The diaphyseal group was further analyzed according to patient and injury factors. Patients who developed compartment syndrome were significantly younger (27.5 years +/- 11.7 SD versus 39.0 years +/- 16.7 SD, P = 0.003, Student t test) than those who did not develop compartment syndrome. The mean arterial pressures upon admission of the patients who developed compartment syndrome were also found to be slightly higher (107 versus 98.5 mm Hg, P = 0.039, Student t test) but not significantly so after Bonferroni adjustment. In multivariate regression analysis, decreasing age remained the only statistically significant independent predictor for the development of compartment syndrome (P = 0.006, regression coefficient = -0.0589) in diaphyseal tibial fractures. Tibial fractures of the diaphysis are more frequently associated with development of compartment syndrome than proximal or distal tibial fractures. More specifically, young patients with diaphyseal fractures are at risk for developing this complication and warrant increased vigilance and suspicion for compartment syndrome. A prospective study with sufficient power is needed to further identify risk factors associated with compartment syndrome in tibial fractures.
    Journal of orthopaedic trauma 08/2009; 23(7):514-8. · 1.78 Impact Factor
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    ABSTRACT: Although hemiarthroplasties are an important treatment for femoral neck fractures, the literature does not provide a clear approach for selecting the implant fixation method. Therefore, we performed a systematic search of the medical literature and identified 11 prospective and retrospective studies that compared results between cemented and uncemented femoral implant fixation methods. After independent blind data extraction, we compared variables between cemented and uncemented cohorts using two different meta-analysis models. Pooled data represented 1632 cemented and 981 uncemented hemiarthroplasties (average age of patients, 78.9 and 77.5 years, respectively). The average operating room times and blood loss volumes were 95 minutes and 467 mL, respectively, for the cemented and 80 minutes and 338 mL for the uncemented cohorts. Postoperative mortality rates, overall complications, and pain were similar between the two cohorts. Despite a few potential trends, we found few statistical differences between cemented and uncemented techniques based on reported outcome measurements. In addition, inspection of this literature underscored the lack of and need for consistent and standardized reporting of outcome variables regarding these procedures.
    Clinical Orthopaedics and Related Research 10/2008; 466(10):2513-8. · 2.79 Impact Factor
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    ABSTRACT: Lower extremity peripheral arterial disease (PAD) and musculoskeletal conditions both produce symptoms of leg pain, and may coexist. This study assesses the prevalence of PAD among patients referred to orthopedic surgery for evaluation of lower extremity pain. Fifty consecutive patients aged 50 years or more who had a chief complaint of leg pain, no history of trauma, and no previous history of PAD were studied prospectively. The presence of known risk factors for PAD and classic claudication symptoms was assessed by telephone interview and medical record review. Individuals were then evaluated by measurement of the ankle-brachial index (ABI) using Doppler and pulse volume recordings (PVR). A patient was deemed to have PAD if the ABI was below 0.9 or if the PVR demonstrated significant abnormalities. Occult PAD was detected in 10 of the 50 patients (20%) on the basis of the non-invasive vascular studies. There were no differences between patients with PAD and those without PAD regarding the presence of risk factors for PAD. None of the patients without PAD had claudication, while only one of the 10 patients with PAD had symptoms of classic claudication. In conclusion, 20% of patients referred by primary care providers to the orthopedic surgery clinic for lower extremity pain were discovered to have occult PAD. The majority of these patients did not have claudication. Orthopedic surgeons and primary care providers must maintain an appropriately high index of suspicion for PAD when evaluating patients with non-traumatic lower extremity pain.
    Vascular Medicine 09/2008; 13(3):235-8. · 1.62 Impact Factor

Publication Stats

101 Citations
44.90 Total Impact Points

Institutions

  • 2010–2012
    • University of Pennsylvania
      • Department of Orthopaedic Surgery
      Philadelphia, PA, United States
  • 2011
    • Philadelphia University
      Philadelphia, Pennsylvania, United States
  • 2009–2011
    • Hospital of the University of Pennsylvania
      • Department of Orthopaedic Surgery
      Philadelphia, Pennsylvania, United States