Ian Connolly

All Publications

• Macrovascular Decompression of the Brainstem and Cranial Nerves: Evolution of an Anteromedial Vertebrobasilar Artery Transposition Technique. Neurosurgery Choudhri, O., Connolly, I. D., Lawton, M. T. 2017

  Abstract

  Tortuous and dolichoectatic vertebrobasilar arteries can impinge on the brainstem and cranial nerves to cause compression syndromes. Transposition techniques are often required to decompress the brainstem with dolichoectatic pathology. We describe our evolution of an anteromedial transposition technique and its efficacy in decompressing the brainstem and relieving symptoms.To present the anteromedial vertebrobasilar artery transposition technique for macrovascular decompression of the brainstem and cranial nerves.All patients who underwent vertebrobasilar artery transposition were identified from the prospectively maintained database of the Vascular Neurosurgery service, and their medical records were reviewed retrospectively. The extent of arterial displacement was measured pre- and postoperatively on imaging.Vertebrobasilar arterial transposition and macrovascular decompression was performed in 12 patients. Evolution in technique was characterized by gradual preference for the far-lateral approach, use of a sling technique with muslin wrap, and an anteromedial direction of pull on the vertebrobasilar artery with clip-assisted tethering to the clival dura. With this technique, mean lateral displacement decreased from 6.6 mm in the first half of the series to 3.8 mm in the last half of the series, and mean anterior displacement increased from 0.8 to 2.5 mm, with corresponding increases in satisfaction and relief of symptoms.Compressive dolichoectatic pathology directed laterally into cranial nerves and posteriorly into the brainstem can be corrected with anteromedial transposition towards the clivus. Our technique accomplishes this anteromedial transposition from an inferolateral surgical approach through the vagoaccessory triangle, with sling fixation to clival dura using aneurysm clips.

  View details for DOI 10.1093/neuros/nyx110

  View details for PubMedID 28402528

• Awake versus asleep deep brain stimulation for Parkinson's disease: a critical comparison and meta-analysis. Journal of neurology, neurosurgery, and psychiatry Ho, A. L., Ali, R., Connolly, I. D., Henderson, J. M., Dhall, R., Stein, S. C., Halpern, C. H. 2017

  Abstract

  No definitive comparative studies of the efficacy of 'awake' deep brain stimulation (DBS) for Parkinson's disease (PD) under local or general anaesthesia exist, and there remains significant debate within the field regarding differences in outcomes between these two techniques.We conducted a literature review and meta-analysis of all published DBS for PD studies (n=2563) on PubMed from January 2004 to November 2015. Inclusion criteria included patient number >15, report of precision and/or clinical outcomes data, and at least 6 months of follow-up. There were 145 studies, 16 of which were under general anaesthesia. Data were pooled using an inverse-variance weighted, random effects meta-analytic model for observational data.There was no significant difference in mean target error between local and general anaesthesia, but there was a significantly less mean number of DBS lead passes with general anaesthesia (p=0.006). There were also significant decreases in DBS complications, with fewer intracerebral haemorrhages and infections with general anaesthesia (p<0.001). There were no significant differences in Unified Parkinson's Disease Rating Scale (UPDRS) Section II scores off medication, UPDRS III scores off and on medication or levodopa equivalent doses between the two techniques. Awake DBS cohorts had a significantly greater decrease in treatment-related side effects as measured by the UPDRS IV off medication score (78.4% awake vs 59.7% asleep, p=0.022).Our meta-analysis demonstrates that while DBS under general anaesthesia may lead to lower complication rates overall, awake DBS may lead to less treatment-induced side effects. Nevertheless, there were no significant differences in clinical motor outcomes between the two techniques. Thus, DBS under general anaesthesia can be considered at experienced centres in patients who are not candidates for traditional awake DBS or prefer the asleep alternative.

  View details for DOI 10.1136/jnnp-2016-314500

  View details for PubMedID 28250028

• Asystole During Onyx Embolization of a Pediatric Arteriovenous Malformation: A Severe Case of the Trigeminocardiac Reflex. World neurosurgery Khatibi, K., Choudhri, O., Connolly, I. D., McTaggart, R. A., Do, H. M. 2017; 98: 884 e1-884 e5

  Abstract

  Trigeminal-cardiac reflex (TCR) from the stimulation of sensory branches of trigeminal nerve can lead to hemodynamic instability. This phenomenon has been described during ophthalmologic, craniofacial, and skull base surgeries. TCR has been reported rarely with endovascular onyx embolization of dural arteriovenous fistulas.We report a case of TCR during endovascular Onyx embolization of an arteriovenous malformation (AVM). A 16-year-old boy presented with a large cerebellar AVM with arterial feeders from the external carotid artery and posterior cerebral artery branches. The middle meningeal artery was catheterized, through which dimethyl sulfoxide was injected, followed by Onyx, into the nidus and the feeders. Near the completion of embolization, patient became bradycardic and proceeded to asystole; he was resuscitated with chest compression, atropine, and vasopressors. We used PubMed to identify the reported cases of Onyx and other endovascular embolizations complicated by hemodynamic instability. We found 16 cases of endovascular onyx embolization complicated by clinically significant hemodynamic changes in the treatment of dural arteriovenous fistula, cavernous carotid fistula, and juvenile nasopharygeal angiofibroma but not with AVMs. In these cases, arterial supply to the nidus involved the sensory receptive field of trigeminal nerve. Hemodynamic changes have been reported during the injection of dimethyl sulfoxide before the introduction of Onyx, as well as Onyx injection and cast formation.TCR can lead to significant hemodynamic changes during endovascular Onyx embolization of vascular malformations (both pial AVM and dural arteriovenous fistulas) involving receptive field of trigeminal nerve. Therefore, the anesthesiologist should be made aware of treatment approach before intervention and appropriate precautions taken.

  View details for DOI 10.1016/j.wneu.2016.07.025

  View details for PubMedID 27436213

• Diagnostic Utility of Intraoperative Neurophysiological Monitoring for Intramedullary Spinal Cord Tumors: Systematic Review and Meta-Analysis. Clinical spine surgery Azad, T. D., Pendharkar, A. V., Nguyen, V., Pan, J., Connolly, I. D., Veeravagu, A., Popat, R., Ratliff, J. K., Grant, G. A. 2017

  Abstract

  Systematic review and meta-analysis.The aim of this study was to systematically evaluate the diagnostic utility of intraoperative neurophysiological monitoring (IONM) for detecting postoperative injury in resection of intramedullary spinal cord tumors (IMSCT).Surgical management of IMSCT can involve key neurological and vascular structures. IONM aims to assess the functional integrity of susceptible elements in real time. The diagnostic value of IONM for ISMCT has not been systematically evaluated.We performed a systematic review of the PubMed and MEDLINE databases for studies investigating the use of IONM for IMSCT and conducted a meta-analysis of diagnostic capability.Our search produced 257 citations. After application of exclusion criteria, 21 studies remained, 10 American Academy of Neurology grade III and 11 American Academy of Neurology grade IV. We found that a strong pooled mean sensitivity of 90% [95% confidence interval (CI), 84-94] and a weaker pooled mean specificity of 82% (95% CI, 70-90) for motor-evoked potential (MEP) recording changes. Somatosensory-evoked potential (SSEP) recording changes yielded pooled sensitivity of 85% (95% CI, 75-91) and pooled specificity of 72% (95% CI, 57-83). The pooled diagnostic odds ratio for MEP was 55.7 (95% CI, 26.3-119.1) and 14.3 (95% CI, 5.47-37.3) for SSEP. Bivariate analysis yielded summary receiver operative characteristic curves with area under the curve of 91.8% for MEPs and 86.3% for SSEPs.MEPs and SSEPs appear to be more sensitive than specific for detection of postoperative injury. Patients with perioperative neurological deficits are 56 times more likely to have had changes in MEPs during the procedure. We observed considerable variability in alarm criteria and interventions in response to IONM changes, indicating the need for prospective studies capable of defining standardized alarm criteria and responses.

  View details for DOI 10.1097/BSD.0000000000000558

  View details for PubMedID 28650882

• Microsurgical vs. Endoscopic Excision of Colloid Cysts: An Analysis of Complications and Costs Using a Longitudinal Administrative Database. Frontiers in neurology Connolly, I. D., Johnson, E., Lamsam, L., Veeravagu, A., Ratliff, J., Li, G. 2017; 8: 259

  Abstract

  Open microsurgical and endoscopic approaches are the two main surgical options for excision of colloid cysts. Controversy remains as to which is superior. Previous studies consist of small cohort sizes. This topic has not been investigated using national administrative claims data which benefits from larger patient numbers.Current Procedural Terminology (CPT) and International Classification of Disease version 9 (ICD-9) coding at inpatient visit was used to select for index surgical procedures corresponding to microsurgical or endoscopic excision of colloid cysts. Comorbidities, costs, and complications were collected.We identified a total of 483 patients. In all, 240 were from the microsurgical cohort and 243 were from the endoscopic cohort. The two groups displayed similar demographic and comorbidity profiles. Thirty-day post-operative complications were also similar between groups with the exception of seizures and thirty-day readmissions, both higher in the open surgical cohort. The seizure rates were 14.7 and 5.4% in the microsurgical and endoscopic cohorts, respectively (p = 0.0011). The thirty-day readmission rates were 17.3 and 9.6% in the microsurgical and endoscopic cohorts, respectively (p = 0.0149). Index admission costs and 90-day post discharge payments were higher in patients receiving microsurgical excision.An analysis of administrative claims data revealed few differences in surgical complications following colloid cyst excision via microsurgical and endoscopic approaches. Post-operative seizures and thirty-day readmissions were seen at higher frequency in patients who underwent microsurgical resection. Despite similar complication profiles, patients undergoing microsurgical excision experienced higher index admission costs and 90-day aggregated costs suggesting that complications may have been more severe in this group.

  View details for DOI 10.3389/fneur.2017.00259

  View details for PubMedID 28649225

  View details for PubMedCentralID PMC5465269

• AN OVERVIEW OF DNA TOPOISOMERASE I INHIBITORS UNDER DEVELOPMENT DRUGS OF THE FUTURE Connolly, I. D., Hixson, J. D., Nagpal, S. 2016; 41 (12): 731-740

  View details for DOI 10.1358/dof.2016.041.12.2563475

  View details for Web of Science ID 000395939300003

• Percutaneous use of a dual lumen Scepter XC balloon for embolization of a complex facial arteriovenous malformation: a technical report CLINICAL NEURORADIOLOGY Heit, J., Connolly, I., Choudhri, O. 2016; 26 (4): 485-491

  View details for DOI 10.1007/s00062-016-0515-2

  View details for Web of Science ID 000389606200014

  View details for PubMedID 27142059

• Operative volume and outcomes of cerebrovascular neurosurgery in children. Journal of neurosurgery. Pediatrics Bekelis, K., Connolly, I. D., Do, H. M., Choudhri, O. 2016; 18 (5): 623-628

  Abstract

  OBJECTIVE The impact of procedural volume on the outcomes of cerebrovascular surgery in children has not been determined. In this study, the authors investigated the association of operative volume on the outcomes of cerebrovascular neurosurgery in pediatric patients. METHODS The authors performed a cohort study of all pediatric patients who underwent a cerebrovascular procedure between 2003 and 2012 and were registered in the Kids' Inpatient Database (KID). To control for confounding, the authors used multivariable regression models, propensity-score conditioning, and mixed-effects analysis to account for clustering at the hospital level. RESULTS During the study period, 1875 pediatric patients in the KID underwent cerebrovascular neurosurgery and met the inclusion criteria for the study; 204 patients (10.9%) underwent aneurysm clipping, 446 (23.8%) underwent coil insertion for an aneurysm, 827 (44.1%) underwent craniotomy for arteriovenous malformation resection, and 398 (21.2%) underwent bypass surgery for moyamoya disease. Mixed-effects multivariable regression analysis revealed that higher procedural volume was associated with fewer inpatient deaths (OR 0.58; 95% CI 0.40-0.85), a lower rate of discharges to a facility (OR 0.87; 95% CI 0.82-0.92), and shorter length of stay (adjusted difference -0.22; 95% CI -0.32 to -0.12). The results in propensity-adjusted multivariable models were robust. CONCLUSIONS In a national all-payer cohort of pediatric patients who underwent a cerebrovascular procedure, the authors found that higher procedural volume was associated with fewer deaths, a lower rate of discharges to a facility, and decreased lengths of stay. Regionalization initiatives should include directing children with such rare pathologies to a center of excellence.

  View details for PubMedID 27494548

• The strokes that killed Churchill, Roosevelt, and Stalin. Neurosurgical focus Ali, R., Connolly, I. D., Li, A., Choudhri, O. A., Pendharkar, A. V., Steinberg, G. K. 2016; 41 (1): E7-?

  Abstract

  From February 4 to 11, 1945, President Franklin D. Roosevelt of the United States, Soviet Union Premier Joseph Stalin, and British Prime Minister Winston Churchill met near Yalta in Crimea to discuss how post-World War II (WWII) Europe should be organized. Within 2 decades of this conference, all 3 men had died. President Roosevelt died 2 months after the Yalta Conference due to a hemorrhagic stroke. Premier Stalin died 8 years later, also due to a hemorrhagic stroke. Finally, Prime Minister Churchill died 20 years after the conference because of complications due to stroke. At the time of Yalta, these 3 men were the leaders of the most powerful countries in the world. The subsequent deterioration of their health and eventual death had varying degrees of historical significance. Churchill's illness forced him to resign as British prime minister, and the events that unfolded immediately after his resignation included Britain's mismanagement of the Egyptian Suez Crisis and also a period of mistrust with the United States. Furthermore, Roosevelt was still president and Stalin was still premier at their times of passing, so their deaths carried huge political ramifications not only for their respective countries but also for international relations. The early death of Roosevelt, in particular, may have exacerbated post-WWII miscommunication between America and the Soviet Union-miscommunication that may have helped precipitate the Cold War.

  View details for DOI 10.3171/2016.4.FOCUS1575

  View details for PubMedID 27364260

• Epilepsy: A Disruptive Force in History. World neurosurgery Ali, R., Connolly, I. D., Feroze, A. H., Awad, A. J., Choudhri, O. A., Grant, G. A. 2016; 90: 685-690

  Abstract

  Since it was first described in a Mesopotamian text in 2000 bc, countless individuals have offered their perspectives on epilepsy's cause, treatment, and even deeper spiritual significance. However, despite the attention the disease has received through the millennia, it has only been within the past half-century that truly effective treatment options have been available. As a result, for the vast majority of recorded history, individuals with epilepsy have not only had to deal with the uncertainty of their next epileptic seizure but also the concomitant stigma and ostracization. Interestingly, these individuals have included several prominent historical figures, including Julius Caesar, Vladimir Lenin, and Fyodor Dostoyevsky. The fact that epilepsy has appeared in the lives of influential historical people means that the disease has played some role in affecting the progress of human civilization. Epilepsy has cut short the lives of key political leaders, affected the output of talented cultural icons, and, especially within the past half century, influenced the collective understanding of neuroscience and the human nervous system. In this article, the authors review how epilepsy throughout history has manifested itself in the lives of prominent figures and how the disease has helped shape the course of humanity's political, cultural, and scientific evolution.

  View details for DOI 10.1016/j.wneu.2015.11.060

  View details for PubMedID 26709155

• Surgical outcomes of cervical spondylotic myelopathy: an analysis of a national, administrative, longitudinal database. Neurosurgical focus Veeravagu, A., Connolly, I. D., Lamsam, L., Li, A., Swinney, C., Azad, T. D., Desai, A., Ratliff, J. K. 2016; 40 (6): E11-?

  Abstract

  OBJECTIVE The authors performed a population-based analysis of national trends, costs, and outcomes associated with cervical spondylotic myelopathy (CSM) in the United States. They assessed postoperative complications, resource utilization, and predictors of costs, in this surgically treated CSM population. METHODS MarketScan data (2006-2010) were used to retrospectively analyze the complications and costs of different spine surgeries for CSM. The authors determined outcomes following anterior cervical discectomy and fusion (ACDF), posterior fusion, combined anterior/posterior fusion, and laminoplasty procedures. RESULTS The authors identified 35,962 CSM patients, comprising 5154 elderly (age ≥ 65 years) patients (mean 72.2 years, 54.9% male) and 30,808 nonelderly patients (mean 51.1 years, 49.3% male). They found an overall complication rate of 15.6% after ACDF, 29.2% after posterior fusion, 41.1% after combined anterior and posterior fusion, and 22.4% after laminoplasty. Following ACDF and posterior fusion, a significantly higher risk of complication was seen in the elderly compared with the nonelderly (reference group). The fusion level and comorbidity-adjusted ORs with 95% CIs for these groups were 1.54 (1.40-1.68) and 1.25 (1.06-1.46), respectively. In contrast, the elderly population had lower 30-day readmission rates in all 4 surgical cohorts (ACDF, 2.6%; posterior fusion, 5.3%; anterior/posterior fusion, 3.4%; and laminoplasty, 3.6%). The fusion level and comorbidity-adjusted odds ratios for 30-day readmissions for ACDF, posterior fusion, combined anterior and posterior fusion, and laminoplasty were 0.54 (0.44-0.68), 0.32 (0.24-0.44), 0.17 (0.08-0.38), and 0.39 (0.18-0.85), respectively. CONCLUSIONS The authors' analysis of the MarketScan database suggests a higher complication rate in the surgical treatment of CSM than previous national estimates. They found that elderly age (≥ 65 years) significantly increased complication risk following ACDF and posterior fusion. Elderly patients were less likely to experience a readmission within 30 days of surgery. Postoperative complication occurrence, and 30-day readmission were significant drivers of total cost within 90 days of the index surgical procedure.

  View details for DOI 10.3171/2016.3.FOCUS1669

  View details for PubMedID 27246481

• Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases JOURNAL OF NEURO-ONCOLOGY Li, Y., Pan, W., Connolly, I. D., Reddy, S., Nagpal, S., Quake, S., Gephart, M. H. 2016; 128 (1): 93-100

  Abstract

  Cerebral spinal fluid (CSF) from brain tumor patients contains tumor cellular and cell-free DNA (cfDNA), which provides a less-invasive and routinely accessible method to obtain tumor genomic information. In this report, we used droplet digital PCR to test mutant tumor DNA in CSF of a patient to monitor the treatment response of metastatic melanoma leptomeningeal disease (LMD). The primary melanoma was known to have a BRAF (V600E) mutation, and the patient was treated with whole brain radiotherapy and BRAF inhibitors. We collected 9 CSF samples over 6 months. The mutant cfDNA fraction gradually decreased from 53 % (time of diagnosis) to 0 (time of symptom alleviation) over the first 6 time points. Three months after clinical improvement, the patient returned with severe symptoms and the mutant cfDNA was again detected in CSF at high levels. The mutant DNA fraction corresponded well with the patient's clinical response. We used whole exome sequencing to examine the mutation profiles of the LMD tumor DNA in CSF before therapeutic response and after disease relapse, and discovered a canonical cancer mutation PTEN (R130*) at both time points. The cellular and cfDNA revealed similar mutation profiles, suggesting cfDNA is representative of LMD cells. This study demonstrates the potential of using cellular or cfDNA in CSF to monitor treatment response for LMD.

  View details for DOI 10.1007/s11060-016-2081-5

  View details for Web of Science ID 000376095600011

  View details for PubMedID 26961773

  View details for PubMedCentralID PMC5412509

• Sports-related brain injuries: connecting pathology to diagnosis NEUROSURGICAL FOCUS Pan, J., Connolly, I. D., Dangelmajer, S., Kintzing, J., Ho, A. L., Grant, G. 2016; 40 (4)

  Abstract

  Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.

  View details for DOI 10.3171/2016.1.FOCUS15607

  View details for Web of Science ID 000373476500004

  View details for PubMedID 27032917

• The "Liquid Biopsy": the Role of Circulating DNA and RNA in Central Nervous System Tumors. Current neurology and neuroscience reports Connolly, I. D., Li, Y., Gephart, M. H., Nagpal, S. 2016; 16 (3): 25-?

  Abstract

  The detection of tumor-derived circulating nucleic acids in patients with cancer, known as the "liquid biopsy," has expanded from use in plasma to other bodily fluids in an increasing number of malignancies. Circulating nucleic acids could be of particular use in central nervous system tumors as biopsy carries a 5-7 % risk of major morbidity. This application presents unique challenges that have limited the use of cell-free DNA and RNA in the diagnosis and monitoring of CNS tumors. Recent work suggests that cerebrospinal fluid may be a useful source of CNS tumor-derived circulating nucleic acids. In this review, we discuss the available data and future outlook on the use of the liquid biopsy for CNS tumors.

  View details for DOI 10.1007/s11910-016-0629-6

  View details for PubMedID 26838352

• Genetic and molecular distinctions in spinal ependymomas: A review. Clinical neurology and neurosurgery Connolly, I. D., Ali, R., Li, Y., Gephart, M. H. 2015; 139: 210-215

  Abstract

  While gross total resection of spinal ependymomas prevents recurrence, this surgical result is not always possible. Increasing evidence suggests that ependymomas occurring in the spine are genetically distinct from those originating in the brain. Herein we review the most recent developments detailing the molecular and genetic characteristics of spinal ependymomas, which may inform more effective and personalized adjuvant therapies for spinal ependymomas that are ineligible for gross total resection. We performed a key-word search for articles published on the molecular, genetic, chromosomal, and epigenetic transformations inherent in spinal ependymomas. We reviewed appropriate articles and their relevant citations. While resection can often achieve favorable outcomes in the treatment of spinal ependymoma, more research on the unique molecular, genetic, chromosomal and epigenetic traits must be conducted in order to tailor treatment and intervention for those patients for whom total resection is not possible.

  View details for DOI 10.1016/j.clineuro.2015.10.011

  View details for PubMedID 26519890

• Craniotomy for Resection of Meningioma: An Age-Stratified Analysis of the MarketScan Longitudinal Database WORLD NEUROSURGERY Connolly, I. D., Cole, T., Veeravagu, A., Popat, R., Ratliff, J., Li, G. 2015; 84 (6): 1864-1870

  Abstract

  We sought to describe complications after resection for meningioma with the use of longitudinal administrative data, which our group has shown recently to be superior to nonlongitudinal administrative data.We identified patients who underwent resection for meningioma between 2010 and 2012 in the Thomson Reuters MarketScan database. Current Procedural Terminology coding at inpatient visit was used to select for meningioma resection procedure. Comorbidities and complications were obtained by use of the International Classification of Diseases, Ninth Revision or Current Procedural Terminology coding. Associations between complications and demographic and clinical factors were evaluated with logistic regression.We identified a total of 2216 patients. Approximately 41% developed 1 or more perioperative complications. Approximately 15% were readmitted within 30 days of their procedure. The most frequent complications that occurred in our cohort were new postoperative seizures (11.8%), postoperative dysrhythmia (7.9%), intracranial hemorrhage (5.9%), and cerebral artery occlusion (5.4%). General neurosurgical complications and general neurologic complications occurred in 4.4% and 16.1% of patients, respectively. Nearly 55% of elderly patients (≥ 70 years) developed 1 or more perioperative complication (vs. 39% of nonelderly patients). After we adjusted for comorbidities, elderly status and male sex were found to be significantly associated with increased odds for a variety of complications.In this study, we report complication rates in patients undergoing resection for meningioma. Because of the longitudinal nature of the MarketScan database, we were able to capture a wide array of specific postoperative complications associated with meningioma resection procedures. Care should be taken in the selection of candidates for meningioma resection.

  View details for DOI 10.1016/j.wneu.2015.08.018

  View details for Web of Science ID 000366286300065

  View details for PubMedID 26318633

• Therapeutic strategies to improve drug delivery across the blood-brain barrier. Neurosurgical focus Azad, T. D., Pan, J., Connolly, I. D., Remington, A., Wilson, C. M., Grant, G. A. 2015; 38 (3): E9-?

  View details for DOI 10.3171/2014.12.FOCUS14758

  View details for PubMedID 25727231

• Tissue engineering of flexor tendons: the effect of a tissue bioreactor on adipoderived stem cell-seeded and fibroblast-seeded tendon constructs. journal of hand surgery Angelidis, I. K., Thorfinn, J., Connolly, I. D., Lindsey, D., Pham, H. M., Chang, J. 2010; 35 (9): 1466-1472

  Abstract

  Tissue-engineered flexor tendons could eventually be used for reconstruction of large tendon defects. The goal of this project was to examine the effect of a tissue bioreactor on the biomechanical properties of tendon constructs seeded with adipoderived stem cells (ASCs) and fibroblasts (Fs).Rabbit rear paw flexor tendons were acellularized and seeded with ASCs or Fs. A custom bioreactor applied a cyclic mechanical load of 1.25 N at 1 cycle/minute for 5 days onto the tendon constructs. Three additional groups were used as controls: fresh tendons and tendons reseeded with either ASCs or Fs that were not exposed to the bioreactor treatment and were left in stationary incubation for 5 days. We compared the ultimate tensile stress (UTS) and elastic modulus (EM) of bioreactor-treated tendons with the unloaded control tendons and fresh tendons. Comparison across groups was assessed using one-way analysis of variance with the significance level set at p<.05. Pairwise comparison between the samples was determined by using the Tukey test.The UTS and EM values of bioreactor-treated tendons that were exposed to cyclic load were significantly higher than those of unloaded control tendons. Acellularized tendon constructs that were reseeded with ASCs and exposed to a cyclic load had a UTS of 66.76 MPa and an EM of 906.68 MPa; their unloaded equivalents had a UTS of 47.90 MPa and an EM of 715.57 MPa. Similar trends were found in the fibroblast-seeded tendon constructs that were exposed to the bioreactor treatment. The bioreactor-treated tendons approached the UTS and EM values of fresh tendons. Histologically, we found that cells reoriented themselves parallel to the direction of strain in response to cyclic strain.The application of cyclic strain on seeded tendon constructs that were treated with the bioreactor helped achieve a UTS and an EM comparable with those of fresh tendons. Bioreactor pretreatment and alternative cell lines, such as ASCs and Fs, might therefore contribute to the in vitro production of strong tendon material.

  View details for DOI 10.1016/j.jhsa.2010.06.020

  View details for PubMedID 20807624

• Tissue Engineering of Flexor Tendons: The Effect of a Tissue Bioreactor on Adipoderived Stem Cell-Seeded and Fibroblast-Seeded Tendon Constructs JOURNAL OF HAND SURGERY-AMERICAN VOLUME Angelidis, I. K., Thorfinn, J., Connolly, I. D., Lindsey, D., Pham, H. M., Chang, J. 2010; 35A (9): 1466-1472

  View details for DOI 10.1016/j.jhsa.2010.06.020

  View details for Web of Science ID 000281526400012