Publications by authors named "Fatih Zor"

74 Publications

Sex Differences Revealed in a Mouse CFA Inflammation Model with Macrophage Targeted Nanotheranostics.

Theranostics 2020 1;10(4):1694-1707. Epub 2020 Jan 1.

Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.

Monocyte derived macrophages (MDMs) infiltrate sites of infection or injury and upregulate cyclooxygenase-2 (COX-2), an enzyme that stimulates prostaglandin-E2 (PgE2). Nanotheranostics combine therapeutic and diagnostic agents into a single nanosystem. In previous studies, we demonstrated that a nanotheranostic strategy, based on theranostic nanoemulsions (NE) loaded with a COX-2 inhibitor (celecoxib, CXB) and equipped with near-infrared fluorescent (NIRF) reporters, can specifically target circulating monocytes and MDMs. The anti-inflammatory and anti-nociceptive effects of such cell-specific COX-2 inhibition lasted several days following Complete Freund's Adjuvant (CFA) or nerve injury in male mice. The overall goal of this study was to investigate the extended (up to 40 days) impact of MDM-targeted COX-2 inhibition and any sex-based differences in treatment response; both of which remain unknown. Our study also evaluates the feasibility and efficacy of a preclinical nanotheranostic strategy for mechanistic investigation of the impact of such sex differences on clinical outcomes. : CFA was administered into the right hind paws of male and female mice. All mice received a single intravenous dose of NIRF labeled CXB loaded NE twelve hours prior to CFA injection. whole body NIRF imaging and mechanical hypersensitivity assays were performed sequentially and NIRF imaging and immunohistopathology of foot pad tissues were performed at the end point of 40 days. : Targeted COX-2 inhibition of MDMs in male and female mice successfully improved mechanical hypersensitivity after CFA injury. However, we observed distinct sex-specific differences in the intensity or longevity of the nociceptive responses. In males, a single dose of CXB-NE administered via tail vein injection produced significant improved mechanical hypersensitivity for 32 days as compared to the drug free NE (DF-NE) (untreated) control group. In females, CXB-NE produced similar, though less prominent and shorter-lived effects, lasting up to 11 days. NIRF imaging confirmed that CXB-NE can be detected up to day 40 in the CFA injected foot pad tissues of both sexes. There were distinct signal distribution trends between males and females, suggesting differences in macrophage infiltration dynamics between the sexes. This may also relate to differences in macrophage turnover rate between the sexes, a possibility that requires further investigation in this model. : For the first time, this study provides unique insight into MDM dynamics and the early as well as longer-term targeted effects and efficacy of a clinically translatable nanotheranostic agent on MDM mediated inflammation. Our data supports the potential of nanotheranostics as presented in elucidating the kinetics, dynamics and sex-based differences in the adaptive or innate immune responses to inflammatory triggers. Taken together, our study findings lead us closer to true personalized, sex-specific pain nanomedicine for a wide range of inflammatory diseases.
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http://dx.doi.org/10.7150/thno.41309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993234PMC
April 2021

The effect of thymus transplantation on donor-specific chimerism in the rat model of composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation.

Microsurgery 2020 Jul 6;40(5):576-584. Epub 2020 Jan 6.

Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio.

Introduction: Research on tolerance has proven that development of donor-specific chimerism (DSC) may accompany tolerance induction in vascularized composite allotransplantation (VCA). In this study, we aimed to determine the effect of thymus transplantation on the induction of DSC in rat VCA model of osseomusculocutaneous sternum (OMCS) and osseomusculocutaneous sternum and thymus (OMCST) allotransplantation.

Materials And Methods: A total of 20 Lewis-Brown Norway and Lewis rats, 5-6 weeks old, weighting between 120 and 150 g, were used in the study. OMCS (n = 5) and OMCST (n = 5) allografts were harvested from Lewis-Brown Norway donors (RT1 ) based on the common carotid artery and external jugular vein, and a heterotopic transplantation was performed to the inguinal region of the Lewis (RT1 ) recipients under cyclosporine A monotherapy (16 mg/kg) protocol tapered to 2 mg/kg and maintained for the duration of the study. The peripheral blood chimerism levels (T-cell, B-cell, and monocyte/granulocyte/dendritic cell-MGDC populations) were evaluated at days 7, 14, 35, 63, 100, and 150 posttransplant by flow cytometry. At Day 150, thymus, spleen, and liver samples were assessed by polymerase chain reaction (PCR) in the presence of DSC.

Results: Total chimerism level increased in both OMCST and OMCS groups at all time points. At 150 days posttransplant, chimerism in OMCST group was significantly higher (12.91 ± 0.16%) than that in OMCS group (8.89 ± 0.53%%, p < .01), and PCR confirmed the presence of donor-derived cells in the liver and spleen of all OMCST recipients and in one liver sample and two spleen samples in OMCS recipients without thymus transplant.

Conclusions: This study confirmed the direct effects of thymus transplantation on the induction and maintenance of DSC in T-cell, B-cell, and MGDC populations. These results confirm correlation between thymus transplantation and DSC induction.
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http://dx.doi.org/10.1002/micr.30555DOI Listing
July 2020

Immunological considerations and concerns as pertinent to whole eye transplantation.

Curr Opin Organ Transplant 2019 12;24(6):726-732

Departments of Surgery, Ophthalmology and Bioengineering, Wake Forest University Health Sciences, Wake Forest Institute for Regenerative Medicine, Winston Salem, North Carolina.

Purpose Of Review: The advent of clinical vascularized composite allotransplantation (VCA), offers hope for whole eye transplantation (WET) in patients with devastating vison loss that fails or defies current treatment options. Optic nerve regeneration and reintegration remain the overarching hurdles to WET. However, the realization of WET may indeed be limited by our lack of understanding of the singular immunological features of the eye as pertinent to graft survival and functional vision restoration in the setting of transplantation.

Recent Findings: Like other VCA, such as the hand or face, the eye includes multiple tissues with distinct embryonic lineage and differential antigenicity. The ultimate goal of vision restoration through WET requires optimal immune modulation of the graft for successful optic nerve regeneration. Our team is exploring barriers to our understanding of the immunology of the eye in the context of WET including the role of immune privilege and lymphatic drainage on rejection, as well as the effects ischemia, reperfusion injury and rejection on optic nerve regeneration.

Summary: Elucidation of the unique immunological responses in the eye and adnexa after WET will provide foundational clues that will help inform therapies that prevent immune rejection without hindering optic nerve regeneration or reintegration.
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http://dx.doi.org/10.1097/MOT.0000000000000713DOI Listing
December 2019

Biocompatibility in regenerative nanomedicine.

Nanomedicine (Lond) 2019 10 15;14(20):2763-2775. Epub 2019 Oct 15.

Wake Forest School of Medicine, Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27101, USA.

Biocompatibility is a very common word that is used within biomaterial science and used for description of the interactions between the foreign material and the body. However, the meaning of biocompatibility as well as the mechanisms that collectively constitutes is still unclear. With the advance of nanotechnology, new concerns have been observed related to biocompatibility of these biomaterials. Due to their small size and variability of their physical and chemical properties, nanoparticles' (NP) distribution within the body and interactions with the target cells and tissues are highly variable. Here, we tried to provide an overview about NPs, the concept of biocompatibility and biocompatibility-related issues in nanomedicine and several different NPs.
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http://dx.doi.org/10.2217/nnm-2019-0140DOI Listing
October 2019

Adipogenesis for soft tissue reconstruction.

Curr Opin Organ Transplant 2019 10;24(5):598-603

Purpose Of Review: It has been increasingly common to use adipose tissue for regenerative and reconstructive purposes. Applications of autologous fat transfer and different stem cell therapies have significant limitations and adipose tissue engineering may have the potential to be an important strategy in the reconstruction of large tissue defects. A better understanding of adipogenesis will help to develop strategies to make adipose tissue more effective for repairing volumetric defects.

Recent Findings: We provide an overview of the current applications of adipose tissue transfer and cellular therapy methods for soft tissue reconstruction, cellular physiology, and factors influencing adipogenesis, and adipose tissue engineering. Furthermore, we discuss mechanical properties and vascularization strategies of engineered adipose tissue, and its potential applications in the clinical settings.

Summary: Autologous fat tissue transfer is the standard of care technique for the majority of surgeons; however, high resorption rates, poor perfusion within a large volume fat graft and widely inconsistent graft survival are the main limitations. Adipose tissue engineering is a promising field to reach the first goal of producing adipose tissue which has more predictable survival and higher graft retention rates. Advancements of scaffold and vascularization strategies will contribute to metabolically and functionally more relevant adipose tissue engineering.
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http://dx.doi.org/10.1097/MOT.0000000000000694DOI Listing
October 2019

Demonstration of technical feasibility and viability of whole eye transplantation in a rodent model.

J Plast Reconstr Aesthet Surg 2019 Oct 18;72(10):1640-1650. Epub 2019 Jun 18.

Departments of Surgery, Ophthalmology and Bioengineering, Wake Forest University Health Sciences, Wake Forest Institute for Regenerative Medicine, Winston Salem, NC, USA. Electronic address:

Introduction: Whole eye transplantation (WET) holds promise for vision restoration in devastating/disabling visual loss (congenital or traumatic) not amenable to surgical or neuroprosthetic treatment options. The eye includes multiple tissues with distinct embryonic lineage and differential antigenicity. Anatomically and immunologically, the eye is unique due to its avascular (cornea) and highly vascular (retina) components. Our goal was to establish technical feasibility, demonstrate graft viability, and evaluate histologic changes in ocular tissues/adnexae in a novel experimental model of WET that included globe, adnexal, optic nerve (ON), and periorbital soft tissues.

Methods: Outbred Sprague-Dawley rats (n = 5) received heterotopic vascularized WET from donors. Each WET included the entire globe, adnexa, ON, and periorbital soft tissues supplied by the common carotid artery and external jugular vein. Viability and perfusion were confirmed by clinical examination, angiography and magnetic resonance imaging (MRI). Globe, adnexal, and periorbital tissues were analyzed for histopathologic changes, and the ON was examined for neuro-regeneration at study endpoint (30 days) or Banff Grade 3 rejection in the periorbital skin (whichever was earlier).

Results: Gross examination confirmed transplant viability and corneal transparency. Average operative duration was 64.0 ± 5.8 min. Average ischemia time was 26.0 ± 4.2 min. MRI revealed loss of globe volume by 36.0 ± 2.8% after transplantation. Histopathology of globe and adnexal tissues showed unique and differential patterns of inflammatory cell infiltration. The ON revealed a neurodegeneration pattern.

Conclusion: The present study is the first in the literature to establish an experimental model of WET. This model holds significant potential in investigating mechanistic pathways, monitoring strategies or developing management approaches involving ocular viability, immune rejection, and ON regeneration after WET.
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http://dx.doi.org/10.1016/j.bjps.2019.05.042DOI Listing
October 2019

Late Correction of Traumatic Nasal Deformities: A Surgical Algorithm and Experience in 120 Patients.

Aesthet Surg J 2018 Nov;38(12):NP182-NP195

Department of Plastic and Reconstructive Surgery, University of Wisconsin, Madison, Wisconsin, USA.

Background: Traumatic nasal deformities have a wide spectrum of presentations, which further complicates their management and preoperative planning. Although many methods and algorithms have been proposed for management of specific posttraumatic nasal deformities, such as twisted, deviated, saddle, or short nose, these algorithms usually focus on a specific deformity in isolation from the remainder of the nose.

Objectives: The aim of this study is to present an algorithm for traumatic nasal deformities and to evaluate the functional and aesthetic outcomes of this new algorithm by a preoperative and postoperative quality-of-life questionnaire.

Methods: Patients with traumatic nasal deformity were operated on according to our surgical algorithm. Preoperative and postoperative Rhinoplasty Outcome Evaluation (ROE) scores, which is a rhinoplasty outcome survey, were evaluated.

Results: A total of 120 patients were included in the study. The mean preoperative ROE score was 3.3 ± 1.9 and mean postoperative ROE score was 20.4 ± 3.2. There was a statistically significant difference between preoperative and postoperative ROE scores (P < 0.001). There was a negative, mild to moderate, statistically significant correlation between preoperative scores and benefit (difference between postoperative and preoperative scores) (r = -0.465, P < 0.001), which means patients with lower scores had more improvement from the surgery. During the follow-up period, relapse of deviation, hypertrophic inferior turbinate, and intranasal synechia were found in 9% (n = 11), 6.6% (n = 8), and 3.3% (n = 4) of patients, respectively.

Conclusions: In this study, a comprehensive surgical algorithm applicable to all traumatic nasal deformities is suggested, and the results of 120 patients with traumatic nasal deformities are presented.

Level Of Evidence 2:
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http://dx.doi.org/10.1093/asj/sjy155DOI Listing
November 2018

A New Composite Eyeball-Periorbital Transplantation Model in Humans: An Anatomical Study in Preparation for Eyeball Transplantation.

Plast Reconstr Surg 2018 04;141(4):1011-1018

Chicago, Ill.; Cleveland, Ohio; Istanbul and Ankara, Turkey; and Buffalo, N.Y.

Background: Vascularized composite allotransplantation offers a new hope for restoration of orbital content and perhaps vision. The aim of this study was to introduce a new composite eyeball-periorbital transplantation model in fresh cadavers in preparation for composite eyeball allotransplantation in humans.

Methods: The composite eyeball-periorbital transplantation flap borders included the inferior border, outlined by the infraorbital rim; the medial border, created by the nasal dorsum; the lateral border, created by the lateral orbital rim; and the superior border, created by the superior part of the eyebrow. The pedicle of the flap included the facial artery, superficial temporal artery, and external jugular vein. The skin and subcutaneous tissues of the periorbital region were dissected and the bony tissue was reached. A coronal incision was performed and the frontal lobe of the brain was reached by means of frontal osteotomy. Ophthalmic and oculomotor nerves were also included in the flap. After a "box osteotomy" around the orbit, the dissection was completed. Methylene blue and indocyanine green injection (SPY Elite System) was performed to show the integrity of the vascular territories after facial flap harvest.

Results: Adequate venous return was observed within the flap after methylene blue dye injection. Laser-assisted indocyanine green angiography identified a well-defined vascular network within the entire composite eyeball-periorbital transplantation flap.

Conclusions: For the first time, a novel composite eyeball-periorbital transplantation model in human cadavers was introduced. Good perfusion of the flap confirmed the feasibility of composite eyeball-periorbital transplantation in the clinical setting. Although harvesting of the flap is challenging, it introduces a new option for reconstruction of the periorbital region including the eyeball.
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http://dx.doi.org/10.1097/PRS.0000000000004250DOI Listing
April 2018

The neurochemistry of peripheral nerve regeneration.

Indian J Plast Surg 2017 Jan-Apr;50(1):5-15

Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Peripheral nerve injuries (PNIs) can be most disabling, resulting in the loss of sensitivity, motor function and autonomic control in the involved anatomical segment. Although injured peripheral nerves are capable of regeneration, sub-optimal recovery of function is seen even with the best reconstruction. Distal axonal degeneration is an unavoidable consequence of PNI. There are currently few strategies aimed to maintain the distal pathway and/or target fidelity during regeneration across the zone of injury. The current state of the art approaches have been focussed on the site of nerve injury and not on their distal muscular targets or representative proximal cell bodies or central cortical regions. This is a comprehensive literature review of the neurochemistry of peripheral nerve regeneration and a state of the art analysis of experimental compounds (inorganic and organic agents) with demonstrated neurotherapeutic efficacy in improving cell body and neuron survival, reducing scar formation and maximising overall nerve regeneration.
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http://dx.doi.org/10.4103/ijps.IJPS_14_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469235PMC
June 2017

The effect of in vivo created vascularized neurotube on peripheric nerve regeneration.

Injury 2017 Jul 11;48(7):1486-1491. Epub 2017 May 11.

Gulhane Military Medical Academy, Dept. of Plastic Surgery, Ankara, Turkey.

Introduction: Creating vascularized nerve conduits for treatment of nerve gaps have been researched, however, these methods need microsurgical anastomosis thereby complicating the nerve repair process. Thus, the concept of vascularized nerve conduits has not popularized up till now. The aim of this study is to evaluate the effects of vascularized and non-vascularized biological conduits on peripheral nerve regeneration.

Material And Methods: Following ethical board approval, 15 Sprague-Dawley rats were used in the study. The rats were equally divided into three groups. In group I, a silicon rod was inserted next to the sciatic nerve of the rat and connective tissue generated around this rod was used as a vascularized biological conduit. In group II, a silicon rod was inserted into the dorsum of the rat and connective tissue generated around this rod was used as a non-vascularized biological conduit. In group III, autogenic nerve graft was used to repair the nerve gap. The contralateral sciatic nerve is used as a control in all rats. Macroscopic, electrophysiological and histomorphometric evaluations were performed to determine the nerve regeneration.

Results: There was no statistically significant difference between groups, in terms of latency. However, the mean amplitude of group I was found to be higher than other groups. The difference between group I and II was statistically significant. Myelinated axonal counts in group I was significantly higher than groups II and III.

Conclusion: Our results showed that vascularized biological conduits provided better nerve regeneration when compared to autografts and non-vascularized biological conduits. Creation and application of vascularized conduits by using the technique described here is easy. Although this method is not an alternative to autogenic nerve grafts, our results are promising and encouraging for further studies.
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http://dx.doi.org/10.1016/j.injury.2017.05.014DOI Listing
July 2017

Native extracellular matrix/fibroin hydrogels for adipose tissue engineering with enhanced vascularization.

Biomed Mater 2017 Jun 6;12(3):035007. Epub 2017 Jun 6.

Department of Biomedical Engineering, Middle East Technical University, Turkey.

Adipose tissue engineering is a promising field for regeneration of soft tissue defects. However, vascularization is needed since nutrients and oxygen cannot reach cells in thick implants by diffusion. Obtaining a biocompatible scaffold with good mechanical properties is another problem. In this study, we aimed to develop thick and vascularized adipose tissue constructs supporting cell viability and adipose tissue regeneration. Hydrogels were prepared by mixing rat decellularized adipose tissue (DAT) and silk fibroin (Fib) at different v/v ratios (3:1, 1:1 and 1:3) and vortexing. Gelation times decreased with increasing fibroin ratio Among hydrogel groups 1:3-DAT:Fib ratio group showed similar mechanical properties with adipose tissue. Both pre-adipocytes and pre-endothelial cells, pre-differentiated from adipose derived stem cells (ASCs), were encapsulated in hydrogels at a 1: 3 ratio. In vitro analyses showed that hydrogels with 1:3 (v/v) DAT:Fib ratio supported better cell viability. Pre-adipocytes had lipid vesicles, and pre-endothelial cells formed tubular structures inside hydrogels only after 3 days in vitro. When endothelial and adipogenic pre-differentiated ASCs (for 7 days before encapsulation) were encapsulated together into 1:3-DAT:Fib hydrogels both cell types continued to differentiate into the committed cell lineage. Vascularization process in the hydrogels implanted with adipogenic and endothelial pre-differentiated ASCs took place between the first and second week after implantation which was faster than observed in the empty hydrogels. ASCs pre-differentiated towards adipogenic lineage inside hydrogels had begun to accumulate lipid vesicles after 1 week of subcutaneous implantation Based on these results, we suggest that 1:3-DAT:Fib hydrogels with enhanced vascularization hold promise for adipose tissue engineering.
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http://dx.doi.org/10.1088/1748-605X/aa6a63DOI Listing
June 2017

Pre-expanded Thoracodorsal Artery Perforator Flap.

Clin Plast Surg 2017 Jan 6;44(1):91-97. Epub 2016 Oct 6.

Department of Plastic, Reconstructive, and Aesthetic Surgery, Gulhane Military Medical Academy, General Dr Tevfik Saglam Cad, Etlik 06010, Ankara, Turkey.

The size of the thoracodorsal artery perforator (TDAP) flap or pedicle, in general, may be found to be inadequate. Pre-expansion of the flap before harvest can be a solution to increase the size of the TDAP flap in such instances. The pre-expanded TDAP flap can be used to reconstruct large-sized defects with the advantage of primary closure of the donor site. This article presents details on the surgical technique and provides discussion of the authors' experiences.
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http://dx.doi.org/10.1016/j.cps.2016.08.010DOI Listing
January 2017

Effects of hPTPβ inhibitor on microcirculation of rat cremaster muscle flap following ischemia-reperfusion injury.

Microsurgery 2017 Sep 17;37(6):624-631. Epub 2016 Nov 17.

Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.

Introduction: Inhibition of protein tyrosine phosphatases (PTP) enhances endothelial receptor tyrosine kinases activation and may have beneficial effects on vessel growth and improve blood flow to ischemic tissue. The purpose of this study is to determine influence of hPTPß inhibitors on ischemia-reperfusion injury in muscle flap.

Materials And Methods: Following cremaster muscle dissection, 60 rats divided into 10 experimental groups (placebo and treatment groups following 0, 1, 2, 3, and 4 h of ischemia). Following group-specific treatment (placebo/hPTPß inhibitor, 15 mg/kg), 2 h of reperfusion is initiated. Observations are performed at 4 h after completion of reperfusion and microcirculatory hemodynamics and leukocyte-endothelial activation were recorded.

Results: Administration of hPTPß inhibitor showed preservation of capillary perfusion in group subjected to 2 h of ischemia when compared with placebo (P < .05). The effect of hPTPβ inhibitor on mean venule diameter was found to be altered by duration of ischemia and this effect was statistically significant (P < .05). Treated ischemic groups (1 h, 2 h, and 3 h) showed decreased activation of rolling, sticking, and transmigrating leukocytes compared to respective placebo groups at all time points. The differences were significant for transmigrating leukocytes after 2 h and 3 h of ischemia (P < .05). Endothelial edema index was also significantly reduced in 2 h ischemia group (P < .05).

Conclusion: Administration of hPTP inhibitors after submission of tissue to subcritical ischemia (1-2 h) improved functional capillary perfusion and decreased leukocyte-endothelial activation after 4 h after reperfusion. These results indicate that hPTP inhibitor has a potential postischemic therapeutic effect applied after tissue ischemia just before the reperfusion injury.
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http://dx.doi.org/10.1002/micr.30131DOI Listing
September 2017

Useful Method for Intraoperative Monitoring of Facial Nerve in a Scarred Bed.

J Craniofac Surg 2016 Oct;27(7):1804-1805

Department of Plastic and Reconstructive Surgery, Gulhane Military Medicine Academy, Ankara, Turkey.

Facial nerve is the main cranial nerve for the innervation of facial expression muscles. Main trunk of facial nerve passes approximately 1 to 2 cm deep to tragal pointer. In some patients, where a patient has multiple operations, fibrosis due to previous operations may change the natural anatomy and direction of the branches of facial nerve. A 22-year-old male patient had 2 operations for mandibular reconstruction after gunshot wound. During the second operation, there was a possible injury to the marginal mandibular nerve and a nerve stimulator was used intraoperatively to monitor the nerve at the tragal pointer because the excitability of the distal segments remains intact for 24 to 48 hours after nerve injuries. Thus, using a nerve stimulator at the operational site may lead to false-positive muscle movements in case of injuries. Using the nerve stimulator to stimulate the main trunk at the tragal point may help to distinguish the presence of possible injuries. A reliable method for intraoperative facial nerve monitoring in a scarred operational site was introduced in this letter.
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http://dx.doi.org/10.1097/SCS.0000000000002991DOI Listing
October 2016

Fetal Cleft Lip/Palate Surgery: End of a Dream?

Fetal Pediatr Pathol 2016 26;35(4):277-81. Epub 2016 Apr 26.

d Department of Radiology , Gulhane Military Medical Academy, Haydarpasa Training Hospital , Istanbul , Turkey.

Recognition that a fetus can scarlessly heal in intrauterine life led to various animal studies in the mid 1980s exploring the possibility of fetal cleft lip/palate surgery. The idea of scarless cleft repair seemed like a possible dream after the promising results from the early animal studies. In this review, we analyze the progress made in the 30 years since our first experience with animal models.
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http://dx.doi.org/10.3109/15513815.2016.1171422DOI Listing
March 2017

Comparison of antemortem clinical diagnosis and postmortem findings in burn-related deaths.

Ulus Travma Acil Cerrahi Derg 2015 Dec;21(6):491-5

Department of Forensic Medicine, Gulhane Military Medical Academy, Ankara, Turkey.

Background: Burn injuries are an important public health problem resulting in high morbidity and mortality. Mortality in burn patients is associated with age, the extent of the burn surface, and the presence of concurrent chronic diseases. Studies have revealed differences between antemortem clinical diagnoses and postmortem findings in burn-related deaths.

Methods: In the present study, postmortem examination reports and autopsy reports issued by the Department of Forensic Medicine in Gülhane Military Medical Academy between 1 January 1994 and 30 May 2013 were retrospectively reviewed together with patient charts in an attempt to compare postmortem findings and antemortem clinical findings in burn-related deaths.

Results: In a period of approximately 20 years, thirty-one (6.9%) of the deaths among 450 cases were burn-related. Of the injuries, 90.3% were caused by flame burns. Mean burn percentage was 70.52%, and the survival of these cases was found to decrease significantly with increasing burn percentage (r=-0.491, p=0.005). According to autopsy findings, pneumonia was the most frequently overlooked antemortem clinical diagnosis, and mortality was associated with systemic organ failures.

Conclusion: Burn-related deaths are an important cause of mortality among soldiers. We believe that postmortem findings revealed by autopsies could significantly contribute to the treatment of burn cases, and that interdisciplinary data sharing would be important in this respect.
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http://dx.doi.org/10.5505/tjtes.2015.36604DOI Listing
December 2015

Staged repair of severe open abdomens due to high-energy gunshot injuries with early vacuum pack and delayed tissue expansion and dual-sided meshes.

Ulus Travma Acil Cerrahi Derg 2015 Dec;21(6):457-62

Department of General Surgery, Gulhane Military Medical Academy, Ankara, Turkey.

Background: Open abdomen is a salvage procedure that prevents catastrophes after severe intraabdominal traumas. However, following this life saving attempt, it is mostly not feasible to close the abdomen immediately after the recovery of intraabdominal injuries. Consequently, a staged reconstruction is required, and the first stage is usually a temporary closing approach. At the end of this stage, resulting giant "ventral hernia" is a burden for both the patient and the surgeon. Therefore a permanent repair is subsequently needed. Although there are many treatment modalities described for this goal, etiologies like high-energy gunshots may cause an exactly nuisance scene which can limit treatment options and reduce final success. Herein, it was the objective of this study to present our staged protocol to restore the abdominal wall defect and strategy for optimizing the results in such conundrum cases.

Methods: Treatment was performed on nine male patients suffering from severe open abdomen due to high-energy gunshot injury. In all patients, temporary closure was provided by negative pressure wound treatment applied directly to the viscera and followed by skin grafting. Late permanent closure was performed with the lamination of expanded abdominal skin and dual-sided meshes.

Results: The follow-up period ranged between 24 months to 4.5 years (mean, 3 years). During this period, no recurrence of ventral hernia, enteric fistula formation, abdominal infection and seroma formation was observed in any patient.

Conclusion: In this study, NPWT, tissue expansion and dual-sided mesh were used together as a staged procedure for optimizing the results in the clinical scenario of an open abdomen due to high-energy gunshot wound. Results were highly satisfactory for patients and acceptable aesthetically.
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http://dx.doi.org/10.5505/tjtes.2015.05942DOI Listing
December 2015

Hemangioma of the Zygomatic Bone.

J Craniofac Surg 2016 Mar;27(2):e200-2

*Department of Plastic, Reconstructive and Aesthetic Surgery †Department of Pathology ‡Department of Oftalmology §Department of Radiology, Gülhane Military Medical School, Ankara, Turkey.

Benign masses arising from facial bones have been reported several times in the literature. Hemangiomas are one of the uncommon benign tumors. In this study, the authors aimed to present a rare patient of zygomatic intraosseos hemangioma and their management. A 40-year-old woman with a mass in her left lateral cantus admitted to our clinic. Preoperative computed tomography and magnetic resonance imaging revealed an osseos mass in her left zygoma. The authors conclude that it should be kept in mind that although they are very rare benign tumors, intraosseos hemangiomas can cause facial masses. Meticulous radiologic examination can give important clues for differential diagnosis before the surgery.
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http://dx.doi.org/10.1097/SCS.0000000000002457DOI Listing
March 2016

A new total hemiface allotransplantation model in rats.

Microsurgery 2016 Mar 21;36(3):230-8. Epub 2016 Jan 21.

Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL.

Introduction: Vascularized composite allotransplantation (VCA), a new reconstructive option for patients suffering from extensive facial defects leads to superior functional and aesthetic outcomes compared to the standard autologous reconstruction. Among VCA recipients, each case involves different facial structures and tissues depending on the patient's injury, thus drawing conclusions on the mechanism of immune interactions between the donor and recipient is challenging. This study introduces a new total hemiface VCA model, including scalp, external ear, mystacial pad, premaxilla, upper/lower lids, nose, and upper/lower lips to evaluate the effect of transplantation of multitissue VCA on the recipient's immune response.

Material And Methods: Ten hemiface allotransplantations were performed in two groups between Lewis-Lewis (isograft) and LBN-Lewis (allograft) rats. Cyclosporine A (CsA) monotherapy was applied in the allograft group to prevent rejection.

Results: All flaps survived up to 100 days post-transplant. The mean warm ischemia time was 45 minutes. Histological analysis revealed normal bone, cartilage (ear and nose), conjunctiva, palpebra, and eyelashes. Flow cytometry confirmed donor-specific chimerism for T cells (CD4/RT1(n) and CD8/RT1(n)) and B cells (CD45RA/RT1(n)) in the peripheral blood of all rats in the allotransplantation group. At post-transplant day 7, chimerism levels were at 1.68% for CD4/RT1(n) , 0.46% for CD8/RT1(n) and 0.64% for CD45RA/RT1(n). However, chimerism levels for CD4/RT1(n), CD8/RT1(n), and CD45RA/RT1(n) populations decreased at long-term follow-up (at post-transplant day 100) to 0.08%, 0.04%, and 0.23%, respectively.

Conclusion: The feasibility and long-term survival of the new hemiface VCA transplantation model was confirmed, donor-specific chimerism and post-transplant tissue changes were evaluated.
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http://dx.doi.org/10.1002/micr.22527DOI Listing
March 2016

The Future of Plastic Surgery: Surgeon's Perspective.

J Craniofac Surg 2015 Nov;26(8):e708-13

*Department of Plastic and Reconstructive Surgery, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul †Department of Plastic and Reconstructive Surgery, Gulhane Military Medical Academy, Ankara, Turkey.

Since the days of Sushruta, innovation has shaped the history of plastic surgery. Plastic surgeons have always been known as innovators or close followers of innovations. With this descriptive international survey study, the authors aimed to evaluate the future of plastic surgeons by analyzing how plastic surgery and plastic surgeons will be affected by new trends in medicine. Aesthetic surgery is the main subclass of plastic surgery thought to be the one that will change the most in the future. Stem cell therapy is considered by plastic surgeons to be the most likely "game changer." Along with changes in surgery, plastic surgeons also expect changes in plastic surgery education. The most approved assumption for the future of plastic surgery is, "The number of cosmetic nonsurgical procedures will increase in the future." If surgeons want to have better outcomes in their practice, they must at least be open minded for innovations if they do not become innovators themselves. Besides the individual effort of each surgeon, international and local plastic surgery associations should develop new strategies to adopt these innovations in surgical practice and education.
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http://dx.doi.org/10.1097/SCS.0000000000002204DOI Listing
November 2015

Response to comments on "Reflectance confocal microscopy as a useful diagnostic tool for monitoring of skin containing vascularized allograft rejection: A Preliminary study on rats".

Microsurgery 2016 Jul 13;36(5):437-438. Epub 2015 Oct 13.

Department of Plastic and Reconstructive Surgery, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey.

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http://dx.doi.org/10.1002/micr.22517DOI Listing
July 2016

Challenging Breast Augmentations: The Influence of Preoperative Anatomical Features on the Final Result.

Aesthet Surg J 2016 Mar 29;36(3):313-20. Epub 2015 Sep 29.

Drs Bayram and Zor are Associate Professors and Dr Ozturk is a Professor, Department of Plastic, Reconstructive, and Aesthetic Surgery, Gulhane Military Medical Academy, Ankara, Turkey. Dr Karagoz is an Associate Professor, Department of Plastic, Reconstructive, and Aesthetic Surgery; GATA Haydarpasha Training Hospital, Istanbul, Turkey. Dr Kulahci is an Associate Professor, Department of Hand Surgery, Gulhane Military Medical Academy, Ankara, Turkey. Dr Afifi is an Assistant Professor, Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Wisconsin, Madison, WI, USA.

Background: Achieving satisfactory results may be difficult in augmentation mammaplasty patients in the presence of breast, chest wall, or vertebral deformities. These deformities have not been classified previously, and the impact of each deformity or combination of deformities has not been defined.

Objectives: The aims of this study are to determine the complicating factors in augmentation mammaplasty, to classify these factors according to their influence on surgical outcome, and to develop an identification system for simplifying the recognition of challenging cases.

Methods: We retrospectively analyzed photographs and records of 100 consecutive patients who underwent augmentation mammaplasty. We observed suboptimal results in 18 cases. Preoperative deformities of the breast, chest wall, and vertebra were recorded in order to determine which factor or factors had complicated the surgeries. Eventually, the relationship between suboptimal surgical results and complicating factors was evaluated.

Results: We observed that some deformities alone caused suboptimal results, whereas others did not. Deformities that caused suboptimal results alone were called major complicating factors, and any others were called minor complicating factors. We observed that suboptimal results were also obtained in patients who had four minor complicating factors. Patients who had suboptimal results because of major or minor complicating factors were considered challenging cases.

Conclusions: In this study, complicating factors for augmentation mammaplasty were defined and classified as major or minor depending on their effect on the surgical outcome. We suggest an identification system that simplifies the recognition of challenging cases in breast augmentation.
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http://dx.doi.org/10.1093/asj/sjv181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127479PMC
March 2016

Challenging Breast Augmentations: The Influence of Preoperative Anatomical Features on the Final Result.

Aesthet Surg J 2016 Mar 29;36(3):313-20. Epub 2015 Sep 29.

Drs Bayram and Zor are Associate Professors and Dr Ozturk is a Professor, Department of Plastic, Reconstructive, and Aesthetic Surgery, Gulhane Military Medical Academy, Ankara, Turkey. Dr Karagoz is an Associate Professor, Department of Plastic, Reconstructive, and Aesthetic Surgery; GATA Haydarpasha Training Hospital, Istanbul, Turkey. Dr Kulahci is an Associate Professor, Department of Hand Surgery, Gulhane Military Medical Academy, Ankara, Turkey. Dr Afifi is an Assistant Professor, Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Wisconsin, Madison, WI, USA.

Background: Achieving satisfactory results may be difficult in augmentation mammaplasty patients in the presence of breast, chest wall, or vertebral deformities. These deformities have not been classified previously, and the impact of each deformity or combination of deformities has not been defined.

Objectives: The aims of this study are to determine the complicating factors in augmentation mammaplasty, to classify these factors according to their influence on surgical outcome, and to develop an identification system for simplifying the recognition of challenging cases.

Methods: We retrospectively analyzed photographs and records of 100 consecutive patients who underwent augmentation mammaplasty. We observed suboptimal results in 18 cases. Preoperative deformities of the breast, chest wall, and vertebra were recorded in order to determine which factor or factors had complicated the surgeries. Eventually, the relationship between suboptimal surgical results and complicating factors was evaluated.

Results: We observed that some deformities alone caused suboptimal results, whereas others did not. Deformities that caused suboptimal results alone were called major complicating factors, and any others were called minor complicating factors. We observed that suboptimal results were also obtained in patients who had four minor complicating factors. Patients who had suboptimal results because of major or minor complicating factors were considered challenging cases.

Conclusions: In this study, complicating factors for augmentation mammaplasty were defined and classified as major or minor depending on their effect on the surgical outcome. We suggest an identification system that simplifies the recognition of challenging cases in breast augmentation.
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http://dx.doi.org/10.1093/asj/sjv181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127479PMC
March 2016

Reflectance confocal microscopy as a useful diagnostic tool for monitoring of skin containing vascularized composite allograft rejection: A preliminary study on rats.

Microsurgery 2016 Feb 11;36(2):144-51. Epub 2015 May 11.

Department of Orthopaedic Surgery, University of Illinois, College of Medicine, Chicago, IL.

Vascularized composite allografts can undergo immune-mediated rejection, and skin biopsies are needed for monitoring of the transplant. However it is an invasive method, and requires processing time and pathological assessment. The purpose of this study is to use a new noninvasive monitoring method of the reflectance confocal microscopy (RCM) to determine severity of the allograft rejection on rats. Five groin flap allotransplantation were performed between 10 male Sprague-Dawley rats. Immunosuppressive therapy with cyclosporine A was given to the recipients during 10 days after surgery and was ended at the 10th postoperative days to allow acute transplant rejection. Following cessation of CsA, concomitant RCM evaluation and skin biopsy was performed every other day from each animal until total rejection of the allograft. Complete rejection of the allograft took nearly about 10 days and 4 or 5 RCM evaluation and skin biopsy was performed from each rat during this period. A total of 17 specimens were evaluated. A scoring system was developed based on the RCM findings. Skin biopsies were evaluated according to the Banff 2007 working classification criteria. RCM evaluation revealed epidermal irregularity and collagen destruction, however mild perivascular inflammation and degeneration of the basal epidermal layer were observed in early and late rejection period respectively with histopathologic evaluation. High correlation was found between the RCM scores and histopathologic grading. The RCM may be the useful tool to reduce the need for skin biopsy for monitoring of the skin containing vascularized composite allograft.
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http://dx.doi.org/10.1002/micr.22419DOI Listing
February 2016

Palmar contracture release with arterialized venous instep flap: An anatomical and clinical study.

J Plast Reconstr Aesthet Surg 2015 Jul 2;68(7):984-9. Epub 2015 Apr 2.

Gulhane Military Medical Academy, Department of Plastic and Reconstructive Surgery, Ankara, Turkey.

Background: Plantar skin has similar histologic features to the palmar area and appears to be the ideal tissue for reconstruction of the palmar region. In this study, an anatomic examination was performed to determine the superficial venous architecture of the instep area, and the use of arterialized venous instep flaps for palmar contracture release was assessed.

Methods: The anatomical study was performed on 12 fresh cadaver feet. The arterialized venous instep flap, including the skin, subcutaneous tissue and superficial venous plexus, was harvested. To determine the venous structure, dissection (n = 6) and injection-corrosion (n = 6) techniques were used. In the clinical study, nine arterialized venous instep flaps were used for palmar contracture release. All flaps were harvested above the deep fascia and included skin, subcutaneous fat, and the superficial venous plexus. At the plantar site of the flap, two or three veins, one of which was used, were dissected for a sufficient length for the arterial anastomosis. The saphenous vein was used for the venous anastomosis.

Results: Dissection and injection-corrosion techniques revealed that the flap had 7-12 and 4-6 veins at its plantar and superior edges, respectively, with numerous anastomoses and interconnections between the veins. The flap dimensions were between 3 × 5 cm and 4 × 6 cm. All flaps survived, with two partial flap necrosis that healed with spontaneous epithelization. No debulking procedures were undertaken and all flaps adapted well to the recipient site.

Conclusions: The arterialized venous instep flap is a good alternative to reconstruct palmar contractures by adding similar tissue that is thin and pliable with minimal donor site morbidity.
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http://dx.doi.org/10.1016/j.bjps.2015.03.024DOI Listing
July 2015

Evaluation of the results of simultaneous open rhinoplasty and Abbe flap for the reconstruction of the secondary bilateral cleft and nasal deformity.

J Plast Reconstr Aesthet Surg 2015 Jun 14;68(6):751-7. Epub 2015 Feb 14.

Gulhane Military Medical Academy, Department of Plastic and Reconstructive Surgery, 06010 Etlik, Ankara, Turkey.

Aims: We aimed to evaluate the results of simultaneous rhinoplasty and Abbe flap for the reconstruction of the secondary bilateral cleft and nasal deformity by means of a newly developed software-based method.

Patients And Methods: A total of 16 patients with the bilateral cleft lip nasal deformity received Abbe flap and simultaneous open rhinoplasty between 2004 and 2010. The mean age of the patients was 21 years, and the average follow-up time was 2.4 years. After the open rhinoplasty procedure, the upper lip was reconstructed with the Abbe flap. Preoperative and postoperative photographs that had been taken laterally were evaluated by using Adobe Photoshop(®) CS4 and Adobe InDesign(®) software. The length of the columella and the relative changes of the most anterior point of the upper lip to the vertical plane tangent to the most anterior point of the lower lip were measured in pixels on standardized preoperative and postoperative images. The differences were calculated and compared as a percentage (%).

Results: There was no flap loss and associated problems. The measurements of columellar length revealed an average increase of 51.8 ± 11.3%, while the relative change of the most anterior point of the upper lip revealed an average increase of 68.6 ± 11.2%.

Conclusion: The results of the treatment modality were successfully evaluated by a newly developed software-based method.
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http://dx.doi.org/10.1016/j.bjps.2015.02.007DOI Listing
June 2015

Morphological and morphometric evaluation of the ilium, fibula, and scapula bones for oral and maxillofacial reconstruction.

Microsurgery 2014 Nov 20;34(8):638-45. Epub 2014 Aug 20.

Department of Oral and Maxillofacial Surgery, Medical Faculty, RWTH Aachen University, Aachen, Germany.

This study aimed to evaluate the osteometric boundaries of the ilium, fibula, and scapula beyond which reconstruction of oromandibular and craniofacial defects, using these free flaps, may not be optimal. Fibula, scapula, and iliac bones were obtained bilaterally from 33 female and 27 male European adult cadavers (n = 60). Adapting classical anthropometric methods to surgical needs by modifying the measuring bone localizations and measurement points, a measuring system of osteometry and morphometry was used, to quantify the usable bone length of the iliac crest, fibula, and lateral border of the scapula and to localize an oval region (OR) in the ilium. The thin, translucent OR of ilium was localized 62.4 ± 5.6 mm posterior to the maximum concavity between the anterior superior (ASIS) and anterior inferior iliac spine and 26.7 ± 6 mm caudal to the intermediate line of the iliac crest. The available iliac crest was measured from ASIS to the posterior superior iliac spine (PSIS) 247.5 ± 12.6 mm, fibula supplied 170.2 ± 19.1 mm harvestable bone, and the lateral border of the scapula 94.3 ± 8.5 mm [Corrected]. The OR influenced the harvestable bone shape and volume of the ilium. Measuring of the localization points of OR, we found that the size of the OR was very variable and that the height of the neomandible reconstructed with iliac crest might alter with aging. Our findings contribute with knowledge of detailed morphometric measurements on commonly used donor bones to the planning strategies of volumetric defects in oral and maxillofacial region by precise osteometric localization method of OR and relativized length measurements.
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http://dx.doi.org/10.1002/micr.22307DOI Listing
November 2014

A new approach to objective evaluation of the success of nasal septum perforation.

Arch Plast Surg 2014 Jul 15;41(4):403-6. Epub 2014 Jul 15.

Deperatment of Plastic and Reconstructive Surgery, Gulhane Military Medical Academy, Ankara, Turkey.

Background: Perforations in the nasal septum (NSP) give rise not only to disintegration of the septum anatomy but also impairment in normal nasal physiology. The successes of these surgical techniques are usually equated to anatomical closure of the perforation. The goal of this study is to evaluate the subjective and objective results of our surgical technique for septal perforation surgery.

Methods: All NSPs in the six patients were closed by inferior turbinate flap. The Nasal Obstruction Symptom Evaluation (NOSE) instrument was used to evaluate the preoperative and postoperative subjective sensation of nasal obstruction. Measurement of preoperative and postoperative nasal airway resistance was performed using active anterior rhinomanometry which is an objective test. Wilcoxson signed rank test and Spearman correlation test were used to analyze correlation between NOSE scores and rhinomanometric measurements.

Results: The full closure of the septal perforations was noted in 100% of patients. The total NOSE score was 14 preoperatively and one postoperatively. The improvement in NOSE scores was statistically significant (P≤0.002). The mean preoperative total resistance (ResT150) value was 0.13 Pa/cm(3)s(-1), which is below the normal range (0.16-0.31 Pa/cm(3)s(-1)), while the mean postoperative ResT150 value was 0.27 Pa/cm(3)s(-1). The correlation between the improvement in NOSE scores and improvements in ResT150 values was statistically significant.

Conclusions: Surgical approaches should aim to solve both the anatomical and physiological problems of NSP. The application of subjective and objective tests in the postoperative period will help surgeons assess the applied techniques.
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http://dx.doi.org/10.5999/aps.2014.41.4.403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113702PMC
July 2014

Mandibular distraction osteogenesis with newly designed electromechanical distractor.

J Craniofac Surg 2014 Jul;25(4):1519-23

From the *Department of Plastic and Reconstructive Surgery, Gulhane Military Medical Academy, Ankara; and †3rd Main Jet Base Medical Center, Konya, Turkey.

Background: The purposes of this study were to design a fully automatic electromechanical distractor for continuous mandibular distraction osteogenesis and to investigate the efficacy of this newly developed distractor on sheep mandible model.

Methods: Five sheep underwent unilateral mandibular osteotomy, and the mechanical component of electromechanical distractor was fixed on both sides of the osteotomy site using pins. After a 5-day latency period, the electromechanical distractor was activated at a rate of 0.30 mm per 8 hours using an electronic control unit. The bone was lengthened for 20 days without any intervention to the electromechanical distractor. The animals were killed on the sixth week of the consolidation period, and 5 distracted mandibles were examined through macroscopic observation and computed tomography. Distracted bone length was measured through computed tomography on sagittal slices.

Results: The device was tolerated by the distraction process without complications in all animals. New callus formation was observed on the distraction gap. Radiologic evaluation showed new callus formation in the distraction gap. New callus length was found to be, in average, 18.28 mm.

Conclusions: In this preliminary study, a newly designed electromechanical distractor was successfully used for mandible distraction, which mainly provided a continuous lengthening during activation period spontaneously without any intervention. We think that the clinical application of this electromechanic distractor may provide patient comfort during distraction. Moreover, electromechanical distractor has the potential for high-resolution movement capacity when compared with annual distraction. The promising results from this prototype are encouraging to further investigations for human applications.
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http://dx.doi.org/10.1097/SCS.0000000000000922DOI Listing
July 2014