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Cataract is a very rare complication of burn injuries in which the eye is not directly marked. A unilateral cataract presented some 85 days after a burn injury to a 21-year-old soldier. The cataract was treated surgically with excellent return of vision. [ABSTRACT FROM AUTHOR]

Abstract: The decision-making process for lower limb replantation involves several critical factors, such as age, comorbidities, ischemia time, type of injury, and psychosocial considerations. Advances in microsurgical techniques have led to a greater focus on enhancing functionality through limb salvage. To improve functional outcomes, it is essential to gain a better understanding of the current challenges in reconstruction and address them in future cases. Objective functional analysis of lower extremity replantation cases holds the potential to guide us in this endeavor. In this report, we present a lower limb replantation case with a 10-year follow-up, including objective functional evaluation with gait analysis., Competing Interests: Conflicts of interest and sources of funding: None declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The field of vascularized composite allotransplantation (VCA) is the new frontier of solid organ transplantation (SOT). VCA spans life-enhancing/life-changing procedures such as upper extremity, craniofacial (including eye), laryngeal, tracheal, abdominal wall, penis, and lower extremity transplants. VCAs such as uterus transplants are life giving unlike any other SOT. Of all VCAs that have shown successful intermediate- to long-term graft survival with functional and immunologic outcomes, lower extremity VCAs have remained largely underexplored. Lower extremity transplantation (LET) can offer patients with improved function compared to the use of conventional prostheses, reducing concerns of phantom limb pain and stump complications, and offer an option for eligible amputees that either fail prosthetic rehabilitation or do not adapt to prosthetics. Nevertheless, these benefits must be carefully weighed against the risks of VCA, which are not trivial, including the adverse effects of lifelong immunosuppression, extremely challenging perioperative care, and delayed nerve regeneration. There have been 5 lower extremity transplants to date, ranging from unilateral or bilateral to quadrimembral, progressively increasing in risk that resulted in fatalities in 3 of the 5 cases, emphasizing the inherent risks. The advantages of LET over prosthetics must be carefully weighed, demanding rigorous candidate selection for optimal outcomes., Competing Interests: Conflicts of interest and sources of funding: Authors have no conflict of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gunshot wounds of the hand are challenging, as these injuries include bones, tendons neurovascular structures, and soft tissue. The osteocutaneous fibula flap has shown to be an excellent option for treating the composite defects, including bone and soft tissue. In this study, reconstructions of gunshot injuries of the metacarpal bones with a fibular flap are presented., Methods: Six patients with gunshot injuries to the hand were treated with free fibula flap. All patients had composite defects reconstructed with osteocutaneous fibula flap. Because of the size mismatch between fibula and metacarpal bone, a longitudinally split fibula was used in 2 patients. In 1 patient, the flap was used in a double-barrel fashion to reconstruct 2 metacarpal bone losses. Tendon repairs were performed either primarily or with tendon graft. All patients received hand rehabilitation. Hand function of the patients was evaluated by grip and pinch strength tests and Jebsen hand function test., Results: All flaps survived with no major postoperative complications. The mean follow-up period was 18 months. Web releasing and an arthrodesis procedure was performed in 1 patient, and tenolysis was performed in 2 others. All flaps adapted well to the recipient area. With respect to routine daily activities, overall hand function measured by grip and pinch strength tests and Jebsen hand function test was considered satisfactory in all patients., Conclusions: The fibular flap is a good alternative for reconstruction of the injured hand with composite defects, including metacarpal bone and soft tissue. It can be used longitudinally or transversely. Osteotomies can be performed to obtain split fibular flap or double-barrel fibular flap according to the bone defect., Competing Interests: Disclosures: The authors disclose no financial or other conflicts of interest., (© 2023 HMP Global. All Rights Reserved. Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of ePlasty or HMP Global, their employees, and affiliates.)

Purpose of Review: Vascularized composite allotransplantation (VCA) has become a clinical reality in the past two decades. However, its routine clinical applications are limited by the risk of acute rejection, and the side effects of the lifelong immunosuppression. Therefore, there is a need for new protocols to induce tolerance and extend VCA survival. Cell- based therapies have emerged as an attractive strategy for tolerance induction in VCA. This manuscript reviews the current strategies and applications of cell-based therapies for tolerance induction in VCA., Recent Findings: Cellular therapies, including the application of bone marrow cells (BMC), mesenchymal stem cells (MSC), adipose stem cells, regulatory T cells (Treg) cells, dendritic cells and donor recipient chimeric cells (DRCC) show promising potential as a strategy to induce tolerance in VCA. Ongoing basic science research aims to provide insights into the mechanisms of action, homing, functional specialization and standardization of these cellular therapies. Additionally, translational preclinical and clinical studies are underway, showing encouraging outcomes., Summary: Cellular therapies hold great potential and are supported by preclinical studies and clinical trials demonstrating safety and efficacy. However, further research is needed to develop novel cell-based immunosuppressive protocol for VCA., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The time between procurement and transplantation of composite tissues, especially regarding the limited donor pool, is a challenge effecting the outcomes of the transplantation. Current preservation techniques mainly include either cold preservation with a solution or machine perfusion using blood or certain oxygen-carrying solutions. However, none enables preservation beyond 24 h. Increasing this time to several days will provide better usage of the donor pool, safer transplantation of VCA with significant muscle content, and gives time to stabilize a patient before long surgical procedures. Herein, we described a novel strategy of xenopreservation (preservation via xenotransplantation) to preserve composite tissues for 7 days, followed by staged transplantation., Materials and Methods: We used two concordant species, female Sprague Dawley rats (n = 10) and female CF-1 mice (n = 10) in this study. Four of pair of animals are used for anatomical study. The groin flap of the rat was used as a xenograft and xenotransplanted to the neck area of the carrier mouse. Cyclosporine (CsA) was administered used as immunosuppressant. After 7 days of preservation on the mouse neck, xenotransplanted groin flap (called xenopreserved flap) was re-harvested, skin and vessels samples were collected for histopathological evaluation, and the xenopreserved flap was transplanted to the donor rat's opposite groin area. Anastomoses were performed between the flap's pedicle and the femoral vessels. Clinical observation regarding inflammation and tissue perfusion of the xenopreserved flap was monitored daily. Fifteen days after the second surgical procedure, the rats were euthanized, and skin and vessel samples were collected. Histologic evaluation, including inflammatory cell numbers, was performed. Wilcoxon test was used to compare the changes in inflammation severity and p < .05 was set for statistical significance., Results: All xenopreserved groin flaps except one survived. Mean lymphocyte count before the second operation (at the end of the xenopreservation procedure) was 20,22 ± 0.44 and reduced to 13,14 ± 0.47 at the end of 15 days, and the difference was statistically significant (p < .05)., Conclusion: This proof-of-concept study with preliminary results showed that xenotransplantation might be a novel strategy for preservation of VCA for a certain period of time. However, additional translational studies are needed to modulate the tissue changes following xenopreservation., (© 2023 The Authors. Microsurgery published by Wiley Periodicals LLC.)

Abstract: The skeletal integrity of the foot is as important as the soft tissue coverage of the foot. In this article, we present reconstruction of arches of foot with free fibula flap. Three patients with composite foot defects underwent reconstruction a with vascularized fibula flap. Free fibula flap was used to reconstruct the transverse arch in 2 cases and longitudinal arch in 1 case. The mean follow-up period was 3.2 years. Functional outcome was evaluated with 3-dimensional motion analyses at 12 months postoperatively. No early or late complications were encountered, and all patients were satisfied with both cosmetic appearance and functional aspects of their foot. Fibular bone showed a very healthy course without any fracture, resorption, extrusion, or migration. Three-dimensional motion analyses revealed acceptable gait capability in all cases showing successful restoration of the foot arches. As a conclusion, osteocutaneous free fibula flap can provide functional and durable reconstruction of longitudinal and transverse arches of the foot, especially if preservation of the length or the width of the foot is desired., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Despite long-term immunosuppression, organ transplant recipients face the risk of immune rejection and graft loss. Tacrolimus (TAC, FK506, Prograf ® ) is an FDA-approved keystone immunosuppressant for preventing transplant rejection. However, it undergoes extensive first-pass metabolism and has a narrow therapeutic window, which leads to erratic bioavailability and toxicity. Local delivery of TAC directly into the graft, instead of systemic delivery, can improve safety, efficacy, and tolerability. Macrophages have emerged as promising therapeutic targets as their increased levels correlate with an increased risk of organ rejection and a poor prognosis post-transplantation. Here, we present a locally injectable drug delivery platform for macrophages, where TAC is incorporated into a colloidally stable nanoemulsion and then formulated as a reversibly thermoresponsive, pluronic-based nanoemulgel (NEG). This novel formulation is designed to undergo a sol-to-gel transition at physiological temperature to sustain TAC release in situ at the site of local application. We also show that TAC-NEG mitigates the release of proinflammatory cytokines and nitric oxide from lipopolysaccharide (LPS)-activated macrophages. To the best of our knowledge, this is the first TAC-loaded nanoemulgel with demonstrated anti-inflammatory effects on macrophages in vitro.

Introduction: Vascularized composite allotransplantation (VCA), with nerve repair/coaptation (NR) and tacrolimus (TAC) immunosuppressive therapy, is used to repair devastating traumatic injuries but is often complicated by inflammation spanning multiple tissues. We identified the parallel upregulation of transcriptional pathways involving chemokine signaling, T-cell receptor signaling, Th17, Th1, and Th2 pathways in skin and nerve tissue in complete VCA rejection compared to baseline in 7 human hand transplants and defined increasing complexity of protein-level dynamic networks involving chemokine, Th1, and Th17 pathways as a function of rejection severity in 5 of these patients. We next hypothesized that neural mechanisms may regulate the complex spatiotemporal evolution of rejection-associated inflammation post-VCA., Methods: For mechanistic and ethical reasons, protein-level inflammatory mediators in tissues from Lewis rats (8 per group) receiving either syngeneic (Lewis) or allogeneic (Brown-Norway) orthotopic hind limb transplants in combination with TAC, with and without sciatic NR, were compared to human hand transplant samples using computational methods., Results: In cross-correlation analyses of these mediators, VCA tissues from human hand transplants (which included NR) were most similar to those from rats undergoing VCA + NR. Based on dynamic hypergraph analyses, NR following either syngeneic or allogeneic transplantation in rats was associated with greater trans-compartmental localization of early inflammatory mediators vs. no-NR, and impaired downregulation of mediators including IL-17A at later times., Discussion: Thus, NR, while considered necessary for restoring graft function, may also result in dysregulated and mis-compartmentalized inflammation post-VCA and therefore necessitate mitigation strategies. Our novel computational pipeline may also yield translational, spatiotemporal insights in other contexts., Competing Interests: YV is a co-founder of, and stakeholder in, Immunetrics, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shah, Aral, Zamora, Gharpure, El-Dehaibi, Zor, Kulahci, Karagoz, Barclay, Yin, Breidenbach, Tuder, Gorantla and Vodovotz.)

The use of autografted nerve in surgical repair of peripheral nerve injuries (PNI) is severely limited due to donor site morbidity and restricted tissue availability. As an alternative, synthetic nerve guidance channels (NGCs) are available on the market for surgical nerve repair, but they fail to promote nerve regeneration across larger critical gap nerve injuries. Therefore, such injuries remain unaddressed, result in poor healing outcomes and are a limiting factor in limb reconstruction and transplantation. On the other hand, a myriad of advanced biomaterial strategies to address critical nerve injuries are proposed in preclinical literature but only few of those have found their way into clinical practice. The design of synthetic nerve grafts should follow rational criteria and make use of a combination of bioinstructive cues to actively promote nerve regeneration. To identify the most promising NGC designs for translation into applicable products, thorough mode of action studies, standardized readouts and validation in large animals are needed. We identify design criteria for NGC fabrication according to the current state of research, give a broad overview of bioactive and functionalized biomaterials and highlight emerging composite implant strategies using therapeutic cells, soluble factors, structural features and intrinsically conductive substrates. Finally, we discuss translational progress in bioartificial conduits for nerve repair from the surgeon's perspective and give an outlook toward future challenges in the field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sanchez Rezza, Kulahci, Gorantla, Zor and Drzeniek.)

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 l + n ) based on the common carotid artery and external jugular vein, and a heterotopic transplantation was performed to the inguinal region of the Lewis (RT1 l ) 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., (© 2020 Wiley Periodicals, Inc.)

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. Methods : 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. In vivo whole body NIRF imaging and mechanical hypersensitivity assays were performed sequentially and ex vivo NIRF imaging and immunohistopathology of foot pad tissues were performed at the end point of 40 days. Results : 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. Conclusions : 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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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.

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.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.

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.

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.

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., (© 2016 Wiley Periodicals, Inc.)

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: There are no conflicts of interest.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

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., (© 2016 Wiley Periodicals, Inc.)

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.

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., (© 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

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., (© 2015 Wiley Periodicals, Inc.)

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.

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.

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.