Safak Uygur

Techniques and materials for enhancement of peripheral nerve regeneration: A literature review

Peripheral nerve surgery performed under unfavorable conditions results in increased scar formation and suboptimal clinical outcomes. Providing the operated nerve with a protective barrier, reduces fibrosis and adhesion formation and may lead to improved outcomes. The ideal coverage material should prevent scar and adhesion formation, and maintain nerve gliding during motion. Nerve protection using autologous tissues has shown good results, but shortcomings include donor site morbidity and limited availability. Various types of methods and materials have been used to protect nerves. There are both advantages and disadvantages associated with the various materials and techniques. In this report we summarize currently used protective materials applied for nerve coverage under various surgical conditions.

A new vascularized cervical lymph node transplantation model: an anatomic study in rats.

IntroductionVascularized lymph node transfer is of high interest for the treatment of lymphedema. Currently, there are few experimental small animal models of vascularized lymph node transplantation. In this article, our aim was to describe a new vascularized cervical lymph node transplantation model in rats. Materials and MethodsTen male Sprague-Dawley rats weighing 200 to 250 g were used in this study. The anatomic features of the neck lymph nodes in rats were explored. Anatomic neck dissections were performed, and lymph node flaps were harvested. The common carotid artery and the jugular vein were used as the vascular pedicles of the lymph node flap. Methylene blue dye was injected into the arterial pedicle. Lymph nodes were identified, and their structure was confirmed by histological evaluation. Laser-assisted indocyanine green angiography was used to confirm perfusion of the lymph node flap. ResultsAn adequate perfusion was observed in the lymph node flap. The dye disseminated evenly within the lymph nodes, indicating that the flap had a well-established vascular network and an adequate blood supply. Macroscopically, perfusion of 5 to 6 lymph nodes was observed. Histological examination of tissue samples confirmed well-defined lymph nodes. After indocyanine green administration, fluorescence was observed throughout the lymph node flap and within the venous pedicle of the flap. ConclusionsTo the best of our knowledge, this is the first report describing vascularized lymph node flap in the head and neck region of a rat. Our lymph node flap preparation technique confirmed the presence of 5 to 6 lymph nodes within the flap. The presented vascularized lymph node flap can be applied to transplantation studies, lymphedema studies, and to studies on immunological mechanism of tolerance and rejection.

Repair of the peripheral nerve gap with epineural sheath conduit to prevent muscle denervation atrophy in the diabetic rat model

UNLABELLED Muscle denervation atrophy is a result of lower motor neuron injury, thus an early restitution of muscle stimulation is essential in prevention of atrophic changes. THE AIM OF THE STUDY To evaluate the new application of naturally occurring epineural sheath conduit in repair of the peripheral nerve gap to prevent development of muscle denervation atrophy. MATERIAL AND METHODS We used the model of 20 mm sciatic nerve gap, resulting in denervation atrophy of the gastrocnemius muscle in the diabetic rats (DM type 2, n=42, Zucker Diabetic Fatty strain). We applied the epineural sheath conduit created from the autologous sciatic nerve for gap repair. Muscle atrophy was assessed with the Gastrocnemius Muscle Index (GMI) and microscopic muscle morphometry (mean fiber area) at 6 and 12 postoperative week. Muscle regeneration in the experimental group was compared to the gold-standard technique of autologous nerve grafting for the repair of created nerve gap. RESULTS The GMI evaluation revealed comparable muscle mass restoration in groups with nerve repair using both epineural sheath and standard autologous nerve grafting (reaching 28 and 35% of contralateral muscle mass at 12 postoperative week, respectively, p=0.1), and significantly better restoration when compared to the negative control group (no repair, 20%, p<0.01). Micromorphometry confirmed significantly larger area of the regenerated muscle fibers in groups with both nerve grafting and epineural sheath conduit repair (reaching for both ca. 42% of the non-operated side), when compared to severe atrophic outcome when no nerve repair was performed (14% of the control fiber area, p<0.0001). The effectiveness of epineural conduit technique in muscle mass restoration was observed between 6 and 12 weeks after nerve repair--when gastrocnemius muscle mass increased by 12%. CONCLUSIONS Peripheral nerve gap repair with naturally occurring epineural sheath conduit is effective in prevention of muscle denervation atrophy. This method is applicable in diabetic model conditions, showing results of regeneration which are comparable to the autologous nerve graft repair.

Vascularized axillary lymph node transfer: A novel model in the rat.

Vascularized lymph node transfer (VLNT) is a promising microvascular free flap technique for the surgical treatment of lymphedema. To date, few experimental animal models for VLNT have been described and the viability of lymph nodes after the transfer tested. We aimed to evaluate the feasibility of axillary VLNT in the rat. Lymph node containing flaps were harvested from the axillary region in 10 Lewis rats based on the axillary vessels. Flaps were transferred to the ipsilateral groin and end‐to‐side microanastomosis was performed to the femoral vessels using 10‐0 sutures. Indocyanine green (ICG) angiography was used to confirm flap perfusion. On postoperative day 7, flaps were elevated to assess their structure and vessel patency. Hematoxylin and eosin staining was used to confirm the presence and survival of lymph nodes. All animals tolerated the procedure well. Immediate post‐procedure ICG angiography confirmed flap perfusion. No signs of ischemia or necrosis were observed in donor extremities. At postoperative day 7, all flaps remained viable with patent vascular pedicles. Gross examination and histology confirmed the presence of 3.6 ± 0.5 lymph nodes in each flap without any signs of necrosis. This study showed that the transfer of axillary lymph nodes based on the axillary vessels is feasible. The flap can be used without the need for donor animals and it contains a consistent number of lymph nodes. This reliable VLNT can be further utilized in studies involving lymphedema, transplantation, and induction of immunologic tolerance.

Sheep as a Large Animal Model for Nerve Regeneration Studies

Despite advances in surgical management and microsurgery, the functional recovery after restoration of large peripheral nerve defects is still unsatisfactory. Currently reconstruction with autologous nerve grafting is the gold standard treatment with suboptimal outcomes. In recent decades, potential peripheral nerve repair treatments and therapies such as using synthetic and natural biomaterials to bridge the segmental nerve defects, application of stem cell based therapies and tissue engineering, are being increasingly used to improve nerve regeneration and to obtain satisfactory functional outcomes. Large animals provide valuable translational nerve models prior to introduction of the promising therapeutic approaches into the human clinical trials. In this chapter, the feasibility of using sheep as a large animal model for nerve regeneration studies and our experience with reconstruction of median nerve gap with autologous median nerve graft and autologous epineural sheath based conduit are described.

Peripheral nerve surgery models crush injury and epineural patch

The regeneration of the peripheral nerves after crush injuries are influenced by many factors, including scar tissue formation within and around the nerve and/or adhesions between the nerve and surrounding tissues. Wrapping the crushed nerve with a protective barrier reduces fibrosis, adhesion formation and may improve clinical outcomes. The ideal wrapping material should be able to protect nerve, prevent neuroma, inhibit adhesion, induce a minimal inflammatory reaction and stimulate axonal regeneration. Various types of autologeous, biologic and synthetic materials have been used as a protective barrier. In this chapter we introduce our epineural sheath patch model, briefly describe the harvesting technique and application to crushed nerve segment as a protective barrier.

Sheep hemifacial and auricular transplantation models: an anatomic study.

IntroductionCurrently, only a few large animal models, including swine, dog, and nonhuman primate, are described for composite face transplantation studies and the literature lacks reports on the large animal model of composite auricular transplantation. Large animal models offer better understanding of the immunological mechanisms and major histocompatibility complex characterization and, for this reason, are preferred to the small animal models for the assessment of new immunosuppressive tolerance induction protocols. Thus, the aim of this study was to demonstrate feasibility of dissection and exploration of vascular territories of the hemifacial and auricle transplantation models in the sheep cadavers. Materials and MethodsTen cadaver sheep heads were studied. The vascular territories of the composite hemifacial flap and composite auricle flap were defined by anatomical dissection. Methylene blue staining and laser-assisted indocyanine green angiography using SPY Elite System were used for vascular territories assessment. ResultsThe dissection of cadaver sheep heads confirmed that the hemifacial flap and auricle flap can be raised on the same pedicle consisting of the common carotid artery and jugular vein. An adequate vascular network was observed in the flaps after injection of methylene blue dye via the arterial pedicle. Laser-assisted indocyanine green angiography identified vascular territories of the hemifacial and auricular vascular network. ConclusionsWe described a new hemifacial and an auricular transplantation models in the sheep cadavers and have confirmed presence of the adequate vascular network as demonstrated by the laser-assisted angiography. This study introduces 2 new large animal models into the armamentarium of vascular composite allotransplantation.

Arterial and Venous Microanastomosis Models

There are several animal models and numerous suturing techniques for microsurgical anastomoses. In this chapter we describe a rat model for microvascular training and research. Common techniques including interrupted suture, continuous suture, locking continuous, continuous horizontal mattress, interrupted horizontal mattress with eversion and sleeve are presented. Different patency testing methods are outlined and advantages and drawbacks of each suturing technique are discussed. In this chapter we also present common rat models for arterial and venous bypasses and grafts using the aorta, carotids, iliac, and femoral vessels. Potential research application of each graft is discussed. Finally, different techniques to manage size discrepancies in microvascular anastomosis are summarized.

Vascularized Lymph Node Transplantation Models

Maintenance of the blood supply to the transferred lymph node is important for both the survival and preservation of function. There are different small and large animal models for lymph node transplantation tested in different models. However, in most of these studies lymph nodes were used as free grafts. In this chapter we are presenting experimental small animal models of vascularized lymph node transplantation including vascularized cervical lymph node model, vascularized inguinal lymph node model and vascularized mesenteric lymph node model.

Abstract 90: donor-recipient chimeric cell transplantation as a novel rescue therapy for acute radiation syndrome: a preliminary report.

PurPose: Victims of nuclear disasters present with acute radiation syndrome as a result of exposure to ionizing radiation. Impairment of immune system with subsequent sepsis is the most common cause of mortality. Following high exposure, stem cell transplantation is the only effective treatment but it carries several risks and access to stem cell sources is insufficient in case of extremely high demands. Therefore there is an urgent need to develop new effective therapies of acute radiation syndrome. The aim of this study was to test efficacy of ex-vivo created donor-recipient chimeric cells (DRCC) in reconstitution of bone marrow compartment following total body γ-irradiation (TBI).