Nerve Capping Techniques for Neuroma Management: A Comprehensive Literature Review.

BACKGROUND/AIM OF THE STUDY: Nerve capping is a method of neuroma treatment or prevention that consists of the transplantation of a proximal nerve stump into an autograft or other material cap, after surgical removal of the neuroma or transection of the nerve. The aim was to reduce neuroma formation and symptoms by preventing neuronal adhesions and scar tissue. In this narrative literature review, we summarize the studies that have investigated the effectiveness of nerve capping for neuroma management to provide clarity and update the clinician's knowledge on the topic. METHODS: A systematic electronic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was performed in the PubMed database combining "neuroma," "nerve," "capping," "conduit," "treatment," "management," "wrap," "tube," and "surgery" as search terms. English-language clinical studies on humans and animals that described nerve capping as a treatment/prevention technique for neuromas were then selected based on a full-text article review. The data from the included studies were compiled based on the technique and material used for nerve capping, and technique and outcomes were reviewed. RESULTS: We found 10 applicable human studies from our literature search. Several capping materials were described: epineurium, nerve, muscle, collagen nerve conduit, Neurocap (synthetic copolymer of lactide and caprolactone, which is biocompatible and resorbable), silicone rubber, and collagen. Overall, 146 patients were treated in the clinical studies. After surgery, many patients were completely pain-free or had considerable improvement in pain scores, whereas some patients did not have improvement or were not satisfied after the procedure. Nerve capping was used in 18 preclinical animal studies, using a variety of capping materials including autologous tissues, silicone, and synthetic nanofibers. Preclinical studies demonstrated successful reduction in rates of neuroma formation. CONCLUSIONS: Nerve capping has undergone major advancements since its beginnings and is now a useful option for the treatment or prevention of neuromas. As knowledge of peripheral nerve injuries and neuroma prevention grows, the criterion standard neuroprotective material for enhancement of nerve regeneration can be identified and applied to produce reliable surgical outcomes.

Repair of Congenital Enlarged Parietal Foramina With Porous Polyethylene Implants.

Enlarged biparietal foramina is an autosomal dominant disorder that is caused by a failure of completion of ossification within the parietal bones. Enlarged parietal foramina measuring more than a few millimeters are uncommon. Even though spontaneous regression has been described, closure is rarely complete, and depending on the size of the resulting defect, an unprotected brain is a concern. There are few reports on the surgical management of persistent enlarged biparietal foramina. This is the first report describing our experience with a custom porous polyethylene implant.

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

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 (RT1l + n ) based on the common carotid artery and external jugular vein, and a heterotopic transplantation was performed to the inguinal region of the Lewis (RT1l ) 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.

Application of epineural sheath conduit for restoration of 6-cm long nerve defects in a sheep median nerve model.

BACKGROUND: Due to limited number of studies, we tested feasibility of autologous epineural sheath conduit (ESC) in repair of 6-cm median nerve gaps in a sheep-the large animal model. MATERIALS AND METHODS: Eight ewes, 6-8 months old, 30-35 kg, were divided into three experimental groups: group 1-no defect repair (n = 4 nerves/group), group 2-autograft controls (n = 6 nerves/group), group 3-autologous ESC filled with saline (n = 6 nerves/group). ESC was constructed from a 6-cm long segment of sheep median nerve and tested for expression of laminin B, Glial fibrillary acidic protein (GFAP), S-100 and CD31 using immunofluorescent staining. At 6 months after nerve repair, nerve conduction velocity and somatosensory evoked potentials (SSEP) assessed neurosensory recovery, while histomorphometry tested nerve regeneration. RESULTS: Ex vivo characterization of ESC, before in vivo nerve gap repair, showed high laminin B expression, which supports axonal growth. At 6 months post-repair, structural integrity of ESC was preserved. ESC was well-vascularized and tissue adhesions were comparable to autograft controls. The maximal conduction velocities (29.80 ± 5.85 ms vs. 32.28 ± 6.75 ms; p = .44), action potential amplitudes (32.68 ± 17.44 mV vs. 44.14 ± 23.10 mV; p = .38) and SSEP amplitude values (6.18 ± 5.84 mV vs. 4.68 ± 2.53 mV; p = .28) were comparable between autograft and ESC groups. Presence of regenerating axons was confirmed in the distal segment of ESC at 6 months after repair. CONCLUSION: The feasibility of ESC in restoration of 6-cm long nerve defects in a sheep median nerve model was confirmed by nerve conduction assessments and correlated with axonal regeneration tested by histomorphometry. We confirmed ESC potential in support of regeneration of long nerve defects.

Development of Targeted Muscle Reinnervation Model in Hind Limb Amputated Rats.

BACKGROUND: Targeted muscle reinnervation (TMR) is a novel approach to postamputation neuroma pain; however, this has not been explicitly studied. The purpose of this study was to develop a TMR model in hind limb amputated rats. METHODS: Ten hind limbs from 5 Sprague Dawley cadaver rats were used. Sciatic nerve, main branches of the sciatic nerve (common peroneal, tibial, sural), motor branches from the sciatic nerve to the biceps femoris and cauda femoris, gluteal nerve and its motor branches to the semimembranosus, and biceps femoris and femoral nerve were dissected to look for consistent nerve anatomy that can be used for TMR in the rat hind limb amputation model. Transfemoral amputation was performed and two types of coaptations were made: common peroneal nerve to motor branch to biceps femoris and tibial nerve to motor branch to semimembranosus. RESULTS: The total surgical time for the dissection, amputation, and coaptation of nerves was ∼90 minutes. A total of 100 nerves were dissected in 10 rat hind limbs. Anatomical dissections were straightforward to perform. Anatomy of the dissected nerves was consistent. Hind limb amputations were performed without damaging the target muscles and nerves. Nerve lengths were sufficient for coaptation without any tension. CONCLUSIONS: To the best of our knowledge, this is the first report on TMR model in hind limb amputated rats. This model will allow for mechanical, electromyography (EMG), and histological analysis for future assessment of neuroma prevention.

Application of Epineural Sheath as a Novel Approach for Fat Volume Maintenance.

INTRODUCTION: Various methods have been suggested to improve fat graft survival and decrease graft loss. The exact mechanism of fat graft survival is still unclear, and new strategies are needed to further investigate it. MATERIALS AND METHODS: The efficacy of epineural sheath in fat volume maintenance was tested in rat model. Five experimental groups were created: group 1, fat graft without any coverage; group 2, epineural sheath tube alone; group 3, epineural sheath tube filled with fat graft; group 4, fat graft mixed with minced epineural sheath without any coverage; and group 5, fat graft covered with the epineural sheath patch. All grafts were implanted into the dorsal subcutaneous region and were followed for up to 12 weeks, when samples were harvested for hematoxylin and eosin and immunostaining for vascular endothelial growth factor expression and perilipin evaluation of fat viability. RESULTS: In groups 1 and 4, over 25% of graft loss was observed at first week, over 50% at third week, and 100% at sixth week postimplantation. The weight of fat graft within the epineural sheath tube and the weight of epineural tube (ET) alone were maintained up to 12 weeks postimplantation. The weight of fat graft within the epineural patch was maintained up to 6 weeks, but 50% of weight loss was observed between 6 and 12 weeks. Structure of the epineural sheath tubes and patches was intact, and no leakage of fat graft was observed. Based on hematoxylin and eosin staining, normal structure and integrity of the fat graft within the ET were preserved up to 12 weeks postimplantation. Characteristic adipocyte morphology was confirmed by perilipin staining, showing viable fat cells in groups 3 and 5 at 12 weeks. Increased vascular endothelial growth factor expression was observed in groups 2, 3, 4, and 5. CONCLUSIONS: Both, the ETs and epineural patches maintained 100% and 50% of fat graft weight at 12 weeks postimplantation, respectively. These results were confirmed by histology and immunostaining showing viable adipocytes within the epineural patches (6 weeks) and tubes (12 weeks). These results are encouraging and justify further evaluation of fat volume maintenance in preclinical large animal model in preparation to clinical application.

Epineural Sheath Jacket as a New Surgical Technique for Neuroma Prevention in the Rat Sciatic Nerve Model.

BACKGROUND: Terminal neuromas resulting from severe nerve injuries and traumatic or surgical limb amputations can become a source of pain, and significantly impair patients' quality of life. Recently, the number of patients with peripheral nerve injuries increased due to modern war conflicts, natural disasters, and traffic accidents. This study investigated the efficacy of the epineural sheath jacket (ESJ) as a novel technique for neuroma prevention in the rat sciatic nerve model. METHODS: A 20-mm segment of the right sciatic nerve was excised in 18 Lewis rats, and the animals were divided into 3 experimental groups (n = 6/group): group I-control, nerve stump without protection; group II-muscle burying group, nerve stump buried in the muscle; group III-ESJ group, nerve stump protected by ESJ. The ESJ was created from the excised sciatic nerve and applied as a "cap" over the proximal nerve stump. The presence of neuropathic pain was assessed weekly by pinprick test and Tinel sign, up to 24 weeks postsurgery. At 24 weeks, assessments, such as macroscopic evaluation, retrograde neuronal labeling analysis, histomorphometry, and neural/connective tissue ratio were performed. RESULTS: Epineural sheath jacket significantly reduced neuroma formation, which was associated with decreased Tinel sign (16.7%, P < 0.05) response compared with the nerve stump control. Moreover, ESJ reduced axonal sprouting, bulb-shaped nerve ending formation and perineural adhesions, as confirmed by macroscopic evaluation. Histological evaluation confirmed that nerve stumps protected with the ESJ showed less fibrosis and presented well-organized axonal structure. Neural/connective tissue ratio and retrograde neuronal labeling analysis revealed significantly improved results in the ESJ group compared to the control nerve stump group (P = 0.032 and P = 0.042, respectively). CONCLUSIONS: The protective effect of the ESJ against neuroma formation was confirmed by behavioral and histological analyses, showing outcomes comparable to the muscle burying technique-the criterion standard of neuroma management.

Effects of Rat Bone Marrow-Derived Mesenchymal Stem Cells and Demineralized Bone Matrix on Cranial Bone Healing.

BACKGROUND: Studies in tissue engineering about mesenchymal stem cells (MSCs) provide promising results for bone regeneration. The aim of this study was to evaluate the effects of rat bone marrow-derived MSCs (rMSCs) alone and when combined with demineralized bone matrix (DBM) on critical-sized cranial defects of rats. METHODS: Ten rats were used to obtain allogeneic rMSCs. Forty rats were separated equally into 4 groups. A full-thickness circular bone defect was created in the frontal bone of the rats. Group 1 was an operative control group. In group 2 DBM, in group 3 rMSCs, and in group 4 DBM combined with rMSCs were applied into the defects. Bone regeneration was evaluated by computed tomographic analysis and immunohistochemistry. RESULTS: In radiological evaluation, the percentage of area healed in group 3 at the 12th week was statistically significantly greater than in group 1. In group 3 and group 4, distributed healing patterns were observed more than in group 2 and in group 1. Immunohistochemical evaluation revealed that group 4 had the best osteoinductive potential. Osteoinductive potential of group 3 was similar to group 2 and was better than group 1. CONCLUSIONS: Allogeneic rMSC applications have created a statistically significant radiologic reduction of the bone defect areas at the end of the 12 weeks. The MSC applications have also increased the bone density and changed the healing patterns. Combined use of the DBM and rMSCs has created more osteoinductive responses. This combination can provide better results in craniofacial bone reconstruction.

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 hemifacial and auricular transplantation models: an anatomic study.

INTRODUCTION: Currently, 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 METHODS: Ten 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. RESULTS: The 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. CONCLUSIONS: We 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.

Feasibility of using external jugular vein and its branches as Y- and X-shaped vein grafts for bridging of arterial defects and providing additional arterial sources for free flap applications in rat model.

BACKGROUND: Venous grafting has been widely used in microsurgical training. Different types of vascular grafts have been described in experimental models. In this study we describe for the first time the Y- and X-shaped vein grafts (YVG, XVG) with accompanying drain-out branches as a new tool for the microsurgical training and free flap applications in rats. METHODS: Twelve adult male Lewis rats were used in this study. The dissections were performed to determine the average diameter and harvestable length of vein grafts in eight rats. In four rats vein grafts were applied for bridging of the common carotid artery gap, whereas the drain-out branches were used as the arterial source for single and bilateral free groin flap applications. The venous anastomoses of groin flaps were performed in end-to-end fashion to the external jugular vein and its branches. The patency of anastomoses was checked 72 hours after repair. RESULTS: The average length of the harvestable vein branches ranged between 5.2 to 11.8 mm. The average surgery time for repair of the arterial gap with the vein grafts was 40 minutes. The ischemia time for single and bilateral groin flap transfer using YVG and XVG was 30 and 70 minutes, respectively. The patency of the interpositional vein graft was 100%. Flap survival rates were 50%. CONCLUSIONS: These vein grafts can be used as an alternative technique for reconstruction of tissue defects that require arterial gap repair with single or multiple free flap applications and also as a new microsurgical training model.

Partial fingertip necrosis following a digital surgical procedure in a patient with primary Raynaud's phenomenon.

Raynaud's phenomenon is a common clinical disorder consisting of recurrent, long-lasting and episodic vasospasm of the fingers and toes often associated with exposure to cold. In this article, we present a case of partial fingertip necrosis following digital surgical procedure in a patient with primary Raynaud's phenomenon.

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

INTRODUCTION: Vascularized 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 METHODS: Ten 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. RESULTS: An 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. CONCLUSIONS: To 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.

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.