Implantable, Bioresorbable Radio Frequency Resonant Circuits for Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is widely used in clinical care and medical research. The signal-to-noise ratio (SNR) in the measurement affects parameters that determine the diagnostic value of the image, such as the spatial resolution, contrast, and scan time. Surgically implanted radiofrequency coils can increase SNR of subsequent MRI studies of adjacent tissues. The resulting benefits in SNR are, however, balanced by significant risks associated with surgically removing these coils or with leaving them in place permanently. As an alternative, here the authors report classes of implantable inductor-capacitor circuits made entirely of bioresorbable organic and inorganic materials. Engineering choices for the designs of an inductor and a capacitor provide the ability to select the resonant frequency of the devices to meet MRI specifications (e.g., 200 MHz at 4.7 T MRI). Such devices enhance the SNR and improve the associated imaging capabilities. These simple, small bioelectronic systems function over clinically relevant time frames (up to 1 month) at physiological conditions and then disappear completely by natural mechanisms of bioresorption, thereby eliminating the need for surgical extraction. Imaging demonstrations in a nerve phantom and a human cadaver suggest that this technology has broad potential for post-surgical monitoring/evaluation of recovery processes.

Comparison of surgical techniques used for prevention of neuroma in order to make more clear the role of the epineurium. An experimental study.

AIM: Several studies have been conducted for the prevention of neuroma and recently published experimental studies include interventions on epineurium. The techniques which include interventions on epinerium were compared to reveal the role of epinurium in neuroma prevention. MATERIAL E METHODS: 55 Sprague-Dawley rats were divided into five groups. Two of the groups were negative and positive controls. The proximal nerve stump was left "free" in the negative control group, while the stump was implanted in a muscle pocket in the positive control group following sciatic nerve transection. Experimental groups include epineural ligation, epineural stripping and epineural capping procedures. Follow-up period was six months. After sacrification of the rats, histopathologic and immunohistochemical examinations were conducted as well as real-time PCR studies for the assessment. Statistical analysis was performed. RESULTS: The most prominent neuroma formation was detected in the epineural capping group, while the least neuroma was observed in the epineural ligation group. DISCUSSION: Statistically significant differences were obtained when the three experimental groups were compared with both control groups. Interestingly there was no significant difference in-between the control groups in terms of preventing neuroma formation. CONCLUSION: epineural ligation group were found to be superior to both control groups as well as experimental groups. Use of epineural capping was concluded to increase the formation of neuroma rather than preventing. Intramuscular implantation of nerve stump had no preventive effect on neuroma formation. KEY WORDS: Capping, Epineurium, Ligation, Neuroma, Stripping.

Peripheral nerve repair is associated with augmented cross-tissue inflammation following vascularized composite allotransplantation.

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.

Comparison of surgical techniques used for prevention of neuroma in order to make more clear of the role of the epineurium: an experimental study.

AIM: Several studies have been conducted for the prevention of neuroma and recently published experimental studies include interventions on epineurium. The techniques which include interventions on epinerium were compared to reveal the role of epinurium in neuroma prevention. MATERIAL E METHODS: 55 Sprague-Dawley rats were divided into five groups. Two of the groups were negative and positive controls. The proximal nerve stump was left "free" in the negative control group, while the stump was implanted in a muscle pocket in the positive control group following sciatic nerve transection. Experimental groups include epineural ligation, epineural stripping and epineural capping procedures. Follow-up period was six months. After sacrification of the rats, histopathologic and immunohistochemical examinations were conducted as well as real-time PCR studies for the assessment. Statistical analysis was performed. RESULTS: The most prominent neuroma formation was detected in the epineural capping group, while the least neuroma was observed in the epineural ligation group. DISCUSSION: Statistically significant differences were obtained when the three experimental groups were compared with both control groups. Interestingly there was no significant difference in-between the control groups in terms of preventing neuroma formation. CONCLUSION: epineural ligation group were found to be superior to both control groups as well as experimental groups. Use of epineural capping was concluded to increase the formation of neuroma rather than preventing. Intramuscular implantation of nerve stump had no preventive effect on neuroma formation. KEY WORDS: Capping, Epineurium, Ligation, Neuroma, Stripping.

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

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.

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.

Immunological considerations and concerns as pertinent to whole eye transplantation.

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.

Adipogenesis for soft tissue reconstruction.

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.

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

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 ±â€¯5.8 min. Average ischemia time was 26.0 ±â€¯4.2 min. MRI revealed loss of globe volume by 36.0 ±â€¯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.

Treatment of partial-thickness burns with a tulle-gras dressing and a hydrophilic polyurethane membrane: a comparative study.

OBJECTIVE: The purpose of this revisited study was to compare the clinical efficacy and long-term scar evaluation of a hydrophilic polyurethane membrane (HPM), Omiderm (Omikron Scientific Ltd., Rehovot, Israel) and an antimicrobial tulle-gras dressing (TGD), Bactigras (Smith & Nephew) in the management of partial-thickness burns. METHOD: Patients with partial-thickness burns were enrolled in this prospective study. Burn areas were divided into two areas and both dressings were applied to each field at the same time. Time to full re-epithelialisation and scar evaluation were compared using the Vancouver Scar Scale (VSS). RESULTS: A total of 21 patients, mean age 36.8 years, with 22 burns areas participated. The results showed that there is no statistically significant difference in terms of full epithelialisation time in the application of either dressing (p>0.05). However, with deep dermal burns, the HPM provided slightly faster epithelialisation (p>0.05). A VSS assessment showed no statistically significant difference (p>0.05) between applying either dressing materials. CONCLUSION: This study indicated that both dressings had the same effectiveness in treatment of partial-thickness burn wounds. However, the use of the HPM, especially in deep dermal second-degree burns, should be one of the first-line clinical choices, based on the advantages discerned by this study.

Three-layer primary closure of the bipedicled TRAM flap donor site for unilateralbreast reconstruction: a 15-year experience with 124 consecutive patients.

BACKGROUND/AIM: The pedicled transverse rectus abdominis myocutaneous (TRAM) flap remains widely used as a breast reconstruction technique. The bipedicled TRAM flap is not as preferable as it was formerly, mainly because of its donor site complications. However, in a number of situations, a bipedicled TRAM flap may be the only alternative. Therefore, a three-layer primary closure technique used with bipedicled TRAM flap breast reconstructions that can avoid donor site complications without using a mesh is presented. MATERIALS AND METHODS: A retrospective study was performed that included patients who underwent bipedicled TRAM flap breast reconstruction with the three-layer primary closure technique. Between 2000 and 2015, 124 breast reconstruction patients were reviewed for donor site morbidity. RESULTS: During the 15-year study period, 106 patients had conventional bipedicled TRAM flaps and 18 had bipedicled TRAM flaps with a surgical delay procedure. For all groups, none of the patients developed abdominal wall hernia, but three patients had bulging. Partial flap loss was the most common flap complication, present in 6 flaps (4.8%). CONCLUSION: The suturing technique studied provided abdominal wall closure without the use of a mesh even when utilizing a bilateral pedicle with very low complication rates.

Pre-expanded Thoracodorsal Artery Perforator Flap.

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.

Comparison of Neurosensory Assessment Methods in Plastic Surgery.

Sensory assessment of the skin is essential to document the function of the sensory fibers of the tested nerves. The Semmes-Weinstein monofilaments, disk-criminator, electrodiagnostic testing, and Pressure-Specified Sensory Device (PSSD) have been currently used to assess sensory function of peripheral nerves. None of these methods is optimal because of different drawbacks; however, an increasing number of articles, which recognize the reliability of PSSD, have been published during the last decade. In this review, following a short overview on basic physiology and assessment methods of the skin sensory receptors, we compared the sensory assessment methods and summarized the applications of the PSSD in the field of different clinical areas, mainly peripheral neuropathies, breast, and flap surgery.

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

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.

A new total hemiface allotransplantation model in rats.

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.

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

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.

Effect of Allogeneic Platelet Lysate and Cyanoacrylate Tissue Glue on the Fibrovascularization of the Porous Polyethylene Implant.

Because of limited autogenous tissue sources, donor site morbidity, and difficulty of shaping the autologous tissue, surgeons often need to use alloplastic frameworks in reconstruction of 3-dimensional tissue defects. Synthetic porous polyethylene (PP) implant is widely used in plastic surgery for 3-dimensional reconstruction of the lost or highly deformed tissues. One of the main factors of PP implant exposure is delayed fibrovascular ingrowth. In the present study, the authors investigated the effect allogeneic plateletlysate (PL) and cyanoacrylate tissue glue (CTG) (2-octyl cyanoacrylate) on the fibrovascularization of the PP implant.Twenty adult female Wistar rats were divided into 4 groups equally, according to the different surgical techniques and implanted materials used. Only PP implant was implanted subcutaneously through a skin incision on the chest wall skin of the rats in the control group; however, CTG was applied with PP implant in the cyanoacrylate group, PL was applied with PP implant in the platelet group, CTG and platelet was applied together with PP implant in the combination group. All of the implants in each group were histologically assessed at postoperative second week. Determination of the collagen density in the tissues, inflammation, and necrosis and vascularization status was assessed semiquantitatively.A denser collagen structure, low inflammation, and necrosis were found in PL groups. There was, however, a significant decrease in vascular density with PL-treated groups. PL treatment may have a potential to reduce complications related to PP implants.