Muscle Patch Research Articles

Magnesium lithospermate B enhances the potential of human-induced pluripotent stem cell-derived cardiomyocytes for myocardial repair.

We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model. In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups ( n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro . MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.

Aneurysm Wrapping as an Adjunct of Clipping of a Premature Rupture of the Middle Cerebral Artery Aneurysm

Aneurysms, abnormal dilatations on cerebral arterial walls, pose a significant health concern due to the morbidity and mortality associated with ruptures causing subarachnoid hemorrhage. The risk of rupture is influenced by aneurysm size and location. Surgical clipping is the preferred treatment, especially for middle cerebral artery (MCA) aneurysms, despite recent endovascular advancements. Intraoperative premature rupture poses a critical challenge, requiring swift decision-making and efficient management techniques. We describe a case of an intraoperative premature aneurysm rupture managed with muscular wrapping as an adjunct to microsurgical clipping. The patient, with a history of spontaneous intracerebral hematoma, underwent urgent microsurgical clipping for a left MCA aneurysm. Premature rupture occurred during clipping, necessitating the use of a muscle patch and fibrin glue for wrapping. The wrapping technique, originally developed for unruptured aneurysms, induces fibrotic scar formation, enhancing vascular stability. Cotton, a common wrapping material, elicits chronic inflammation. Autologous tissues and synthetic materials, like muscle, offer alternatives with potential benefits. Factors associated with increased rupture risk include aneurysm location, irregular shape, and prior rupture. Vigilance and preparedness are crucial, especially for high-risk cases. As the availability of computed tomography scans increases, more aneurysm cases are diagnosed, requiring comprehensive patient assessments before interventions. The presented case demonstrates the effectiveness of on-site wrapping in controlling premature rupture. The combined use of muscle patch and fibrin glue postaneurysmal clipping may assist in preventing rebleeding events. Intraoperative ruptures demand careful consideration, and the described wrapping technique provides a valuable option for managing such complications.

Perspective: Timely diagnosis and repair of intraoperative thoracic/lumbar cerebrospinal fluid (CSF) leaks.

Our review of 12 articles for this perspective showed the frequency of intraoperative thoracic and/or lumbar CSF fistulas/dural tears (DT) ranged from 2.6% - 8% for primary surgical procedures. Delayed postoperative CSF leak/DT were also diagnosed in 0.83% (17/2052 patients) to 14.3% (2/14 patients) of patients undergoing thoracic and/or lumbar procedures. Further, the rate of recurrent postoperative CSF leaks/DT varied from 13.3% (2/15 patients) to 33.3% (4/12 patients). Intraoperative, postoperative delayed, and recurrent postoperative traumatic postsurgical thorac CSF leaks/DT can be limited by performing initially sufficient operative decompressions and/or decompressions/fusions (i.e., utilizing adequate open exposures vs. inadequate minimally invasive (MI) approaches). The incidence of CSF leaks/DT can be further reduced by spine surgeons' utilization of operating microscopes, and their avoiding routine attempts at total synovial cyst excision and/or complete resection of hypertrophied/ossified yellow ligament in the presence of significant dural adhesions. Multiple CSF leak/CT repair techniques included; using interrupted, non-resorbable sutures for direct dural repairs (i.e. 7-0 Gore-Tex sutures where the suture is larger than the needle thus plugging needle holes), and adding where needed muscle patch grafts, microfibrillar collagen, the rotation of Multifidus muscle pedicle flaps, fibrin sealants (FS)/fibrin glues (FG), lumbar drains (LD), and/or lumbo-peritoneal (LP) shunts. Intraoperative, postopertive delayed, and/or recurrent postoperative thorac and/or lumbar traumatic surgical CSF leaks can be reduced by choosing to initially perform the appropriately extensive open operative decompressions and/or decompresssions/fusions. It is critical to use an operating microscope, non-resorbable interrupted sutures, and where necessary, muscle patch grafts, microfibrillar collagen, the rotation of Multifidus Muscle Pedicle Flaps, FS/FG, LD, and/or LP shunts.

Engineered muscle from micro-channeled PEG scaffold with magnetic Fe3O4 fixation towards accelerating esophageal muscle repair

Engineered scaffolds are used for repairing damaged esophagus to allow the precise alignment and movement of smooth muscle for peristalsis. However, most of these scaffolds focus solely on inducing cell alignment through directional apparatus, often overlooking the promotion of muscle tissue formation and causing reduced esophageal muscle repair effectiveness. To address this issue, we first introduced aligned nano-ferroferric oxide (Fe3O4) assemblies on a micropatterned poly(ethylene glycol) (PEG) hydrogel to form micro-/nano-stripes. Further modification using a gold coating was found to enhance cellular adhesion, orientation and organization within these micro-/nano-stripes, which consequently prevented excessive adhesion of smooth muscle cells (SMCs) to the thin PEG ridges, thereby effectively confining the cells to the Fe3O4-laid channels. This architectural design promotes the alignment of the cytoskeleton and elongation of actin filaments, leading to the organized formation of muscle bundles and a tendency for SMCs to adopt synthetic phenotypes. Muscle patches are harvested from the micro-/nano-stripes and transplanted into a rat esophageal defect model. In vivo experiments demonstrate the exceptional viability of these muscle patches and their ability to accelerate the regeneration of esophageal tissue. Overall, this study presents an efficient strategy for constructing muscle patches with directional alignment and muscle bundle formation of SMCs, holding significant promise for muscle tissue regeneration.

Complex duodenal fistulae: a surgical nightmare

IntroductionA common feature of external duodenal fistulae is the devastating effect of the duodenal content rich in bile and pancreatic juice on nearby tissues with therapy-resistant local and systemic complications. This study analyzes the results of different management options with emphasis on successful fistula closure rates.MethodsA retrospective single academic center study of adult patients treated for complex duodenal fistulas over a 17-year period with descriptive and univariate analyses was performed.ResultsFifty patients were identified. First line treatment was surgical in 38 (76%) cases and consisted of resuture or resection with anastomosis combined with duodenal decompression and periduodenal drainage in 36 cases, rectus muscle patch, and surgical decompression with T-tube in one each. Fistula closure rate was 29/38 (76%). In 12 cases, the initial management was nonoperative with or without percutaneous drainage. The fistula was closed without surgery in 5/6 patients (1 patient died with persistent fistula). Among the remaining 6 patients eventually operated, fistula closure was achieved in 4 cases. There was no difference in successful fistula closure rates among initially operatively versus nonoperatively managed patients (29/38 vs. 9/12, p = 1.000). However, when considering eventually failed nonoperative management in 7/12 patients, there was a significant difference in the fistula closure rate (29/38 vs. 5/12, p = 0.036). The overall in-hospital mortality rate was 20/50 (40%).ConclusionsSurgical closure combined with duodenal decompression in complex duodenal leaks offers the best chance of successful outcome. In selected cases, nonoperative management can be tried, accepting that some patients may require surgery later.

Endoscopic Repair of Internal Carotid Artery Injury with a Lateral Tongue Muscle Patch Graft: Novel Technique and Literature Review.

Objectives Iatrogenic injury to the internal carotid artery (ICA) is one of the most catastrophic complications of endoscopic sinus and skull base surgery. Previous research has shown that packing with a crushed muscle graft at the injury site can be an effective management technique to control bleeding and prevent the need for ICA sacrifice. Here, we describe a novel and readily available repair donor site-an autologous lateral tongue muscle patch. Design Three representative cases of a successful repair of ICA injuries using a lateral tongue muscle patch are included in this study. The graft measured approximately 2 × 3 cm and was taken from the lateral intrinsic tongue musculature. We describe the harvest of the graft, its advantages, and the details of operative repair. Results The lateral tongue provides a large and readily accessible source of muscle within the surgical field that can be quickly harvested during an endoscopic procedure. For the first case, an expanding parasellar ICA pseudoaneurysm was managed with a tongue muscle patch and nasal packing. In the second case, a cavernous ICA injury was sustained during craniopharyngioma resection. Case three involved an ICA injury during endonasal debridement of invasive fungal rhinosinusitis. None of the patients required embolization or neurovascular stenting. Postoperative angiograms and serial computed tomography angiograms showed complete resolution of the pseudoaneurysm, and the patients continued to do well at least 1 year after repair. Conclusion Lateral tongue muscle graft is an effective and efficient method to manage ICA injuries during endoscopic endonasal surgery. Advantages include the speed of harvest, donor site being readily accessible in the surgical field, and low donor site morbidity. It should be added to the repertoire of possible donor sites for addressing catastrophic sinonasal bleeding.

Engineering a conduction-consistent cardiac patch with graphene oxide modified butterfly wings and human pluripotent stem cell-derived cardiomyocytes.

Engineering a conduction-consistent cardiac patch has direct implications to biomedical research. However, there is difficulty in obtaining and maintaining a system that allows researchers to study physiologically relevant cardiac development, maturation, and drug screening due to the issues around inconsistent contractions of cardiomyocytes. Butterfly wings have special nanostructures arranged in parallel, which could help generate the alignment of cardiomyocytes to better mimic the natural heart tissue structure. Here, we construct a conduction-consistent human cardiac muscle patch by assembling human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on graphene oxide (GO) modified butterfly wings. We also show this system functions as a versatile model to study human cardiomyogenesis by assembling human induced pluripotent stem cell-derived cardiac progenitor cells (hiPSC-CPCs) on the GO modified butterfly wings. The GO modified butterfly wing platform facilitated the parallel orientation of hiPSC-CMs, enhanced relative maturation as well as improved conduction consistency of the cardiomyocytes. In addition, GO modified butterfly wings enhanced the proliferation and maturation characteristics of the hiPSC-CPCs. In accordance with data obtained from RNA-sequencing and gene signatures, assembling hiPSC-CPCs on GO modified butterfly wings stimulated the differentiation of the progenitors into relatively mature hiPSC-CMs. These characteristics and capabilities of GO modified butterfly wings make them an ideal platform for heart research and drug screening.

An Engineered Living Intestinal Muscle Patch Produces Macroscopic Contractions that can Mix and Break Down Artificial Intestinal Contents.

The intestinal muscle layers execute various gut wall movements to achieve controlled propulsion and mixing of intestinal content. Engineering intestinal muscle layers with complex contractile function is critical for developing bioartificial intestinal tissue to treat patients with short bowel syndrome. Here, the first demonstration of a living intestinal muscle patch capable of generating three distinct motility patterns and displaying multiple digesta manipulationsis reported. Assessment of contractility, cellular morphology, and transcriptome profile reveals that successful generation of the contracting muscle patch relies on both biological factors in a serum-free medium and environmental cues from an elastic electrospun gelatin scaffold. By comparing gene-expression patterns among samples, it is shown that biological factors from the medium strongly affect ion-transport activities, while the scaffold unexpectedly regulates cell-cell communication. Analysis of ligandreceptor interactome identifies scaffold-driven changes in intercellular communication, and 78% of the upregulated ligand-receptor interactions are involved in the development and function of enteric neurons. The discoveries highlight the importance of combining biomolecular and biomaterial approaches for tissue engineering. The living intestinal muscle patch represents a pivotal advancement for building functional replacement intestinal tissue. It offers a more physiological model for studying GI motility and for preclinical drug discovery.

Engineering a conduction-consistent cardiac patch with rGO/PLCL electrospun nanofibrous membranes and human iPSC-derived cardiomyocytes.

The healthy human heart has special directional arrangement of cardiomyocytes and a unique electrical conduction system, which is critical for the maintenance of effective contractions. The precise arrangement of cardiomyocytes (CMs) along with conduction consistency between CMs is essential for enhancing the physiological accuracy of in vitro cardiac model systems. Here, we prepared aligned electrospun rGO/PLCL membranes using electrospinning technology to mimic the natural heart structure. The physical, chemical and biocompatible properties of the membranes were rigorously tested. We next assembled human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on electrospun rGO/PLCL membranes in order to construct a myocardial muscle patch. The conduction consistency of cardiomyocytes on the patches were carefully recorded. We found that cells cultivated on the electrospun rGO/PLCL fibers presented with an ordered and arranged structure, excellent mechanical properties, oxidation resistance and effective guidance. The addition of rGO was found to be beneficial for the maturation and synchronous electrical conductivity of hiPSC-CMs within the cardiac patch. This study verified the possibility of using conduction-consistent cardiac patches to enhance drug screening and disease modeling applications. Implementation of such a system could one day lead to in vivo cardiac repair applications.

Cardiac muscle patches containing four types of cardiac cells derived from human pluripotent stem cells improve recovery from cardiac injury in mice.

We have shown that human cardiac muscle patches (hCMPs) containing three different types of cardiac cells-cardiomyocytes (CMs), smooth muscle cells (SMCs), and endothelial cells (ECs), all of which were differentiated from human pluripotent stem cells (hPSCs)-significantly improved cardiac function, infarct size, and hypertrophy in a pig model of myocardial infarction (MI). However, hPSC-derived CMs (hPSC-CMs) are phenotypically immature, which may lead to arrhythmogenic concerns; thus, since hPSC-derived cardiac fibroblasts (hPSC-CFs) appear to enhance the maturity of hPSC-CMs, we compared hCMPs containing hPSC-CMs, -SMCs, -ECs, and -CFs (4TCC-hCMPs) with a second hCMP construct that lacked hPSC-CFs but was otherwise identical [hCMP containing hPSC-CMs, -AECs, and -SMCs (3TCC-hCMPs)]. hCMPs were generated in a fibrin scaffold. MI was induced in severe combined immunodeficiency (SCID) mice through permanent coronary artery (left anterior descending) ligation, followed by treatment with cardiac muscle patches. Animal groups included: MI heart treated with 3TCC-hCMP; with 4TCC-hCMP; MI heart treated with no patch (MI group) and sham group. Cardiac function was evaluated using echocardiography, and cell engraftment rate and infarct size were evaluated histologically at 4 weeks after patch transplantation. The results from experiments in cultured hCMPs demonstrate that the inclusion of cardiac fibroblast in 4TCC-hCMPs had (i) better organized sarcomeres; (ii) abundant structural, metabolic, and ion-channel markers of CM maturation; and (iii) greater conduction velocities (31 ± 3.23 cm/s, P < 0.005) and action-potential durations (APD50 = 365 ms ± 2.649, P < 0.0001; APD = 408 ms ± 2.757, P < 0.0001) than those (velocity and APD time) in 3TCC-hCMPs. Furthermore, 4TCC-hCMPs transplantation resulted in better cardiac function [ejection fraction (EF) = 49.18% ± 0.86, P < 0.05], reduced infarct size (22.72% ± 0.98, P < 0.05), and better engraftment (15.99% ± 1.56, P < 0.05) when compared with 3TCC-hCMPs (EF = 41.55 ± 0.92%, infarct size = 39.23 ± 4.28%, and engraftment = 8.56 ± 1.79%, respectively). Collectively, these observations suggest that the inclusion of hPSC-CFs during hCMP manufacture promotes hPSC-CM maturation and increases the potency of implanted hCMPs for improving cardiac recovery in mice model of MI.

Incidental Durotomy Repair in Lumbar Spine Surgery: Institutional Experience and Review of Literature.

: Retrospective Chart Review. Incidental durotomies (IDs) are common spine surgery complications. In this study, we present a review on the most commonly utilized management strategies, report our institutional experience with case examples, and describe a stepwise management algorithm. A retrospective review was performed of the electronic medical records of all patients who underwent a thoracolumbar or lumbar spine surgery between March 2017 and September 2019. Additionally, a literature review of the current management approaches to treat IDs and persistent postoperative CSF leaks following lumbar spine surgeries was performed. We looked at 1133 patients that underwent posterior thoracolumbar spine surgery. There was intraoperative evidence of ID in 116 cases. Based on our cohort and the current literature, we developed a progressive treatment algorithm for IDs that begins with a primary repair, which can be bolstered by dural sealants or a muscle patch. If this fails, the primary repair can be followed by a paraspinal muscle flap, as well as a lumbar drain. If the patient cannot be weaned from temporary CSF diversion, the final step in controlling postoperative leak is longterm CSF diversion via a lumboperitoneal shunt. In our experience, these shunts can be weaned once the patient has no further clinical or radiographic signs of CSF leak. There is no standardized management approach of IDs and CSF leaks in the literature. This article intends to provide a progressive treatment algorithm and contribute to the development process of a treatment consensus.

Advances in Cardiac Tissue Engineering.

Tissue engineering has paved the way for the development of artificial human cardiac muscle patches (hCMPs) and cardiac tissue analogs, especially for treating Myocardial infarction (MI), often by increasing its regenerative abilities. Low engraftment rates, insufficient clinical application scalability, and the creation of a functional vascular system remain obstacles to hCMP implementation in clinical settings. This paper will address some of these challenges, present a broad variety of heart cell types and sources that can be applied to hCMP biomanufacturing, and describe some new innovative methods for engineering such treatments. It is also important to note the injection/transplantation of cells in cardiac tissue engineering.

Abstract 10786: Cardiac Muscle Patches Containing Four Types of Cardiac Cells Derived From Human Pluripotent Stem Cells Improve Recovery From Cardiac Injury

Introduction: We have shown that human cardiac muscle patches (hCMPs) containing three different types of cardiac cells—cardiomyocytes (CMs), smooth-muscle cells (SMCs), and endothelial cells (ECs), all of which were differentiated from human pluripotent stem cells (hPSCs)—significantly improved cardiac function, infarct size, and hypertrophy in a pig model of myocardial infarction (MI). However, hPSC-CMs are phenotypically immature, which may lead to arrythymogenic concerns; thus, since hPSC-derived cardiac fibroblasts (hPSC-CFs) appear to enhance the maturity of hPSC-CMs, we compared hCMPs containing hPSC-CMs, -SMCs, -ECs, and -CFs (4TCC-hCMPs) with a second hCMP construct that lacked hPSC-CFs but was otherwise identical (3TCC-hCMPs). Methods: hCMPs were generated in a fibrin scaffold. MI was induced in SCID mice through permanent coronary artery (LAD) ligation, followed by treatment with cardiac muscle patches. Animal groups included: MI heart treated with 3TCC-hCMP; with 4TCC-hCMP; MI heart treated with no patch (MI group) and sham group. Cardiac function was evaluated via echocardiography, and cell engraftment rate while infarct size was evaluated histologically at four weeks after patch transplantation. Results: The results from experiments in cultured hCMPs demonstrate: 1) that structural, metabolic, and ion-channel markers for CM maturation were significantly more abundant in 4TCC-hCMPs; and 2) that conduction velocities and action-potential durations were significantly greater in hPSC-CMs from 4TCC-hCMPs (18 cm/s ± 0.72 vs. 31 cm/s ± 3.23, p&lt;0.005, 3TCC vs. 4TCC). Furthermore, when 3TCC- and 4TCC-hCMPs were compared in a mouse MI model, measures of cardiac function ( EF: 41.55% ± 0.92 vs. 49.18% ± 0.86, p&lt;0.05, 3TCC vs. 4TCC), infarct size (39.23% ± 4.28 vs. 22.72% ± 0.98, p&lt;0.05, 3TCC vs. 4TCC), hypertrophy, and CM engraftment were significantly better in animals treated with 4TCC-hCMPs than in the 3TCC-hCMP-treatment group (8.56% ± 1.79 vs. 15.99% ± 1.56, p&lt;0.05, 3TCC vs. 4TCC). Conclusions: These results demonstrate that the inclusion of hPSC-CFs in hCMP manufacture promotes hPSC-CM maturation and increases the efficacy of hCMPs for myocardial repair.

Clinical Efficacy of Superficial Temporal Artery-middle Cerebral Artery Bypass Grafting Surgery Combined With Temporal Muscle Patch on Patients With Moyamoya Disease

To analyze the clinical efficacy of superficial temporal artery-middle cerebral artery (STA-MCA) bypass grafting surgery combined with temporal muscle patch and STA-MCA bypass grafting surgery alone on patients with moyamoya disease. Totally 73 patients confirmed with moyamoya disease in our hospital between January 2019 and December 2021 were enrolled. Among them, 43 patients treated with STA-MCA bypass grafting surgery combined with temporal muscle patch were assigned to the experiment group, whereas 30 patients treated with STA-MCA bypass grafting surgery alone to the control group. The following items of the 2 groups were compared: clinical efficacy, total effective rate, and disease control rate 6 months after surgery, the changes of modified Rankin Scale (mRS) and Karnofsky performance scale (KPS) scores before and on the seventh day and 6 months after surgery, and changes of Glasgow coma scale scores before and 24 hours after surgery. In addition, the incidences of cerebral ischemia and cerebral hemorrhage within 1 year after surgery were counted. The cerebral perfusion-associated indexes including relative mean transit time (rMTT), relative time-to-peak, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV) on the seventh day and 6 months after surgery were compared between the 2 groups, and the predictive value of cerebral perfusion-associated indexes before surgery for clinical efficacy on patients was analyzed. The Glasgow coma scale score after surgery ( P >0.05) was similar between the 2 groups, but the clinical efficacy and total effective rate of the 2 groups were notably different (both P <0.05). Compared with those before surgery, mRS scores of both groups declined, whereas KPS scores increased (both P <0.05) on the seventh day after surgery. In addition, compared with those before surgery and on the seventh day after surgery, mRS scores of both groups decreased 6 months after surgery, whereas KPS scores increased (both P <0.05). Both the groups showed decreased rMTT and rTPP, and increased rCBF and rCBV on the seventh day after surgery than those before surgery (all P <0.05). In addition, both the groups still showed decreased rMTT and rTPP, and increased rCBF and rCBV 6 months after surgery than those before surgery and on the seventh day after surgery (all P <0.05). Most notably, the experimental group displayed improved cerebral perfusion-associated indexes than the control group 6 months after surgery (all P <0.05). The relief group showed notably higher rCBF and rCBV levels than the nonrelief group (both P <0.05). According to ROC analysis, the areas under the curves of rCBF and rCBV in forecasting the clinical efficacy on patients were 0.842 and 0.823, respectively. Superficial temporal artery-middle cerebral artery bypass grafting surgery combined with temporal muscle patch can deliver a higher total clinical curative rate for patients with moyamoya disease and can alleviate their coma.

The ‘muscle wonton’ repair – A case series of internal carotid artery injuries at a single Centre during its 10-year experience in endoscopic transsphenoidal pituitary surgery

Introduction Although rare, injury to the internal carotid artery (ICA) during pituitary surgery may result in serious morbidity such as stroke or death. This case series explores a single centre’s incidence and outcomes of ICA injury during endoscopic transsphenoidal pituitary surgery, discusses the current management options, and introduces the ‘muscle wonton’ (morcellised muscle wrapped in a single sheet of Surgicel®) as being a viable repair option. Methods All patients undergoing pituitary operations from January 2010 to December 2019 at the Queen Elizabeth Hospital, Birmingham, UK were included. Primary outcome was number of internal carotid artery injuries during pituitary surgery. Secondary outcome measures included pre-operative (demographic, risk factors such as previous radiotherapy, number of previous operations, imaging available), operative (intra-operative image guidance, intra-operative doppler ultrasound, which side ICA was damaged, repair technique) and post-operative result (death, cranial nerve VI palsy, or stroke). Results 7 out of 893 patients (0.8%) were identified as having an ICA injury. Four of the injuries were left sided. Average age was 54 years old, five were male. In four of the ICA injuries intra-operative navigation imaging was used, and a further two concurrently used ultrasound doppler. Three of the seven cases resulted in permanent morbidity (stroke). There were no other consistent demographic, pre-operative, operative, or post-operative similarities. The two patients with muscle wonton repair suffered no permanent serious complication of ICA injury (i.e. death, abducens nerve palsy, stroke). Discussion Our findings resemble the current literature, with left sided ICA injury being more common. Different methods for repairing ICA injury exist, however morcellised muscle patches have shown significant promise in animal models, and the perforated Surgicel® helps create an easy delivery method. The muscle wonton is a viable surgical option for repairing ICA injuries during pituitary surgery.

Retrosigmoid Infralabyrinthine (Suprajugular) Approach to the Jugular Foramen: Indications, Limitations, and Surgical Nuances.

Among the several approaches described to the jugular foramen (JF), the retrosigmoid infralabyrinthine (suprajugular) approach was one of the most recently described. To describe the indications, limitations, and operative nuances of the suprajugular approach. We provided a pertinent review of the anatomy, indications, preoperative evaluation, surgical steps and nuances, and postoperative management. The suprajugular approach is suitable for tumors occupying the intracranial compartment with limited extension into the JF. Volume, width, and configuration of the foramen dictate the feasibility of the approach. Tumors invading the venous system are not suitable for this approach. Preoperative 3-dimensional MRI and computed tomography are used to evaluate intrajugular extension, relationship between the tumor and the jugular bulb (JB), venous system invasion, and shape of the JF. During surgery, exposition of the entire posterior border of the sigmoid sinus is needed and removing the bone over the JB. After identification of the JF, the jugular notch and intrajugular process of the roof of the foramen are removed and intrajugular resection is completed. In cases of high-riding JB, it may be gently pushed down to allow visualization of the anterior foramen. In cases of JB laceration, it may be repaired using a muscle patch and usually does preclude further resection. The suprajugular approach is variation of the retrosigmoid approach that, when properly indicated, provides excellent exposure of the medial JF, with most anatomical variations and intraoperative complications predicted by a comprehensive preoperative evaluation.

Layer-By-Layer Fabrication of Thicker and Larger Human Cardiac Muscle Patches for Cardiac Repair in Mice.

The engineered myocardial tissues produced via most manufacturing techniques are typically just a few dozen micrometers thick, which is too thin for therapeutic applications in patients. Here, we used a modified layer-by-layer (LBL) fabrication protocol to generate thick human cardiac muscle patches (hCMPs) with thicknesses of ~3.75 mm. The LBL-hCMPs were composed of a layer of endothelial cells (ECs) sandwiched between two layers of cardiomyocytes (CMs): both cell populations were differentiated from the same human induced pluripotent stem cell line (hiPSCs) and suspended in a fibrin matrix, and the individual layers were sutured together, leaving channels that allowed the culture medium to access the internal cell layer. The LBL-hCMPs were cultured on a dynamic culture platform with electrical stimulation, and when compared to Control-hCMPs consisting of the same total number of hiPSC-ECs and -CMs suspended in a single layer of fibrin, hiPSC-CMs in the LBL-hCMPs were qualitatively more mature with significantly longer sarcomeres and expressed significantly higher levels of mRNA transcripts for proteins that participate in cardiomyocyte contractile activity and calcium handing. Apoptotic cells were also less common in LBL- than in Control-hCMPs. The thickness of fabricated LBL-hCMP gradually decreased to 0.8 mm by day 28 in dynamic culture. When the hCMP constructs were compared in a mouse model of myocardial infarction, the LBL-hCMPs were associated with significantly better measurements of engraftment, cardiac function, infarct size, hypertrophy, and vascularity. Collectively these observations indicate that our modified LBL fabrication protocol produced thicker hCMPs with no decline in cell viability, and that LBL-hCMPs were more potent than Control-hCMPs for promoting myocardial repair in mice.

Development of a management protocol for internal carotid artery injury during endoscopic surgery: a modified Delphi method and single-center multidisciplinary working group

BackgroundIntra-operative internal carotid artery (ICA) injury during transnasal endoscopic surgery is a potentially catastrophic event. Such an injury is life-threatening in the immediate setting, with a reported peri-operative mortality rate of 10%. Nasal packing, muscle patches, direct vessel closure, and endovascular techniques have been described as useful strategies for managing ICA bleeds. The objective of this study was to develop a formalized management protocol for intra-operative ICA injury through engagement with a multi-disciplinary panel.MethodsA modified Delphi method including literature review, iterative rounds of stakeholder feedback, and expert panel discussions was used to develop a management protocol for ICA injury during transnasal endoscopic surgery. The 10-person multi-disciplinary panel included otolaryngologists, neurosurgeons, interventional neuroradiologists, anesthesiologists, and operating room nursing staff.ResultsAfter three rounds of stakeholder engagement with the expert panel, consensus was reached on important elements to include within the protocol. The protocol was divided in three categories: Alert, Control, and Transfer. ‘Alert’ focusses on early communication with anesthesia and nursing staff. ‘Control’ focusses on techniques to expose the injury and obtain hemostasis or adequate tamponade. Lastly, ‘Transfer’ describes the process of contacting neuro-interventional radiology and safely transferring the patient. A one-page handout of the protocol was developed for placement in operating theatres.ConclusionDue to the life-threatening nature of ICA injury, it is imperative that endoscopic sinus and skull base surgeons are prepared to manage this complication. Using a modified Delphi method with a multidisciplinary expert panel, a protocol for management of intra-operative ICA injury was developed.Graphical

Management of an Internal Carotid Artery Injury During Open Skull Base Surgery With a Crushed Muscle Patch - Technical Note and Lessons Learned.

Iatrogenic internal carotid artery (ICA) injury is a catastrophic complication in open skull base surgery. There is a lack of information regarding the most appropriate techniques on how to manage this complication. To highlight the difficulties encountered when an ICA injury arises intraoperatively and discuss the role and the potential pitfalls of the crushed muscle patch in the management of an ICA injury during open skull base surgery. In this technical video, we demonstrate the management of intraoperative ICA injury, which occurred during the resection of a diffuse planum sphenoidale meningioma via a left pterional craniotomy. When isolation of the defect with temporary clips failed, we opted for a crushed muscle graft to plug the defect. Hemostasis was achieved, but because of prolonged pressure application and "overpacking," the parent vessel was occluded. The crushed muscle patch can be easily applied; however, care must be taken not to "overpack" and occlude the ICA.

Abstract P447: Layer-by-layer Fabrication Of Thick Cardiac Muscle Patches With High Viability And Maturity

Conventionally manufactured human cardiac muscle patches (hCMPs) typically rely on diffusion for oxygen and nutrient delivery to the cells and, consequently, the thickness of the hCMP is limited to 100-200 μm. Here, we tested our hypothesis that our layer-by-layer (lbl) manufacturing protocol could increase hCMP thickness without compromising the viability of individual cell populations. Human induced-pluripotent stem cells were differentiated into cardiomyocytes (CMs) or endothelial cells (ECs); then, layers composed of CMs or ECs were fabricated by mixing a cell-containing fibrinogen solution with thrombin and pouring the mixture into a mold, and the layers were stacked into a CM-EC-CM “sandwich”. hCMP viability was assessed via TUNEL staining, vascularization via expression of the EC marker CD144, and maturation via immunofluorescence and qPCR assessments of the expression of contractile (cTnT, cTnI), connective (Cx43, N-cad), and calcium-handling (RyR2, SERCA2, BIN1, Kir2.1) proteins. Sarcomere length was evaluated by staining for α-sarcomeric actinin, and hCMP ultrastructure was examined via transmission electron microscopy. The lbl-manufactured hCMP was 10 mm x 10 mm and 1.8 mm thick after fabrication. Minimal cells in the lbl-hCMP were apoptotic or necrotic. Compared to assessments in a single-layered patch containing the same number and proportion of cells, the lbl-hCMP was vascularized with higher levels of contractile, connective, and calcium-handling protein expression. Contractile proteins were also better aligned in the lbl-hCMP (deviation from global alignment 12.3 ± 3° vs. 24.3° ± 1.9°, p&lt;0.05). The lbl-hCMP contained longer sarcomeres (2.05 ± 0.015 vs. 1.74 ± 0.026 um, p&lt;0.05) with well-ordered I-bands, A-bands, M-lines, Z-lines, desmosomes, and intercalated discs. Thus, our lbl-manufacturing technique produced thicker and more mature patches that can be potentially clinically applicable for hearts with postinfarction LV remodeling.