Subcutaneous Pocket Research Articles

Intermuscular placement and defibrillation with the extravascular ICD: a single-centre experience

Abstract Background Extravascular (EV) implantable cardiac defibrillators (ICD) with substernal lead have recently proved to be a safe and effective alternative to conventional transvenous (TV) and subcutaneous defibrillators (S-ICD), owing to the possibility to deliver antitachycardia and asystole pacing while saving intravascular hardware. The proposed implantation technique for EV-ICDs is a subcutaneous pocket along the mid axillary line, although an intermuscular ICD placement can potentially reduce the risk of pocket complications, device migration and improve patient comfort and aesthetic outcomes. Purpose exploring the safety and feasibility of extravascular ICDs implantation with a substernal coil and an intermuscular generator placement. Methods Seventeen patients with a class I or IIa ICD indication either for primary (14/17) or secondary (3/17) prevention underwent EV-ICD implantation in our centre as part of the EV ICD Pivotal Study from May 2021 to November 2022. Access and tunnelling along the retrosternal space were performed based on current standard recommendations for EV-ICDs implantation. An intermuscular pocket for generator placement was obtained between the latissimus dorsi and the serratus anterior muscles beyond the left mid-axillary line. Results Mean age, BMI, NYHA class and left ventricular ejection fraction (LVEF) were respectively 53±9yrs, 25.3 ±6 kg/m2, 2 ±0.7, and 39±14%. The main aetiology was non ischemic cardiomyopathy (12/17), including 3 arrhythmogenic cardiomyopathy patients and one with hypertrophic cardiomyopathy. The implantation was successful in 16 (6 females) out of 17 patients, with one implant failure due to inadequate sensing (0,5 mV); the median sensing amplitude was 2,3 mV (min = 1,3 mV; max = 5,8 mV), with R1R2 being the final sensing vector chosen for 14/16 and R2-Can for 2/16. Defibrillation Testing (DFT) was performed in all patients: a 15 J shock terminated induced ventricular fibrillation (VF) in 12/16 patients, 20 J terminated VF in 3, a single patient had VF terminated at 30 J. No patient had infection or skin erosion or complained pain/discomfort at the pocket site along an 18±4 months follow-up. Only 1/16 patients had ventricular tachycardia at follow-up, successfully treated by the device. Conclusions Intermuscular placement of the EV ICD may be a feasible and reliable alternative to a subcutaneous one in terms of defibrillation efficacy, enabling patient comfort and aesthetic acceptance in thin-habit or young patients. Additional long-term data and larger patient cohorts are required to confirm its advantage compared to the subcutaneous placement.

Abstract 15121: Bioresorbable Molybdenum Electrodes: Towards a Novel Generation of Temporary Epicardial Pacing Wires

Introduction: Cardiac pacing with temporary epicardial pacing wires (TEPW) is used to treat rhythm disturbances after cardiac surgery. Removal is recommended on day 4-7. Occasionally, TEPW cannot be mechanically extracted, have to stay in the thorax and may rarely cause serious complications like migration and infection. We aim to develop novel, bioresorbable TEPW that will dissolve over time even if postoperative removal is unsuccessful. Methods and Results: We manufactured prototypical braided molybdenum (Mo) leads (16 Mo wires of 40 μM diameter each, length 18 cm for ex-vivo, 7.5 cm for in-vivo trials) coated with the biodegradable polymers poly(lactide-co-glycolic acid) (PLGA, inner coating) and polycaprolactone (PCL, outer coating) for shaping and electrical insulation. Mo electrodes showed similar pacing and sensing properties to conventional steel electrodes (Osypka) in Langendorff-perfused rat hearts, even with somewhat lower stimulation thresholds. In artificial body fluid at 37°C, polymer-coated Mo electrodes dissolved at a rate of 1.6 ± 0.3 μg/cm 2 ·d (n=5) compared to uncoated electrodes with 30.3 ± 0.8 μg/cm 2 ·d (n = 4, p < 0.001). Assessing apoptosis and necrosis in human cardiomyocytes and cardiac fibroblasts, we detected no toxicity at Mo concentrations up to 0.52 mM. To test Mo TEPW in vivo, we sutured them epicardially onto the anterior wall of hearts of female Wistar rats, led them out of the thorax and placed them in a subcutaneous pocket. We tested electrophysiological properties directly after implantation, after two weeks and one month. Mo electrodes showed similar pacing and sensing properties directly upon implantation and after two weeks. After one month, all but one pair of Mo electrodes were mechanically broken at their exit from the thorax, the site of assumedly highest mechanical stress. Conventional steel TEPW had similar electrical properties following implantation, after two weeks and one month with no signs of breakage. Conclusion: We demonstrate that Mo TEPW can feasibly be used for epicardial pacing in vivo for up to two weeks. These findings represent an important step in the development of bioresorbable TEPW as a novel and even safer approach to temporary epicardial pacing.

CARD9-Mediated Macrophage Responses and Collagen Fiber Capsule Formation Caused by Textured Breast Implants.

An increasing number of women are undergoing breast implantation for cosmetic purposes or for reconstructive purposes after breast excision. The surface morphology of the breast implant is a key factor associated with the induction of capsule contraction. The effect of surface morphology on the inflammatory response after implant insertion remains unclear, however. The authors conducted comparative analyses to determine the effect of the textured and smooth surface morphology of silicone sheets. Each type of silicone sheet was inserted into the subcutaneous pocket below the panniculus carnosus in C57BL/6 mice and mice with genetic disruption of CARD9 , Dectin-1 , Dectin-2 , or Mincle . The authors analyzed collagen fiber capsule thickness, histologic findings, and macrophage inflammatory response, including transforming growth factor (TGF)-β synthesis. The authors found that textured surface morphology contributed to the formation of collagen fiber capsules and the accumulation of fibroblasts and myofibroblasts, and was accompanied by the accumulation of TGF-β-expressing macrophages and foreign-body giant cells. CARD9 deficiency attenuated collagen fiber capsule formation, macrophage responses, and TGF-β synthesis, although the responsible C-type lectin receptors remain to be clarified. These results suggest that CARD9 may have a strong impact on silicone sheet morphology through the regulation of macrophage responses. Silicone breast implants have been widely used for postmastectomy and cosmetic augmentation mammaplasty breast reconstruction. The authors sought to elucidate the surface morphology of the breast implant as one of the key factors associated with the formation of collagen fiber capsules. Therapeutic, V.

Evaluation of biocompatibility of four different one-step self-etching adhesives by animal experimental method

Aims: The success of materials used in dentistry is closely related to their biological safety. In recent years, there has been growing concern about the biocompatibility of self-etch adhesives, which are frequently used in restorative dental treatment. The aim of this study is to compare the biocompatibility of four different single-stage self-etch adhesive materials (Prime & Bond One Select, Optibond All-in-One, Clearfil Universal Bond, and Single Bond Universal) with the animal test method and evaluate them histopathologically. Methods: The experimental materials were polymerized by filling 10 mm-long, 2 mm-diameter polyurethane tubes. For each adhesive, 21 tubes were used. The tubes were placed in the subcutaneous pockets formed by four different incisions in the backs of 21 adult male albino rats. On the 7th, 30th, and 60th days, rats were randomly divided into three groups. At the end of these durations, the tube and the surrounding 2 cm2 of tissue were excised together. The sections were taken into preparation and stained with hematoxylen and eosin. The severity of inflammation, inflammatory cell count, and fibrous capsule thickness were evaluated histologically by light microscopy. Results: On the 7th day of samples, lesions due to acute inflammation, edema, and PMNL infiltration were observed. In the 30th-day samples, it was observed that inflammation decreased against all materials and fibrocollagen tissue increased. On the 60th day, granulation and fibrous tissue increased due to regeneration and reparation processes. On the 60th day, the number of inflammatory cells decreased significantly compared to the 7th day. When the fibrous tissue formation was evaluated, it was found that the 7th day score was significantly lower than the 60th day score. Conclusion: The severity of the inflammatory reaction at the beginning of all materials can be explained by the effects of residual monomer release and surgical trauma.

Customization of Soft Tissue Expanders: Improving Safety, Accuracy, and Efficiency for Treatment of Large and Complicated Skin Lesions.

Soft tissue expansion is a common technique for restoring large skin defects. Fixed-type expanders may be inappropriate for the following reasons: (1) the shapes and sizes of the defects vary in different patients; and (2) the bulged base of the fixed-type expander does not fit the curve of the human body, which may induce complications such as concave deformities or nerve palsy from continuous mechanical compression. The customized expander adjusts better to the shape and the topography of the expansion site compared with the fixed-type expander. It improves expansion efficiency and reduces complications caused by compression. Between 2016 and 2022, customized soft tissue expansion was performed in 38 patients with skin lesions, including giant congenital melanocytic nevi and postburn scars. This series of patients included patients with a specific donor site shape that is unsuitable for fixed-type expanders. An expander was customized according to the shape of the donor site and then implanted in the subcutaneous pocket. After the expander reached a sufficient volume, the expander was removed, and the extra expanded skin flap was transferred to resurface the skin lesion. In the follow-up, the outcome and the complications were recorded. All the customized expanders fit not only the dimension but also the topography of the donor site. During expansion, 2 patients experienced leakage of the expander, and 3 patients suffered a skin rupture. In the remaining 33 patients, the expansion was successfully completed, and the expanded flaps restored the skin lesions as designed. The color and texture of the skin flaps remained satisfactory after long-term follow-up. Unlike fixed-type expanders, our customized expanders make it possible for "accurate" expansion, irrespective of the dimension and topography of the donor area. Customization of the expander helps increase efficiency and reduce complications caused by undue compression.

Aesthetic transaxillary subpectoral placement of vagus nerve stimulator in children and young adults: A technical note

IntroductionVagus nerve stimulation (VNS) is a neuromodulation therapy for drug-resistant epilepsy (DRE), refractory status epilepticus, and treatment-resistant depression. The lead is tunneled into the subcutaneous space and connected to the generator, which is usually implanted in a subcutaneous pocket below the clavicle. Surgical complications in the chest region include skin breakdown or infection. An alternative approach is to perform a subclavear subpectoral implantation. In our surgical series, we report a new aesthetic implantation method for VNS generators in children and young patients: the transaxillary subpectoral placement. Materials and methodsFrom May 2021 to May 2023, 10 vagus nerve stimulation generators were placed subpectorally with a transaxillary approach by the authors. We considered operative time, surgical complications such as blood loss, infections, device migration, pain, and adverse events at follow-up. ResultsIn this surgical series, we reviewed all cases of subpectoral implantation of VNS generators in children and young adults at our institution in the last 2 years. All patients were treated with subpectoral Sentiva 1000 (Livanova PLC) insertion with axillary access by a neurosurgeon and a pediatric surgeon. The operative time was slightly longer compared to the traditional subcutaneous implant. All generators reported impedances within the optimal range. Blood loss was not significant and no other perioperative complications were reported. Patients and families were highly satisfied with the outcomes in terms of comfort and aesthetic results after surgery and at the last follow-up. No cases of infection occurred, and no malfunctions or displacements of the generator were registered at clinical follow-up. ConclusionThe transaxillary subpectoral placement of theVNS generator is an aesthetic and anatomic approach, which provides several benefits to children and young adults.

Injectable gelatin/glucosamine cryogel microbeads as scaffolds for chondrocyte delivery in cartilage tissue engineering

In this study, we fabricate squeezable cryogel microbeads as injectable scaffolds for minimum invasive delivery of chondrocytes for cartilage tissue engineering applications. The microbeads with different glucosamine concentrations were prepared by combining the water-in-oil emulsion and cryogelation through crosslinking of gelatin with glutaraldehyde in the presence of glucosamine. The physicochemical characterization results show the successful preparation of cryogel microbeads with uniform shape and size, high porosity, large pore size, high water uptake capacity, and good injectability. In vitro analysis indicates proliferation, migration, and differentiated phenotype of rabbit chondrocytes in the cryogel scaffolds. The seeded chondrocytes in the cryogel scaffold can be delivered by injecting through an 18G needle to fully retain the cell viability. Furthermore, the incorporation of glucosamine in the cryogel promoted the differentiated phenotype of chondrocytes in a dose-dependent manner, from cartilage-specific gene expression and protein production. The in vivo study by injecting the cryogel microbeads into the subcutaneous pockets of nude mice indicates good retention ability as well as good biocompatibility and suitable biodegradability of the cryogel scaffold. Furthermore, the injected chondrocyte/cryogel microbead constructs can form ectopic functional neocartilage tissues following subcutaneous implantation in 21 days, as evidenced by histological and immunohistochemical analysis.

Establishment of a Model for Human Hypertrophic Scar Using Tissue Engineering Method.

Treatment of human hypertrophic scar (HS) is a challenge for plastic surgeons, whereas the clinical and experimental research has been limited due to the lack of an ideal model of human HS tissue. To establish a model of human HS using tissue engineering method, to improve the research for HS in the clinic and laboratory. Hypertrophic scar fibroblasts (HSFBs) were transferred to polylactic acid (PLA)/polyglycolic acid (PGA) scaffolds. Biocompatibility of HSFBs-PLA/PGA composites was evaluated using scanning electron microscopy. Composites of HSFBs-PLA/PGA were implanted in subcutaneous pockets in athymic mice after 4 weeks in vitro culture. A re-entry operation was performed to obtain the HS-like tissues after 12 weeks of in vivo culture. The histological stain, the expression of type I collagen, the proliferation ability, and vitality of HSFBs were compared between human HS tissue and HS-like tissue. The structure of PLA/PGA scaffolds facilitates HSFBs adhesion and proliferation. The HSFBs-PLA/PGA composites were in vivo cultured for 12 weeks, and then HS-like tissues were harvested from nude athymic mice. There was no statistical significance in the expression of type I collagen, cell cycle, and cell proliferation between human HS tissue and HS-like tissue. The authors successfully established a model of human HS using the tissue engineering method, which could provide HS-like tissue for research. And it also could provide enough HS-like tissues to help reduce experimental variability within groups. This model can be used to investigate in prevention and treatment of HS and further explore the mechanisms of HS.

Upscaled Skeletal Muscle Engineered Tissue with In Vivo Vascularization and Innervation Potential.

Engineering functional tissues of clinically relevant size (in mm-scale) in vitro is still a challenge in tissue engineering due to low oxygen diffusion and lack of vascularization. To address these limitations, a perfusion bioreactor was used to generate contractile engineered muscles of a 3 mm-thickness and a 8 mm-diameter. This study aimed to upscale the process to 50 mm in diameter by combining murine skeletal myoblasts (SkMbs) with human adipose-derived stromal vascular fraction (SVF) cells, providing high neuro-vascular potential in vivo. SkMbs were cultured on a type-I-collagen scaffold with (co-culture) or without (monoculture) SVF. Large-scale muscle-like tissue showed an increase in the maturation index over time (49.18 ± 1.63% and 76.63 ± 1.22%, at 9 and 11 days, respectively) and a similar force of contraction in mono- (43.4 ± 2.28 µN) or co-cultured (47.6 ± 4.7 µN) tissues. Four weeks after implantation in subcutaneous pockets of nude rats, the vessel length density within the constructs was significantly higher in SVF co-cultured tissues (5.03 ± 0.29 mm/mm2) compared to monocultured tissues (3.68 ± 0.32 mm/mm2) (p < 0.005). Although no mature neuromuscular junctions were present, nerve-like structures were predominantly observed in the engineered tissues co-cultured with SVF cells. This study demonstrates that SVF cells can support both in vivo vascularization and innervation of contractile muscle-like tissues, making significant progress towards clinical translation.

Biocompatibility and histological responses of eggshell membrane for dental implant-guided bone regeneration.

Guided bone regeneration (GBR) utilizing eggshell membrane (ESM) as a potential biomaterial for dental implant therapy augmentation was explored in this study. ESM, an environmentally friendly waste product, possesses collagen-rich characteristics. The biocompatibility and histological responses of ESM were investigated in a rat model. Twelve young adult Wistar rats were used in this study. ESM samples were implanted in subcutaneous and intramuscular pockets, and samples were collected at 48 hours, 4 weeks, and 8 weeks post-implantation. Histological analysis revealed the changes in ESM over time. Results showed that ESM maintained its structural integrity, induced a moderate cellular response, and exhibited slow degradation, indicating potential biocompatibility. However, the lack of organized collagen arrangement in ESM led to the formation of irregular and polymorphic spaces, allowing cell migration. Encapsulation of ESM by newly proliferating collagen fibers and multinucleated giant cells was observed at later time points, indicating a foreign body reaction. Crosslinking might improve its performance as a separation membrane, as it has the potential to resist enzymatic degradation and enhance biomechanical properties. In conclusion, ESM demonstrated biocompatibility, slow degradation, and lack of foreign body reaction. While not suitable as a complete separation membrane due to irregular collagen arrangement, further research involving crosslinking could enhance its properties, making it a viable option for guided bone regeneration applications in dental implant therapy. This study highlights the potential of repurposing waste materials for medical purposes and underscores the importance of controlled collagen structure in biomaterial development.

Feasibility and outcomes of Micra implant after cardiac implantable electronic device extraction

Abstract Funding Acknowledgements Type of funding sources: None. Background The specific and well-known design features of leadless pacing system (Micra Transcatheter Pacing System, M-TPS) have suggested his use in patients that previously underwent transvenous lead extraction (TLE) for any reason. The study aimed to investigate feasibility and long-term outcomes of M-TPS implant in patients underwent TLE. Methods Patients undergone M-TPS implantation in our Institution from May 2014 to September 2022 were included in the study. All patients fulfilled standard criteria for PM implantation (VVI or VDD mode). Follow-up (FU) was scheduled at discharge, after 1 month and every 6 months thereafter and electrical parameters were checked. Major complications were defined as life-threatening events, requiring surgical intervention or any event causing significant hemodynamic instability or resulting in death. Study population was divided between "naïve pacing" and "post-extraction" patients. Results We enrolled 193 patients (76.7% males), 57 (29.5%) received M-TPS implantation after TLE, needed because of infection in 91.4% of cases. Indications for pacing were permanent AF with bradycardia in 107 (55.5%) patients, complete AVB in 59 (30.5%), symptomatic sinus node dysfunction in 20 (10%), and advanced AVB or bifascicular bock in 7 (4%). There were no statistically significant differences between groups for demographics characteristics and primary PM implant indications, except mean age at implant that was significantly inferior in the post-extraction group [80 (IQR 75-84) vs 78 (IQR 72-83), p=0.04]. Implant procedure was successful in all and no complications were recorded. No differences between groups in procedure duration [40 (IQR 30-50) vs 45 (30-65) min, p=0.34], fluoroscopy time [9 (6-14) vs 9 (6-11) min, p=0.31] and single device delivery (64.9% vs 67.9%, p=0.35) were observed. The mean FU was 12 (1-36) months, maximum 8 years. Pacing variables at implantation [pacing threshold 0.5 (0.38-0.63) vs 0.5 (0.38-0.88) V/0.24 ms, p=0.15; impedance 720 (600-837) vs 675 (615-825) Ohm, p=0.51; R wave amplitude 9 (6.25-12.87) vs 8.2 (5.65-12) mV, p=0.47], discharge [pacing threshold 0.38 (0.38-0.63) vs 0.38 (0.38-0.63) V/0.24 ms, p=0.27; impedance 685 (580-770) vs 610 (560-750) Ohm, p=0.16; R wave amplitude 10.25 (7.2-14.5) vs 9.3 (6.5-16.5) mV, p=0.6], and at 6 months [pacing threshold 0.5 (0.38-0.5) vs 0.5 (0.38-1.25) V/0.24 ms, p=0.64; impedance 580 (520-680) vs 570 (510-640) Ohm, p=0.63; R wave amplitude 11.9 (8.2-16.4) vs 11.7 (9-20) mV, p=0.68; battery voltage 3.09 (3.05-3.11) vs 3.09 (3.04-3.13) V, p=0.71] did not show differences. Conclusion M-TPS is an efficacious and safe alternative to conventional PM, with the main advantage of the absence of transvenous leads and a surgically created subcutaneous pocket, avoiding all the related complications. These devices are a reliable alternative after TLE, with similar electrical performances than those observed in patients who did not previously received pacing.

Reducing radiation exposure and incision time in pacemakers implantation procedures using direct percutaneous axillary vein puncture

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Radiation exposure during device implantation depends overall on the operator experience but also on the type of venous access, type of device and number of leads implanted. Purpose to investigate radiation exposure/incision time for uni/bicameral pacemakers (PM) implantation procedures using direct percutaneous axillary vein puncture without primary fluoroscopy guidance and to assess the safety and the efficiency of this procedure strategy. Methods single center retrospective cohort study of patients implanted with unicameral and bicameral PM between January 2020 and December 2020 using direct percutaneous axillary vein puncture. All pts were given detailed explanations and informed consent. Procedural steps were: (I) direct percutaneous axillary vein puncture (anatomical landmarks: 1 or 2 cm medial and parallel to the deltopectoral groove at the level of the coracoid process); obtain separate vein access: 1 or 2 punctures; (II) skin incision and subcutaneous pocket dissection; (III) right ventricle (RV) ± right atrium (RA) lead placement and fixation. We analyzed the following data: fluoroscopy/incision time, dose area product (DAP) and the outcome related to procedure difficulties and complications. Results We collected data from 209 consecutive implant procedures; 152 patients (pts) underwent bicameral PM implantation, 57 pts received a unicameral device. All the procedures were done by the same operator (54 yo, 22 years of experience in PM implantation) using axillary access alone (2 years' experience in this technique). In 37 patients (18%) fluoroscopy guided puncture was needed. The mean fluoroscopy time was: bicameral PM 1.2±1.0 min (average incision time: 8.4±5.2 min); unicameral PM 0.4±0.3 min (average incision time: 6.5±4.3 min). The mean DAP was: bicameral PM 0.00358±0.00545 mGy/cm2; unicameral PM 0.00285±0.00449 mGy/cm2. In short term follow-up 1 patient (0.4%) developed pneumothorax and subsequent drainage was needed. Total follow-up period 19.7±4.3 months: at 6 months follow-up 1 patient (0.4%) presented lead fracture; 1 patient with DDD PM (0.4%) presented pocket infection; leads extraction were successful performed and another device was implanted. No other complications were noted. Conclusion Single venous access using axillary vein puncture was associated with reduced radiation exposure and decreased incision time. Our data showed a low incidence of complications.

40. Understanding Periprosthetic Capsule Pathology in Pre-pectoral Versus Sub-pectoral Implant-based Breast Reconstruction: Development of a Rat Model

PURPOSE: Clinical practices in implant-based breast reconstruction continue to evolve with ongoing innovation in both the surgical approach and implant design. Development of standardized models is increasingly important to evaluate the effect of these changes in the outcomes of implant-based reconstruction. In this study, we designed a physiological rat breast implant model to assess the effects of pre-pectoral and sub-pectoral implant placement on breast implant capsule formation. METHODS: Miniature silicone implants measuring 2cc in diameter were optimized for placement in the pre-pectoral and sub-pectoral planes bilaterally in Lewis rats for an internally controlled model. A submammary approach was simulated in rats by making skin incisions at the inferior aspect of the pectoralis muscle bilaterally. For sub-pectoral implant placement the lateral edge of the pectoralis muscle was elevated, a sub-pectoral plane was established with blunt dissection, and a sterile implant was secured in the sub-pectoral plane with complete pectoralis coverage. For pre-pectoral implant placement, blunt dissection was used on the contralateral side to establish a subcutaneous plane. A sterile implant was secured in this subcutaneous pocket. Samples were harvested at 12 weeks and histological analysis of capsule formation was performed with H&E and Trichrome staining. RESULTS: The rats showed immediate signs of bilateral forelimb use with walking and grasp following recovery from anesthesia. The surgical sites healed well over two-week follow-up with no signs of wound-site mutilation, discomfort, or dehiscence. Histological analysis demonstrated both pre-pectoral and sub-pectoral capsule formation compared to sham surgery samples. Prepectoral implant capsules showed lamellar collagen architecture whereas subpectoral implant capsules demonstrated increased thickness, hypercellularity and synovial metaplasia. CONCLUSIONS: This model demonstrates that a physiological approach with pre-pectoral and sub-pectoral implant placement to model breast implant reconstruction is feasible in rats and thus improves upon previous models that utilize dorsal subcutaneous pockets instead of pectoral planes. These earlier approaches do not replicate the anatomy and mechanics of the clinical prepectoral and subpectoral space. Additionally, this model demonstrates differences in the periprosthetic fibrotic processes in pre-pectoral and sub-pectoral approaches for implant placement. This model facilitates further mechanistic understanding of the physiology and pathology associated with breast implant reconstruction including outcomes such as capsular contracture and BIA-ALCL and will provide a valuable platform to test treatments and strategies that may mitigate them.

47. Flowable Decellularized Dermal Hydrogel Improves Integration of Acellular Dermal Matrices

PURPOSE: Acellular dermal matrices (ADM) have revolutionized pre-pectoral implant-based breast reconstruction allowing for improved pocket control and more rapid expansion but with the drawback of an increased risk of seroma that can lead to major complications including implant loss. The majority of these complications are a result of delayed or insufficient wound healing and integration of the ADM. ADM bio-integration can be accelerated by increasing the surface area of the ADM:host soft tissue interface. To address the issue of persistent contact of the ADM with the patient, we investigated the application of a hydrogel, derived from ADM to increase the conduction of the cells and molecular signals and increase vascularization, is critical to biointegration. METHODS: C57bl/6 mice received bilateral subcutaneous pockets. A 5mm diameter ADM implant was placed into each pocket and into one, 0.5 mL of decellularized dermal hydrogel was injected. Implants were harvested at terminal endpoints at 1, 3, and 6 weeks. Flow cytometry was performed to assess a panel of 12 macrophage markers (pan-, M1, M2, or transition) to evaluate inflammatory effects. Immunohistochemical staining for vimentin was used to assess fibroblast migration into the ADM. Hematoxylin and eosin (H&E) staining of implant cross sections was performed for pathological analysis of fibrosis via capsule formation. Capsule thickness, cellularity, foreign bodies, and smooth muscle actin (SMA) were graded (0 = none, 1 = mild, 2 = moderate, 3 = severe). RESULTS: H&E staining demonstrated that the dermal hydrogel persisted adjacent to the ADM implant. Flow cytometry results demonstrated that DPD hydrogel and ADM did not elicit an increased macrophage response compared to ADM implants alone. Vimentin expression demonstrated an upward trend in fibroblast infiltration from 3 to 6, with the dermal hydrogel group fibroblast increase outpacing that of the ADM control. Pathological analysis showed minimal capsule formation and no significant increase in fibrosis between hydrogel and no hydrogel groups. CONCLUSIONS: Our dermal hydrogel was able to flow easily into the surgical pocket, polymerized at physiological temperatures, and remained in place over the course of 6 weeks, demonstrating its potential to bridge the gap between ADM and the overlying skin envelope within human breast reconstructions. Our murine model revealed that the dermal hydrogel did not lead to an increased inflammatory immune response, with no statistical difference in fibrosis scores between t ADM-only implants. Although not statistically significant, immunohistochemistry quantifying the amount of vimentin present in the hydrogel-ADM complex showed promising trends with ADM integration into host tissue. Future work will include expansion of the model to incorporate radiation in order to examine the ability of the dermal hydrogel to aid in wound healing and ADM integration within an environment mirroring that seen in irradiated mastectomy cases.

PO-04-084 LOW SHOCK IMPEDANCE OF SUBCUTANEOUS IMPLANTABLE CARDIAC DEFIBRILLATOR (S-ICD) IN THE SETTING OF ACUTE DECOMPENSATED HEART FAILURE

Shock impedance represents the resistance between the coil and generator of subcutaneous ICDs. It is an important metric to predict device defibrillation success. Several factors have been implicated in determining system impedance of S-ICDs such as generator-lead distance, body habitus as well as generator position (subcutaneous vs. intermuscular pocket). We present a case report highlighting the impact of volume status on shock impedance. N/A A 60-year-old female presents to the office. She has a past medical history of obesity, Heart Failure with Preserved Ejection Fraction (HFpEF), ventricular fibrillation followed by implantation of transvenous ICD. This was complicated by device infection requiring device extraction and implantation of S-ICD. She has been having progressive shortness of breath with minimal exertion weeks prior to presentation. She denied chest pain, palpitations or dizziness but endorsed generalized fatigue as well as significant weight gain. She usually weighs around 165-170 lbs, but was 220 lbs on presentation. Her physical exam was remarkable for elevated jugular venous pressure, anasarca with crackles in the lung bases as well as abdominal ascites and lower extremity edema. Interrogation of her device was performed which showed no significant arrythmias. However, device detected low system impedance of <30 ohms. Her previous interrogation about 3 months earlier showed impedance of 50 Ohms. She was admitted for inpatient intravenous diuresis. Chest radiograph demonstrated normal position of the generator in the posterolateral chest wall and normal lead position in the parasternal area. Serial device interrogations were performed during the hospitalization showing gradual improvement in system impedance up to 45 Ohms once euvolemia was achieved (Figure 1). Due to improvement in shock impedance with diuresis, defibrillation threshold testing (DFT) was deferred and patient was discharged home in stable condition. Her repeat interrogation at follow up showed an impedance of 60 ohms. In the setting of heart failure exacerbation, excess fluid accumulation in the chest and abdominal cavities may result in a decrease in S-ICD shock impedance. Interpretation of device impedance should factor in patient’s volume status. Further studies are needed to ascertain if low impedance caused by fluid overload can impact device defibrillation success rate.

PO-05-044 LEADLESS VS SINGLE CHAMBER PACEMAKER IMPLANTATION IN POST-TRANSCATHETER AORTIC VALVE REPLACEMENT PATIENTS: INSIGHTS FROM THE NATIONWIDE READMISSIONS DATABASE

Bradycardic conduction disturbance after transcatheter aortic valve replacement (TAVR) requiring permanent pacemaker (PPM) is a well-recognized complication. Leadless pacemakers (LPs) have been increasingly used in patients with indications for pacing after TAVR. Given the route of implantation and lack of a subcutaneous pocket, LPs may provide theoretical advantages in terms of efficiency and readmissions when compared to traditional transvenous single chamber pacemaker (TV-VVI). We hypothesized that patients receiving LPs in the post-TAVR setting would have a shorter length of stay (LOS) and fewer readmissions compared to those with TV-VVI implantations. To compare LOS, 30-day readmission rates, and total charges of hospitalization in patients receiving LP or TV-VVI after TAVR. The Nationwide Readmissions Database (NRD) is a nationally representative sample of all US hospitalizations, containing longitudinal patient data on almost half of all hospitalizations. The 2019 NRD was used to identify all patients who underwent TAVR and required implantation of a LP or TV-VVI from January to November 2019. Patient comorbidities and outcomes were extracted from diagnosis codes. Analysis accounted for the complex survey design of the NRD. Per NRD data reporting guidelines, any variable with n<10 was not reported. Out of 70,278 patients who underwent TAVR during the study period, 264 patients (0.4%) underwent LP implantation and 515 (0.7%) underwent TV-VVI implantation. Baseline comorbidities were similar between the two groups, except for a higher rate of atrial fibrillation (90.7% vs 70.0%, p<0.01) and tricuspid valve disease in the TV-VVI group (19.6% vs 8.2%, p<0.01). Length of stay (7.3±0.5 vs7.4 ± 0.6 days, p=0.84), time from PPM to discharge (5.6±0.6 vs 5.6±0.5, p=0.99), mortality (1.5% vs 0.8%, p=0.51), effusion/tamponade (2.1% vs 3.2%, p=0.58), and 30-day readmissions (18.8% vs 20.8%, p=0.58) were similar. There were no significant differences between hospital or payor characteristics. Total charges were significantly higher in the LP group ($290,676 ± $14,946 vs $343,320, ± $18,343, p<0.01) and remained significant on multivariate analysis (p=0.01). LP did not provide any advantage over TV-VVI in the management of post-TAVR bradyarrhythmias in terms of length of stay, 30-day readmissions, or mortality, despite similar baseline comorbidities in both groups. LP implants were also associated with a significantly higher total charges during hospitalization.

Injectable Cartilage Microtissue Regenerated by Autologous Chondrocytes for Nasal Augmentation: A 5-Year Follow-Up Study.

A lack of ideal filling materials is a critical limitation in current rhinoplasty. Cartilage sheet regeneration by autologous chondrocytes is expected to provide an ideal source of material. However, the inability to perform minimally invasive transplantation of cartilage sheets has greatly limited the clinical application of this material. In this article, the authors propose the concept of injectable cartilage microtissue (ICM) based on cartilage sheet technology, with the aim of achieving minimally invasive augmentation rhinoplasty in clinical practice. Approximately 1.0 cm2 of posterior auricular cartilage was collected from 28 patients. Isolated chondrocytes were expanded, then used to construct autologous cartilage sheets by high-density seeding and in vitro culture in chondrogenic medium with cytokines (eg, transforming growth factor beta-1 and insulin-like growth factor-1) for 3 weeks. Next, ICM was prepared by granulation of the cartilage sheets; it was then injected into a subcutaneous pocket for rhinoplasty. ICM was successfully prepared in all patients, and its implantation efficiently raised the nasal dorsum. Magnetic resonance imaging confirmed that regenerative tissue was present at the injection site; histologic examinations demonstrated mature cartilage formation with typical cartilage lacunae and abundant cartilage-specific deposition of extracellular matrix. Excellent or good postoperative patient satisfaction results were achieved in 83.3% of patients over 5 years of follow-up. Obvious absorption of grafts occurred in only two patients (8.3%). These results demonstrated that ICM could facilitate stable cartilage regeneration and long-term maintenance in the human body; the implantation of ICM enabled natural augmentation of the depressed nasal dorsum. Therapeutic, IV.

Encapsulation of Human Umbilical Cord Mesenchymal Stem Cells in LunaGel Photocrosslinkable Extracellular Matrix and Subcutaneous Transplantation in Mice

Stem cells have significant potential in regenerative medicines. However, a major issue with implanting stem cells in the regeneration of new tissue is the methods to implant them and cell viability and functions before and after implantation. Here we developed a simple yet effective method that used photo-crosslinkable gelatin-based hydrogel (LunaGelTM) as a scaffold for the encapsulation, expansion, and eventually, transplantation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) into mice subcutaneously. We demonstrated the proliferation and maintenance of the original expression of mesenchymal stem cell markers as well as the ability to differentiate into mesoderm-derived cells. The hydrogel was highly stable with no signs of degradation after 20 days in PBS. The hUC-MSCs remained viable after transplantation into mice's subcutaneous pockets and migrated to integrate with the surrounding tissues. We showed a collagen-rich layer surrounding the transplanted cell-laden scaffold indicating the effects of growth factors secreted by the hUC-MSCs. A connective tissue layer was found between the implanted cell-laden scaffold and the collagen layer, and immunohistochemical staining results suggested that this tissue was derived from the MSCs which migrated from within the scaffold. The results, thus, also suggested a protective effect the scaffold has on the encapsulated cells from the antibodies and cytotoxic cells of the host immune system.

Strategies for Safe Implantation and Effective Performance of Single-Chamber and Dual-Chamber Leadless Pacemakers.

Leadless pacemakers (LPMs) have emerged as an alternative to conventional transvenous pacemakers to eliminate the complications associated with leads and subcutaneous pockets. However, LPMs still present with complications, such as cardiac perforation, dislodgment, vascular complications, infection, and tricuspid valve regurgitation. Furthermore, the efficacy of the leadless VDD LPMs is influenced by the unachievable 100% atrioventricular synchrony. In this article, we review the available data on the strategy selection, including appropriate patient selection, procedure techniques, device design, and post-implant programming, to minimize the complication rate and maximize the efficacy, and we summarize the clinical settings in which a choice must be made between VVI LPMs, VDD LPMs, or conventional transvenous pacemakers. In addition, we provide an outlook for the technology for the realization of true dual-chamber leadless and battery-less pacemakers.

Abstract Number ‐ 13: Endovascular BCI to Restore Motor Control for the Command of Digital Devices in Severe Quadriparesis

Introduction Brain‐computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore the transmission of neural signal from the cerebral cortex to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. Methods COMMAND is an FDA‐approved, NIH‐funded single arm, open‐label, prospective early feasibility study designed to enroll 6 patients with severe quadriparesis to receive an endovascular implantable motor neuroprosthesis (Stentrode, Synchron Inc, Brooklyn, NY). The primary outcome measures include treatment related serious adverse events within 12‐month after device implantation. Secondary outcome measures include restoration of neural signal from the cerebral cortex utilized for neuromuscular control of digital devices, resulting in the successful execution of non‐mechanical digital commands, e.g., for the control of personal computers. The study device comprises of three parts: 1) Endovascular electrode array and lead (StentrodeTM), implanted percutaneously via the jugular vein in the superior sagittal sinus adjacent to the motor cortex using endovascular approach; 2) Implantable Receiver Transmitter Unit (IRTU) implanted in the pectoral region; and 3) Controller, including an External Receiver Transmitter Unit (ERTU), Signal Control Unit (SCU) and Software Application. Results A 67 year‐old patient with complete quadriplegia from amyotrophic lateral sclerosis (ALS) enrolled into the study and completed a screening process, which included CTV and MRV to ascertain normal venous sinus anatomy, with two patent jugular veins and bilateral patent transverse sinuses. Using a right internal jugular vein access, the investigational endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. Co‐registration to enable accurate anatomical targeting was achieved by fusing structural MRI data with intra‐procedurally acquired 3D‐volume (3D‐DSA). A sub‐clavicular subcutaneous pocket was created to place the IRTU. Then, the lead was tunneled to the pocket and connected to the IRTU. Before closure of the wound, impedance measurement was taken which confirmed functionality of the system. The patient tolerated the procedure very well, was successfully extubated after the procedure and remained neurologically at his baseline. The patient was started on dual antiplatelet therapy 2 weeks prior to the surgery and will be continued on this regimen for 3 months.The participant will undergo machine‐learning‐assisted training to use wirelessly transmitted electrocorticography signals associated with attempted movements to control multiple mouse‐click actions, including zoom and left‐click. Used in combination with an eye‐tracker for cursor navigation, the patient will practice controlling a computer to conduct instrumental activities of daily living (IADL) tasks. Conclusions We describe the first US in‐human experience of a minimally invasive, fully implanted, wireless motor neuroprosthesis using an endovascular stent‐electrode array to transmit electrocorticography signals from the motor cortex for multiple command control of digital devices.