Artificial organs最新文献

We would like to report the first-in-human implantation of the novel DuoCor-BiVAS biventricular assist device (BiVAD). This system features a single driveline and compact peripheral components, offering a promising mechanical support option for patients with terminal biventricular heart failure ineligible for heart transplantation.

Background: Regional citrate anticoagulation (RCA) improves the biocompatibility of hemodialysis (HD) by reducing activation of complement, leukocytes, and platelets. Despite the new possibility of expanded hemodialysis (HDx), RCA and unfractionated heparin (UFH) have not been compared in this dialysis modality. This study compared the biocompatibility and efficacy of RCA versus full-dose UFH during HDx.

Methods: In a randomized cross-over trial, 32 chronic HD patients each underwent two HDx sessions with a Theranova dialyzer: one with RCA and one with UFH. Biocompatibility was assessed by plasma complement factor 3a (C3a), myeloperoxidase (MPO), and platelet factor 4 (PF4) measured pre-HDx, after 15 min, and at session end. In a subset of patients (n = 5), scanning electron microscopy (SEM) visualized cell adhesion and clotting on dialyzer fibers. Efficacy outcomes were overall clearances and reduction ratios (RR) for creatinine, urea, and β2-microglobulin.

Results: MPO and C3a increased after 15 min of HDx only with UFH (p < 0.001). In the available PF4 data, a significant increase after 15 min of HDx occurred only with UFH (p = 0.02). SEM showed minimal cell adhesion with both anticoagulants. Overall clearances and RRs of creatinine, urea, and β2-microglobulin did not differ. RCA was well tolerated, with no significant electrolyte disturbances.

Conclusions: RCA during HDx provided superior biocompatibility over UFH, eliminating complement, granulocyte, and platelet activation without improving dialysis efficacy.

Background: Despite advances in durable left ventricular assist device (LVAD) technology and improved survival outcomes, significant disparities persist in its utilization across Europe, particularly in Southern regions.

Aims: To evaluate variability in LVAD implantation rates among representative European countries and estimate the unmet needs in Greece.

Methods: Market data reflecting the sales of long-term LVAD systems across various countries from 2019 to 2024 were combined with registry-based LVAD implantation records to estimate the number of eligible patients and actual LVAD implantations in selected European countries. A stepwise epidemiological modeling approach was applied to estimate LVAD-eligible patients in Greece.

Results: In several Southern European countries, LVAD implantation rates in 2024 were no more than 2 per million population (Greece: 0.78/million, Italy: 1.89/million, Spain: 1.79/million, Portugal: 0.88/million). In Greece, even though an estimated 349 patients were eligible for LVAD implantation in 2024, based on demographic and clinical criteria, only seven devices were implanted while 24 patients underwent heart transplantation, reflecting a treatment gap of 318 patients (approximately 91% of the eligible population). In contrast, countries in Western and Northern Europe (Austria: 4.57/million, Germany: 8.74/million, France: 2.47/million, the Netherlands: 5.71/million, Switzerland: 3.28/million, Hungary: 2.08/million, Czech Republic: 6.19/million, Sweden: 2.19/million) reported LVAD implantation rates up to 9 per million. Significant discrepancies were reported also in the number of available LVAD centers as well as LVAD implantations per million between Greece and countries with similar populations (≈10 million residents) from Europe and Asia.

Conclusions: LVAD implantation rates vary among representative Southern European countries, with the lowest rates being observed in Greece. Insufficient number of implanting centers, limited reimbursement, and fragmented post-implant care contribute to this disparity.

Background: Awake veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) has been introduced to mitigate complications associated with prolonged sedation and invasive mechanical ventilation. However, concerns remain regarding delayed hemorrhagic complications, such as iliopsoas hematoma. This study aimed to identify factors associated with the development of iliopsoas hematoma in patients undergoing awake V-V ECMO.

Methods: Among 41 patients, we retrospectively reviewed data of seven patients who developed delayed iliopsoas hematoma during awake V-V ECMO. The ECMO configurations at our institute include: (1) femorojugular, with drainage from the femoral vein and return to the jugular vein; (2) jugulofemoral, with drainage from the jugular vein and return to the femoral vein; and (3) jugulojugular, which performs both drainage and return. Patient characteristics, timing of onset, management, and outcomes were evaluated.

Results: All seven patients developed hematomas several days after ECMO initiation, often following mobilization. Compared with those without hematomas, affected patients were predominantly female (n = 6, 25%, p = 0.0352), achieved standing during rehabilitation in fewer days (4 [4, 4.5] vs. 8 [5.8, 12.3] days, p = 0.0301), and had a longer hospital stay (52.5 [47.8, 84.5] vs. 32 [19, 52] days, p = 0.043). The diagnosis was primarily made using computed tomography, and most patients were successfully treated with transcatheter arterial embolization. No death was directly attributed to the hematoma.

Conclusions: Awake V-V ECMO facilitates early mobilization but may increase the risk of delayed retroperitoneal bleeding, particularly iliopsoas hematoma. Heightened awareness and prompt recognition of this complication are essential for optimal management.

Background: To compare overall and hemocompatibility-related outcomes across third-generation centrifugal-flow HeartMate 3 (HM3) versus second-generation axial-flow HeartMate II (HMII) and centrifugal-flow HeartWare (HVAD) in routine clinical practice.

Methods: We conducted a multicenter observational cohort of adult LVAD recipients (n = 327: HVAD n = 112, HMII n = 142, HM3 n = 73). Baseline characteristics and perioperative variables were recorded. Overall survival was analyzed using Kaplan-Meier and Cox proportional hazards models with HM3 as reference. Hemocompatibility-related adverse events (HRAE; pump thrombosis, ischemic stroke, major bleeding) were assessed with cumulative incidence functions (Aalen-Johansen) and Fine-Gray competing-risk regression with death as a competing event; the hemocompatibility score (HCS) summarized event burden over follow-up.

Results: HM3 demonstrated superior long-term survival compared with both HMII and HVAD in Kaplan-Meier analyses (log-rank p < 0.001); this advantage persisted in multivariable Cox models. HRAE-free survival was also higher with HM3 on competing-risk analysis, driven by substantially lower pump thrombosis and fewer ischemic strokes relative to HMII and HVAD. Bleeding burden did not differ materially between devices, consistent with a class effect of continuous-flow support. LDH-based hemolysis markers and HCS distributions further favored HM3. Perioperative course and general postoperative complications were otherwise broadly comparable across devices.

Conclusions: In this real-world, multicenter cohort, HM3 was associated with better overall survival and a lower thromboembolic burden than HMII and HVAD, while bleeding risk remained similar. These findings support preferential selection of HM3 when device choice is feasible, and emphasize the need for targeted strategies to mitigate hemostatic complications across all LVADs.

Introduction: Tissue engineering has opened new horizons with the introduction of biological scaffolds obtained by decellularization techniques as novel tools in regenerative medicine. Chemical agents such as SDS, although effective in cell removal, can cause cytotoxicity. Herbal agents can be a safer and more biocompatible alternative. This study aimed to investigate the efficacy of Acanthophelium extract (ACP) as a herbal agent in decellularization of sheep pericardium and compare it with SDS for use in skin engineering.

Methods: Pericardial tissues were decellularized with different concentrations of ACP (5, 7.5% and 10%) and SDS (1%), as well as the combination of ACP + SDS. Tissue staining, biocompatibility (MTT), hemolysis, blood clotting index (BCI), scanning electron microscopy (SEM), ATR-FTIR spectroscopy, mechanical testing, contact angle, and antibacterial activity were performed.

Results: Complete cell removal was observed in the ACP + SDS combination groups, while the ECM structure was preserved. Biocompatibility was more than 90% in all groups. ACP-based scaffolds had less hemolysis, a more favorable coagulation index, preserved protein structure, higher porosity, and higher hydrophilicity. Although the mechanical properties were slightly reduced, they remained acceptable. The 10% ACP + 0.1% SDS group reported the highest antibacterial effect.

Conclusions: ACP extract, as a plant agent in pericardial decellularization, has an effective and biocompatible function, and in combination with a small amount of SDS, it can provide a balanced scaffold with desirable properties for skin engineering.

Background: The sclera, a dense tissue that provides structural support to the eye, can be damaged by various factors, necessitating surgical repair. Decellularization techniques, which preserve the essential extracellular matrix (ECM) while removing cells, offer a promising solution. This study aimed to develop an optimized decellularization protocol for human sclera and evaluate its effectiveness using a rabbit model for scleral defects.

Methods: Twelve New Zealand white rabbits underwent lamellar sclerectomy. The right eye was grafted with human native sclera (HNS), while the left eye received human acellular sclera (HAS) patches prepared by methods A, B, and C. Method A used sodium dodecyl sulfate (SDS); Method B combined SDS with Triton X-100; and Method C used a mix of SDS, EDTA, Triton X-100, and trypsin. Outcomes were assessed through cell nucleus visualization, cytotoxicity tests, SDS residue checks, structural assessments, slit lamp evaluations, AS-OCT scans, and histopathological reviews.

Results: All protocols successfully decellularized tissues, confirmed by DAPI staining. With 80% cell viability, cytotoxicity was minimal and SDS residues were safely reduced. Method C best preserved collagen structures and ECM integrity. Slit lamp tests showed distinctions between HNS and HAS patches for Methods A and B, while Method C had superior biodegradability. All rabbits displayed conjunctival congestion, more so with HNS patches. AS-OCT showed the thinnest grafts with Method C. By the study's end, all patches had effectively healed the defects. Despite evident inflammation, especially in HNS patches, inflammation levels across HAS patches remained consistent.

Conclusion: The decellularized human sclera emerges as an ideal material for reconstructing the sclera. The proposed decellularization processes efficiently retained ECM while eliminating cells, making them robust and safe choices for mending damaged scleral tissue. This optimized biomaterial holds the potential to improve surgical outcomes in scleral reconstruction procedures.

Background: Ex situ normothermic machine perfusion (NMP) holds great promise in preserving and concomitantly evaluating the viability of kidney grafts. NMP for 1 to 2 h has been shown to be feasible and safe, demonstrating no adverse impact on early graft function. Prolonging the duration of NMP offers an extended timeframe for evaluation, besides creating a window for pretransplant therapeutical interventions. This study aimed to assess the feasibility of extending the duration of perfusion to 6 h.

Methods: We investigated the prerequisites to extend the warm perfusion of donor kidneys safely for up to 6 h. Human donor kidneys deemed unsuitable for transplantation were included for experimental NMP. Throughout the perfusion process, we assessed metabolic activity, as well as the extent of biochemical, hemolytic, and histological injury through biopsy, urine, and perfusate analyses. Stepwise alterations were made to the protocol accordingly.

Results: An analysis of 30 discarded kidneys revealed that improvements in erythrocyte quality, oncotic pressure, and correction of electrolyte imbalances facilitated the achievement of steady flow volumes and ensured a favorable macroscopic appearance of the graft. Extending the perfusion period to 6 h displayed preserved renal viability and stable histological characteristics.

Conclusions: The presented protocol shows prolonging NMP of donor kidneys to 6 h is feasible. We have implemented pivotal elements including the use of fresh (≤ 7 days) washed red blood cells, the addition of albumin, and urine recirculation, resulting in a stable and balanced perfusion. Ongoing refinements are necessary to enable the clinical application of a more prolonged NMP.

This study aimed to develop a three-dimensional biological model of testicular tissue and assess the differentiation of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) into germ-like cells. In the first phase, three decellularization protocols were compared. Quantitative DNA assays and histological analysis revealed that the combination of SDS (sodium dodecyl sulfate) and SDC (sodium deoxycholate) (S3) achieved the greatest DNA reduction and the best preservation of the extracellular matrix (ECM) structure. Immunohistochemistry and Alisian Blue staining confirmed superior retention of type IV collagen, fibronectin, and glycosaminoglycans in this group. The MTT assay indicated no significant cytotoxicity from residual detergents. In the second phase, MSCs were isolated from Wharton's Jelly and cultured, maintaining their morphology and expressing CD105 and CD44 while lacking CD34. Viability and cell-counting tests showed that an initial density of 30 000 cells per well provided optimal survival on the selected scaffold. Finally, hWJ-MSCs were seeded on the Group 3 scaffold and cultured in different differentiation systems. After 2 weeks, qRT-PCR analysis showed that the G3 differentiation group (supplemented with Sertoli cell-conditioned medium and growth factors) had the highest expression of pluripotency and germ cell-related genes (OCT4, Dmc1, Tp2) as well as the anti-apoptotic gene Bcl2, while Bax expression was significantly reduced. Electron microscopy and BrdU assays confirmed cell presence and proliferation on the ECM surface within 2 weeks. Overall, the SDS + SDC-derived scaffold, with its preserved ECM architecture and favorable biocompatibility, provided a suitable microenvironment for the attachment, proliferation, and differentiation of hWJ-MSCs into germ-like cells, offering a promising model for testicular regeneration.

Background: Electrical stimulation is commonly employed for activation of paralyzed muscles in patients with neurological diseases and injuries. However, there are differences in the treatment approaches that are possible for upper motor neuron and lower motor neuron injuries.

Methods: This narrative review synthesizes findings from preclinical studies and clinical reports published over the past decades. Key topics include stimulation parameters, muscle physiology under denervation, and outcomes of invasive and noninvasive interventions. The selection of sources was based on their relevance to denervated muscle stimulation in both experimental and therapeutic contexts.

Results: This review critically examined the physiological and therapeutic differences between indirect and direct stimulation of muscles in upper motor neuron and lower motor neuron injury situations. It then focused on the much less well-established field of stimulation of denervated muscle, where there remains a pressing need for new clinical approaches. We explained the rationale for stimulating denervated muscles and the practical difficulties encountered in doing so, describing the use of both invasive and noninvasive devices in animal experiments and clinical trials. We then discussed related research using artificial reinnervation for denervated muscle stimulation and suggested directions for future exploration in this dynamic field.

Conclusion: Stimulation of denervated muscle remains a promising but underdeveloped area. Electrical stimulation of denervated muscle can preserve muscle mass and potentially restore function. However, its clinical adoption has been limited by the exceptionally high stimulation thresholds required, which are approximately one thousand times higher than those for indirect muscle stimulation via intact lower motor neurons. These demands lead to significant challenges including discomfort, limited specificity due to the need for large electrodes, and the risk of tissue damage. Artificial reinnervation may offer a promising solution by enabling the use of conventional low-energy stimulation techniques. Additionally, the application of stimulation in free muscle transfers may further expand therapeutic options in this area.