Advancing Myocardial Infarction Treatment: Harnessing Multi-Layered Recellularized Cardiac Patches with Fetal Myocardial Scaffolds and Acellular Amniotic Membrane.

PURPOSE: Myocardial infarction (MI) is a leading cause of irreversible functional cardiac tissue loss, requiring novel regenerative strategies. This study assessed the potential therapeutic efficacy of recellularized cardiac patches, incorporating fetal myocardial scaffolds with rat fetal cardiomyocytes and acellular human amniotic membrane, in adult Wistar rat models of MI. METHODS: Decellularized myocardial tissue was obtained from 14 to 16 week-old human fetuses that had been aborted. Chemical detergents (0.1% EDTA and 0.2% sodium dodecyl sulfate) were used to prepare the fetal extracellular matrix (ECM), which was characterized for bio-scaffold microstructure and biocompatibility via scanning electron microscopy (SEM) and MTT assay, respectively. Neonatal cardiomyocytes were extracted from the ventricles of one-day-old Wistar rats' littermates and characterized through immunostaining against Connexin-43 and α-smooth muscle actin. The isolated cells were seeded onto decellularized tissues and covered with decellularized amniotic membrane. Sixteen healthy adult Wistar rats were systematically allocated to control and MI groups. MI was induced via arterial ligation. Fourteen days post-operation, the MI group was received the engineered patches. Following a two-week post-implantation period, the animals were euthanized, and the hearts were harvested for the graft evaluation. RESULTS: Histological analysis, DAPI staining, and ultra-structural examination corroborated the successful depletion of cellular elements, while maintaining the integrity of the fetal ECM and architecture. Subsequent histological and immunohistochemichal (IHC) evaluations confirmed effective cardiomyocyte seeding on the scaffolds. The application of these engineered patches in MI models resulted in increased angiogenesis, reduced fibrosis, and restricted scar tissue formation, with the implanted cardiomyocytes remaining viable at graft sites, indicating prospective in vivo cell viability. CONCLUSIONS: This study suggests that multi-layered recellularized cardiac patches are a promising surgical intervention for myocardial infarction, showcasing significant potential by promoting angiogenesis, mitigating fibrosis, and minimizing scar tissue formation in MI models. These features are pivotal for enhancing the therapeutic outcomes in MI patients, focusing on the restoration of the myocardial structure and function post-infarction.

Whole-organ decellularization of the human uterus and in vivo application of the bio-scaffolds in animal models.

PURPOSE: The aim of this investigation was to design a perfusion-based decellularization protocol to provide whole human uterine bio-scaffolds with preserved structural and componential characteristics and to investigate the in vivo properties of the decellularized tissues. METHODS: Eight human uteri, donated by brain-dead patients, were decellularized by perfusion of sodium dodecyl sulfate (SDS) through the uterine arteries using a peristaltic pump. The bio-scaffolds were evaluated and compared with native human uterus regarding histological, immunohistochemical, structural, and bio-mechanical properties, in addition to CT angiographies to examine the preservation of the vascular networks. Subsequently, we obtained acellular patches and implanted them on uterine defects of female Wistar rats to investigate the bio-compatibility and regenerative potential of the bio-scaffolds. Finally, we performed immunostaining to investigate the potential role of circulating stem cells in recellularization of the implanted bio-scaffolds. RESULTS: The outcomes of this investigation confirmed the efficacy of the proposed protocol to provide whole human uterine scaffolds with characteristics and extra-cellular matrix components similar to the native human uterus. Subsequent in vivo studies demonstrated the bio-compatibility and the regenerative potential of the scaffolds and suggested a signaling pathway as an underlying mechanism for the regenerative process. CONCLUSIONS: To the best of our knowledge, this investigation provides the first efficient perfusion-based decellularization protocol for the human uterus to obtain whole-organ scaffolds. The outcomes of this investigation could be employed in future human uterus tissue engineering studies which could ultimately result in the development of novel treatments for female infertile patients.

Transgluteal ultrasonography in spica cast in postreduction assessment of developmental dysplasia of the hip.

PURPOSE: The position of the femoral head in spica cast after the reduction of developmental dysplasia of the hip (DDH) should be examined and followed up closely and regularly. The study aimed to use the transgluteal ultrasonography approach for this purpose and compare its accuracy with the results of CT scan, which is the most commonly used modality. METHODS: Twenty-three patients with an average age of 20-21 months were examined for 1 year after the reduction of DDH, both closed and open. Ultrasonography and CT scan were performed on the patients on the same day, and the results were interpreted by different radiologists. Transgluteal ultrasonography in spica cast was performed while the legs were abducted, internally rotated, and flexed. A blanket was placed under the patient to elevate the cast. RESULTS: Thirty cases of proper reduction (81%) and 7 cases of dislocated hip (19%) were reported in transgluteal ultrasonography, and 29 cases of proper reduction (78%) and 8 cases of dislocated hip (22%) were reported in the CT scan. The rate of agreement between the results of ultrasonography and CT scan was 91%. CONCLUSION: Transgluteal ultrasonography can be used as an excellent modality to examine the position of the femoral head in relation to the posterior rim of the acetabulum in spica cast. The position of the femoral head can be viewed properly needless of perineal opening in the cast. Thus, transgluteal ultrasonography can replace the CT scan to assess the position of the femoral head. Sonography does not expose patients to radiation and does not require sedation.

Correction to: Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

This article was unintentionally published twice in this journal, by the same authors. Following should be considered the version of record and used for citation purposes.

Correction to: Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

The original version of this article unfortunately contained a mistake. The affiliation of Fariba Ghorbani should be Tracheal Diseases Research Center (TDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Correction to: Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

The original version of this article unfortunately contained a mistake. The affiliation of Fariba Ghorbani should be Tracheal Diseases Research Center (TDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

PURPOSE: The main purpose of this investigation was to determine an efficient whole-organ decellularization protocol of a human-sized uterus and evaluate the in vivo properties of the bioscaffold. METHODS: Twenty-four ovine uteri were included in this investigation and were decellularized by three different protocols (n 6). We performed histopathological and immunohistochemical evaluations, 4,6-diamidino-2-phenylindole (DAPI) staining, DNA quantification, MTT assay, scanning electron microscopy, biomechanical studies, and CT angiography to characterize the scaffolds. The optimized protocol was determined, and patches were grafted into the uterine horns of eight female Wistar rats. The grafts were extracted after 10 days; the opposite horns were harvested to be evaluated as controls. RESULTS: Protocol III (perfusion with 0.25% and 0.5% SDS solution and preservation in 10% formalin) was determined as the optimized method with efficient removal of the cellular components while preserving the extracellular matrix. Also, the bioscaffolds demonstrated native-like biomechanical, structural, and vascular properties. Histological and immunohistochemical evaluations of the harvested grafts confirmed the biocompatibility and recellularization potential of bioscaffolds. Also, the grafts demonstrated higher positive reaction for CD31 and Ki67 markers compared with the control samples which indicated eminent angiogenesis properties and proliferative capacity of the implanted tissues. CONCLUSIONS: This investigation introduces an optimized protocol for whole-organ decellularization of the human-sized uterus with native-like characteristics and a prominent potential for regeneration and angiogenesis which could be employed in in vitro and in vivo studies. To the best of our knowledge, this is the first study to report biomechanical properties and angiographic evaluations of a large animal uterine scaffold.