Silicone-based composites as surgical breast models for oncoplasty training

Surgeons-in-training necessitate practice to improve their skill sets and the shift towards simulation-based trainings enables trainees to learn at their own pace and experience custom-based cases rather than responding to the immediate needs of the patients. Oncoplasty for breast cancer encompasses tumor removal and subsequent breast reconstruction; and there are several oncoplastic techniques to master for proper treatment of the patients. For training purposes, closest media to reality, fresh cadavers, are hard to obtain due to their price and/or unavailability. There is a need for a sustainable, reliable, and affordable platform to diffuse simulation-based trainings to medical curricula and provide trainings even in resource-limited settings. Silicone-based composite models can be designed and manufactured to fulfil the necessities of breast surgery such as precise incision, epidermal undermining, suturing, and resisting suture tension after excision of a considerable mass. We have shown the performance of such a stand-alone breast model for two oncoplastic techniques, “Batwing Mammoplasty” and “Modified Inferior Flap Rezai”. This model can be used in settings where it is difficult and/or expensive to find fresh cadavers. This cost-effective and practical solution also eliminates the need for chemical/cold storage and risk of infections/molding, thus making it a preferable tool for teaching hospitals and also for individual practice. In addition, the model is suitable to be used in self-diagnosis trainings, as well as a communication platform between surgeons and patients

Fabrication and Characterization of Self-Assembled Tissue Rings using Patient Cells with Variants in Aneurysm Genes

Aortic Abdominal Aneurysm (AAA) is a chronic degenerative disease of the arterial wall. The aortic vessel wall abnormally dilates due to multiple possible causes and may eventually rupture. It is characterized by several factors leading to the extreme dilation due to the degeneration of the vessel wall extracellular matrix (ECM). It is often asymptomatic making it difficult to diagnose before rupture. The etiology of AAA is complex and not yet fully understood. Hallmarks of the disease are; loss of elastin and vascular smooth muscle cells, influx of inflammatory cells which produce proteases, increased stiffness due to higher collagen content, disturbed ECM network organization and an eventual destruction of the ECM leading to the vessel rupture. These changes may be related to environmental factors in combination with a genetic susceptibility, or by major defects in genes involved in the ECM homeostasis. Family history and genetic conditions play an important role in aneurysms. In approximately 20 % of aneurysm patients there is a familial disease or a family history of aneurysms, and in these families a major genetic defect is to be expected. Aneurysm patients show pathogenic variants in less than 5 % of the screened patients however, variants of unknown clinical significance in aneurysm genes occur at a much higher frequency. To determine the effect of these variants in aneurysm genes, functional assays which display a change in the function of the gene product needs to be established. Tissue engineering, in recent years, have become an alternative approach to animal models in developing tissue repair/replacement grafts or disease models. For this study, a cell-derived self-assembly tissue ring culture method was chosen and optimized for the use of patient cells with different pathogenic variants in aneurysm genes. After optimizing the culture conditions, the ring formation and structural ECM characteristics were compared for patient and control cases. The kinetics of ring formation showed differences in behavior and speed for patient and control cell lines. Patient lines took longer to settle into the ring shape and contract to their final thickness. The incidence of ring failure was higher in patient cases. The final patient rings were significantly thinner and non-uniform, additionally they showed a significantly lower area fraction of collagen compared to the controls. The tissue rings could not be mechanically tested due to their fragility. However, it was possible to identify the structural differences between the patient and control cases which were expected due to the pathogenic variants in the aneurysm genes of these patients. With further improvements, this method could be a potential functional assay for revealing the effects of variants of unknown significance in aneurysm genes, waiting to be identified

Flow affects the structural and mechanical properties of the fibrin network in plasma clots

The fibrin network is one of the main components of thrombi. Altered fibrin network properties are known to influence the development and progression of thrombotic disorders, at least partly through effects on the mechanical stability of fibrin. Most studies investigating the role of fibrin in thrombus properties prepare clots under static conditions, missing the influence of blood flow which is present in vivo. In this study, plasma clots in the presence and absence of flow were prepared inside a Chandler loop. Recitrated plasma from healthy donors were spun at 0 and 30 RPM. The clot structure was characterized using scanning electron microscopy and confocal microscopy and correlated with the stiffness measured by unconfined compression testing. We quantified fibrin fiber density, pore size, and fiber thickness and bulk stiffness at low and high strain values. Clots formed under flow had thinner fibrin fibers, smaller pores, and a denser fibrin network with higher stiffness values compared to clots formed in absence of flow. Our findings indicate that fluid flow is an essential factor to consider when developing physiologically relevant in vitro thrombus models used in researching thrombectomy outcomes or risk of embolization. Graphical Abstract: [Figure not available: see fulltext.].</p

3D bioprinting of graphene oxide-incorporated cell-laden bone mimicking scaffolds for promoting scaffold fidelity, osteogenic differentiation and mineralization

Bioprinting is a promising technique for facilitating the fabrication of engineered bone tissues for patient-specific defect repair and for developing in vitro tissue/organ models for ex vivo tests. However, polymer-based ink materials often result in insufficient mechanical strength, low scaffold fidelity and loss of osteogenesis induction because of the intrinsic swelling/shrinking and bioinert properties of most polymeric hydrogels. Here, we developed a human mesenchymal stem cells (hMSCs)-laden graphene oxide (GO)/alginate/gelatin composite bioink to form 3D bone-mimicking scaffolds using a 3D bioprinting technique. Our results showed that the GO composite bioinks (0.5GO, 1GO, 2GO) with higher GO concentrations (0.5, 1 and 2 mg/ml) improved the bioprintability, scaffold fidelity, compressive modulus and cell viability at day 1. The higher GO concentration increased the cell body size and DNA content, but the 2GO group swelled and had the lowest compressive modulus at day 42. The 1GO group had the highest osteogenic differentiation of hMSC with the upregulation of osteogenic-related gene (ALPL, BGLAP, PHEX) expression. To mimic critical-sized calvarial bone defects in mice and prove scaffold fidelity, 3D cell-laden GO defect scaffolds with complex geometries were successfully bioprinted. 1GO maintained the best scaffold fidelity and had the highest mineral volume after culturing in the bioreactor for 42 days. In conclusion, GO composite bioinks had better bioprintability, scaffold fidelity, cell proliferation, osteogenic differentiation and ECM mineralization than the pure alginate/gelatin system. The optimal GO group was 1GO, which demonstrated the potential for 3D bioprinting of bone tissue models and tissue engineering applications.ISSN:1742-7061ISSN:1878-756