Current scaffold‐based tissue engineering approaches are subject to several limitations, such as design inflexibility, poor cytocompatibility, toxicity, and post‐transplant degradation. Thus, scaffold‐free tissue‐engineered structures can be a promising solution to overcome the issues associated with classical scaffold‐based materials in clinical transplantation. The present study seeks to optimize the culture conditions and cell combinations used to generate scaffold‐free structures using a Bio‐3D printing system. Human cartilage cells, human fibroblasts, human umbilical vein endothelial cells, and human mesenchymal stem cells from bone marrow are aggregated into spheroids and placed into a Bio‐3D printing system with dedicated needles positioned according to 3D configuration data, to develop scaffold‐free trachea‐like tubes. Culturing the Bio‐3D‐printed structures with proper flow of specific medium in a bioreactor facilitates the rearrangement and self‐organization of cells, improving physical strength and tissue function. The Bio‐3D‐printed tissue forms small‐diameter trachea‐like tubes that are implanted into rats with the support of catheters. It is confirmed that the tubes are viable in vivo and that the tracheal epithelium and capillaries proliferate. This tissue‐engineered, scaffold‐free, tubular structure can represent a significant step toward clinical application of bioengineered organs.
Various strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this study, we developed a scaffold-free structure with a mixture of cell types using bio-three-dimensional (3D) printing technology and assessed its characteristics in vitro and in vivo after transplantation into rats. Normal human dermal fibroblasts, human esophageal smooth muscle cells, human bone marrow-derived mesenchymal stem cells, and human umbilical vein endothelial cells were purchased and used as a cell source. After the preparation of multicellular spheroids, esophageal-like tube structures were prepared by bio-3D printing. The structures were matured in a bioreactor and transplanted into 10-12-week-old F344 male rats as esophageal grafts under general anesthesia. Mechanical and histochemical assessment of the structures were performed. Among 4 types of structures evaluated, those with the larger proportion of mesenchymal stem cells tended to show greater strength and expansion on mechanical testing and highly expressed α-smooth muscle actin and vascular endothelial growth factor on immunohistochemistry. Therefore, the structure with the larger proportion of mesenchymal stem cells was selected for transplantation. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents. The structures were maintained in vivo for 30 days after transplantation. Smooth muscle cells were maintained, and flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects.
Background Although R0 resection for colorectal cancer liver metastasis (CRLM) is a promising treatment with improved prognosis, the recurrence rate is still high. No prognostic markers have been reported after resection of CRLM. In this study, we investigated the association between inflammation-based score and prognosis after R0 resection in patients with CRLM. Methods We retrospectively investigated 90 patients who underwent R0 resection for CRLM between 2008 and 2018. We calculated colon inflammatory index (CII) (CII0, low risk; CII1, intermediate risk; and CII2, high risk), modified Glasgow prognostic score, prognostic nutritional index, and CRP-to-albumin ratio; and retrospectively assessed the relationship between these scores, the clinicopathological features, and prognosis. Results The median follow-up period was 44 months (range, 2–101 months). Five-year relapse-free survival (RFS) (CII2; 12.5%, CII1; 14.5%, CII0; 42.9%) and 5-year overall survival (OS) (CII2; 32.4%, CII1; 25.4%, CII0; 57.7%) were significantly lower in the high CII groups (CII1–2) compared with the low CII group (CII0) (p = 0.021 and p = 0.006, respectively). CEA level was significantly higher in the high CII group than the low CII group (12.4 vs 7.3, p = 0.004). Multivariate analysis showed CII score as an independent predictor of RFS (hazard ratio 2.128, 95%CI 1.147–3.430, p = 0.015) and OS (hazard ratio 2.639, 95%CI 1.331–5.323, p = 0.005). Conclusion CII shows promise as a prognostic marker after R0 liver resection in patients with CRLM.
Background Hemostasis is very important for a safe surgery, particularly in endoscopic surgery. Accordingly, in the last decade, vessel-sealing systems became popular as hemostatic devices. However, their use is limited due to thermal damage to organs, such as intestines and nerves. We developed a new method for safe coagulation using a vessel-sealing system, termed flat coagulation (FC). This study aimed to evaluate the efficacy of this new FC method compared to conventional coagulation methods. Methods We evaluated the thermal damage caused by various energy devices, such as the vessel-sealing system (FC method using LigaSure™), ultrasonic scissors (Sonicision™), and monopolar electrosurgery (cut/coagulation/spray/soft coagulation (SC) mode), on porcine organs, including the small intestine and liver. Furthermore, we compared the hemostasis time between the FC method and conventional methods in the superficial bleeding model using porcine mesentery. Results FC caused less thermal damage than monopolar electrosurgery’s SC mode in the porcine liver and small intestine (liver: mean depth of thermal damage, 1.91 ± 0.35 vs 3.37 ± 0.28 mm; p = 0.0015). In the superficial bleeding model, the hemostasis time of FC was significantly shorter than that of electrosurgery’s SC mode (mean, 19.54 ± 22.51 s vs 44.99 ± 21.18 s; p = 0.0046). Conclusion This study showed that the FC method caused less thermal damage to porcine small intestine and liver than conventional methods. This FC method could provide easier and faster coagulation of superficial bleeds compared to that achieved by electrosurgery’s SC mode. Therefore, this study motivates for the use of this new method to achieve hemostasis with various types of bleeds involving internal organs during endoscopic surgeries.
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