Remote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia–reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury. Thirty rats were randomly assigned to four groups: I/R; I/R + RIPC; Sham; Sham + RIPC. Animals were anesthetized and the superior mesenteric artery was clamped for 30 min, followed by 60 min of reperfusion. RIPC-treated rats received 3 × 5 min of bilateral hindlimb I/R prior to surgery, sham groups obtained laparotomy without clamping. After I/R injury serum/tissue was analyzed for: Mucosal damage, Caspase-3/7 activity, expression of cell stress proteins, hydrogen peroxide (H2O2) and malondialdehyde (MDA) production, Hypoxia-inducible factor-1α (HIF-1α) protein expression and matrix metalloproteinase (MMP) activity. Intestinal I/R resulted in increased mucosal injury (P < 0.001) and elevated Caspase-3/7 activity (P < 0.001). RIPC significantly reduced the histological signs of intestinal I/R injury (P < 0.01), but did not affect Caspase-3/7 activity. Proteome profiling suggested a RIPC-mediated regulation of several cell stress proteins after I/R injury: Cytochrome C (+ 157%); Cited-2 (− 39%), ADAMTS1 (+ 74%). Serum concentrations of H2O2 and MDA remained unchanged after RIPC, while the reduced intestinal injury was associated with increased HIF-1α levels. Measurements of MMP activities in serum and intestinal tissue revealed an attenuated gelatinase activity at 130 kDa within the serum samples (P < 0.001) after RIPC, while the activity of MMPs within the intestinal tissue was not affected by I/R injury or RIPC. RIPC ameliorates intestinal I/R injury in rats. The underlying mechanisms may involve HIF-1α protein expression and a decreased serum activity of a 130 kDa factor with gelatinase activity.

In various disciplines, robotic-assisted surgery is a well-proven routine procedure, but have never been established in vascular surgery so far. This review summarizes the results to date of robotic-assisted abdominal aortic surgery (RAAS) in the treatment of aorto-iliac occlusive disease (AIOD) and abdominal aortic aneurysm (AAA). Web-based literature search of robotic-assisted surgical procedures on the abdominal aorta and iliac arteries between 1990 and 2020 including the Cochrane Library, OVID Medline, Embase, and PubMed medical databases. All studies conducting Robotic-assisted surgery were included in the quantitative analysis regarding operative and cross-clamping times, conversion rates, mortality and morbidity within the first 30 days, and in-hospital stay. Case reports and case studies (< 5 patients) were not included. Twenty-four studies were deemed thematically eligible for inclusion; after exclusion of duplicate publications, nine met the inclusion criteria for further analysis. A total of 850 patients who had either abdominal aortic aneurysm or aorto-iliac occlusive disease underwent RAAS. One study of abdominal aortic aneurysm, three of aorto-iliac occlusive disease, and five studies of both disease entities were analyzed quantitatively. For AAA, conversion rates ranged from 13.1 to 20% and perioperative mortality ranged from 0 to 1.6% with in-hospital stay of 7 days. For aorto-iliac occlusive disease, conversion rates ranged from 0 to 20%, and perioperative mortality ranged from 0 to 3.6% with in-hospital stay of 5–8 days. RAAS has been shown to be technically feasible with acceptable short-term outcomes and questionable benefits in terms of in-hospital stay and complication rates. RAAS is currently considered only an outsider procedure. Randomized-controlled trials are indispensable for regular use in vascular surgery as well as a clear approval situation for the vascular sector.

Background: Macrophages are involved in tissue homeostasis, angiogenesis and immunomodulation. Proangiogenic and anti-inflammatory macrophages (regulatory macrophages, Mreg) can be differentiated in-vitro from CD14⁺ monocytes by using a defined cell culture medium and a stimulus of IFNγ. Aim of the study: To scrutinize the potential impact of temporal IFNγ exposure on macrophage differentiation as such exposure may lead to the emergence of a distinct and novel macrophage subtype. Methods: Differentiation of human CD14⁺ monocytes to Mreg was performed using a GMP compliant protocol and administration of IFNγ on day 6. Monocytes from the same donor were in parallel differentiated to Mreg_IFNγ0 using the identical protocol but with administration of IFNγ on day 0. Cell characterization was performed using brightfield microscopy, automated and metabolic cell analysis, transmission electron microscopy, flow cytometry, qPCR and secretome profiling. Results: Mreg and Mreg_IFNγ0 showed no differences in cell size and volume. However, phenotypically Mreg_IFNγ0 exhibited fewer intracellular vesicles/vacuoles but larger pseudopodia-like extensions. Mreg_IFNγ0 revealed reduced expression of IDO and PD-L1 (P < 0.01 for both). They were positive for CD80, CD14, CD16 and CD38 (P < 0.0001vs. Mreg for all), while the majority of Mreg_IFNγ0 did not express CD206, CD56, and CD103 on their cell surface (P < 0.01 vs. Mreg for all). In terms of their secretomes, Mreg_IFNγ0 differed significantly from Mreg. Mreg_IFNγ0 media exhibited reduced levels of ENA-78, Osteopontin and Serpin E1, while the amounts of MIG (CXCL9) and IP10 were increased. Conclusion: Exposing CD14⁺ monocytes to an alternatively timed IFNγ stimulation results in a novel macrophage subtype which possess additional M1-like features (Mreg_IFNγ0). Mreg_IFNγ0 may therefore have the potential to serve as cellular therapeutics for clinical applications beyond those covered by M2-like Mreg, including immunomodulation and tumor treatment.

A novel developed 4D bioprinting technique is used for the manufacturing of human‐scale, small‐diameter vascular grafts. Accordingly, a bio‐ink is synthesized from a hybrid molecule containing sodium alginate (SA) and collagen peptide (COP). Endothelial progenitor cells (EPC) isolated from human whole blood are integrated into the bioartificial vascular graft as an autologous cell source. Likewise, human umbilical vein endothelial cells (HUVEC) are used as experimental standard. The evolving vascular grafts are printed by a customized 4D bioprinter into CaCl₂ support medium for rapid cross‐linking inducing the temporospatial shaping of the grafts. After culturing for 21 days, histological and ultrastructural analyses of the bioartificial vascular grafts reveal a well‐organized matrix with imbedded EPC or HUVEC. Live‐3D‐cell–imaging and cell viability assays demonstrate a multitude of vital and metabolically active cells. Biomechanics of the grafts are proven to be comparable to human saphenous veins. Coagulation analysis reveals low thrombogenicity and high functional integrity of the vascular grafts. Surgical implantation of the grafts in a perfused cadaver model can be performed effectively and without technical issues. Finally, the current study describes for the first time the 4D bioprinting and characterization of a small‐diameter, human‐scale vascular graft for putative clinical translation.

Remote ischemic preconditioning (RIPC) protects the heart against myocardial ischemia/reperfusion (I/R) injury and recent work also suggested chronic remote ischemic conditioning (cRIPC) for cardiovascular protection. Based on current knowledge that systemic immunomodulatory effects of RIPC and the anti-inflammatory capacity of monocytes might be involved in cardiovascular protection, the aim of our study was to evaluate whether RIPC/cRIPC blood plasma is able to induce in-vitro angiogenesis, identify responsible factors and evaluate the effects of RIPC/cRIPC on cell surface characteristics of circulating monocytes. Eleven healthy volunteers were subjected to RIPC/cRIPC using a blood pressure cuff inflated to > 200 mmHg for 3 × 5 min on the upper arm. Plasma and peripheral blood monocytes were isolated before RIPC (Control), after 1 × RIPC (RIPC) and at the end of 1 week of daily RIPC (cRIPC) treatment. Plasma concentrations of potentially pro-angiogenic humoral factors (CXCL5, Growth hormone, IGFBP3, IL-1α, IL-6, Angiopoietin 2, VEGF, PECAM-1, sTie-2, IL-8, MCSF) were measured using custom made multiplex ELISA systems. Tube formation assays for evaluation of in-vitro angiogenesis were performed with donor plasma, monocyte conditioned culture media as well as IL-1α, CXCL5 and Growth hormone. The presence of CD14, CD16, Tie-2 and CCR2 was analyzed on monocytes by flow cytometry. Employing in-vitro tube formation assays, several parameters of angiogenesis were significantly increased by cRIPC plasma (number of nodes, P < 0.05; number of master junctions, P < 0.05; number of segments, P < 0.05) but were not influenced by culture medium from RIPC/cRIPC treated monocytes. While RIPC/cRIPC treatment did not lead to significant changes of the median plasma concentrations of any of the selected potentially pro-angiogenic humoral factors, in-depth analysis of the individual subjects revealed differences in plasma levels of IL-1α, CXCL5 and Growth hormone after RIPC/cRIPC treatment in some of the volunteers. Nevertheless, the positive effects of RIPC/cRIPC plasma on in-vitro angiogenesis could not be mimicked by the addition of the respective humoral factors alone or in combination. While monocyte conditioned culture media did not affect in-vitro tube formation, flow cytometry analyses of circulating monocytes revealed a significant increase in the number of Tie-2 positive and a decrease of CCR2 positive monocytes after RIPC/cRIPC (Tie-2: cRIPC, P < 0.05; CCR2: RIPC P < 0.01). Cardiovascular protection may be mediated by RIPC and cRIPC via a regulation of plasma cytokines as well as changes in cell surface characteristics of monocytes (e.g. Tie-2). Our results suggest that a combination of humoral and cellular factors could be responsible for the RIPC/cRIPC mediated effects and that interindividual variations seem to play a considerable part in the RIPC/cRIPC associated mechanisms.