Review: bioreactor design towards generation of relevant engineered tissues: focus on clinical translation

In tissue engineering and regenerative medicine, studies that utilize 3D scaffolds for generating voluminous tissues are mostly confined in the realm of in vitro research and preclinical animal model testing. Bioreactors offer an excellent platform to grow and develop 3D tissues by providing conditions that mimic their native microenvironment. Aligning the bioreactor development process with a focus on patient care will aid in the faster translation of the bioreactor technology to clinics. In this review, we discuss the various factors involved in the design of clinically relevant bioreactors in relation to their respective applications. We explore the functional relevance of tissue grafts generated by bioreactors that have been designed to provide physiologically relevant mechanical cues on the growing tissue. The review discusses the recent trends in non‐invasive sensing of the bioreactor culture conditions. It provides an insight to the current technological advancements that enable in situ, non‐invasive, qualitative and quantitative evaluation of the tissue grafts grown in a bioreactor system. We summarize the emerging trends in commercial bioreactor design followed by a short discussion on the aspects that hamper the ‘push’ of bioreactor systems into the commercial market as well as ‘pull’ factors for stakeholders to embrace and adopt widespread utility of bioreactors in the clinical setting. Copyright © 2017 John Wiley & Sons, Ltd.     

Case report and a review of the literature of two patients with gastric MALToma and pulmonary metastasis

Gastric mucosa‐associated lymphoid tissue lymphoma (or MALToma) is a relatively rare form of low‐grade B‐cell malignancy arising from the mucosal associated lymphoid tissue of the stomach. The majority of cases can be treated with Helicobacter pylori eradication with good prognosis. However, few reports have been published on the treatment of gastric MALToma with pulmonary metastasis. We report two such cases managed with systemic chemotherapy. At the time of writing, one of the cases was in static disease while the other had complete remission. In both patients, pulmonary metastases were detected upon staging thoracic computed tomography.     

Perceval Sutureless Valve – are Sutureless Valves Here?

With the advent of transcatheter aortic valve implantation (TAVI) techniques, a renewed interest has developed in sutureless aortic valve concepts in the last decade. The main feature of sutureless aortic valve implantation is the speed of insertion, thus making implantation easier for the surgeon. As a result, cross clamp times and myocardial ischemia may be reduced. The combined procedures (CABG with AVR in particular) can be done with a short cross clamp time. Perceval valve also provides an increased effective orifice area as compared with a stented bioprosthesis. Sutureless implantation of the Perceval valve is not only associated with shorter cross-clamp and cardiopulmonary bypass times but improved clinical outcomes too. This review covers the sutureless aortic valves and their evolution, with elaborate details on Perceval S valve in particular (which is the most widely used sutureless valve around the globe).     

Dual role of tumor necrosis factor-alpha in hepatic ischemia-reperfusion injury: studies in tumor necrosis factor-alpha gene knockout mice

Although hepatic ischemia-reperfusion (IR) injury is partially mediated by tumor necrosis factor-alpha (TNF), we recently found that low-dose TNF before IR is hepatoprotective. We examined the seemingly conflicting roles of TNF in mediating liver injury in a partial hepatic IR model using TNF gene knockout (TNF ko) mice to allow TNF replacement at specified times. Compared with wild-type mice, TNF ko mice exhibit minimal alanine aminotransferase release and few hepatonecrotic lesions during the early (time, 2 hours) and late (time, 24 hours) phases of IR. TNF ko mice differed from wild-type mice in that TNF ko mice exhibited no activation or induction of nuclear factor-kappa B, p38, cyclin D1, or proliferating cell nuclear antigen after IR. A single low-dose TNF injection 1 minute before the onset of hepatic ischemia restored hepatic IR injury in TNF ko mice. To clarify the importance of TNF for hepatoprotection, preconditioning (10 minutes of ischemia and 10 minutes of reperfusion) was performed before the onset of IR for TNF ko mice whose capacity to undergo IR injury had been restored by TNF replacement. Ischemic preconditioning failed to protect these mice from TNF-augmented IR injury; however, following the administration of intravenous TNF (1 microg per kg body weight, which mimics the early increase in hepatic and plasma TNF levels that is mobilized by ischemic preconditioning), significant hepatoprotection against both the early and late phases of TNF-augmented IR injury was observed. In conclusion, TNF appears to mediate both the early and late phases of liver injury in hepatic IR, but it also is an essential mediator of hepatoprotective effects brought about by ischemic preconditioning.