Cancer immunotherapy has become an emerging strategy recently producing durable immune responses in patients with varieties of malignant tumors. However, the main limitation for the broad application of immunotherapies still to reduce side effects by controlling and regulating the immune system. In order to improve both efficacy and safety, biomaterials have been applied to immunotherapies for the specific modulation of immune cells and the immunosuppressive tumor microenvironment. Recently, researchers have constantly developed biomaterials with new structures, properties and functions. This review provides the most recent advances in the delivery strategies of immunotherapies based on localized biomaterials, focusing on the implantable and injectable biomaterial scaffolds. Finally, the challenges and prospects of applying implantable and injectable biomaterial scaffolds in the development of future cancer immunotherapies are discussed.
The strategy of using a combination of scaffold-based physical and biochemical cues to repair spinal cord injury (SCI) has shown promising results. However, integrating conductivity and neurotrophins into a scaffold that recreates the electrophysiologic and nutritional microenvironment of the spinal cord (SC) remains challenging. In this study we investigated the therapeutic potential of a soft thermo-sensitive polymer electroactive hydrogel (TPEH) loaded with nerve growth factor (NGF) combined with functional electrical stimulation (ES) for the treatment of SCI. The developed hydrogel exhibits outstanding electrical conductance upon ES, with continuous release of NGF for at least 24 days. In cultured nerve cells, TPEH loaded with NGF promoted the neuronal differentiation of neural stem cells and axonal growth, an effect that was potentiated by ES. In a rat model of SCI, TPEH combined with NGF and ES stimulated endogenous neurogenesis and improved motor function. These results indicate that the TPEH scaffold that combines ES and biochemical cues can effectively promote SC tissue repair.
BackgroundMucinous adenocarcinoma (MC) is a special kind of colorectal adenocarcinoma that occurs more frequently in young patients and females, but the prognostic effect of lymph nodes in MC patients is unclear. This population-based study was conducted to analyze the prognostic value of the number of lymph nodes examined in different stages of colorectal MC.MethodsWe included 17,001 MC patients from the Surveillance, Epidemiology, and End Results program database between 2003 and 2013, of which 12,812 (75%) had >12 lymph nodes examined.ResultsCompared to the group with insufficient lymph nodes examined, patients with more lymph nodes (>12) examined tended to come from east and central America, were more frequently female and young, were diagnosed after 2008, had larger-sized tumors of less differentiated grade and in later stages, had not received radiation therapy and had more positive nodal status. Patients with more lymph nodes (>12) examined demonstrated significantly better survival than those with insufficient lymph nodes examined only in stages II and III (stage II: overall, P<0.001; cancer-specific, P<0.001; stage III: overall, P=0.093; cancer-specific, P=0.032), even though the overall (P<0.001) and cancer-specific survival (P<0.001) showed significant differences between the two groups. Both univariate (overall, HR=0.739, 95% CI=0.703–0.777, P<0.001; cancer-specific, HR=0.742, 95% CI=0.698–0.788, P<0.001) and multivariate (overall, HR=0.601, 95% CI=0.537–0.673, P<0.001; cancer-specific, HR=0.582, 95% CI=0.511–0.664, P<0.001) Cox proportional hazards models verified the association between >12 lymph nodes examined and better survival.ConclusionMore number of lymph nodes (.12) examined significantly increased the survival probability of MC patients in stages II and III, but had no significant influence on patients in stages I and IV, indicating the effect of number of lymph nodes examined was a stage-dependent prognostic factor in clinical utility.
The behavior of nerve cells plays a crucial role in nerve regeneration. The mechanical, topographical, and electrical microenvironment surrounding nerve cells can activate cellular signaling pathways of mechanical transduction to affect the behavior of nerve cells. Recently, biological scaffolds with various physical properties have been developed as extracellular matrix to regulate the behavior conversion of nerve cell, such as neuronal neurite growth and directional differentiation of neural stem cells, providing a robust driving force for nerve regeneration. This review mainly focused on the biological basis of nerve cells in mechanical transduction. In addition, we also highlighted the effect of the physical cues, including stiffness, mechanical tension, two-dimensional terrain, and electrical conductivity, on neurite outgrowth and differentiation of neural stem cells and predicted their potential application in clinical nerve tissue engineering.
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