Nowadays, bioprinting is rapidly evolving and hydrogels are a key component for its success. In this sense, synthesis of hydrogels, as well as bioprinting process, and cross-linking of bioinks represent different challenges for the scientific community. A set of unified criteria and a common framework are missing, so multidisciplinary research teams might not efficiently share the advances and limitations of bioprinting. Although multiple combinations of materials and proportions have been used for several applications, it is still unclear the relationship between good printability of hydrogels and better medical/clinical behavior of bioprinted structures. For this reason, a PRISMA methodology was conducted in this review. Thus, 1,774 papers were retrieved from PUBMED, WOS, and SCOPUS databases. After selection, 118 papers were analyzed to extract information about materials, hydrogel synthesis, bioprinting process, and tests performed on bioprinted structures. The aim of this systematic review is to analyze materials used and their influence on the bioprinting parameters that ultimately generate tridimensional structures. Furthermore, a comparison of mechanical and cellular behavior of those bioprinted structures is presented. Finally, some conclusions and recommendations are exposed to improve reproducibility and facilitate a fair comparison of results.

Mesenchymal stem cells have proven to be a promising alternative to conventional steroids to treat canine inflammatory bowel disease (IBD). However, their administration requires a washout period of immunosuppressive drugs that can lead to an exacerbation of the symptoms. Therefore, the feasibility and effects of the combined application of stem cells and prednisone in IBD-dogs without adequate response to corticosteroids was evaluated for the first time in this study over a long- term follow up. Two groups of dogs with IBD, one without treatment and another with prednisone treatment, received a single infusion of stem cells. The clinical indices, albumin and cobalamin were determined prior to the infusion and after one, three, six and 12 months. In both groups, all parameters significantly improved at each time point. In parallel, the steroid dosage was gradually reduced until it was suppressed in all patients a year after the cell therapy. Therefore, cell therapy can significantly and safely improve the disease condition in dogs with IBD receiving or not receiving prednisone. Furthermore, the steroid dosage can be significantly reduced or cancelled after the stem cell infusion. Their beneficial effects are stable over time and are long lasting.

Adipose-derived mesenchymal stem cells (Ad-MSCs) exhibit anti-inflammatory and immunomodulatory activities. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have been reported as novel biomarkers of the inflammatory state; however, they have never been examined in dogs with chronic inflammatory enteropathy (CIE) treated with Ad-MSCs. This study aimed to compare the clinical evolution and the changes in the NLR, PLR, and SII in dogs with CIE before and after cell therapy. Sixteen dogs with CIE were administered a single intravenous dose of Ad-MSCs. The canine chronic enteropathy clinical activity index (CCECAI), NLR, PLR, and SII were assessed before treatment (T0) and at 2 (T2) and 9 (T9) months post-treatment and compared over time and with the reference values obtained from a group of healthy dogs. NLR, PLR, and SII were significantly increased at T0 compared to the reference values, decreasing significantly over time. At T9, the NLR and SII did not differ from the reference values, but PLR remained above the reference values. A correlation was observed between CCECAI and the three markers. These findings show that the clinical improvement of dogs with CIE treated with Ad-MSCs is accompanied by a normalization of the inflammatory status.

Acute myocardial infarction (AMI) is a manifestation of ischemic heart disease where the immune system plays an important role in the re-establishment of homeostasis. We hypothesize that the anti-inflammatory activity of secretomes from menstrual blood-derived mesenchymal stromal cells (S-MenSCs) and IFNγ/TNFα-primed MenSCs (S-MenSCs*) may be considered a therapeutic option for the treatment of AMI. To assess this hypothesis, we have evaluated the effect of S-MenSCs and S-MenSCs* on cardiac function parameters and the involvement of immune-related genes using a porcine model of AMI. Twelve pigs were randomly divided into three biogroups: AMI/Placebo, AMI/S-MenSCs, and AMI/S-MenSCs*. AMI models were generated using a closed chest coronary occlusion-reperfusion procedure and, after 72 h, the different treatments were intrapericardially administered. Cardiac function parameters were monitored by magnetic resonance imaging before and 7 days post-therapy. Transcriptomic analyses in the infarcted tissue identified 571 transcripts associated with the Gene Ontology term Immune response, of which 57 were differentially expressed when different biogroups were compared. Moreover, a prediction of the interactions between differentially expressed genes (DEGs) and miRNAs from secretomes revealed that some DEGs in the infarction area, such as STAT3, IGFR1, or BCL6 could be targeted by previously identified miRNAs in secretomes from MenSCs. In conclusion, the intrapericardial administration of secretome early after infarction has a significant impact on the expression of immune-related genes in the infarcted myocardium. This confirms the immunomodulatory potential of intrapericardially delivered secretomes and opens new therapeutic perspectives in myocardial infarction treatment.

Acute myocardial infarction (AMI) is the consequence of an acute interruption of myocardial blood flow delimiting an area with ischemic necrosis. The loss of cardiomyocytes initiates cardiac remodeling in the myocardium, leading to molecular changes in an attempt to recover myocardial function. The purpose of this study was to unravel the differences in the molecular profile between ischemic and remote myocardium after AMI in an experimental model. To mimic human myocardial infarction, healthy pigs were subjected to occlusion of the mid-left anterior descending coronary artery, and myocardial tissue was collected from ischemic and remote zones for omics techniques. Comparative transcriptome analysis of both areas was accurately validated by proteomic analysis, resulting in mitochondrion-related biological processes being the most impaired mechanisms in the infarcted area. Moreover, Immune system process-related genes were up-regulated in the remote tissue, mainly due to the increase of neutrophil migration in this area. These results provide valuable information regarding differentially expressed genes and their biological functions between ischemic and remote myocardium after AMI, which could be useful for establishing therapeutic targets for the development of new treatments.