Tumoroids, a valid preclinical screening platform for monitoring cancer angiogenesis.

In recent years, biologists and clinicians have witnessed prominent advances in in vitro 3D culture techniques related to biomimetic human/animal tissue analogs. Numerous data have confirmed that unicellular and multicellular (tumoroids) tumor spheroids with dense native cells in certain matrices are sensitive and valid analytical tools for drug screening, cancer cell dynamic growth, behavior, etc. in laboratory settings. Angiogenesis/vascularization is a very critical biological phenomenon to support oxygen and nutrients to tumor cells within the deep layer of solid masses. It has been shown that endothelial cell (EC)-incorporated or -free spheroid/tumoroid systems provide a relatively reliable biological platform for monitoring the formation of nascent blood vessels in micron/micrometer scales. Besides, the paracrine angiogenic activity of cells within the spheroid/tumoroid systems can be monitored after being treated with different therapeutic approaches. Here, we aimed to collect recent advances and findings related to the monitoring of cancer angiogenesis using unicellular and multicellular tumor spheroids. Vascularized spheroids/tumoroids can help us in the elucidation of mechanisms related to cancer formation, development, and metastasis by monitoring the main influencing factors.

Endothelial progenitor cells for fabrication of engineered vascular units and angiogenesis induction.

The promotion of vascularization and angiogenesis in the grafts is a crucial phenomenon in the healing process and tissue engineering. It has been shown that stem cells, especially endothelial progenitor cells (EPCs), can stimulate blood vessel formation inside the engineered hydrogels after being transplanted into the target sites. The incorporation of EPCs into the hydrogel can last the retention time, long-term survival, on-target delivery effects, migration and differentiation into mature endothelial cells. Despite these advantages, further modifications are mandatory to increase the dynamic growth and angiogenesis potential of EPCs in in vitro and in vivo conditions. Chemical modifications of distinct composites with distinct physical properties can yield better regenerative potential and angiogenesis during several pathologies. Here, we aimed to collect recent findings related to the application of EPCs in engineered vascular grafts and/or hydrogels for improving vascularization in the grafts. Data from the present article can help us in the application of EPCs as valid cell sources in the tissue engineering of several ischemic tissues.

Multiprotein collagen/keratin hydrogel promoted myogenesis and angiogenesis of injured skeletal muscles in a mouse model.

Volumetric loss is one of the challenging issues in muscle tissue structure that causes functio laesa. Tissue engineering of muscle tissue using suitable hydrogels is an alternative to restoring the physiological properties of the injured area. Here, myogenic properties of type I collagen (0.5%) and keratin (0.5%) were investigated in a mouse model of biceps femoris injury. Using FTIR, gelation time, and rheological analysis, the physicochemical properties of the collagen (Col)/Keratin scaffold were analyzed. Mouse C2C12 myoblast-laden Col/Keratin hydrogels were injected into the injury site and histological examination plus western blotting were performed to measure myogenic potential after 15 days. FTIR indicated an appropriate interaction between keratin and collagen. The blend of Col/Keratin delayed gelation time when compared to the collagen alone group. Rheological analysis revealed decreased stiffening in blended Col/Keratin hydrogel which is favorable for the extrudability of the hydrogel. Transplantation of C2C12 myoblast-laden Col/Keratin hydrogel to injured muscle tissues led to the formation of newly generated myofibers compared to cell-free hydrogel and collagen groups (p < 0.05). In the C2C12 myoblast-laden Col/Keratin group, a low number of CD31+ cells with minimum inflammatory cells was evident. Western blotting indicated the promotion of MyoD in mice that received cell-laden Col/Keratin hydrogel compared to the other groups (p < 0.05). Despite the increase of the myosin cell-laden Col/Keratin hydrogel group, no significant differences were obtained related to other groups (p > 0.05). The blend of Col/Keratin loaded with myoblasts provides a suitable myogenic platform for the alleviation of injured muscle tissue.

Exosome-bearing hydrogels and cardiac tissue regeneration.

BACKGROUND: In recent years, cardiovascular disease in particular myocardial infarction (MI) has become the predominant cause of human disability and mortality in the clinical setting. The restricted capacity of adult cardiomyocytes to proliferate and restore the function of infarcted sites is a challenging issue after the occurrence of MI. The application of stem cells and byproducts such as exosomes (Exos) has paved the way for the alleviation of cardiac tissue injury along with conventional medications in clinics. However, the short lifespan and activation of alloreactive immune cells in response to Exos and stem cells are the main issues in patients with MI. Therefore, there is an urgent demand to develop therapeutic approaches with minimum invasion for the restoration of cardiac function. MAIN BODY: Here, we focused on recent data associated with the application of Exo-loaded hydrogels in ischemic cardiac tissue. Whether and how the advances in tissue engineering modalities have increased the efficiency of whole-based and byproducts (Exos) therapies under ischemic conditions. The integration of nanotechnology and nanobiology for designing novel smart biomaterials with therapeutic outcomes was highlighted. CONCLUSION: Hydrogels can provide suitable platforms for the transfer of Exos, small molecules, drugs, and other bioactive factors for direct injection into the damaged myocardium. Future studies should focus on the improvement of physicochemical properties of Exo-bearing hydrogel to translate for the standard treatment options.