Cancer is one of the greatest threats facing our society, being the second leading cause of death globally. Currents strategies for cancer diagnosis consist of the extraction of a solid tissue from the affected area. This sample enables the study of specific biomarkers and the genetic nature of the tumor. However, the tissue extraction is risky and painful for the patient and in some cases is unavailable in inaccessible tumors. Moreover, a solid biopsy is expensive and time consuming and cannot be applied repeatedly. New alternatives that overcome these drawbacks are rising up nowadays, such as liquid biopsy. A liquid biopsy is the analysis of biomarkers in a non-solid biological tissue, mainly blood, which has remarkable advantages over the traditional method; it has no risk, it is non-invasive and painless, it does not require surgery and reduces cost and diagnosis time. The most studied cancer non-invasive biomarkers are circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. These circulating biomarkers play a key role in the understanding of metastasis and tumorigenesis, which could provide a better insight into the evolution of the tumor dynamics during treatment and disease progression. Improvements in isolation technologies, based on a higher grade of purification of CTCs, exosomes, and ctDNA, will provide a better characterization of biomarkers and give rise to a wide range of clinical applications, such as early detection of diseases, and the prediction of treatment responses due to the discovery of personalized tumor-related biomarkers.

New biocompatible materials have enabled the direct 3D printing of complex functional living tissues, such as skeletal and cardiac muscle. Gelatinmethacryloyl (GelMA) is a photopolymerizable hydrogel composed of natural gelatin functionalized with methacrylic anhydride. However, it is difficult to obtain a single hydrogel that meets all the desirable properties for tissue engineering. In particular, GelMA hydrogels lack versatility in their mechanical properties and lasting 3D structures. In this work, a library of composite biomaterials to obtain versatile, lasting, and mechanically tunable scaffolds are presented. Two polysaccharides, alginate and carboxymethyl cellulose chemically functionalized with methacrylic anhydride, and a synthetic material, such as poly(ethylene glycol) diacrylate are combined with GelMA to obtain photopolymerizable hydrogel blends. Physical properties of the obtained composite hydrogels are screened and optimized for the growth and development of skeletal muscle fibers from C2C12 murine cells, and compared with pristine GelMA. All these composites show high resistance to degradation maintaining the 3D structure with high fidelity over several weeks. Altogether, in this study a library of biocompatible novel and totally versatile composite biomaterials are developed and characterized, with tunable mechanical properties that give structure and support myotube formation and alignment.

The spleen is a secondary lymphoid organ specialized in the filtration of senescent, damaged, or infected red blood cells.

Cancer represents one of the conditions with the most causes of death worldwide. Common methods for its diagnosis are based on tissue biopsies—the extraction of tissue from the primary tumor, which is used for its histological analysis. However, this technique represents a risk for the patient, along with being expensive and time-consuming and so it cannot be frequently used to follow the progress of the disease. Liquid biopsy is a new cancer diagnostic alternative, which allows the analysis of the molecular information of the solid tumors via a body fluid draw. This fluid-based diagnostic method displays relevant advantages, including its minimal invasiveness, lower risk, use as often as required, it can be analyzed with the use of microfluidic-based platforms with low consumption of reagent, and it does not require specialized personnel and expensive equipment for the diagnosis. In recent years, the integration of sensors in microfluidics lab-on-a-chip devices was performed for liquid biopsies applications, granting significant advantages in the separation and detection of circulating tumor nucleic acids (ctNAs), circulating tumor cells (CTCs) and exosomes. The improvements in isolation and detection technologies offer increasingly sensitive and selective equipment’s, and the integration in microfluidic devices provides a better characterization and analysis of these biomarkers. These fully integrated systems will facilitate the generation of fully automatized platforms at low-cost for compact cancer diagnosis systems at an early stage and for the prediction and prognosis of cancer treatment through the biomarkers for personalized tumor analysis.

Three-dimensional (3D) bioprinted culture systems allow to accurately control microenvironment components and analyze their effects at cellular and tissue levels. The main objective of this study was to identify, quantify and localize the effects of physical-chemical communication signals between tumor cells and the surrounding biomaterial stiffness over time, defining how aggressiveness increases in SK-N-BE(2) neuroblastoma (NB) cell line. Biomimetic hydrogels with SK-N-BE(2) cells, methacrylated gelatin and increasing concentrations of methacrylated alginate (AlgMA 0%, 1% and 2%) were used. Young’s modulus was used to define the stiffness of bioprinted hydrogels and NB tumors. Stained sections of paraffin-embedded hydrogels were digitally quantified. Human NB and 1% AlgMA hydrogels presented similar Young´s modulus mean, and orthotopic NB mice tumors were equally similar to 0% and 1% AlgMA hydrogels. Porosity increased over time; cell cluster density decreased over time and with stiffness, and cell cluster occupancy generally increased with time and decreased with stiffness. In addition, cell proliferation, mRNA metabolism and antiapoptotic activity advanced over time and with stiffness. Together, this rheological, optical and digital data show the potential of the 3Din vitrocell model described herein to infer how intercellular space stiffness patterns drive the clinical behavior associated with NB patients.