Biohybrid Hydrogels for Tumoroid Culture

Abstract

Tumoroids are 3D in vitro models that recapitulate key features of in vivo tumors, such as their architecture — hypoxic center and oxygenated outer layer — in contrast with traditional 2D cell cultures. Moreover, they may be able to preserve the patient‐specific signature in terms of cell heterogeneity and mutations. Tumoroids are, therefore, interesting tools for improving the understanding of cancer biology, developing new drugs, and potentially designing personalized therapeutic plans. Currently, tumoroids are most often established using basement membrane extracts (BME), which provide a multitude of biological cues. However, BME are characterized by a lack of well‐defined composition, limited reproducibility, and potential immunogenicity as a consequence of their natural origin. Synthetic polymers can overcome these problems but lack structural and biochemical complexity, which can limit the functional capabilities of organoids. Biohybrid hydrogels consisting of both natural and synthetic components can combine their advantages and offer superior 3D culture systems. In this review, it is summarized efforts devoted to producing tumoroids using different types of biohybrid hydrogels, which are classified according to their crosslinking mechanism.

Leveraging Biomaterial Platforms to Study Aging-Related Neural and Muscular Degeneration

“…This is particularly the case for hydrogels, as their physio-chemical properties can be designed to be comparable to those of the native extracellular matrix (ECM), the polymeric meshwork that surrounds cells in vivo. Thus, hydrogels have become the preferred biomaterials for engineering 3D in vitro tissue models [52][53][54].…”

Exploiting Matrix Stiffness to Overcome Drug Resistance

“…This can be achieved by modifying the polymer with various peptide motifs or creating composite hydrogels with synthetic and natural biomaterials. 212,224,230,231 Another approach is decellularization of the actual ECM or TME from tumor tissue. 232−234 The decellularization can provide the tissue ECM/TME without any attached cells.…”

“…There are various approaches to mimic the native ECM and TME in terms of its composition, shape, and mechanobiological aspects. The first approach uses naturally derived materials such as collagen, alginate, gelatin, chitosan, and hyaluronic acid. ,− With those materials, the primary approach is to mimic the ECM components and to design studies with more minor scales or using similar polysaccharides to the ECM components to screen the behavior of the cells and 3D cell clusters (spheroid, organoids, tumoroids). − Composite structures can combine one or multiple naturally derived materials to mimic ECM construction. These approaches target the cells’ adhesiveness or 3D cell clusters into the designed mesh.…”

“…for cell adhesions and transducing primary survival signaling pathways. − To overcome these problems, hybrid-type hydrogel systems can be used. This can be achieved by modifying the polymer with various peptide motifs or creating composite hydrogels with synthetic and natural biomaterials. ,,, …”