Biomaterials‐Based Approaches to Tumor Spheroid and Organoid Modeling

Abstract

Evolving understanding of structural and biological complexity of tumors has stimulated development of physiologically relevant tumor models for cancer research and drug discovery. A major motivation for developing new tumor models is to recreate the 3D environment of tumors and context-mediated functional regulation of cancer cells. Such models overcome many limitations of standard monolayer cancer cell cultures. Under defined culture conditions, cancer cells self-assemble into 3D constructs known as spheroids. Additionally, cancer cells may recapitulate steps in embryonic development to self-organize into 3D cultures known as organoids. Importantly, spheroids and organoids reproduce morphology and biologic properties of tumors, providing valuable new tools for research, drug discovery, and precision medicine in cancer. This Progress Report discusses uses of both natural and synthetic biomaterials to culture cancer cells as spheroids or organoids, specifically highlighting studies that demonstrate how these models recapitulate key properties of native tumors. The report concludes with the perspectives on the utility of these models and areas of need for future developments to more closely mimic pathologic events in tumors.

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

“…The natural proteins used as cell culture matrices are collagen, gelatin, fibrin, silk protein (mainly referring to silk fibroin), poly‐ l ‐lysine (PLL), and soy protein . These proteins can interact with cells and supply physiologically relevant microenvironments to guide cellular behaviors by presenting componential cues . In addition, Matrigel and decellularized extracellular matrices (dECM) are typical animal‐derived mixtures of various polysaccharides (e.g., HA and heparan), proteins (e.g., collagen and laminin), and growth factors.…”

“…Synthetic hydrogels are often considered to be permissive biomaterials for cell culture due to their bioinert properties . The common synthetic polymers in previous reports include polyethylene glycol (PEG) and its derivates, polylactic acid (PLA), poly(lactic‐ co ‐glycolic acid) (PLGA), poly(vinyl alcohol) (PVA), poly(ε‐caprolactone) (PCL), polyacrylic acid (PAA), polyacrylamide (PAm), poly(2‐hydroxyethyl methacrylate) (PHEMA), and polyurethane (PU) . They are usually blended/modified with proteins (e.g., laminin) or peptides (e.g., Arg‐Gly‐Asp, RGD) to increase their biocompatibility for employment as 3D scaffolds.…”

Self‐Assembling Peptide Gels for 3D Prostate Cancer Spheroid Culture

“…In all matrices, E‐cadherin was enriched at cell–cell boundaries, and laminin‐332 appeared to be interspersed throughout the spheroid, with slight concentrations at cell–cell boundaries (Figure ). These results indicated that the LNCaP cells assume a disorganized, non‐polarized morphology within the spheroids, consistent with the behavior of LNCaP cells in previously investigated synthetic matrices such as functionalized hyaluronic acid …”

“…In response to the shortcomings of Matrigel, multiple synthetic 3D culture systems have received considerable interest . Synthetic matrices may avoid the most limiting aspects of Matrigel but must be designed to recapitulate the extracellular matrix's mechanical properties, transport properties, specific biological interactions, and degradation/remodeling processes that occur within the tumor microenvironment .…”

Design and Fabrication of Three-Dimensional Printed Scaffolds for Cancer Precision Medicine

“…Organoids have been utilized as microphysiological systems to study the important morphogenetic and functional hallmarks found in the human tissues. 42,43 Recently, organoids have emerged as alternative platforms to understand cancer biology. 44,45 Hence, organoid cultures have been established for many cancer types with success rates between 15% and 100%.…”