Emerging biomaterials and technologies to control stem cell fate and patterning in engineered 3D tissues and organoids

Abstract

The ability to create complex three-dimensional cellular models that can effectively replicate the structure and function of human organs and tissues in vitro has the potential to revolutionize medicine. Such models could facilitate the interrogation of developmental and disease processes underpinning fundamental discovery science, vastly accelerate drug development and screening, or even be used to create tissues for implantation into the body. Realization of this potential, however, requires the recreation of complex biochemical, biophysical, and cellular patterns of 3D tissues and remains a key challenge in the field. Recent advances are being driven by improved knowledge of tissue morphogenesis and architecture and technological developments in bioengineering and materials science that can create the multidimensional and dynamic systems required to produce complex tissue microenvironments. In this article, we discuss challenges for in vitro models of tissues and organs and summarize the current state-of-the art in biomaterials and bioengineered systems that aim to address these challenges. This includes both top-down technologies, such as 3D photopatterning, magnetism, acoustic forces, and cell origami, as well as bottom-up patterning using 3D bioprinting, microfluidics, cell sheet technology, or composite scaffolds. We illustrate the varying ways that these can be applied to suit the needs of different tissues and applications by focussing on specific examples of patterning the bone-tendon interface, kidney organoids, and brain cancer models. Finally, we discuss the challenges and future prospects in applying materials science and bioengineering to develop high-quality 3D tissue structures for in vitro studies.

Stem cell-derived intestinal organoids: a novel modality for IBD

“…Scaffold-based culture systems allow cells to attach to a scaffold composed of solid particles or liquid gels, which are made to float in the culture medium by gentle agitation [ 38 ]. With the development of technology, scaffold appears in more and more forms to solve different problems [ 67 ]. According to the source of scaffold, it can be divided into scaffold supported by natural extracellular matrix (ECM) and scaffold supported by synthetic materials [ 38 , 67 , 79 ].…”

“…With the development of technology, scaffold appears in more and more forms to solve different problems [ 67 ]. According to the source of scaffold, it can be divided into scaffold supported by natural extracellular matrix (ECM) and scaffold supported by synthetic materials [ 38 , 67 , 79 ].…”

“…Synthetic materials have consistency, stability, and biocompatibility bias, and cannot provide growth factors and small molecule compounds needed for cell culture. The synthetic scaffold can be divided into hydrogel and solid scaffold according to the attachment method of cells [ 67 , 79 ].…”

“…Hydrogels can alter cell signaling by increasing or decreasing protein concentration and changing the density of cell adhesion ligands [ 39 , 66 ]. Polymeric gelling agents can be pre-designed, and functional additives can be adjusted as required, allowing the hydrogel to obtain specific properties such as temperature, magnetic properties, and pH, and meet a wider range of research requirements [ 39 , 40 , 67 ].…”

“…Solid scaffolds prepared by applying biodegradable polymers, such as PLA, have been extensively studied for their good biocompatibility and proper porous structure [ 89 , 90 ]. Enables efficient 3D cell attachment for superior cell viability [ 67 , 89 , 91 ].…”