Abstract
3-dimensional (3D) in vitro models were developed in order to mimic the complexity of real organ/tissue in a dish. They offer new possibilities to model biological processes in more physiologically relevant ways which can be applied to a myriad of applications including drug development, toxicity screening and regenerative medicine. Hydrogels are the most relevant tissue-like matrices to support the development of 3D in vitro models since they are in many ways akin to the native extracellular matrix (ECM). For the purpose of further improving matrix relevance or to impart specific functionalities, composite hydrogels have attracted increasing attention. These could incorporate drugs to control cell fates, additional ECM elements to improve mechanical properties, biomolecules to improve biological activities or any combinations of the above. In this Review, recent developments in using composite hydrogels laden with cells as biomimetic tissue- or organ-like constructs, and as matrices for multi-cell type organoid cultures are highlighted. The latest composite hydrogel systems that contain nanomaterials, biological factors, and combinations of biopolymers (e.g., proteins and polysaccharide), such as Interpenetrating Networks (IPNs) and Soft Network Composites (SNCs) are also presented. While promising, challenges remain. These will be discussed in light of future perspectives toward encompassing diverse composite hydrogel platforms for an improved organ environment in vitro.
Highlights
In vivo, cells are embedded within a complex 3D microenvironment composed of combinations of extracellular matrix (ECM) components, biological factors, neighboring cells etc. (Benders et al, 2013; Huang et al, 2017)
Validation of reliability and reproducibility of 3D tissue models will be critical for future adoption as standard testing platforms and for clinical transplantation. This is especially important for 3D culture models that rely on decellularized ECM or natural ECM components to guide cell fate, because these are often poorly defined with limited reproducibility due to batch-to-batch variations
Composite hydrogels with reproducible properties have the potential to improve the efficiency and consistency of 3D cultures compared with traditional, single component matrices
Summary
Cells are embedded within a complex 3D microenvironment composed of combinations of extracellular matrix (ECM) components, biological factors, neighboring cells etc. (Benders et al, 2013; Huang et al, 2017). The essence of developing 3D in vitro models is to build tissue- or organ-like constructs that have similar structural and/or functional characteristics as real tissues or organs with the recapitulation of multiple cell type interactions and biological responses. Organoids lack complete structural and functional features of real tissues or organs, their relative ease of bio-assembly, reproducibility, and the ability to capture cellular heterogeneity allows them to be suitable platforms for screening drugs and diseases as alternative to 2D cell-based assays and animal models (Clevers, 2016; Nguyen et al, 2018). While bio-printing functional tissues and organs for clinical transplantation has not become a reality, the method has provided new impetus for the evolvement of more sophisticated in vitro models that bring us closer to real tissues and organs in a dish
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