8/3/2023 0 Comments 3d model of fibrin jmol![]() They also offer the opportunity to understand the biological processes of cells, tissues, and organs in vitro, and have been applied in the fields of tumor research, tissue generation, disease screenings, and more ( Huh et al., 2011 Ranga et al., 2014 Sambale et al., 2015 Alhaque et al., 2018 Drost and Clevers, 2018). Thus, 3D in vitro models are viable alternatives to animal studies to screen biochemical compounds for drug development. Their 3D microenvironment enable cells to interact with neighboring cells and matrix components in all directions (instead of directly interacting with a synthetic hard plastic surface in the case of 2D cultures), and in doing so, guide cellular behavior and functions under more physiologically relevant conditions ( Alhaque et al., 2018 Kaushik et al., 2018 Hong et al., 2019). For decades, 3D in vitro models have captured the imagination of scientists since they could mimic some of the structural and functional characteristics of native tissues and organs ( Sart et al., 2014 Knight and Przyborski, 2015 Bersini et al., 2016). Unfortunately, animal models are time consuming, expensive, raises ethical dilemmas and are often limited by species-specific anatomy and physiology ( Elliott and Yuan, 2011). Therefore, animal tests are usually conducted after 2D cell culture studies, before clinical trials. 2D cell culture assays may provide misleading and non-predictive data as they are unable to capture the anatomical and biochemical complexities of native tissues and organs ( Horrobin, 2003 Hogenesch and Nikitin, 2012 Edmondson et al., 2014). However, researchers have been aware of the limitations of 2D compared to 3D cultures since the 1970s ( Elsdale and Bard, 1972). 2D (monolayer) cell cultures as the common practice in cell-based assays are simple, high throughput options for various biomedical research purposes ( Ashammakhi et al., 2018). ![]() Under this microenvironment, cells are constantly spreading, migrating, proliferating, differentiating, and interacting with each other and their surroundings in response to biological stimuli. In vivo, cells are embedded within a complex 3D microenvironment composed of combinations of extracellular matrix (ECM) components, biological factors, neighboring cells etc. These will be discussed in light of future perspectives toward encompassing diverse composite hydrogel platforms for an improved organ environment in vitro. 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. 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. 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. For the purpose of further improving matrix relevance or to impart specific functionalities, composite hydrogels have attracted increasing attention. 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). 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. Chan School of Public Health, Harvard University, Boston, MA, United Statesģ-dimensional (3D) in vitro models were developed in order to mimic the complexity of real organ/tissue in a dish. 4Center for Nanotechnology and Nanotoxicology, Harvard T.H.3Skin Research Institute of Singapore, Singapore, Singapore.2Environmental Chemistry & Materials Centre, Nanyang Environment and Water Research Institute (NEWRI), Nanyang Technological University, Singapore, Singapore.1School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore. ![]() Zhitong Zhao 1 †, Catarina Vizetto-Duarte 1 †, Zi Kuang Moay 1, Magdiel Inggrid Setyawati 1, Moumita Rakshit 1, Mustafa Hussain Kathawala 1 and Kee Woei Ng 1,2,3,4 * ![]()
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