![]() ![]() ![]() However, other technologies such as hanging drop, low-binding plastic, pyramid plates, etc., are also available for culturing cells in 3D. We will focus on the “physical” differently shaped hydrogel formats like beads, moldable gels, injectable gels and macroporous structures. There are several formats and materials available that enable 3D cell culture. To better predict the clinical outcome of medical treatments such as chemotherapy, the selection of drugs can be optimized based on the response from isolated cancer cells from the patient. Reducing the number of animal trials would also be in alignment with the principles of the 3Rs (Replacement, Reduction, Refinement) which are considered an ethical framework for conducting scientific experiments using animals humanely. Consequently, appropriate cell models would also reduce the need for animal trials, especially for toxicity assays. Most drugs fail due to efficacy, which likely could have been revealed at an earlier time point with more reliable cell culture models. One example relates to drug development where, currently, only 12% of drugs that enter clinical trials are eventually approved for use in humans. The significance and potential of in vitro cell culture studies are great considering the need for more cost efficient development of new drugs, time efficient treatment of cancer patients, and an understanding of developmental biology and mechanisms of stem cell differentiation. There is no doubt that 3D systems are biologically more relevant and 3D cell culture is therefore expected to also provide cellular responses that will be of higher biological relevance. Significant changes comparing cells cultured in 2D compared to 3D can be found associated with key biological processes such as immune system activation, defense response, cell adhesion and tissue development. A powerful and reliable tool for evaluation of cell behavior is gene expression data. However, forcing cells to adapt to an artificial flat and a rigid surface can alter cell metabolism and change or reduce functionality, thereby providing results that may not be similar to expected behavior in vivo. A few of these are: cell culture and tumor formation of malignant cells more relevant drug development and testing in vitro culture of multi-cellular tissue for later implantation.ĭespite the major differences compared to the naturally occurring 3D cell environments found in tissue, most cell culture studies in vitro are performed using cells cultured as monolayers (2D) on hard plastic or glass surfaces because of the ease, convenience and high cell viability associated with this culture method. Growing cells in 3D adds a variety of aspects more physiologically significant than would be possible in 2D. Today, there is a need for more realistic and controllable culture systems that support cell growth, organization and differentiation essentially as found in tissues and organs. Since the 1940s, cells have been cultured, often attached to glass or plastic surfaces, essentially in two dimensions. The world around us, including the human body, is constructed in three dimensions. Now, several commercial products based on alginate are being used as 3D cell culture systems that also demonstrate the possibility of replacing or regenerating tissue. Historically, cells were encapsulated in alginate droplets cross-linked with calcium for the development of artificial organs. Alginate has a history and a future in 3D cell culture. Finally, delayed gelling, injectable, alginate systems show utility in the translation of in vitro cell culture to in vivo tissue engineering applications. Newer matrices such as macroporous scaffolds are now entering the 3D cell culture product market. Droplets or beads have been utilized since the 1980s for immobilizing cells. Gelation of alginate with concomitant immobilization of cells can take various forms. The use of peptide-coupled alginate can control cell–matrix interactions. Gel elasticity as well as hydrogel stability can be impacted by the type of alginate used, its concentration, the choice of gelation technique (ionic or covalent), and divalent cation chosen as the gel inducing ion. Knowledge of alginate chemical structure and functionality are shown to be important parameters in design of alginate-based matrices for cell culture. This review compiles information regarding the use of alginate, and in particular alginate hydrogels, in culturing cells in 3D. ![]()
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