Paper has recently attracted increasing attention as a substrate for various biomedical applications. By modifying its physical and chemical properties, paper can be used as an alternative to conventional cell culture substrates. Because it can be stacked into a three-dimensional (3D) structure, which can better mimic the in vivo cell microenvironment. Paper has shown great potential as a 3D cell culture platform for developing normal and diseased models. This platform gives precise control over extracellular matrix (ECM) composition as well as cell distribution and precise analysis of the interactions between cells. Paper-based platforms have been applied for pathophysiological studies and therapeutic intervention studies. In this paper, we first discuss the modifications of the physical and chemical properties of paper to develop various 2D and 3D cell culture platforms. We then review the applications of paper-based cell culture platforms for the construction of in vitro disease models, drug screening, and cell cryopreservation applications. Because of its advantages such as biocompatibility, eco-friendliness, cost efficiency, and ease of large-scale production, we believe that paper-based cell culture platforms would play an important role in the fields of biomedicine.
Paper, as one of the most ancient inventions, has led to tremendous changes to human beings along the history. In ancient Egyptians, Greek, and Romans, ‘papyruses’ (paper-like materials) were used to record information, while the modern paper that is composed of cellulose fibers held by hydrogen bonds was invented and used in ancient China. Ever since its invention, paper has been used in a wide range of fields, from the original writing substrates to sanitary products, packaging, and even bank notes (cash). Recently, with the significant advances in biotechnology, paper has been applied as substrates to a variety of biomedical applications, such as the production of low-cost and disposable analytical test papers in healthcare applications [1–3], flexible electronics [4,5], paper-based biosensors [6–8], and most recently, cell culture platforms [9–14]. This is mostly attributed to its attractive intrinsic properties, such as biocompatibility, ease of chemical and physical modifications, cost efficiency, eco-friendliness, and ease of largescale manufacturing.
Conclusion and future perspectives
Paper has emerged as a promising cell culture substrate that could offer high potentials in developing 2D and 3D cell culture platforms, although modifications of its chemical and physical properties are required. For instance, paper needs to be coated with some beneficial chemical groups to provide binding sites for cell attachment or its surface roughness and stiffness can be adjusted to allow a better cell growth. Existing 3D cell cultures based on hydrogel and porous scaffold are mostly nonuniform in dimension, failing to provide information about cells in different areas within a single 3D construct, and this physical isolation of cells from different regions of the 3D construct are needed before staining and biochemical characterization [10,90]. Meanwhile, paper-based cell culture platforms that have been used in many biomedical applications show better results. For example, the CiGiP system can better mimic condition of in vivo microenvironment to create 3D normal or diseased tissue models, such as ischemic diseased models[9–12].