Transparent Microcrystalline Cellulose/Polyvinyl Alcohol Paper as New Platform for 3D Cell Culture.

Tang, Ruihua; Liu, Li Na; Li, Min; Yao, Xue; Yang, Yaowei; Zhang, Sufeng; Li, Fei

Multilayered and stacked cellulose paper has emerged as a promising platform for construction of three-dimensional (3D) cell culture due to its low cost, good biocompatibility and high porosity. However, its poor light transmission makes it challenging to directly and clearly monitor cell behaviors (e.g., growth and proliferation) on the paper-based platform using optical microscope. In this work, we developed a transparent microcrystalline cellulose/polyvinyl alcohol (MCC/PVA) paper with irregular pores through dissolution and regeneration of microcrystalline nanocellulose (MCC), addition of porogen reagent (NaCl) and subsequently dipping in PVA solutions. The transparent MCC paper displays high porosity (up to 90%), adjustable pore size (between 23 μm and 46 μm) and large thickness (from 315 μm to 436 μm) and high light transmission under water (>95%). Through further modification of transparent MCC paper with PVA, the obtained transparent MCC/PVA paper shows enhanced mechanical properties (dry and wet strengths), good hydrophilicity (with a contact angle of 70.8°) and improved biocompatibility (cell viability up to 90%). By stacking and destacking multiple layers of the transparent MCC/PVA paper, it has been used for both 2D and 3D cell culture platforms. The transparent MCC/PVA paper under water enables both direct observation of cell morphology by optical microscope via naked eyes and fluorescence microscope after staining. We envision that the developed transparent MCC/PVA paper holds great potential for future applications in various bioanalytical and biomedical fields, such as drug screening, tissue engineering and organ-on-chips.