Paper-Based Microfluidics for Tissue Engineering and Regenerative Medicine

Background: Paper-based microfluidics have gained significant attention as cost-effective and biocompatible platforms for various biological and medical applications. These devices facilitate the replication of complex tissue environments and offer a versatile alternative to traditional microfluidic systems. Summary: This review highlights recent advances in paper-based microfluidics for tissue engineering and regenerative medicine. Key applications include 3D cell culture, bioanalysis assays, and high-throughput screening systems. Innovations in fabrication methods, such as wax printing and inkjet printing, have enhanced the functionality and scalability of these devices. Furthermore, the integration of biomaterials and surface modification techniques has improved their utility in replicating physiological conditions and studying cellular behaviors. Challenges such as mechanical robustness, imaging compatibility, and immune antigenicity are also addressed, alongside potential solutions and future directions. Key Messages: Paper-based microfluidic systems provide a transformative platform for tissue engineering and regenerative medicine, offering simplicity, affordability, and functional versatility. With ongoing innovations, these devices are poised to bridge the gap between laboratory research and clinical applications, supporting advancements in personalized medicine, regenerative therapies, and disease modeling.

Paper is made of cellulose fibers, inside which capillary microchannels and networks are formed between fibers. Paper-based microfluidics uses paper as a cost-effective and versatile material to create small-scale channels for control of fluid movement. These systems work without complex machinery and provide unique benefits, such as affordability, easy manufacturing, and biocompatibility. In tissue engineering and regenerative medicine, paper-based microfluidics helps create 3D environments that mimic the natural conditions of living tissues. These environments support advanced studies, such as investigating how cells grow, respond to drugs, and interact with their surroundings. This review highlights key advancements in designing and building paper-based microfluidic devices, including new methods to improve their precision and adaptability. For example, the use of multiple layers of paper creates 3D systems for replicating complex tissue conditions. We believe that paper-based microfluidics has the potential to advance human healthcare by making high-quality tissue models that are highly accessible for drug testing, disease studies, and personalized therapies.