Centimeter-Scale Alignment of Fibrillar Proteins Utilizing Viscous Polymers for Tissue Engineering

Extracellular matrix (ECM) organization is important for integrating interactions between cells into functional tissues. A well-known example is the cellular alignment in skeletal and cardiac muscles, tendons, bones, and corneas, all of which are guided by aligned ECM fibrils. However, no current ECM alignment technique is adequate for disease modeling and regenerative medicine, which require tissue-scale scaffolds with multicentimeter ECM alignment. To address this, we developed a new method to align fibrillar ECM at the centimeter scale by leveraging strong dipole-dipole interactions between viscous long-chain polymers, which corral fibrillar ECM proteins during hydrogel formation. Simply mixing viscous long-chain polymers with fibrillar ECM solutions can robustly achieve large-scale alignment of ECM and encapsulated cells. We demonstrated that this principle is generalizable across diverse viscous polymers and fibrillar ECM proteins. We also showed that this method is safe for biomedical applications. Encapsulated cells were aligned with high viability comparable to that of the control group. Our new method opens a new and highly customizable design space for creating various tissue scaffolds featuring aligned ECM fibrils and encapsulated cells using viscous long-chain polymers and ECM proteins suitable for individual applications.