3D Printed Nanofibrous Multidomain Peptide Hydrogels for Regenerative Medicine

Tissues vary in their biological, mechanical, and structural properties. In the field of regenerative medicine, 3D printing has emerged as a powerful technique for producing hydrogel scaffolds that replicate the geometric complexity of tissues. Biologically derived polymers are commonly used as hydrogel inks in 3D printing due to their inherent bioactivity. However, these polymers lack the mechanical flexibility offered by synthetic counterparts. In addition, many biologically derived polymers lack the fibrous composition that naturally exists at the nano and micro scale within the body. This necessitates the development of hydrogel inks that are both bioactive and fibrous in structure to better replicate tissues. Here, we present the use of Multidomain Peptides (MDPs), a class of self-assembling peptides that form a nanofibrous hydrogel, as a novel ink for 3D printing [1]. After optimizing MDPs for 3D printing, we show that they can be used to create complex, overhanging structures, and multi material prints. In addition, we demonstrate how cationic and anionic MDPs can be strategically patterned to influence cell behavior.<br/>Building upon this work, we have developed a novel fabrication method for producing MDP hydrogels with aligned nanofibers, resembling the alignment present in tissues such as skeletal muscle and peripheral nerve. We show that these anisotropic MDP scaffolds can guide cell growth and spreading. Further, by fabricating hydrogel scaffolds with controlled degrees of alignment, we observe that cells exhibit distinct growth patterns in response to nanoscale differences. Leveraging 3D printing, we have scaled this fabrication method to create multilayer hydrogel scaffolds with precise control over the direction of fibrous alignment. The ability to generate aligned hydrogel scaffolds in a scalable manner sets this fabrication technology apart from other techniques. This work highlights the unique potential of using self-assembling multidomain peptides as 3D printable inks, enabling the creation of improved scaffolds for regenerative medicine.<br/><br/><b>References:</b><br/>1. A.C. Farsheed, A.J. Thomas, B.H. Pogostin, J.D. Hartgerink, “3D Printing of Self-assembling Nanofibrous Multidomain Peptide Hydrogels” Adv. Mater. (2023), 35, 11, 2210378, https://doi.org/10.1002/adma.202210378