Engineering complex human tissues in a laboratory setting has long been a major goal for regenerative medicine and disease modeling. To help overcome the significant challenge of recreating the intricate environments of the human body, E. Thomas Pashuck, an assistant professor of bioengineering in Lehigh University’s P.C. Rossin College of Engineering and Applied Science, has been awarded a grant from the National Institutes of Health (NIH) to develop innovative, smart biomaterials.
Limitations of traditional tissue scaffolds
Traditional tissue engineering approaches often utilize hydrogels—water-swollen polymer networks—to mimic the natural matrix that surrounds cells in living tissue. While these scaffolds can be tailored to support specific cell types, different cells thrive under vastly different conditions.
For instance, the cells that form blood vessels require a very soft matrix to grow, while bone-forming cells require a much stiffer environment. Because native human tissues comprise diverse, co-existing cell populations, creating a single material that satisfies these competing needs has been a fundamental hurdle in the field.
Programmable hydrogels for diverse cell populations
Pashuck’s research aims to solve this problem by designing hydrogels that allow cells to dynamically engineer their own local microenvironments. Rather than forcing all cells into a uniform matrix, the project focuses on fabricating scaffolds crosslinked with specialized peptides that respond to cell-secreted enzymes.
Because each cell type releases a unique combination of these enzymes, the hydrogel can be programmed to degrade and adapt differently depending on which cell is interacting with it.
Synthesis and co-culture testing
Using an advanced “split-and-pool” peptide synthesis technique, Pashuck’s team will generate and screen hundreds of peptide variants to fine-tune these degradation rates. The project will specifically test this approach by co-culturing bone-forming stem cells and blood-vessel-forming cells within the same system, with the goal of finding a single material that simultaneously supports both biological processes.
By combining biomaterial synthesis and cell culture, this research aims to pioneer a highly versatile platform. The project holds promise for developing powerful new ways to recreate the complex organization of native human tissues for both advanced regenerative therapies and medical research.
