A team of chemists and bioengineers at Rice University and the University of Houston have reached a major milestone in their work to create a biomaterial that can be used to grow biological tissues outside the human body. The development of a new manufacturing process to create aligned nanofibrous hydrogels could offer new possibilities for tissue regeneration after injury and provide a way to test therapeutic drug candidates without the use of animals.
The research team, led by Jeffrey Hartgerink, professor of chemistry and bioengineering, has developed peptide-based hydrogels that mimic the aligned structure of muscle and nerve tissues. Alignment is critical for tissue functionality, but is a difficult feature to reproduce in the laboratory as it involves the alignment of individual cells.
For more than ten years, the group has been designing multidomain peptides (MDPs) that self-assemble into nanofibers. These resemble the fibrous proteins found naturally in the body, like a spider web on a nanoscale.
In their latest study, published online and published on the cover of the journal ACS Nano, researchers discovered a new method for creating aligned “noodles” from MDP nanofibers. By first dissolving the peptides in water and then extruding them into a saline solution, they were able to create aligned peptide nanofibers—like twisted strands of rope smaller than a single cell. By increasing the concentration of ions, or salt, in the solution and repeating the process, they achieved even greater alignment of the nanofibers.
“Our findings demonstrate that our method can produce aligned peptide nanofibers that effectively guide cell growth in a desired direction,” explained lead author Adam Farsheed, who recently received his Ph.D. in bioengineering from Rice. “This is a critical step toward creating functional biological tissues for regenerative medicine applications.”
One of the key findings of the study was an unexpected discovery: When the alignment of the peptide nanofibers was too strong, the cells were no longer aligned. Further research revealed that the cells had to be able to “pull” the peptide nanofibers to recognize the alignment. When the nanofibers were too stiff, the cells could not exert this force and failed to arrange themselves into the desired configuration.
This insight into cell behavior could have broader implications for tissue engineering and biomaterial design. Understanding how cells interact with these nanoscale materials could lead to more effective strategies for tissue engineering.”
Jeffrey Hartgerink, professor of chemistry and bioengineering
Additional study co-authors from Rice include chemistry department Ph.D. graduate students Tracy Yu and Carson Cole, graduate student Joseph Swain, and undergraduate researcher Adam Thomas. Undergraduate bioengineering researcher Jonathan Makhoul, graduate student Eric Garcia Huitron and professor K. Jane Grande-Allen were also co-authors on the study. The team of researchers from the University of Houston includes Ph.D. student Christian Zevallos-Delgado, research assistant Sajede Saeidifard, research assistant professor Manmohan Singh, and engineering professor Kirill Larin.
This work was supported in part by grants from the National Institutes of Health (R01DE021798, R01EY022362, R01HD095520, R01EY030063), the National Science Foundation (2129122), the National Science Foundation Graduate Research Program, and the Welch Foundation (C)211- . The content in this press release is the sole responsibility of the authors and does not necessarily represent the official views of the funding agencies.
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Journal Reference:
Farsheed, AC, et al. (2024) Tunable macroscopic alignment of self-assembled peptide nanofibers. ACS Nano. doi.org/10.1021/acsnano.4c02030.