Innovative Techniques to Tailor Living Materials for Enhanced Tissue Engineering, Drug Delivery, and 3D Printing

The findings, published in a special issue of ACS Synthetic Biology, emphasize modifications to protein matrices—networks of proteins that give ELMs their shape. The research team found that by making slight genetic adjustments, they could significantly alter the behavior of these materials. This breakthrough could lead to improvements in areas such as tissue engineering, drug delivery, and even 3D printing living devices.

“We are designing cells to develop customizable materials with unique characteristics,” stated Caroline Ajo-Franklin, a professor of biosciences and the lead author of the study. “Although synthetic biology provides tools to modify these properties, the relationship between the genetic sequence, material structure, and behavior has remained largely uncharted until now.”

Utilizing techniques from synthetic biology, the team examined a bacterium called Caulobacter crescentus. Earlier researchers in the lab engineered the bacteria to produce a protein named BUD (which stands for “bottom-up de novo”), which enables cells to bond and form a supportive matrix. This innovation allowed the bacteria to develop structures up to centimeters in size, referred to as BUD-ELMs.

Following this engineering strategy, the researchers adjusted the lengths of certain protein segments known as elastin-like polypeptides (ELPs) to generate new materials. They characterized the initial midlength BUD-ELM and two new variations, revealing that each variation exhibited distinct properties. The first material, called BUD₄₀, featured the shortest ELPs and resulted in thicker fibers and a stiffer material. The second, BUD₆₀, with midlength ELPs, was a mix of globules and fibers, demonstrating the strongest strength under deformation oscillation stress. Lastly, BUD₈₀, which had the longest ELPs, produced thinner fibers, resulting in a less rigid material that was more prone to breakage when stressed.

Advanced imaging and mechanical evaluations indicated that these differences were not merely superficial — they impacted how the materials managed stress and behaved under pressure. For instance, BUD₆₀ was capable of enduring more force and adapting more efficiently to environmental changes, ideal for applications like 3D printing or drug delivery.

All three materials shared two characteristics: they exhibited shear-thinning behavior and retained a significant amount of water—approximately 93% of their weight—which makes them ideal for biomedical applications, such as scaffolding for cell growth in tissue engineering or systems for controlled drug release.

“This research is one of the first to emphasize building living materials from the ground up with tailored mechanical properties rather than simply adding biological functions,” explained Esther Jimenez, a biosciences graduate student and the primary author of the study. “By making minor adjustments to protein sequences, we have gained important insights into designing materials with specific mechanical traits.”

The potential applications extend beyond biomedical uses; these self-assembling materials might be adapted for environmental remediation or renewable energy initiatives, such as the creation of biodegradable structures or utilizing natural processes for energy generation.

“This study underscores the significance of comprehending sequence-structure-property links,” remarked senior Carlson Nguyen, a biosciences major and co-author of the study. “By recognizing how certain genetic changes influence material attributes, we are laying the groundwork for the creation of next-generation living materials.”

This research received support from a National Science Foundation Graduate Research Fellowship, the Cancer Prevention and Research Institute of Texas, and the Welch Foundation.