Materials designed to replicate tissues and extracellular matrices (ECMs)—the biological frameworks made up of proteins and molecules that support tissues and cells—have traditionally faced challenges that limit their practical use. To address these issues, scientists have developed a new biomaterial that better mimics certain functions found in biological tissues, advancing fields such as regenerative medicine, disease modeling, and soft robotics.

Previous versions of the material, a hydrogel made from water-rich polymer networks, that was developed by researchers at Penn State (University Park, PA, USA) were synthetic and failed to combine the necessary mechanical responsiveness with biological mimicry of ECMs. Specifically, these materials were unable to replicate nonlinear strain-stiffening, a key behavior in ECM networks where the material becomes stiffer when subjected to physical forces from cells or external stimuli. Nonlinear strain-stiffening is crucial for providing structural support and enabling cell signaling. Moreover, the materials lacked the self-healing properties essential for tissue survival and structure. The earlier synthetic hydrogels struggled to strike the right balance between complexity, biocompatibility, and the mechanical properties needed to mimic ECMs effectively.

To overcome these limitations, the researchers developed an acellular (cell-free) material that dynamically mimics ECM behavior, which plays a critical role in tissue structure and cellular functions. The team introduced acellular nanocomposite living hydrogels (LivGels), made from “hairy” nanoparticles. These nanoparticles, known as "nLinkers," consist of nanocrystals with cellulose chains, or "hairs," at their ends. These hairs impart anisotropy, meaning the properties of the nLinkers vary depending on their orientation, and enable dynamic bonding with biopolymer networks. In this case, the nanoparticles bonded with a matrix made from modified alginate, a natural polysaccharide derived from brown algae.

The nLinkers form dynamic bonds within the alginate matrix, enabling the hydrogel to exhibit strain-stiffening behavior—mimicking the ECM’s response to mechanical stress—and self-healing properties, which allow the material to recover its integrity after damage. Rheological testing, which assesses how materials behave under stress, was used to measure the speed at which the LivGels regained their structure after being subjected to high strain. This design approach enabled the researchers to fine-tune the mechanical properties of the material to closely resemble those of natural ECMs. The resulting material is entirely composed of biological materials, avoiding synthetic polymers that might present biocompatibility concerns, as reported in Materials Horizons.

In addition to overcoming the limitations of previous materials, LivGels successfully achieve nonlinear mechanical behaviors and self-healing characteristics without compromising structural integrity. The nLinkers enable precise control over the stiffness and strain-stiffening properties of the material. This advancement turns traditional static hydrogels into dynamic hydrogels that more accurately replicate ECMs. The potential applications for this technology include scaffolding for tissue regeneration in regenerative medicine, simulating tissue behavior for drug testing, and creating realistic environments for studying disease progression. The team also sees potential for using the material in 3D bioprinting of customizable hydrogels and in the development of soft robotics with adaptable mechanical properties.

“Our next steps include optimizing LivGels for specific tissue types, exploring in vivo applications for regenerative medicine, integrating LivGels with 3D bioprinting platforms and investigating potential in dynamic wearable or implantable devices,” said corresponding author Amir Sheikhi.
 

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