New Biomaterial for Regenerative Medicine

A study published in Materials Horizons reports that Penn State researchers have developed a biomaterial capable of mimicking key behaviors of extracellular matrices (ECMs). This material has potential applications in regenerative medicine, disease modeling, and soft robotics.

Existing materials designed to replicate tissues and ECMs—biological frameworks of proteins and molecules supporting cells and tissues—have limitations restricting their practical use. To address these challenges, the research team developed a bio-based hydrogel with self-healing properties that replicates ECM responses to mechanical stress.

We developed a cell-free—or acellular—material that dynamically mimics the behavior of ECMs, which are key building blocks of mammalian tissues that are crucial for tissue structure and cell functions.

Amir Sheikhi, Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair, Biomaterials and Regenerative Engineering, Pennsylvania State University

Previous versions of synthetic hydrogels lacked the appropriate balance of biological mimicry and mechanical responsiveness. “Specifically, these materials need to replicate nonlinear strain-stiffening, which is when ECM networks stiffen under strain caused by physical forces exerted by cells or external stimuli,” Sheikhi stated, emphasizing its importance in structural support and cell signaling.

He also added, “The materials also need to replicate the self-healing properties necessary for tissue structure and survival. Prior synthetic hydrogels had difficulties in balancing material complexity, biocompatibility, and mechanical mimicry of ECMs.”

To overcome these limitations, the researchers developed acellular nanocomposite living hydrogels (LivGels) composed of “hairy” nanoparticles. These nanoparticles consist of nanocrystals, or “nLinkers,” with disordered cellulose chains ("hairs") at their ends.

The anisotropic nature of these nLinkers, where their behavior varies with directional orientation, enables dynamic bonding within biopolymer networks. In this study, the nanoparticles formed a biopolymeric matrix using modified alginate, a natural polysaccharide derived from brown algae.

“These nLinkers form dynamic bonds within the matrix that enable strain-stiffening behavior, that is, mimicking ECM's response to mechanical stress; and self-healing properties, which restore integrity after damage,” Sheikhi stated, noting that the researchers used rheological testing, which gauges how material behaves under various stressors, to determine how quickly the LivGels recovered their structure following high strain.

He added, “This design approach allowed fine-tuning of the material's mechanical properties to match those of natural ECMs.”

The biomaterial is entirely derived from biological components, avoiding the biocompatibility challenges associated with synthetic polymers. LivGels integrate nonlinear mechanical properties and self-healing capabilities while maintaining structural integrity.

The nLinkers facilitate dynamic interactions, allowing precise control over stiffness and strain-stiffening characteristics. This approach transforms static hydrogels into dynamic biomaterials that more closely resemble ECMs.

Potential applications include tissue scaffolding for regenerative medicine, drug testing platforms that replicate tissue behavior, and environments for studying disease progression. The material could also be adapted for 3D bioprinting or the development of soft robotics with tunable 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,” Sheikhi stated.

The research was co-authored by Roya Koshani, a postdoctoral scholar in chemical engineering at Penn State, and Sina Kheirabadi, a Ph.D candidate in chemical engineering at Penn State. Sheikhi is also affiliated with the Departments of Biomedical Engineering, Chemistry, and Neurosurgery, as well as the Huck Institutes of Life Sciences.

The study was supported by Penn State through funding from the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair; the Convergence Center for Living Multifunctional Material Systems; the Cluster of Excellence Living, Adaptive, and Energy-Autonomous Materials Systems Living Multifunctional Materials Collaborative Research Seed Grant Program; the Materials Research Institute; and the College of Engineering’s Materials Matter at the Human Level seed grants.

Journal Reference:

Koshani, R. et. al. (2025) Nano-enabled dynamically responsive living acellular hydrogels. Materials Horizons. doi.org/10.1039/D4MH00922C