A new biomaterial that imitates specific characteristics of biological tissues has the potential to enhance fields like regenerative medicine, disease modeling, and soft robotics, as revealed by researchers at Penn State.
According to researchers at Penn State, a new biomaterial capable of imitating certain characteristics of biological tissues could revolutionize regenerative medicine, disease modeling, soft robotics, and more.
Up until now, materials designed to replicate tissues and extracellular matrices (ECMs)—which serve as the body’s biological scaffolding of proteins and molecules that support tissues and cells—have faced challenges that limit their effective use. The research team has tackled these issues by creating a bio-based, “living” material that features self-healing properties and mimics how ECMs react to mechanical stress.
Their findings were published in Materials Horizons, where the research was also highlighted on the journal’s cover.
“We’ve created an acellular material that dynamically simulates the behavior of ECMs, which are essential elements of mammalian tissues, critical for their structure and cell functions,” stated Amir Sheikhi, the study’s lead author and an associate professor of chemical engineering, who holds the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair in Biomaterials and Regenerative Engineering.
The researchers noted that earlier versions of their material—a hydrogel or a polymer network rich in water—were synthetically made and didn’t have the right mix of mechanical responsiveness and biological imitation of ECMs.
“These materials specifically needed to reproduce nonlinear strain-stiffening, which occurs when ECM networks become more rigid under strain from physical forces exerted by cells or external stimuli,” Sheikhi explained. This property is vital for providing structural support and aiding cell communication. “Additionally, they needed self-healing capabilities to maintain tissue structure and viability. Earlier synthetic hydrogels struggled to balance complexity, biocompatibility, and mechanical imitation of ECMs.”
The team addressed these challenges by creating acellular nanocomposite living hydrogels (LivGels) made from “hairy” nanoparticles. These nanoparticles consist of nanocrystals, called “nLinkers,” with disordered cellulose chains—referred to as “hairs”—at their ends. This configuration introduces anisotropy, giving the nLinkers varying properties based on their orientation and enabling them to bond dynamically with biopolymer networks. In this instance, the nanoparticles bonded with a biopolymeric matrix of modified alginate, a natural polysaccharide derived from brown algae.
“These nLinkers create dynamic bonds within the matrix, promoting strain-stiffening behavior that mimics the ECM’s response to mechanical stress and self-healing features that restore integrity after damage,” Sheikhi elaborated. The researchers employed rheological testing, which assesses how materials behave under different stressors, to evaluate how quickly the LivGels regained their shape after experiencing considerable strain. “This design method allowed us to fine-tune the material’s mechanical characteristics to align with those of natural ECMs.”
Importantly, Sheikhi emphasized that this material is entirely composed of biological components, avoiding synthetic polymers that may carry biocompatibility risks. Aside from overcoming the previous material limitations, LivGels successfully combine nonlinear mechanics and self-healing abilities without sacrificing structural stability. The nLinkers specifically enable dynamic interactions that permit precise adjustments of stiffness and strain-stiffening characteristics. Altogether, this design approach shifts static, bulk hydrogels into dynamic hydrogels that closely imitate ECMs.
Potential applications for this material include providing scaffolding for tissue repair and regeneration in regenerative medicine, replicating tissue behavior for drug testing purposes, and creating realistic environments for researching disease progression. The researchers also noted its potential in 3D bioprinting customizable hydrogels and the development of soft robotics with flexible mechanical properties.
“Our next steps involve refining LivGels for particular tissue types, exploring in vivo uses in regenerative medicine, integrating LivGels with 3D bioprinting technologies, and investigating their potential in dynamic wearable or implantable devices,” Sheikhi mentioned.
Co-authors of the study include Roya Koshani, a post-doctoral researcher in chemical engineering at Penn State, and Sina Kheirabadi, a doctoral student in the same field. Sheikhi is also associated with the Departments of Biomedical Engineering, Chemistry, Neurosurgery, and the Huck Institutes of the Life Sciences.
This research received support from various Penn State initiatives, including the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair; the Convergence Center for Living Multifunctional Material Systems; the Cluster of Excellence for Living, Adaptive, and Energy-autonomous Materials Systems; the Materials Research Institute; and seed grant programs from the College of Engineering Materials Matter at the Human Level.
