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Innovative Biomaterial Mimics Biological Tissues for Regenerative Medicine

Researchers at Penn State have developed a biomaterial capable of emulating certain characteristics of biological tissues, potentially transforming fields such as regenerative medicine, disease modeling, and soft robotics.

The team noted that previous materials designed to replicate tissues and the extracellular matrix (ECM)—the biological scaffolding composed of proteins and molecules surrounding cells—have faced various limitations that hinder practical use. Their new creation is a bio-based, “living” material that possesses self-healing capabilities and mimics the ECM’s responses to mechanical stress.

These findings were published in Materials Horizons, where the research also gained recognition on the journal’s cover.

Amir Sheikhi, the study’s lead author and an associate professor of chemical engineering at Penn State, explained, “We created an acellular material that dynamically imitates the behavior of ECMs. These ECMs are essential components of mammalian tissues, playing a critical role in maintaining structural integrity and facilitating cellular functions.”

The researchers highlighted that earlier versions of their material, which consisted of a hydrogel—a water-rich polymer network—were primarily synthetic and inadequate in achieving the right balance of mechanical responsiveness and biological mimicry needed to effectively replicate ECMs.

“To function properly, these materials must exhibit nonlinear strain-stiffening behavior, allowing them to become more rigid under physical strain caused by external forces or cellular activity,” Sheikhi elaborated. “This stiffness is vital for supporting tissue structure and enabling cell signaling. Moreover, self-healing properties are essential for maintaining tissue integrity and vitality. Prior synthetic hydrogels often struggled to balance complexity, biocompatibility, and mechanical emulation of ECMs.”

To surmount these challenges, the research team developed acellular nanocomposite living hydrogels, referred to as LivGels, utilizing “hairy” nanoparticles known as nLinkers. These structures, consisting of disordered cellulose chains or “hairs,” provide anisotropic properties, meaning their characteristics vary based on orientation, facilitating dynamic bonds with biopolymer matrices. In this instance, the nanoparticles were combined with modified alginate, a polysaccharide derived from brown algae.

Sheikhi remarked, “These nLinkers create dynamic bonds within the matrix, enabling the material to mimic the ECM’s response to mechanical stress and possess self-healing traits, ensuring structural restoration after injury.” The researchers conducted rheological testing—an evaluation of material behavior under different stress levels—to determine how quickly the LivGels regained their structure following high strain. “This innovative design allowed us to finely tune the material’s mechanical properties to align with those of natural ECMs,” he added.

Significantly, this biomaterial is composed entirely of biological components, avoiding synthetic polymers that might raise biocompatibility concerns. LivGels not only address limitations of past materials but also achieve a unique combination of nonlinear mechanics and self-healing capabilities without compromising structural integrity. The nLinkers specifically enhance dynamic interactions, granting precise control over stiffness and strain-stiffening features, converting traditional static hydrogels into dynamic counterparts that closely mimic the natural ECM.

The potential uses of this advancement are vast, ranging from scaffolds for tissue repair and regeneration in regenerative medicine to creating realistic environments for drug testing and modeling disease progression. The researchers also foresee possibilities in 3D bioprinting customizable hydrogels and developing soft robotic systems with flexible mechanical properties.

“Our future work will involve optimizing LivGels for various tissue types, investigating in vivo applications in regenerative medicine, integrating these materials with 3D bioprinting technology, and exploring their potential in dynamic wearable or implantable devices,” Sheikhi noted.

Co-authors of the study include Roya Koshani, a post-doctoral researcher in chemical engineering at Penn State, and Sina Kheirabadi, a doctoral candidate in the same field. Sheikhi holds affiliations with the Departments of Biomedical Engineering, Chemistry, and Neurosurgery, as well as the Huck Institutes of the Life Sciences.

This research was supported by Penn State, with contributions from various initiatives, including the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair, the Convergence Center for Living Multifunctional Material Systems, and the College of Engineering’s seed grant programs.

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