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Nanofibrous-Composite Hydrogels for Modulating Stem Cell Behavior
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DOI：10.1159/000552028.png)
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Abstract
En 中文
Background: Hydrogels are widely used as extracellular matrix (ECM)-mimetic biomaterials, but most lack the nanofibrous hierarchy of the native extracellular matrix, which is essential for regulating human stem cells (hSCs) behavior. Nanofibrous-composite hydrogels address this limitation by incorporating fibrillar cues, either intrinsically formed, dispersed within the matrix, or applied at the surface, to better replicate the structural and mechanotopographical features of the stem cell niche. Summary: This review systematically compares three nanofiber-hydrogel architectures: self-assembling nanofiber matrices, hydrogels with encapsulated electrospun fibers, and hydrogels surface-decorated with fibrous coatings. We examine how differences in fiber chemistry, stiffness, degradability, and spatial organization regulate key hSCs' behaviors, including adhesion, viability, morphology, proliferation, migration, differentiation, and secretion. Polymeric, natural, hybrid, magnetic, and bioactive nanoparticle reinforced fibers are each discussed to highlight how each configuration generates distinct biophysical and biochemical cues. By linking fabrication strategies to resulting cellular outcomes, this review outlines architecture-specific advantages and limitations that inform the rational design of next-generation ECM-mimetic scaffolds. Key Messages: Nanofibrous hydrogels bridge the gap between conventional hydrogel mechanics and the nanoscale organization of the native ECM, enabling more physiologically relevant control of hSCs' behavior. Each architecture provides distinct structural and mechanobiological cues suited to different therapeutic or manufacturing goals. Hybrid and multifunctional fiber systems, such as magnetic systems, ion-releasing platforms, and nanoparticle-enhanced fibers, deliver synergistic biochemical and mechanical signals that enhance differentiation and paracrine activity. Understanding how fiber properties and organization influence cell responses provides a roadmap for designing ECM-mimetic biomaterials optimized for scalable hSCs expansion and regenerative applications.Hydrogels are soft, water-rich materials widely used to grow human stem cells in the laboratory and to support tissue repair. However, many conventional hydrogels do not reproduce the fibrous structure that cells normally experience in natural tissues. In the body, cells interact with networks of tiny fibers that provide physical support and guide how cells attach, move, and develop. Without these structural features, traditional hydrogels cannot fully recreate the environment that stem cells encounter in living tissues. This review explains how researchers combine nanoscale fibers with hydrogels to better mimic these natural conditions. Three main strategies are discussed. In the first approach, the material itself forms very thin fibers during assembly. In the second approach, short fibers are mixed throughout the hydrogel, creating a three-dimensional structure that cells can interact with. In the third approach, fibrous layers are placed on the surface of the hydrogel, giving cells a structured surface that supports spreading and movement. Different types of fibers can also provide additional signals that influence stem cell behavior. For example, some fibers are made from natural proteins, while others include materials that respond to external stimuli or release biologically active components. By comparing these different designs, this review highlights how fibrous hydrogels can better support stem cell growth and development. These materials may help researchers design improved biomaterials for tissue engineering, regenerative medicine, and stem cell manufacturing.
Keywords:
Nanofibrous hydrogels
Composite hydrogels
Stem cell behavior
Cell-matrix interactions
Stem cell therapy
Journal
C
IF:
1.9
Papers:
14
Citations:
0