Within solid tissues, cells are embedded in a 3D network of fibrous proteins, enabling long range physical communication and structures that guide mechanical properties and cell behavior. Hydrogels can be fabricated to mimic features of the extracellular matrix (ECM); however, bulk hydrogels lack the structure of native ECM and electrospun fibrous hydrogels have limited cell infiltration. To address these limitations, we introduce a unique class of fibrous hydrogels, fabricated through the assembly of single fibers engineered to (i) have tunable properties (e.g. length, porosity, stiffness), (ii) display strain-stiffening behavior to mimic ECM mechanics, and (iii) permit cell encapsulation. Norbornene modified hyaluronic acid (NorHA) was electrospun with dithiol crosslinker and a photoinitiator to photocrosslink and stabilize fibers. Due to weak inter-fiber crosslinks in electrospun NorHA, fiber mats could be fragmented into single fibers while maintaining intra-fiber bonds and fiber shape. 3D fibrous hydrogels were fabricated by photocrosslinking concentrated solutions (25-100 v/v %) of single fibers back into a network. 3D fibrous hydrogels have tunable porosity, stiffness, and undergo acute stiffening in response to strain, similar to natural fibrous gels such as collagen. Importantly, mesenchymal stromal cells could be encapsulated within fibrous hydrogels and they remodel local fibers similar to collagen gels. This work introduces a new approach to fabricate 3D fibrous hydrogels that have strain-stiffening behavior, allow for cell encapsulation, and can be used towards mechanobiology and tissue engineering applications.

Bioinspired 3D fibrous hydrogels for biomedical applications

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.