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Tunable Fibrin-Alginate Interpenetrating Network Hydrogels to Guide Cell Behavior

28 Pages Posted: 18 Nov 2019 Publication Status: Accepted

See all articles by Charlotte E. Vorwald

Charlotte E. Vorwald

University of California, Davis - Department of Biomedical Engineering

Tomas Gonzalez-Fernandez

University of California, Davis - Department of Biomedical Engineering

Shreeya Joshee

University of California, Davis - Department of Biomedical Engineering

Pawel Sikorski

Norwegian University of Science and Technology (NTNU) - Department of Physics

J. Kent Leach

University of California, Davis - Department of Biomedical Engineering; University of California, Davis - Department of Orthopaedic Surgery

Abstract

Hydrogels are effective platforms for use as artificial extracellular matrices, cell carriers, and to present bioactive cues. Two common natural polymers, fibrin and alginate, are broadly used to form hydrogels and have numerous advantages over synthetic materials. Fibrin is a provisional matrix containing native adhesion motifs for cell engagement, yet the interplay between mechanical properties, degradation, and gelation rate is difficult to decouple. Conversely, alginate is highly tunable yet bioinert and requires modification to present necessary adhesion ligands. To address these challenges, we developed a fibrin-alginate interpenetrating network (IPN) hydrogel to combine the desirable adhesion and stimulatory characteristics of fibrin with the tunable mechanical properties of alginate. We tested its efficacy by examining capillary network formation with entrapped co-cultures of mesenchymal stromal cells (MSCs) and endothelial cells (ECs). We manipulated thrombin concentration and alginate crosslinking density independently to modulate the fibrin structure, mesh size, degradation, and biomechanical properties of these constructs. In IPNs of lower stiffness, we observed a significant increase in total cell area (1.72x105 +/- 7.9x104 um2) and circularity (0.56 +/- 0.03) compared to cells encapsulated in stiffer IPNs (3.98x104 +/- 1.49x104 um2 and 0.77 +/- 0.09, respectively). Fibrinogen content did not influence capillary network formation. However, higher fibrinogen content led to greater retention of these networks confirmed via increased spreading and presence of F-actin at 7 days. This is an elegant platform to decouple cell adhesion and hydrogel bulk stiffness that will be broadly useful for cell instruction and delivery.

Keywords: Interpenetrating network, endothelial cell, mesenchymal stromal cell, fibrin, alginate

Suggested Citation

Vorwald, Charlotte E. and Gonzalez-Fernandez, Tomas and Joshee, Shreeya and Sikorski, Pawel and Leach, J. Kent, Tunable Fibrin-Alginate Interpenetrating Network Hydrogels to Guide Cell Behavior. Available at SSRN: https://ssrn.com/abstract=3485137 or http://dx.doi.org/10.2139/ssrn.3485137

Charlotte E. Vorwald

University of California, Davis - Department of Biomedical Engineering

United States

Tomas Gonzalez-Fernandez

University of California, Davis - Department of Biomedical Engineering

United States

Shreeya Joshee

University of California, Davis - Department of Biomedical Engineering

United States

Pawel Sikorski

Norwegian University of Science and Technology (NTNU) - Department of Physics

Trondheim
Norway

J. Kent Leach (Contact Author)

University of California, Davis - Department of Biomedical Engineering ( email )

United States

University of California, Davis - Department of Orthopaedic Surgery ( email )

United States

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