Fibrin Gels as Cell-Instructive Substrates for Regenerative Medicine

Abstract

Fibrin hydrogels are an exciting platform for cell-based therapies, as they contain necessary cues for adhesion, can be remodeled by entrapped cells, and the biophysical properties can be modified with a plethora of strategies. Furthermore, fibrin acts as a provisional matrix in vivo for tissue regeneration. While the majority of studies seek to manipulate fibrin gel properties by changing the concentration of clotting proteins, these studies highlight our capacity to change bulk stiffness and fiber properties by supplementing the solutions with sodium chloride (NaCl). Physical properties including fiber thickness, porosity, compressive modulus, and fluid uptake capacity were dependent on NaCl content, with gels containing 2.60% (w/v) NaCl exhibiting compressive moduli threefold higher than gels without NaCl. These material properties, in turn, affected the gel morphology along with the osteogenic and pro-angiogenic response of entrapped mesenchymal stem/stromal cells (MSCs). The osteoconductivity of fibrin gels can be enhanced by inclusion of apatite-coated polymer substrata to nucleate mineral, while the efficacy of engineered fibrin gels to simultaneously deploy small molecules with cells to enhance endogenous angiogenic potential has been demonstrated. Collectively, these data demonstrate the broad capacity of engineered fibrin gels to regulate function of entrapped cells for use in tissue engineering and regenerative medicine.