Assessments of injectable alginate particle-embedded fibrin hydrogels for soft tissue reconstruction

Soft tissue reconstruction is often needed after massive traumatic damage or cancer removal. In this study, we developed a novel hybrid hydrogel system consisting of alginate particles and a fibrin matrix that could maintain tissue volume long term. Alginate particles were fabricated by mixing 5% alginate with a 20 mM calcium solution. Cells and these alginate particles were then embedded in fibrin (alginate-fibrin) hydrogels using a dual syringe mixer. Cell-hydrogel constructs were evaluated in terms of cell survival and proliferation in the constructs in vitro. The results indicated that cellular viability, spreading and proliferation in the alginate-fibrin hydrogels were significantly higher compared to constructs fabricated with fibrin or alginate only. In vivo explants showed that cells contained within fibrin-only hydrogels did not contribute to neo-tissue formation, and the fibrin was fully degraded within a 12 week period. In the alginate-fibrin system, higher cellularity and vascular ingrowth were observed in vivo. This resulted in neo-tissue formation in the alginate-fibrin hydrogels. These results demonstrate that fibrin may enhance cell proliferation and accelerate the formation of extracellular matrix proteins in the alginate-fibrin system, while the alginate particles could contribute to volume retention. This injectable hybrid system composed of degradable and non-degradable hydrogels may be a preferable approach to the repair of soft tissue defects.