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

Abstract

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.

Dynamic assembly of ultrasoft colloidal networks enables cell invasion within restrictive fibrillar polymers

“…We examine cell morphology and spreading in previously reported nonpermissive fibrin formulations at concentrations of 8 mg/mL. In accord with previous reports (19,20), cells in the fibrin-only samples display a round morphology, as shown in Fig. 4A.…”

Injectable hydrogels for cartilage and bone tissue engineering

“…In addition, because alginate microbeads are stable and biocompatible, this hydrogel has been widely applied among injectable hydrogel systems for tissue regeneration. 125 Hwang et al 134 have developed a novel hybrid hydrogel system using alginate particles and a fibrin matrix. In this hydrogel, the introduction of alginate particles into a fibrin matrix enhances cellular mobility and proliferation, volume retention, and vascularization in vivo , thus making the injectable hybrid system a desirable approach for cartilage tissue-engineering applications.…”

Hybrid elastin-like recombinamer-fibrin gels: physical characterization and in vitro evaluation for cardiovascular tissue engineering applications

“…Thus, whereas the polymer chains are soluble in water below the T t , above this temperature they self-assemble into nanoand micro-aggregates and become insoluble in a completely reversible process. Fibrin has been extensively physically and biologically described 7,8 , and its potential as scaffold material for regenerative medicine and tissue engineering has been shown for cartilage repair 8 , nerve regeneration 9 , soft tissues reconstruction 10 , cardiovascular tissue engineering 11 , cell culture and differentiation 12 .…”