Fibrin-Loaded Porous Poly(Ethylene Glycol) Hydrogels as Scaffold Materials for Vascularized Tissue Formation

Abstract

Vascular network formation within biomaterial scaffolds is essential for the generation of properly functioning engineered tissues. In this study, a method is described for generating composite hydrogels in which porous poly(ethylene glycol) (PEG) hydrogels serve as scaffolds for mechanical and structural support, and fibrin is loaded within the pores to induce vascularized tissue formation. Porous PEG hydrogels were generated by a salt leaching technique with 100-150-μm pore size and thrombin (Tb) preloaded within the scaffold. Fibrinogen (Fg) was loaded into pores with varying concentrations and polymerized into fibrin due to the presence of Tb, with loading efficiencies ranging from 79.9% to 82.4%. Fibrin was distributed throughout the entire porous hydrogels, lasted for greater than 20 days, and increased hydrogel mechanical stiffness. A rodent subcutaneous implant model was used to evaluate the influence of fibrin loading on in vivo response. At weeks 1, 2, and 3, all hydrogels had significant tissue invasion, but no difference in the depth of invasion was found with the Fg concentration. Hydrogels with fibrin loading induced more vascularization, with a significantly higher vascular density at 20 mg/mL (week 1) and 40 mg/mL (weeks 2 and 3) Fg concentration compared to hydrogels without fibrin. In conclusion, we have developed a composite hydrogel that supports rapid vascularized tissue ingrowth, and thus holds great potential for tissue engineering applications.

In situ vascularization of injectable fibrin/poly(ethylene glycol) hydrogels by human amniotic fluid‐derived stem cells

“…[38,53] Control hydrogels without cells injected in this murine model showed host cell infiltration on the order of 20-25 µm/day, which is in agreement with reported values of PEG/fibrin hydrogels with similar fibrinogen concentrations. [48] A subpopulation of invading cells stained positive for αSMA, suggesting proliferation and migration of fibroblasts from the underlying fascia layer.…”

Capillary-Like Network Formation by Human Amniotic Fluid-Derived Stem Cells Within Fibrin/Poly(Ethylene Glycol) Hydrogels

“…18 The main limitation associated with fibrin in tissue engineering is rapid degradation, which leads to loss of implant volume within days. 19 Incorporation of poly(ethylene glycol) (PEG), which is known for biocompatibility and tunable physical properties, allows for increased mechanical stability while retaining the key benefits of fibrin-based scaffoldsquick formation, biocompatibility, and angiogenic stimulation. 20 Based on these data, we hypothesized that a population of stem cells derived from human amniotic fluid (AF) and differentiated into endothelial cells could form cohesive vascular networks within a fibrin/PEG matrix.…”

Hydrogels based on collagen and fibrin – frontiers and applications

“…For example, one approach described in the literature is the encapsulation of fibrin ribbons into a PEG hydrogel [50]. Another group, Jiang et al, loaded fibrin into a porous PEG hydrogel resulting in a decreased degradation rate of fibrin, which in turn induced vascularized tissue ingrowth due to the prolonged fibrin lifetime [51]. Collagen can be modified with PEG in a semi-IPN leading to higher viscoelasticity and elongation.…”