A novel poly(ethylene glycol)-fibrinogen hydrogel for tibial segmental defect repair in a rat model

The aim of this study is to investigate regeneration in a segmental bone defect using a novel fibrinogen-based hydrogel material. The use of hydrogels made from poly(ethylene glycol) (PEG) conjugated to fibrinogen for this purpose may be better to conventional fibrin-based materials as it offers an additional degree of control over the structural characteristics and biodegradation of the material. At the same time, it maintains some of the inherent biofunctionality of the fibrinogen molecule. PEGylated fibrinogen hydrogels with various degrees of proteolytic resistance based on PEG and fibrinogen composition were designed for slow, intermediate, and fast biodegradation. The hydrogels were implanted into 7-mm segmental rat tibial defects without additional osteoinductive factors with the rationale that the ingrowth matrix will displace the normal fibrin clot while sustaining a similar healing effect for a longer duration. Histological and X-ray results confirmed that the extent and distribution of newly formed bone in the defect after 5 weeks strongly parallels the biodegradation pattern of the implanted material. When compared to nonunions in animals treated with the fast-degrading implants and untreated control animals, the rats implanted with the intermediate-degrading material exhibited osteoneogenesis. This data supports the hypothesis that the perseverance of the PEGylated fibrinogen material can be synchronized with the optimal healing characteristics of a segmental osseous defect and that the consequent sustained release of fibrinogen fragments facilitates the osteogenic response at the injury site. The PEGylated fibrinogen material may, therefore, be a highly efficacious material for promoting the healing of bone defects and especially nonunion fractures.