Cell-free macro-porous fibrin scaffolds for in situ inductive regeneration of full-thickness cartilage defects

Macro-porous fibrin scaffolds with regular and adjustable inter-connective pores were fabricated through a porogen-leaching method for the in situ inductive regeneration of full-thickness cartilage defects in vivo. In vitro tests proved the survival and proliferation of BMSCs in the scaffolds. In vivo repair experiment was conducted by implantation of the cell-free macro-porous fibrin scaffolds into full-thickness cartilage defects (4 mm in diameter and 4 mm in depth with bone marrow blood effusion) of New Zealand white rabbits for 6 and 12 w. The neo-cartilage integrated well with the surrounding cartilage as well as the subchondral bone. Immunochemical and GAG staining revealed the abundant deposition of type II collagen and GAGs in the neo-cartilage after regeneration for 12 w. Histological score of the regenerated tissues was 2.6. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) revealed that the cartilage-related genes and proteins were significantly up-regulated compared with those of the normal cartilage. With the cell-free advantage and positive restoration of full-thickness cartilage defect in vivo, the fibrin scaffold is shelf-ready and is expected to be conveniently used in clinics.