Intra‐articular injection of rhFGF‐18 improves the healing in microfracture treated chondral defects in an ovine model

Abstract

Microfracture is a common cartilage repair procedure. Strategies to improve healing post-microfracture include the use of growth factors to enhance hyaline cartilage production. This study investigates the effect of intra-articular recombinant human fibroblastic growth factor 18 (rhFHF18) on the healing of a chondral defect treated with microfracture in an ovine model. Chondral defects (8 mm diameter) were created in the medial femoral condyle of 80 sheep (n ¼ 16/treatment group). Defects were treated with microfracture alone or microfracture þ intra-articular rhFGF-18 (administered either as one or two cycles of 3Â weekly injections). Outcome measures included mechanical testing, macroscopic International Cartilage Repair Society repair score, modified O'Driscoll histology score, qualitative histology, and immunohistochemistry for types I, II, and VI collagen. In treated animals, there was a statistically significant improvement in ICRS tissue repair score and tissue infill score, in the modified O'Driscoll score between control and 1 cycle of rhFGF-18 at 6 m, and in the cartilage repair score and structural characteristic score between the control and both rhFGF-18 groups at 6 m. There was no evidence of degeneration of adjacent cartilage in the rhFGF-18 treated cartilage. The increase in hyaline cartilage-like tissue formed in the microfracture þ rhFGF-18 treated groups indicates that rhFGF-18 potentiates the formation of hyaline cartilage repair following microfracture. ß

Microsphere-Based Gradient Implants for Osteochondral Regeneration: a Long-Term Study in Sheep

“…LFC: Lateral femoral condyle; MFC: Medial femoral condyle. The results of the microfracture group are consistent with previous reports on the performance of the microfracture technique, which have also indicated that defects treated with microfracture heal via formation of a repair tissue that filled in the microfracture 'holes' and 'crept' over the surface of the defect, forming islands of cartilage that deteriorated with mechanical loading in the long term [48]. Though microfracture is the 'gold standard treatment' for repairing cartilage defects, microfracture has been reported to form granulation tissue that is replaced by fibrocartilage and eventually fibrous tissue [2].…”

Deletion of the PH-domain and Leucine-rich Repeat Protein Phosphatase 1 (Phlpp1) Increases Fibroblast Growth Factor (Fgf) 18 Expression and Promotes Chondrocyte Proliferation

“…Moreover, gain-of-function Fgfr3 mutations expand the pool of proliferative, Sox9-positive chondrocytes and decrease chondrocyte hypertrophy (50,51). Fgf18 also promotes chondrogenesis, chondrocyte proliferation and cartilage regeneration in surgically induced models of osteoarthritis (31,32,43,(52)(53)(54)(55)(56). In clinical trials, intra-articular injections of recombinant Fgf18 resulted in dose-dependent increases in total cartilage content, even though thickness of the central medial femorotibial compartment cartilage was unchanged (57).…”

Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering

“…The whole joint surfaces including the implants were harvested for examination and photography. For gross evaluation, the surface of the osteochondral defect areas were blindly evaluated by two surgeons using the International Cartilage Repair Society (ICRS) score [64]. The scoring system includes three criteria with the score in the range of 0 to 4 in each category.…”