Preclinical Use of FGF-18 Augmentation for Improving Cartilage Healing Following Surgical Repair: A Systematic Review

Abstract

Objective To evaluate the efficacy of fibroblast growth factor-18 (FGF-18) augmentation for improving articular cartilage healing following surgical repair in preclinical ( in vivo) animal models. Design A systematic review was performed evaluating the efficacy of FGF-18 augmentation with cartilage surgery compared with cartilage surgery without FGF-18 augmentation in living animal models. Eligible intervention groups were FGF-18 treatment in conjunction with orthopedic procedures, including microfracture, osteochondral auto/allograft transplantation, and cellular-based repair. Outcome variables were: International Cartilage Repair Society (ICRS) score, modified O’Driscoll histology score, tissue infill score, qualitative histology, and adverse events. Descriptive statistics were recorded and summarized for each included study. Results In total, 493 studies were identified and 4 studies were included in the final analysis. All studies were randomized controlled trials evaluating in vivo use of recombinant human FGF-18 (rhFGF-18). Animal models included ovine ( n = 3) and equine ( n = 1), with rhFGF-18 use following microfracture ( n = 3) or osteochondral defect repair ( n = 1). The rhFGF-18 was delivered via intra-articular injection ( n = 2), collagen membrane scaffold ( n = 1), or both ( n = 1). All studies reported significant, positive improvements in cartilage defect repair with rhFGF-18 compared with controls based on ICRS score ( n = 4), modified O’Driscoll score ( n = 4), tissue infill ( n = 3), and expression of collagen type II ( n = 4) ( P < 0.05). No adverse events were reported with the intra-articular administration of this growth factor, indicating short-term safety and efficacy of rhFGF-18 in vivo. Conclusion This systematic review provides evidence that rhFGF-18 significantly improves cartilage healing at 6 months postoperatively following microfracture or osteochondral defect repair in preclinical randomized controlled trials.

Advancements in tissue engineering for articular cartilage regeneration

“…FGF-18, which is highly expressed in the superficial zone of AC, stimulates the expression and accumulation of COL2 and proteoglycan in articular chondrocytes [ 148 , 149 ], preserving cartilage phenotype and thickness to protect AC against degeneration [ 112 ]. DePhillipo et al [ 150 ] confirmed significant improvement in cartilage healing at 6 months after microfracture or osteochondral defect repair in preclinical randomized controlled trials with the use of FGF-18.…”