eCM (Eur Cell Mater / e Cells & Materials) Not-for-Profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2018   Volume No 38 – pages 23-34

Title: Recombinant human FGF18 preserves depth-dependent mechanical inhomogeneity in articular cartilage

Authors: GR Meloni, A Farran, B Mohanraj, H Guehring, R Cocca, E Rabut, RL Mauck, GR Dodge

Address: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 110A Stemmler Hall, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA.

E-mail: gdodge at pennmedicine.upenn.edu

Abstract: Articular cartilage is a specialised tissue that has a relatively homogenous endogenous cell population but a diverse extracellular matrix (ECM), with depth-dependent mechanical properties. Repair of this tissue remains an elusive clinical goal, with biological interventions preferred to arthroplasty in younger patients. Osteochondral transplantation (OCT) has emerged for the treatment of cartilage defects and osteoarthritis. Fresh allografts stored at 4 °C have been utilised, though matrix and cell viability loss remains an issue. To address this, several studies have developed media formulations to maintain cartilage explants in vitro. One promising factor for these applications is sprifermin, a human-recombinant fibroblast growth factor-18, which stimulates chondrocyte proliferation and matrix synthesis and is in clinical trials for the treatment of osteoarthritis. The study hypothesis was that addition of sprifermin during storage would maintain the unique depth-dependent mechanical profile of articular cartilage explants, a feature not often evaluated. Explants were maintained for up to 6 weeks with or without a weekly 24 h exposure to sprifermin (100 ng/mL) and the compressive modulus was assessed. Results showed that sprifermin-treated samples maintained their depth-dependent mechanical profile through 3 weeks, whereas untreated samples lost their mechanical integrity over 1 week of culture. Sprifermin also affected ECM balance by maintaining the levels of extracellular collagen and suppressing matrix metalloproteinase production. These findings support the use of sprifermin as a medium additive for OCT allografts during in vitro storage and present a potential mechanism where sprifermin may impact a functional characteristic of articular cartilage in repair strategies.

Key Words: Articular cartilage, fibroblast growth factor-18, mechanical properties.

Publication date: August 8th 2019

Article download: Pages 23-34 (PDF file)
DOI:
10.22203/eCM.v038a03

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