Current treatments for cartilage lesions are often associated with fibrocartilage
formation and donor site morbidity. Mechanical and biochemical stimuli play an important
role in hyaline cartilage formation. Biocompatible scaffolds capable of transducing
mechanical loads and delivering bioactive instructive factors may better support cartilage
regeneration. In this study we aimed to test the interplay between mechanical and
FGF-18 mediated biochemical signals on the proliferation and differentiation of primary
bovine articular chondrocytes embedded in a chondro-conductive Fibrin-Hyaluronan (FB/HA)
based hydrogel. Chondrocytes seeded in a Fibrin-HA hydrogel, with or without a chondro-inductive,
FGFR3 selective FGF18 variant (FGF-18v) were loaded into a joint-mimicking bioreactor
applying controlled, multi-axial movements, simulating the natural movements of articular
joints. Samples were evaluated for DNA content, sulphated glycosaminoglycan (sGAG)
accumulation, key chondrogenic gene expression markers and histology. Under moderate
loading, samples produced particularly significant amounts of sGAG/DNA compared to
unloaded controls. Interestingly there was no significant effect of FGF-18v on cartilage
gene expression at rest. Following moderate multi-axial loading, FGF-18v upregulated
the expression of Aggrecan (ACAN), Cartilage Oligomeric Matrix Protein (COMP), type
II collagen (COL2) and Lubricin (PRG4). Moreover, the combination of load and FGF-18v,
significantly downregulated Matrix Metalloproteinase-9 (MMP-9) and Matrix Metaloproteinase-13
(MMP-13), two of the most important factors contributing to joint destruction in OA.
Biomimetic mechanical signals and FGF-18 may work in concert to support hyaline cartilage
regeneration and repair. STATEMENT OF SIGNIFICANCE: Articular cartilage has very limited
repair potential and focal cartilage lesions constitute a challenge for current standard
clinical procedures. The aim of the present research was to explore novel procedures
and constructs, based on biomaterials and biomechanical algorithms that can better
mimic joints mechanical and biochemical stimulation to promote regeneration of damaged
cartilage. Using a hydrogel-based platform for chondrocyte 3D culture revealed a synergy
between mechanical forces and growth factors. Exploring the mechanisms underlying
this mechano-biochemical interplay may enhance our understanding of cartilage remodeling
and the development of new strategies for cartilage repair and regeneration.