Abstract
Cell migration has a central role in osteochondral defect repair initiation and biomaterial-mediated regeneration. New advancements to reestablish tissue function include biomaterials and factors promoting cell recruitment, differentiation and tissue integration, but little is known about responses to mechanical stimuli. In the present pilot study, we tested the influence of extrinsic forces in combination with biomaterials releasing chemoattractant signals on cell migration. We used an ex vivo mechanically stimulated osteochondral defect explant filled with fibrin/hyaluronan hydrogel, in presence or absence of platelet-derived growth factor-BB or stromal cell-derived factor 1, to assess endogenous cell recruitment into the wound site. Periodic mechanical stress at early time point negatively influenced cell infiltration compared to unloaded samples, and the implementation of chemokines to increase cell migration was not efficient to overcome this negative effect. The gene expression at 15 days of culture indicated a marked downregulation of matrix metalloproteinase (MMP)13 and MMP3, a decrease of β1 integrin and increased mRNA levels of actin in osteochondral samples exposed to complex load. This work using an ex vivo osteochondral mechanically stimulated advanced platform demonstrated that recurrent mechanical stress at early time points impeded cell migration into the hydrogel, providing a unique opportunity to improve our understanding on management of joint injury.
Highlights
Articular cartilage plays a key role in the function of joints, and when damaged it becomes inefficient to withstand harsh conditions over time, posing a significant challenge among clinicians.The very poor intrinsic healing capacity of this tissue in combination with the high incidence of trauma place at risk many asymptomatic young and healthy patients toward the evolution of degenerative conditions with reduced possibility of interventions [1]
In the present pilot study, we addressed the hypothesis that mechanical compression and shear would modulate the early stage of cell migration into a FB/HA hydrogel implanted in an osteochondral defect ex vivo
Osteochondral defect plugs filled with FB/HA hydrogel in presence or absence of 2 μg/mL platelet-derived growth factor-BB (PDGF-BB) or
Summary
With such regenerative tools in our hands, our goal was to test the influence of applied extrinsic forces on the endogenous cell recruitment process by using our custom-made joint bioreactor
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