Mechanical Stress Inhibits Early Stages of Endogenous Cell Migration: A Pilot Study in an Ex Vivo Osteochondral Model

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.

Modeling early changes associated with cartilage trauma using human-cell-laden hydrogel cartilage models

“…Mechanical loads have been to date difficult to apply to synovial joint MPS, including traumatic loads, the causative event in the development of PTOA and responsible A review of studies on chondrocyte construct loading reveals the use of dynamic cyclic compression with physiological loading frequencies with rest periods replicating daily activity and continued exercise over multiple days. In the existing synovial joint MPS [29][30][31][32][33][34][35][36], the mechanical stimulation used has a strain of 0-35% at a frequency of 0.2-1 Hz [51]. These conditions are good for establishing joint tissue homeostasis and possibly modeling chronic overload as a cause of OA under the right (to be determined) conditions.…”

Ex Vivo Systems to Study Chondrogenic Differentiation and Cartilage Integration

“…These studies suggest that the application of mechanical forces of engineered joints influence the tribological properties of the synovial interfaces, which in turn would affect the local mechanobiological environment of the cells within articulated tissues. Mechanical stimulation of osteochondral explants is also possible [ 289 ].…”