Abstract
The implantation of materials into the body elicits a foreign body response (FBR) that includes formation of a fibrous capsule around the implanted material. The formation of the fibrous capsule has many similarities to fibrotic responses to other insults or stressors. A number of biochemical factors are known to promote a fibrotic response including growth factors, cytokines, and hormones. Much less is known regarding the role of biomechanical forces in tissue fibrosis. The biomechanical environment plays a fundamental role in embryonic development, tissue maintenance, and pathogenesis. Mechanical forces play particularly important roles in the regulation of connective tissues including not only bone and cartilage but also the interstitial tissues of most organs. In vivo studies have correlated changes in mechanical load to modulation of the extracellular matrix and have indicated that increased mechanical force contributes to the enhanced expression and deposition of extracellular matrix components or fibrosis. A variety of in vitro models have been utilized to evaluate the effects of mechanical force on extracellular matrix-producing cells. In general, application of mechanical stretch, fluid flow, and compression results in enhanced expression and deposition of extracellular matrix components. More recent studies have indicated that tissue rigidity also provides profibrotic signals to cells. This is particularly relevant to implants as the implanted material generally alters the local biomechanical environment, which may promote fibrosis or the formation of the fibrous capsule. The mechanisms whereby cells detect mechanical signals and transduce them into biochemical responses have received considerable attention. Cell surface receptors for extracellular matrix components and intracellular signaling pathways are instrumental in the mechanotransduction process. Understanding the effects of the biomechanical environment and the mechanisms, whereby mechanical forces are transduced into biochemical and molecular signals in the cell, will provide important insight into tissue fibrosis and fibrous capsule formation.
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Carver, W., Esch, A.M., Fowlkes, V., Goldsmith, E.C. (2017). The Biomechanical Environment and Impact on Tissue Fibrosis. In: Corradetti, B. (eds) The Immune Response to Implanted Materials and Devices. Springer, Cham. https://doi.org/10.1007/978-3-319-45433-7_9
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