Suchergebnisse

Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations' processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies ; M.N. acknowledges financial support from the German Research Foundation (DFG) via the scholarship "Forschungsstipendium" (PN: 387071423). L.G.A. acknowledges funding through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH–CREATE–INNOVATE co-financed by the European Union and Greek national funds (Project Code: T1EDK-02829). K.W. acknowledges funding from the Swiss National Science Foundation (SNF PP00P2_163678/1). L.B., C.R.W., M.A.G.B., and J.N. acknowledge financial support from the Spanish Ministry of Science and Innovation (HOLOA-DPI2016-80283-C2-1-R, RYC-2015-18888). L.B., C.L.M., C.R.W., L.G.A., M.A.G.B., and J.N. further acknowledge financial support from the European Commission (Disc4All-H2020-MSCA-ITN-ETN-2020 GA: 955735).