A translational approach integrating developmental biology and tissue engineering towards regeneration of the annulus fibrosus of the intervertebral disc (PrintDisc)

Background

Intervertebral disc (IVD) degeneration can lead to severe and chronic low back pain, which represents the leading cause of disability worldwide. IVD degeneration can be characterized by the dehydration of the central nucleus pulposus (NP) and subsequent structural breakdown of the peripheral annulus fibrosus (AF). Currently, there are no clinically acceptable solutions for sealing the ruptured AF, so biologic based therapies, such as tissue engineering, are being investigated. The current state of AF tissue engineering may be advanced with a strategy that captures the essential building blocks of AF tissue morphogenesis: Biomimetic cell patterning, mechanical forces to induce circumferential cell elongation, and an extracellular matrix (ECM)-based molecular cocktail that supports tissue assembly. 


Goal

Herein we aim for three important milestones: 1) The development of a novel, gentle method for preparation of AF decellularized ECM from bovine donors which preserves bioactivity. 2) The development of a free-form reversible embedding technique that supports biomimetic cell patterning, mechanical loading, and long-term culture of patterned cells. 3) The combination of these approaches in a 3D bioprinted construct that supports the spontaneous assembly of AF tissue with biomimetic histoarchitecture. The outcome of this work will be a platform which can be adapted to tissue morphogenesis of the central NP of the IVD, paving the way towards the goal of regenerating a whole tissue.


  • Publication

    Alexeev D, Cui S, Grad S, Li Z, Ferguson S. Mechanical and biological characterisation of a composite annulus fibrosus repair strategy in an endplate delamination model. JOR Spine. 2020 Jul 16;3(4):e1107. doi: 10.1002/jsp2.1107. eCollection 2020 Dec.

    Pfannkuche JJ, Guo W, Cui S, Ma J, Lang G, Peroglio M, Richards RG, Alini M, Grad S, Li Z. Intervertebral disc organ culture for the investigation of disc pathology and regeneration - benefits, limitations, and future directions of bioreactors. Connect Tissue Res. 61(3-4):304-321, 2020. doi: 10.1080/03008207.2019.1665652.

    Vernengo AJ, Grad S, Eglin D, Alin M, Li Z. Bioprinting Tissue Analogues with Decellularized Extracellular Matrix Bioink for Regeneration and Tissue Models of Cartilage and Intervertebral Discs. Adv. Funct. Mater. 2020, 1909044. DOI: 10.1002/adfm.201909044

    Kluser N. 3D Printed Multi-Scale Scaffolds with Topographical Guidance for Annulus Fibrosus Regeneration. 2020 ETH Zürich (A. Vernengo, S. Grad, S. Ferguson) – MSc ETH HST (Thesis)

    Zhang F, Liu X, Li B, Li Z, Grad S, Chen D, Gao M, Liu S.  The effect of hyaluronic acid on nucleus pulposus extracellular matrix production through hypoxia-inducible factor-1alpha transcriptional activation of CD44 under hypoxia.  Eur Cell Mater. 2021;41:142-52 https://www.doi.org/10.22203/eCM.v041a10
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