3D printed multi-scale, cell instructive tissue engineering scaffolds for annulus fibrosus tissue regeneration
Intervertebral disc (IVD) degeneration is characterized by fissures or ruptures in its peripheral annulus fibrosus (AF). Current clinical approaches to AF closure do not address the long-term need for functional tissue to prevent or postpone further degeneration. The proposed research is aimed at advancing the state of AF tissue engineering. The AF is a complex, multilamellar structure comprised of fibers which possess a gradient in composition, angular orientation, and cell phenotype from the outer towards the inner AF. We have developed a melt-extrusion-based 3D printing method for the fabrication of multi-scale tissue engineering scaffolds with defined surface topographies that guide cellular organization. Polycaprolactone (PCL) was thermally extruded through custom-designed printer nozzles possessing varying circumferential sinusoidal patterns (smooth, 30, 60, or 120 μm peak height). Extrusion through the nozzles resulted in cylindrical struts possessing longitudinally aligned surface grooves. The aim of this study is to evaluate mesenchymal stem cell (MSC) lineage commitment to AF phenotypes mediated by longitudinally aligned grooves on PCL surfaces. We hypothesize that: 1) Longitudinal surface grooves can serve as biophysical cues to induce cell alignment and the deposition of ECM along the surface pattern; 2) Increasing peak height of the grooves can be used to tune MSC differentiation towards phenotypes of the inner, middle or outer AF, resulting in ECM deposition mimicking the regional tissue organization and composition.
Kluser N, Sprecher C, Häckel S, Albers C, Li Z, Alini M, Grad S, Eglin D, Vernengo A. 3D printed annulus fibrosus tissue engineering scaffolds with multiscale, uniaxial surface topographies that promote the spatial control of cell density and alignment. 2021 ORS virtual (oral)Kluser N, Sprecher C, Häckel S, Alini M, Grad S, Eglin D, Vernengo A. 3D printed scaffolds with multiscale surface topography inducing three-dimensional cell patterning. 2021 eCM cancelled (poster)/abstract published. https://www.ecmconferences.org/abstracts/2021/Collection3/poster.pdf
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)