Engineered full-organ 3D intervertebral disc as a standardized model for studying disc degeneration and disease (INDEED)

Background

Disc degeneration is a major source of pain and disability worldwide, and a significant financial burden on healthcare providers. Attempts at understanding the mechanisms behind intervertebral disc (IVD) degeneration are limited by the lack of suitable models recapitulating IVD physiology and disease. IVD is a complex heterogeneously composed organ situated between the vertebrae, where it is subjected to a challenging mechanical and biochemical environment. Presently available models of the IVD are inadequate, differing in composition, organization, and mechanical properties. Despite previous efforts, a standardized full IVD 3D model recapitulating key features of the native tissue and providing the necessary biochemical cues and mechanical performance, has not been reported yet.

An illustrated example of the IVD model fabrication using extrusion-based bioprinting

Goal

The aim of the INDEED project is to address these shortcomings by developing a reproducible 3D bioprinted IVD model, composed of materials natively present in our bodies, and with similar mechanical properties. To that end, we are utilizing our combined expertise on disc biology and materials science to develop composite bioinks which allow independent tuning of extrusion and post-printing properties. We employ computational approaches to optimize both the bioprinting process and disc design. We believe that by allowing us to independently vary each of its parameters, this model will be of great interest in furthering our understanding of disc degeneration. Additionally, this project will contribute developing 3D bioprinting technologies to engineer human tissues.

Publication

Diaz-Payno PJ, Kalogeropoulou M, Muntz I, Kingma E, Kops N, D'Este M, Koenderink GH. Fratila-Apachitei LE, van Osch G, Zadpoor AA. Swelling-dependent shape-based transformation of a human mesenchymal stromal cells-laden 4D bioprinted construct for cartilage tissue engineering. Adv Healthc Mater. 2022;epub Oct 29:e2201891. https://doi.org/10.1002/adhm.202201891

Okoro PD, Frayssinet A, De Oliveira S, Rouquier L, Miklosic G, D'Este M, Potier E, Helary C.Combining biomimetic collagen/hyaluronan hydrogels with discogenic growth factors promotes mesenchymal stroma cell differentiation into Nucleus Pulposus like cells. Biomater Sci. 2023;epub Oct 12. https://doi.org/10.1039/D3BM01025B
Presentation

Miklosic G, Eglin D, D'Este M. Towards a reproducible intervertebral disc model – a bioprintable nucleus pulposus-like material. 2020 GR forscht virtual (oral)

Miklosic G, Hélary C, Ferguson SJ, D'Este M. Extracellular matrix-based bioink for the printing of nucleus pulposus analogues. 2021 BIOFAB online (poster)

Miklosic G, Hélary C, Ferguson SJ, D'Este M. Dense extracellular matrix derivatives for the bioprinting of nucleus pulposuslike structures. 2021 ES Biomat virtual (poster)

Miklosic G, De Oliveira S, Grastilleur S, Hélary C, Ferguson SJ, D'Este M. Extracellular matrix-based biomaterial ink for the printing of nucleus pulposus-like structures. 2021 eCM cancelled (oral)/abstract published. https://www.ecmconferences.org/abstracts/2021/Collection3/oral.pdf

De Oliveira S, Miklosic G, D'Este M, Hélary C. Collagen/hyaluronan polyionic complexes as a new building block to develop a bioink for muskulo-skeletal applications. 2021 eCM cancelled (poster)/abstract published. https://www.ecmconferences.org/abstracts/2021/Collection3/poster.pdf

Grastilleur S, Humbert P, Miklosic G, de Oliveira S, Halgand B, Loll F, Delplace V, D'Este M, Hélary C, Clouet J, Fusellier M, Guicheux J, Le Visage C. In vitro evaluation of ovine IVD cells interactions with a collagen/hyaluronic acid biomaterial ink: On the way to a bio-printed IVD model. 2022 eCM (poster)

Miklosic G, De Oliveira S, Grastilleur S, Hélary C, Ferguson SJ, D'Este M. Hyaluronan-collagen composite bioink for the printing of nucleus pulposus-like structures. 2022 eCM (poster)De Oliveira S, Miklosic G, D'Este M, Hélary C. Optimized collagen/hyaluronan formulations to develop a novel biomimetic ink to synthesize composite hydrogels for tissue engineering. 2022 PNG (poster)

Miklosic G, De Oliveira S, Grastilleur S, Hélary C, Ferguson SJ, D'Este M. Hyaluronan-collagen composite bioink for the printing of nucleus pulposus-like structures. 2022 SSB+RM (poster)

Miklosic G, De Oliveira S, Grastilleur S, Hélary C, Ferguson SJ, D'Este M. Hyaluronan-collagen composite bioink for the printing of nucleus pulposus-like structures. 2022 Biofabrication (oral)

Miklosic G, De Oliveira S, Grastilleur S, Hélary C, Ferguson SJ, D'Este M. Hyaluronan-collagen bioink for the printing of intervertebral disc models. 2022 GR forscht (oral)Miklosic G, De Oliveira S, Grastilleur S, Hélary C, Ferguson SJ, D'Este M. Hyaluronan-collagen composite bioink for the printing of nucleus pulposus-like structures. 2022 ESB (Biomaterials) (poster)

De Oliveira S, Miklosic G, D'Este M, Grastilleur S, Véziers J, Hélary C. Collagen/hyaluronan polyionic complexes as a new building block to develop a novel bioink to model the intervertebral disc. 2022 ESB (Biomaterials) (poster)

Le Visage C, Grastilleur S, Humbert P, Miklosic G, Halgand B, Loll F, D'Este M, Hélary C, Fusellier M, Guicheux J. On the way to a bio-printed intervertebral disc (IVD) model: In vitro evaluation of the interactions of ovine IVD cells with a collagen/hyaluronic acid bio-ink. 2022 TERMIS AP (poster)

Miklosic G, De Oliveira S, Grastilleur S, Le Visage C, Hélary C, Ferguson SJ, D'Este M. Printing the intervertebral disc: a hyaluronan-collagen bioink analogue of the nucleus pulposus. 2023 YSS SSB+RM (oral)

Hélary C, Frayssinet A, Okoro PD, D'Este M, Potier E. Combining physical properties of collagen/hyaluronan hydrogels and chemical stimulation with growth factors promotes mesenchymal stem cells differentiation into NP cells. 2023 TERMIS-EU (oral)

Tankus EB, Miklosic G, Mainardi A, Sharma N, D'Este M, Barbero A, Thieringer FM. 3D bioprinting of a hypoxia-gradient for generating heterogenous cartilage scaffolds. 2023 TERMIS-EU (oral)

Miklosic G, De Oliveira S, Grastilleur S, Le Visage C, Hélary C, Ferguson SJ, D'Este M. Printing the intervertebral disc: a hyaluronan-collagen bioink analogue of the nucleus pulposus. 2023 SfB (poster)

Tankus EB, Miklosic G, Basoli V, Sharma N, D'Este M, Barbero A, Thieringer FM. Advancing cartilage formation: hypoxic culture and 3D‐bioprinting for osteochondral defect treatment. 2023 3D Printing for Life Sciences (oral)

Hélary C, Frayssinet A, Okoro PD, D'Este M, Potier E. Combining physical properties of collagen/hyaluronan hydrogels and chemical stimulation with growth factors promotes mesenchymal stem cells differentiation into NP cells. Tissue Eng Part A. 2023;29(13-14):202 (TERMIS EU / oral)https://doi.org/10.1089/ten.tea.2023.29043.abstracts

Tankus EB, Miklosic G, Mainardi A, Sharma N, D'Este M, Barbero A, Thieringer FM. 3D bioprinting of a hypoxia-gradient for generating heterogenous cartilage scaffolds. Tissue Eng Part A. 2023;29(13-14):58 (TERMIS EU / oral). https://doi.org/10.1089/ten.tea.2023.29043.abstracts

De Oliveira S, Miklosic G, D'Este M, Grastilleur S, Véziers J, Le Visage C, Hélary C. Anisotropic collagen/hyaluronan 3D printed hydrogels as novel model of Annulus Fibrosus. 2023 ESB (Biomaterials) / (oral)

Miklosic G, De Oliveira S, Grastilleur S, Le Visage C, Hélary C, Ferguson SJ, D'Este M. Printing the intervertebral disc: a hyaluronan-collagen bioink analogue of the nucleus pulposus. 2023 ESB (Biomaterials) / (oral)

Tankus EB, Miklosic G, Basoli V, Sharma N, D'Este M, Barbero A, Thieringer FM. From nasal chondrocytes to a 3D bioprinted osteochondral tissue. 2023 SSBE (poster)