Decellularized extracellular matrix-based scaffold and hypoxic priming: A promising combination to improve the phenotype of degenerate intervertebral disc cells

Penolazzi, Letizia; Lambertini, Elisabetta; D’Agostino, Stefania; Pozzobon, Michela; Notarangelo, Maria Pina; Greco, Pantaleo; Bonis, Pasquale De; Nastruzzi, Claudio; Piva, Roberto

doi:10.1016/j.lfs.2022.120623

Cited by 6 publications

(7 citation statements)

References 56 publications

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“…Given the diversity in structure and function of mature organs, there is no such thing as a typical RM tissue production process. However, whether it is a decellularization/recellularization process to generate intervertebral discs ( 2 ) or a 3D-printed scaffold seeded with iPSC-derived retinal progenitor cells ( 3 ), most in vitro tissue-forming processing has similar basic stages as shown in Figure 1 . Cells are isolated from tissue, expanded in vitro , and there may or may not be manipulation such as derivation of induced pluripotent stem cells or the correction of a genetic problem.…”

Section: Sensing the Needs Of Cells In Culturementioning

confidence: 99%

Cytocentric measurement for regenerative medicine

Henn¹,

Pereira²,

Hunsberger³

et al. 2023

Front. Med. Technol.

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Any Regenerative Medicine (RM) business requires reliably predictable cell and tissue products. Regulatory agencies expect control and documentation. However, laboratory tissue production is currently not predictable or well-controlled. Before conditions can be controlled to meet the needs of cells and tissues in culture for RM, we have to know what those needs are and be able to quantify them. Therefore, identification and measurement of critical cell quality attributes at a cellular or pericellular level is essential to generating reproducible cell and tissue products. Here, we identify some of the critical cell and process parameters for cell and tissue products as well as technologies available for sensing them. We also discuss available and needed technologies for monitoring both 2D and 3D cultures to manufacture reliable cell and tissue products for clinical and non-clinical use. As any industry matures, it improves and standardizes the quality of its products. Cytocentric measurement of cell and tissue quality attributes are needed for RM.

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Section: Sensing the Needs Of Cells In Culturementioning

confidence: 99%

Cytocentric measurement for regenerative medicine

Henn¹,

Pereira²,

Hunsberger³

et al. 2023

Front. Med. Technol.

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“…Intervertebral disc disease caused by trauma, degeneration, protrusion, and other factors can cause low back pain, which seriously affects the quality of life of patients. As an ideal treatment for disc diseases, tissue engineering has become a hot topic at home and abroad. − Huang et al successfully prepared a decellularized intervertebral disc scaffold. Although the decellularized scaffold only tested the cell behavior in a short period of time and could not reflect the long-term situation, it still laid the foundation for the creation of a better decellularized scaffold in the future …”

Section: The Application Of Decellularized Scaffolds In Tissue Engine...mentioning

confidence: 99%

Biomedical Application of Decellularized Scaffolds

Zhang,

Gao,

Jiang

et al. 2023

ACS Appl. Bio Mater.

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“…14 Interestingly, the Wharton's jelly mucoid connective tissue has a composition very similar to that of IVD ECM. 15,16 Notably, Wharton's Jelly is rich in matrix components such as hyaluronic acid, various types of collagens, and sulfated glycosaminoglycans; in addition, growth factors (FGF, IGFBP 1, 2, 3, 4, and 6) are present, together with TGF-α, GH, and PDGF-AA. Immunomodulatory cytokines (RANTES, IL-6R, and IL-16), pro-inflammatory cytokines (MCSFR, MIP-1a), anti-inflammatory cytokines (TNF-RI, TNF-RII, and IL-1RA), homeostatic cytokines (TIMP-1 and TIMP-2), cytokines associated with wound healing and regenerative properties (ICAM-1, G-CSF, GDF-15, MCP-1, and GDNF), and extracellular vesicles, are also present.…”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19][20][21] In consideration of the exceptionally rich and favorable composition, Wharton's Jelly could be employed to produce several bioinspired scaffolds, characterized by the preservation of both the architecture and the biological components useful also to support the reparative processes in the IVD tissue. 15,16 In this respect, we had previously demonstrated that human degenerated IVD cells are able to restore at molecular level their normal phenotype when combined with DWJ. 15 This suggests that, if the decellularization process is well designed and controlled, the obtained ECM retains the architecture of the natural cell environment, together with the complex biomolecular and physical cues, giving support to the cell viability and functions.…”

Section: Introductionmentioning

confidence: 99%

Wharton's jelly‐derived multifunctional hydrogels: New tools to promote intervertebral disc regeneration in vitro and ex vivo

Penolazzi,

Chierici,

Notarangelo

et al. 2024

J Biomedical Materials Res

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The degeneration of intervertebral disc (IVD) is a disease of the entire joint between two vertebrae in the spine caused by loss of extracellular matrix (ECM) integrity, to date with no cure. The various regenerative approaches proposed so far have led to very limited successes. An emerging opportunity arises from the use of decellularized ECM as a scaffolding material that, directly or in combination with other materials, has greatly facilitated the advancement of tissue engineering. Here we focused on the decellularized matrix obtained from human umbilical cord Wharton's jelly (DWJ) which retains several structural and bioactive molecules very similar to those of the IVD ECM. However, being a viscous gel, DWJ has limited ability to retain ordered structural features when considered as architecture scaffold. To overcome this limitation, we produced DWJ‐based multifunctional hydrogels, in the form of 3D millicylinders containing different percentages of alginate, a seaweed‐derived polysaccharide, and gelatin, denatured collagen, which may impart mechanical integrity to the biologically active DWJ. The developed protocol, based on a freezing step, leads to the consolidation of the entire polymeric dispersion mixture, followed by an ionic gelation step and a freeze‐drying process. Finally, a porous, stable, easily storable, and suitable matrix for ex vivo experiments was obtained. The properties of the millicylinders (Wharton's jelly millicylinders [WJMs]) were then tested in culture of degenerated IVD cells isolated from disc tissues of patients undergoing surgical discectomy. We found that WJMs with the highest percentage of DWJ were effective in supporting cell migration, restoration of the IVD phenotype (increased expression of Collagen type 2, aggrecan, Sox9 and FOXO3a), anti‐inflammatory action, and stem cell activity of resident progenitor/notochordal cells (increased number of CD24 positive cells). We are confident that the DWJ‐based formulations proposed here can provide adequate stimuli to the cells present in the degenerated IVD to restart the anabolic machinery.

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Decellularized extracellular matrix-based scaffold and hypoxic priming: A promising combination to improve the phenotype of degenerate intervertebral disc cells

Cited by 6 publications

References 56 publications

Cytocentric measurement for regenerative medicine

Cytocentric measurement for regenerative medicine

Biomedical Application of Decellularized Scaffolds

Wharton's jelly‐derived multifunctional hydrogels: New tools to promote intervertebral disc regeneration in vitro and ex vivo

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