3D Bioprinting of Human Adipose-Derived Stem Cells and Their Tenogenic Differentiation in Clinical-Grade Medium

International Journal of Molecular Sciences

卷:21

Deborah Stanco¹  Gianluca Ciardelli¹  Monica Boffito¹  Alessia Bogni²  Josefa Barrero²  Luca Puricelli²  Gianni Soldati³ 

[1] Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy;

[2] European Commission, Joint Research Centre (JRC), Via E. Fermi, 2749, 21027 Ispra, Italy;

[3] Swiss Stem Cell Foundation, Via in Pasquée 32, 6925 Gentilino, Switzerland;

关键词: 3D bioprinting;    adipose-derived stem cells;    tendon tissue engineering;    tenogenic differentiation;    xenogenic-free;    collagen;   

DOI  :  10.3390/ijms21228694

来源: DOAJ

【 摘 要 】

Defining the best combination of cells and biomaterials is a key challenge for the development of tendon tissue engineering (TE) strategies. Adipose-derived stem cells (ASCs) are ideal candidates for this purpose. In addition, controlled cell-based products adherent to good manufacturing practice (GMP) are required for their clinical scale-up. With this aim, in this study, ASC 3D bioprinting and GMP-compliant tenogenic differentiation were investigated. In detail, primary human ASCs were embedded within a nanofibrillar-cellulose/alginate bioink and 3D-bioprinted into multi-layered square-grid matrices. Bioink viscoelastic properties and scaffold ultrastructural morphology were analyzed by rheology and scanning electron microscopy (SEM). The optimal cell concentration for printing among 3, 6 and 9 × 10⁶ ASC/mL was evaluated in terms of cell viability. ASC morphology was characterized by SEM and F-actin immunostaining. Tenogenic differentiation ability was then evaluated in terms of cell viability, morphology and expression of scleraxis and collagen type III by biochemical induction using BMP-12, TGF-β3, CTGF and ascorbic acid supplementation (TENO). Pro-inflammatory cytokine release was also assessed. Bioprinted ASCs showed high viability and survival and exhibited a tenocyte-like phenotype after biochemical induction, with no inflammatory response to the bioink. In conclusion, we report a first proof of concept for the clinical scale-up of ASC 3D bioprinting for tendon TE.

【 授权许可】

Unknown