Chondroitin and Dermatan Sulfate Bioinks for 3D Bioprinting and Cartilage Regeneration

Cartilage is a connective tissue which a limited capacity for healing and repairing. In this context, osteoarthritis (OA) disease may be developed with high prevalence in which the use of scaffolds may be a promising treatment. In addition, three-dimensional (3D) bioprinting has become an emerging additive manufacturing technology because of its rapid prototyping capacity and the possibility of creating complex structures. This study is focused on the development of nanocellulose-alginate (NC-Alg) based bioinks for 3D bioprinting for cartilage regeneration to which it is added chondroitin sulfate (CS) and dermatan sulfate (DS). First, rheological properties are evaluated. Then, sterilization effect, biocompatibility, and printability on developed NC-Alg-CS and NC-Alg-DS inks are evaluated. Subsequently, printed scaffolds are characterized. Finally, NC-Alg-CS and NC-Alg-DS inks are loaded with murine D1-MSCs-EPO and cell viability and functionality, as well as the chondrogenic differentiation ability are assessed. Results show that the addition of both CS and DS to the NC-Alg ink improves its characteristics in terms of rheology and cell viability and functionality. Moreover, differentiation to cartilage is promoted on NC-Alg-CS and NC-Alg-DS scaffolds. Therefore, the utilization of MSCs containing NC-Alg-CS and NC-Alg-DS scaffolds may become a feasible tissue engineering approach for cartilage regeneration.
The authors thank the Basque Government for granted fellowship to S.Ruiz-Alonso (PRE_2020_2_0143). This study was financially supported bythe Basque Country Government (IT907-16), the Ministerio de Economía,Industria y Competitividad (FEDER funds, project RTC-2016-5451-1). Theyalso wish to thank the intellectual and technical assistance from the ICTS“NANBIOSIS,” more specifically by the Drug Formulation Unit (U10)of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the University of Basque Country (UPV/EHU). This research wasalso supported by Fundación Mutua Madrileña (project FMM-AP17196-2019), Consejería de Economía, Conocimiento, Empresas y Universi-dad de la Junta de Andalucía (ERDF funds, projects B-CTS-230-UGR18,SOMM17-6109, and P18-FR-2465), and the Instituto de Salud Carlos III,ERDF funds (DTS19/00145 and DTS21/00098). The authors also thank toSpanish Ministry of Science and Innovation (MICINN) (project PID2020-114086RB-100). The corresponding author information was updated onMarch 14, 2022.