In vitro biological response of human osteoblasts in 3D chitosan sponges with controlled degree of deacetylation and molecular weight

abstract

We have studied the effect of chitosan sponges, produced from chitosan batches with distinct degree of deacetylation (DDA) and molecular weight (Mw), on the adhesion, growth and differentiation of primary human osteoblasts with an aim to offer a suitable tool for guided bone regeneration. All the chitosan sponges revealed similar microstructure, irrespective of the DDA (58, 73, 82, 88, and 91 %) and Mw (749, 547, 263, 215, and 170 kDa, respectively). Cell spreading was higher on sponges having a higher DDA. Higher DDA induced a more pronounced increase in alkaline phosphatase activity, osteopontin (OPN), vascular endothelial growth factor-A (VEGF), interleukin-6 (IL-6), and reduction in monocyte chemoattractant protein-1 (MCP-1), sclerostin (SOST) and dickkopf related protein-1 as compared to lower DDA. Lower DDA induced the increased secretion of osteoprotegerin and SOST as compared to higher DDA. The combination of higher DDA and Mw induced an increased secretion of VEGF and IL-6, however reduced the secretion of OPN as compared to chitosan with similar DDA but with lower Mw. In summary, the variations in cellular responses to the different chitosan sponges indicate a potential for individual tailoring of desired responses in guided bone regeneration.

keywords

IONIC-STRENGTH; SCAFFOLD; DIFFERENTIATION; ACETYLATION; ENDOTOXINS; HYDROGELS; DELIVERY; CHITIN; GROWTH; CELLS

subject category

Chemistry, Applied; Chemistry, Organic; Polymer Science

authors

Sukul, M; Sahariah, P; Lauzon, HL; Borges, J; Masson, M; Mano, JF; Haugen, HJ; Reseland, JE

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

Marine Origin Biopolymers as Innovative Building Blocks from the Sea for the Development of Bioresorbable Multilayered Membranes for guided bone regeneration (BLUETEETH)

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

acknowledgements

This work was supported by The Marine Biotechnology ERA-NET project, Blueteeth (ERA-MBT/0002/2015) financed under EU FP7 (Grant Agreement number: 604814). This is a co-funded project coordinated by the University of Aveiro, Portugal (supported by the Portuguese Foundation for Science and Technology (FCT)), and having the company Primex ehf and University of Iceland, Iceland (supported by the Icelandic Technical Development Fund grant No. 179012-0612) and the University of Oslo, Norway (supported by the Norway Research Council, Project ID 269522/O70) as partners. This work was developed within the scope of the project CICECO -Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the Foundation for Science and Technology/MCTES. J. Borges gratefully acknowledges the financial support by FCT through his individual contract (CEECIND/03202/2017). The authors would like to thank Aina-Mari Lian for the contribution in Luminex experiment and Liebert Parreiras Nogueira for nano CT analyses and, and Dr. Svetlana Solodova for assistance with the GPC analysis.