Cross-linked gelatin-nanocellulose scaffolds for bone tissue engineering

•Porous scaffolds were produced from wood-based nanocellulose and gelatin (Gel-CNF).•Gel-CNF was cross-linked by either DHT, or a combination of HMDA, genipin, and DHT.•Gel-CNF hydrogels are cytocompatible with no adverse biological effects.•The porous hydrogel scaffolds promote osteogenic differentiation of MSCs.•The novel scaffolds hold potential for bone tissue engineering applications. Wood-based cellulose nanofibrils (CNFs) have, in addition to high specific surface area and high surface reactivity, ability to mimic nanostructured collagen in bone extracellular matrix. These properties make CNFs promising materials for bone tissue engineering (BTE). The CNFs degrade slowly in vivo. By blending and cross-linking gelatin (Gel) with CNFs, scaffolds were produced with tuned degradation rate and enhanced mechanical properties, more suitable for BTE applications. This in vitro study aimed to examine initial biological responses of human bone marrow mesenchymal stem cells to cross-linked Gel-CNF scaffolds. The scaffolds were fabricated from 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized CNF blended with Gel and cross-linked either by dehydrothermal treatment (DHT) or by a combination of hexamethylenediamine, genipin, and DHT. CNF scaffolds without cross-linking served as control. The produced scaffolds supported cell attachment, spreading, and osteogenic differentiation. However, the early cell attachment after 1 day and the expression of RUNX2 and SPP1 genes after 7 days were highest in the CNF scaffolds. The results suggest that cross-linked Gel-CNF are cytocompatible and holds potential for BTE applications.