In addition to good mechanical properties needed for three-dimensional tissue engineering, the combination of alginate dialdehyde, gelatin and nano-scaled bioactive glass (45S5) is supposed to combine excellent cellular adhesion, proliferation and differentiation properties, good biocompatibility and predictable degradation rates. The goal of this study was to evaluate the in vitro and in vivo biocompatibility as a first step on the way to its use as a scaffold in bone tissue engineering. In vitro evaluation showed good cell adherence and proliferation of bone marrow derived mesenchymal stem cells seeded on covalently crosslinked alginate dialdehyde-gelatin (ADA-GEL) hydrogel films with and without 0.1% nano-Bioglass^® (nBG). Lactate dehydrogenase (LDH)- and mitochondrial activity significantly increased in both ADA-GEL and ADA-GEL-nBG groups compared to alginate. However, addition of 0.1% nBG seemed to have slight cytotoxic effect compared to ADA-GEL. In vivo implantation did not produce a significant inflammatory reaction, and ongoing degradation could be seen after four weeks. Ongoing vascularization was detected after four weeks. The good biocompatibility encourages future studies using ADA-GEL and nBG for bone tissue engineering application.

Hydrogels are gaining interest as scaffolds for bone tissue regeneration due to ease of incorporation of cells and biological molecules such as enzymes. Mineralization of hydrogels, desirable for bone tissue regeneration applications, may be achieved enzymatically by incorporation of alkaline phosphatase (ALP). Additive manufacturing techniques such as bioplotting enable the layer-by-layer creation of three-dimensional hydrogel scaffolds with highly defined geometry and internal architecture. In this study, we present a novel method to produce macroporous hydrogel scaffolds in combination with cell-loaded capsule-containing struts by 3D bioplotting. This approach enables loading of the capsules and strut phases with different cells and/or bioactive substances and hence makes compartmentalization within a scaffold possible. 3D porous alginate scaffolds enriched with ALP and MG-63 osteoblast-like cells were produced by bioplotting struts of alginate which were loaded with pre-fabricated alginate capsules. Two combinations were compared, namely ALP in the struts and cells in the capsules and vice-versa. Both combinations were cytocompatible for cells and mineralization of scaffolds could be detected in both cases, according to an OsteoImage staining. ALP had no adverse effect on cytocompatibility and enhanced mitochondrial activity.

Collagen is increasingly attracting attention for bone tissue engineering applications. However, due to its low mechanical properties, applications including mechanical loads or requiring structural integrity are limited. To tackle this handicap, collagen can be combined with (nanoscale) silica in a variety of composite materials that are attractive for bone tissue engineering. Considering research carried out in the past 15 years, this article reviews the literature discussing the development of silica/collagen composites that have been synthesized by adding silica from different sources as inorganic bioactive material to collagen as organic matrix. Different routes for the fabrication of collagen/silica composites are presented, focusing on nanocomposites. In vitro cell bioactivity studies demonstrated the osteogenic and, in some cases, angiogenic potential of the composites. Relevant in vivo studies discussing integration of the materials in bone tissue are discussed. Due to the understanding of possible interaction between silicon species and collagen, the effect of different silica precursors on the collagen self-assembly process is also discussed. On the basis of literature results and as discussed in this review, collagen/silica nanocomposites and hybrids represent attractive biomaterials for bone regeneration applications.