Abstract
Progress in bone scaffold development relies on cost-intensive and hardly scalable animal studies. In contrast to in vivo, in vitro studies are often conducted in the absence of dynamic compression. Here, we present an in vitro dynamic compression bioreactor approach to monitor bone formation in scaffolds under cyclic loading. A biopolymer was processed into mechanically competent bone scaffolds that incorporate a high-volume content of ultrasonically treated hydroxyapatite or a mixture with barium titanate nanoparticles. After seeding with human bone marrow stromal cells, time-lapsed imaging of scaffolds in bioreactors revealed increased bone formation in hydroxyapatite scaffolds under cyclic loading. This stimulatory effect was even more pronounced in scaffolds containing a mixture of barium titanate and hydroxyapatite and corroborated by immunohistological staining. Therefore, by combining mechanical loading and time-lapsed imaging, this in vitro bioreactor strategy may potentially accelerate development of engineered bone scaffolds and reduce the use of animals for experimentation.
Highlights
Progress in bone scaffold development relies on cost-intensive and hardly scalable animal studies
Mechanical loading plays a vital role in bone remodeling, and it was demonstrated that controlled cyclic loading can improve fracture healing in long bones and may even be used as stimulus where healing is impaired[2,3]
We hypothesized that in scaffolds cultured in dynamic compression bioreactors under cyclic loading, more mineral is formed by extracellular matrix (ECM) mineralization than under static conditions
Summary
Progress in bone scaffold development relies on cost-intensive and hardly scalable animal studies. After seeding with human bone marrow stromal cells, time-lapsed imaging of scaffolds in bioreactors revealed increased bone formation in hydroxyapatite scaffolds under cyclic loading. This stimulatory effect was even more pronounced in scaffolds containing a mixture of barium titanate and hydroxyapatite and corroborated by immunohistological staining. We used the time-lapsed images to calculate a spatial bone formation rate (BFR) that, in combination with immunohistological images, allows us to distinguish cellmediated mineral from medium precipitation We showed that this bioreactor approach enabled comparison between scaffolds containing pure hydroxyapatite and a mixture of hydroxyapatite and barium titanate. We demonstrate a holistic and rigorous in vitro testing framework for bone scaffold development with efficacy testing of mineral formation that aims to close the gap between in vitro and in vivo experiments by detailed microstructural analysis of in vitro formed mineral
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