Abstract
Bone scaffolds made of calcium phosphate polymer nanocomposites have limited osteoinductive properties. Piezoelectric materials have attracted considerable interest in bone tissue engineering due to their potential to promote osteogenesis through additional electrical stimulation. Time-lapsed micro-CT imaging is a time-effective tool for in vitro optimization of such scaffolds but is challenged by nanocomposites with a high attenuation coefficient, such as one containing high amounts of piezoelectric barium titanate. We used high-resolution end-point micro-CT scans combined with histology and Raman spectroscopy to screen polydopamine functionalized nanocomposites containing 3–27 vol% barium titanate for collagenous extracellular matrix formation and mineralization. All compositions showed well-connected extracellular matrix and birefringent matured collagen after seven weeks of static human mesenchymal stem cell cultures. Nevertheless, high-resolution micro-CT analysis combined with smart thresholding during image processing enabled us to observe modest differences in ECM mineralization between groups suggesting that a volume fraction of 9–21% barium titanate facilitated the formation of dense mineral clusters in the pores even in the absence of mechanical stimuli, further corroborated by Raman spectroscopy. The same image processing approach facilitated the analysis of time-lapsed micro-CT images of scaffold cultures in dynamic compression bioreactors where 9 vol% barium titanate was the best nanocomposite composition, resulting in a significant twofold increased maturation rate under dynamic conditions. On the other hand, barium titanate content of ≥15 vol% did not improve mineralization. At 27 vol%, the biomineralization of the collagenous extracellular matrix was even impeded in the nanocomposite scaffolds, as evidenced by histology stainings. Overall, our approach enables time-lapsed quantitative assessment of high X-ray absorbing nanocomposite scaffolds for biomineralization under dynamic compression, facilitating the optimization of such mechanically responsive scaffolds.
Highlights
Bone is a natural hierarchically structured composite composed of highly organized collagen bundles reinforced with hydroxyapatite nanocrystals
The hydrophilicity and cell adhesion of hydrophobic barium titanate polymer nanocomposite scaffolds were improved by systematically investigating the effect of polydopamine surface functionalization on the water contact angle (Supplementary Figure S1)
The bioactivity of polymer nanocomposite scaffolds containing mixtures of barium titanate and hydroxyapatite nanoparticles with volume ratios from 1:9 to 9:1, corresponding to 3–27 vol% of barium titanate, was tested under static cell culture conditions. We refer to these nanocomposites with the following group names: B1H9, B3H7, B1H1, B7H3, B9H1, where the numbers reflect the volume ratio and the letter stands for the material, i.e., B for barium titanate and H for hydroxyapatite
Summary
Bone is a natural hierarchically structured composite composed of highly organized collagen bundles reinforced with hydroxyapatite nanocrystals. This tissue composition is piezoelectric and generates electrical charges under mechanical deformation (Khare et al, 2020). Removing a bone tumor or traumatic injury can cause defects beyond a critical size (Schemitsch, 2017), requiring surgical intervention using fixation, bone autografts, or allografts. Such procedures are associated with increased risk and additional trauma for the patient, especially in aged individuals, continue to drive materials design for bone scaffolds (Koons et al, 2020). Inspired by bone’s piezoelectric properties, a growing body of literature uses such materials to improve the scaffold’s efficacy for bone regeneration (Liu et al, 2020; Zhang et al, 2021)
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