Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration

Bioactive Materials, 2021 · DOI: https://doi.org/10.1016/j.bioactmat.2021.02.024 · Published: March 9, 2021

Biomedical Regenerative Medicine & Stem Cells

Simple Explanation

This study investigates how mechanical forces affect the behavior of stem cells on bone scaffolds, specifically focusing on inflammation and bone formation. The researchers applied cyclic mechanical loading to stem cells seeded on hydroxyapatite scaffolds to see how it influenced their inflammatory response. The study also explored whether scaffolds created under mechanical stress could influence the polarization of macrophages, immune cells important for tissue repair. They evaluated the anti-inflammatory and regenerative effects of these scaffolds on macrophages in vitro and in a rabbit bone defect model in vivo. The findings suggest that mechanical loading during scaffold biofabrication can modulate the inflammatory response of stem cells and promote bone regeneration. This could lead to improved strategies for creating bone biomaterials.

Study Duration

7, 14, or 21 days

Participants

Forty-two male New Zealand white rabbits

Evidence Level

Not specified

Key Findings

1
Mechanical loading downregulated inflammatory mediators (IL1B and IL8) and upregulated osteogenic markers (ALP and COL1A1) in MSCs seeded on scaffolds.
2
ECM-based scaffolds biofabricated with mechanical loading enhanced M2 polarization-related biomarkers (Arginase 1 and Mrc1) of macrophages in vitro.
3
ECM-based scaffolds biofabricated with mechanical loading increased bone volume/total volume ratio in vivo.

Research Summary

The study demonstrates that cyclic mechanical loading can modulate the immunoinflammatory microenvironment and stimulate osteogenic differentiation of MSCs seeded on 3D scaffolds. ECM-based scaffolds fabricated with mechanical loading facilitated M2 polarization of macrophages in vitro and enhanced new bone formation in vivo. The findings suggest that mechanical loading is a promising biofabrication strategy for developing bone regenerative biomaterials with low immunoinflammatory properties.

Practical Implications

Improved Bone Biomaterials

Mechanical loading during biofabrication can create bone biomaterials with enhanced osteogenic properties and reduced inflammation.

Enhanced Macrophage Polarization

ECM-based scaffolds biofabricated with mechanical loading promote M2 macrophage polarization, which is essential for bone regeneration.

Advanced Bone Regeneration Strategies

Mechanical stimuli can be used as a biofabrication approach to overcome the drawbacks of traditional bone tissue engineering techniques.

Study Limitations

1
The inflammatory response estimates are based on in vitro experiments, which may not fully represent in vivo conditions.
2
Inconsistent conclusions in previous studies on cellular fates under compressive mechanical loading due to differences in bioreactor parameters, cell types, and biomaterials.
3
The mechanical loading stress produced by the bioreactor could not be fully applied to the cell-scaffold composites in the expected linear wave mode.

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