Engineering osteoclast resorption units via sacrificial microgels in a bone-on-chip platform

Area of Science:

• Biomaterials Science
• Cell Biology
• Tissue Engineering

Background:

• Bone remodeling is crucial for skeletal health, involving bone multicellular units (BMUs).
• Existing models struggle to replicate human BMU complexity and face imaging challenges in mineralized bone.
• Advanced 3D models are needed for accurate osteoclast activity monitoring.

Purpose of the Study:

• To develop a bone-on-chip platform for localized, non-invasive analysis of human osteoclast function.
• To overcome limitations in spatial confinement and imaging for studying bone remodeling in vitro.
• To create a human-relevant 3D microenvironment for osteoclast research.

Main Methods:

• Utilized microfluidic droplet generation to encapsulate osteoclasts in dextran-tyramine (Dex-TA) microgels.
• Embedded microgels in mineralized collagen hydrogels, followed by selective degradation to form confined microstructures.
• Employed reflection confocal microscopy for non-destructive monitoring of matrix degradation.

Main Results:

• Confirmed osteoclast differentiation and function within the 3D microenvironment.
• Demonstrated increased matrix resorption in response to RANKL, validating osteoclast activity assessment.
• Showcased non-destructive monitoring of degradation using microcavity contrast.

Conclusions:

• The developed bone-on-chip platform enables spatial confinement and controlled degradation for studying osteoclast behavior.
• This model overcomes traditional system limitations, offering functional readouts in a human-relevant 3D setting.
• The platform is a versatile tool for bone remodeling research, disease modeling, and drug screening for bone disorders.