An ex vivo model to study transport processes and fluid flow in loaded bone

Area of Science:

• Biomechanical Engineering
• Skeletal Biology
• Biophysics

Background:

• Load-induced fluid flow in bone is hypothesized to transmit mechanical signals and drive adaptation.
• Direct measurement of fluid displacement in cortical bone is challenging.
• Existing indirect evidence relies on phenomena like strain-generated potentials.

Purpose of the Study:

• To develop and validate an ex vivo perfusion model for studying bone transport processes under mechanical loading.
• To quantify load-induced fluid flow and its effect on molecular transport in cortical bone.
• To investigate the relationship between loading parameters and transport enhancement.

Main Methods:

• Established a closed-loop perfusion system in explanted sheep forelimbs.
• Introduced a molecular tracer intra-arterially before cyclic mechanical loading.
• Applied cyclic compressive strain (0.2%) to one limb while the contralateral limb served as a control.
• Measured tracer concentration in cortical bone cross-sections at various time points (2, 4, 8, 16 min).

Main Results:

• Significantly higher tracer concentration was found in loaded bone compared to unloaded controls.
• Early loading (8 cycles, 2 min) showed enhanced transport, but this effect diminished with increased loading or perfusion time.
• Transport enhancement was dependent on tracer size and the specific loading mode applied.

Conclusions:

• The developed ex vivo model successfully demonstrated that load-induced fluid flow enhances molecular transport in cortical bone.
• Fluid flow is a critical mechanism for signal transmission and potential adaptation within the bone's lacunocanalicular system.
• The extent of transport enhancement is influenced by tracer characteristics and mechanical loading conditions.