Bone-on-a-Chip Pack

What is a bone-on-a-chip, and why would it be required?

The bone-on-a-chip is a microfluidic system that mimics the in vitro physiological microenvironment of bone tissue in a continuous, regulated perfusion. This is required because the bone is one of the most complex organs in the body, functioning through a fine balance between osteocytes, which form new bone, and osteoclasts, which break it down. Such a dynamic and interactive environment is extremely difficult to reproduce in traditional cell culture systems, which are large in volume, poorly controlled, and incapable of maintaining the cell-to-cell interactions central to bone physiology.

What are the biological structures that this model is intended to model?

The organisation of bone cells is around osteons, cylindrical structures parallel to the bone’s longitudinal axis that harbour blood vessels and nerve fibres. The structures regulate local nutrient delivery, mechanical signalling, and ionic gradients across cell types. Easy to grow in standard culture formats, they are naturally incorporated into pillar-based microfluidic chips, such as the Fluidic 261 from ChipShop, which more closely resembles the architectural geometry of these units of the osteon, thereby significantly enhancing the morphological relevance of the model.

What are the two fundamental functions of the bone-on-a-chip setup?

The platform is developed based on two main functions. To begin with, it ensures stable, continuous perfusion and recirculation of culture media, thereby maintaining a tightly controlled microenvironment during the experiment. Second, it also has a fail-safe mechanism, which helps prevent the experiment from clogging, which is a frequent failure mode in long-duration microfluidic cell cultures, so that weeks of effort are not wasted in case of a single blockage in the fluidic circuit.

What is contained in the bone-on-a-chip pack?

The pack itself includes a flow sensor (Galileo, MIC), level sensors, a flow controller, valves, fittings, tubing and luer connectors, reservoirs, the Galileo user interface software, user instructions on each of the instruments, and a microfluidic chip, compatible with bone cell culture – the Fluidic 261 Pillar Chip of ChipShop will be the default choice. Everything is compatibility tested, and can be configured in a plug-and-play configuration, available even to microfluidics scientists unfamiliar with it.

What is the role of shear stress in bone cell culture on chip?

The mechanical force applied to cells by moving media, known as shear stress, has been reported to affect gene expression and cellular behaviour in bone cultures. In a study involving human embryonic stem cell-derived mesenchymal progenitor cells (hES-MPs) in three-week cultures, it was shown that the flow profile strongly influences osteogenic differentiation and mineralized matrix deposition. It is important to note that an intermittent flow profile was demonstrated to favour cell differentiation and greater matrix mineralisation compared to constant flow, highlighting the value of accurate flow direction in this model.

What is the maximum duration that cell cultures can be sustained on this platform?

The platform allows cell cultures of up to three weeks. The length of this period is made possible by the automated media recirculation system which supplies the nutrients to the chip continuously and ensures the conditions of stable flow. The built-in fail-safe clogging prevention system also ensures that experiment integrity is maintained throughout this duration thus minimising the possibility of surprise culture loss as is common in long-duration microfluidic systems.

Is it possible to use the pack to do drug testing or inject compound?

Yes. A rotary valve may be introduced into the setup to allow the use of drugs or test compounds when there is a need to introduce them to an ongoing culture. This option enables the researcher to inject certain substances at set time points throughout the experiment without interfering with the continuous perfusion, which makes the platform appropriate in pharmacological studies, tests of toxicity and studies of the role of drugs on bone cells behaviour or matrix composition over time.

Does it support other MIC platforms or instruments?

Yes. The bone-on-a-chip pack can be extended to the automated cell culture platform offered by MIC that offers even greater degree of integration and automation. It is also made in the same modular Galileo instrument ecosystem as the other organ-on-chip packs of MIC; this implies that those researchers that are already accustomed to the flow sensor and software backbone can easily switch bone culture experiments without requiring an extensive learning curve.

Is it possible to sterilise the setup between experiments?

Yes. This pack has a specially designed sterilisation and cleaning procedure, which is also included with the user manual. This is necessary to allow the system to be decontaminated safely between experimental runs, a requirement to preserve cell culture integrity across successive applications and/or in other applications where the control of contamination must be paramount, e.g. in long-term studies of osteogenesis or in experiments with primary patient-derived cells.

How do I get the pack, or tailor it, to use in my application?

The pack can be made extremely customisable, and our microfluidic experts will recommend the most suitable instrument configuration depending on the objectives of your research, the type of flow sensor used, the number of channels of the controller, the choice of chip, and any other modules, like a rotary valve to inject drugs. Since the pack is in beta testing, a preliminary discussion with our team is required before placing an order. It is also possible to access individual instruments using the beta programme.