Regenerative Medicine

Regenerative medicine is a branch of translational medicine whose purpose is to restore or establish the normal function of damaged tissues or organs. Due to the ever-increasing demand caused by the aging population, researchers have made great efforts to develop new regeneration strategies, which involve stem cells, soluble factors, biomaterials or combinations thereof. Regenerative medicine is a multidisciplinary research field that uses therapeutic stem cells and tissue engineering methods to achieve its goals.

Microfluidics has proven its maturity in realizing high-throughput screening platforms, and may provide a new way to accelerate research and development in the field of regenerative medicine. Besides, microfluidics also have other advantages, such as creating an in-vivo-like microenvironment.

Microfluidic Regenerative Medicine

Researchers of regenerative medicine must not only understand the reasons for tissue damage, but also understand the methods of restoring tissue function and the mechanism by which stem cells repair tissues. Using a more accurate model can help us better understand the causes of organizational failures. Microfluidic chips can provide a highly controlled environment for cell and tissue culture.

Alfa Chemistry can manufacture microfluidic devices for the following applications in regenerative medicine:

• Create a soluble gradient
• Chemical and mechanical signals
• Real-time analysis using embedded sensors
• Easy to use biomaterials and hydrogels as tissue constructs
• Provide a biologically relevant microenvironment for cell and tissue culture

In recent years, various organs have become the target of microfluidic regenerative medicine. These on-chip regeneration methods include:

• Neuroregeneration
• Revascularization
• Lung regeneration
• Heart regeneration
• Kidney regeneration
• Musculoskeletal regeneration

Neuron Regeneration

Microfluidic systems have a long history in the field of neuron regeneration. The geometry of the microenvironment is essential for studying neuronal degeneration and regeneration. Closed and separated compartments are often used to study the growth of axons and their response to stimuli. For this purpose, a device with compartments, such as the Campenot room, can be used. In these devices, vacuum grease is used to connect fluoropolymer separators to standard petri dishes. The neuron body is plated in the central compartment, and the axons can be sealed by vacuum grease or "rough" scratches made on the surface of the petri dish with a knife to grow into the surrounding compartment.

Fig.1 Schematic diagram of a Campenot chamber. (A) Top-view with cell bodies in the center and axons spreading to the outer chambers by scratches in the surface or through vacuum grease. (B) Side-view of situation in A. (C) Alternative seeding possibility from the left chamber, so the middle part of the axons can be exposed to treatment separately. (Harink B, et al. 2013)

However, it is still subject to many limitations, including limited resolution within the neuron size range, cumbersome assembly, high risk of leakage, and prone to axon growth, destruction and tension under the slightest mechanical action.

Revascularization and Wound Healing

Vascularization is essential for proper oxygen and nutrient supply in regenerative medicine. The formation of new blood vessels is an important part of every regeneration strategy. Since the size of the microfluidic channel is comparable to the size of natural microvessels, microchips are very attractive for realizing capillaries or studying the process of angiogenesis.

So far, soft lithography has been used to successfully create an in vitro microvascular network from type 1 collagen gel. Human umbilical vein endothelial cells (HUVEC) can be seeded in a 100μm×100μm microchannel, allowed to attach and proliferate on the wall, and then perfused with culture medium or whole blood. To study the interaction between HUVEC and perivascular cells, perivascular cells are added to the collagen gel before the device is manufactured. After treatment with growth factors and angiogenic factors, sprouting angiogenic structures are observed in the gel matrix.

Fig.2 Gel-based 3D microvascular network made of collagen type-I gel. (A) Schematic representation of research possibilities on this platform. (B) Fluorescent microscopy image of human umbilical vein endothelial cells (HUVEC) on the walls of the gel-based networks, stained for the nuclei (blue) and CD31 (red), an angiogenic marker. (C) Schematic side-view representation of the microvascular networks. (Harink B, et al. 2013)

The same micro-device has been successfully applied to study the cell-to-cell interaction between pericytes and smooth muscle cells, and as a thrombus model for chemically induced thrombosis. This artificial capillary network is of great significance not only for the testing of materials and compounds used in the regenerative medicine strategy, but also as a potential implant candidate.

Does your research focus on on-chip regeneration? Please contact us to learn more about the use of microfluidics in regenerative medicine research.

Reference

• Harink B, et al. (2013). "Regeneration-on-a-chip? The perspectives on use of microfluidics in regenerative medicine" Lab Chip. 13: 3512-3528.

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