Tissue Engineering PDF Print E-mail
Overview of Tissue Engineering »
Nerve regeneration »

Overview of Tissue Engineering

Of the many challenges daunting clinicians today, the most vital is the perpetual shortage of implantable tissues for major tissue repair. Acute, chronic or congenital injuries often require treatment with replacement tissues and organs to insure patient survival. However, transplant waiting lists are extensive and many people die waiting for a new organ. Beyond whole organ replacement, the need for tissues to treat acute trauma is also vital. Reconstructive surgeries following cancer resection and tissue loss from traumatic injury can require extensive amounts of tissue, often with the patient as the sole source for autologous materials. Creating artificial means to generate supplement tissue has many significant process barriers. In order to generate physiologically correct tissue scaffolds, bioabsorbable polymer substrates must be created in 3-D, which is very difficult using current fabrication methods and the limits these processes place on selecting a process compatible material. This is where MicroFab’s ink-jet printing technology creates an advantage. This technology is best integrated in our printing platform family. These platforms enable the end user to precisely deposit materials onto a number of substrates in a non-contact format in a cleanroom, sterile environment.

Sterile tissue culture hood with integrated JetLabR II.

Thermal controllers in the printing device and substrate allow for printing at either hot or cold temperatures depending on the specific needs.

Cold jetting assembly with reservoir and printhead kept at constant low temperature.

Cold jetting assembly mounted in sterile hood.

Printhead for dispensing materials at elevated temperatures.

An array of dispensing devices are available for this family of printing platforms, that allow a user to print materials ranging from polymers and sensitive protein solutions to tissue extracts and live cells. The printing devices can be heat-sterilized or gamma irradiated without changing their functional characteristics.

Jetting devices.

Jetting device with protected tip.

Drops ejecting from a side jetting device. This type of device can be used to deposit drops on the inner surface of tubes.

The printing process can be scaled-up through the use of multiple printing devices, array print-heads or multiple substrates simultaneously.

Integrated array print-heads. Left - printhead with 10 individual fluid supplies. Right - integrated array printhead dispensing simultaneously with multiple channels.

Nerve regeneration

If a traumatic injury takes place causing a loss of nerve tissue, the clinician only has the option of taking nerve from another portion of the patient’s body to replace the “more important” nerve deficit. While up to 80% successful, autologous nerve grafts create further trauma to the patient. Tissue engineers have recognized the need for an artificial means to facilitate nerve regeneration and have pursued bioabsorbable nerve guidance conduits as a solution. Bioabsorbable nerve conduits are designed to facilitate nerve regeneration by optimizing growth conditions at the wound site in a number of ways. When a peripheral nerve guidance conduit is surgically implanted, the proximal and distal nerve stumps are sutured into the conduit. This allows the conduit to act as a physical guiding pathway for nerve growth, as well as a reservoir that sequesters important growth factors that further guide the sprouting daughter axons in the proximal nerve stump. Finally, by building the conduits with bioabsorbable polymers, the conduit is absorbed by the body within the time required to complete the repair process and thus, there is no need for surgery to remove them.

Bifurcated nerve conduit. Each segment is 1.8mm in diameter with a total length of 20mm. The joint at the apex flowingly connects each segment.

Nerve guidance conduits with jetted reinforcing rings printed on a JetLabR platform variant.

The technology allows:

  1. applying outside/inside conduit coatings;
  2. loading the conduits with ink-jet dispensed cells;
  3. loading the conduits with ink-jet dispensed drug microspheres.

Jetted microspheres that can be loaded with nerve growth factors.

Captured image of the cell jetting process.

Furthermore, the high precision nature of ink-jet method enables one to create and control protein amount or gradients within conduit material, and conduit surface texture and physical dimensions.

Jetted NGF unidirectional gradient - variation by spacing.

Two orthogonal jetted dye gradients - variation by amount.

Nerve guiding conduit with modified surface for mechanical reinforcement.

While peripheral nerve regeneration has been our main focus to date, we are currently exploring other tissue engineering fields such as cardiovascular and esophageal stents.

3D polymer structure mimicking blood vessel network (120µm wide branches).