Monday 2nd September marks the start of Organ Donation Week, a time to highlight the importance of organ donation and celebrate the selflessness of donors. Currently over 6,300 people in the UK are waiting for an organ transplant, and sadly everyday around three people die waiting. As part of the efforts to increase the number of donors and reduce some of these preventable deaths, England is moving to an "opt out" system in 2020. Unless they have recorded a decision not to donate, or are in one of the excluded groups, all adults in England will be considered an organ donor.
While this approach will hopefully lead to a reduction in how long a patient has to wait for a suitable organ for transplant, it doesn’t address the other main issue of transplantation – rejection. Transplant recipients’ immune systems recognize donor organs as "foreign" and can attack them in a bid to eliminate them from the body. Immunosuppressive drugs can help to minimise the magnitude of rejection but are not always successful long-term and their use comes with adverse effects of their own.
In an ideal world, there would be no need to rely on donor organs. Anyone needing a transplant would receive a personalized organ generated in the lab from their own cells. Meaning no waiting for a human donor and minimal chance of rejection. Although this may currently seem a rather futuristic idea, several research groups are taking the first steps to one day making this a reality.
3D bioprinting technologies are at the heart of many of these projects. Building on the principles of 3D printing, bioprinting uses bioinks made from cells to print living tissues layer by layer. Some form of scaffold is also usually involved in the process to support and protect the cells. By carefully controlling which cells are put where, bioprinting can enable the production of intricate biological structures. A number of projects are underway to harness this technology to print functional human tissues, the first step to printing an entire organ.
Scientists from Carnegie Mellon University recently demonstrated the ability to print full-scale heart components, including cardiomyocytes, heart valves and ventricles. "What we've shown is that we can print pieces of the heart out of cells and collagen into parts that truly function, like a heart valve or a small beating ventricle," explained Adam Feinberg, a Professor of Biomedical Engineering and Materials Science and Engineering in a press release.
Using a specially developed hydrogel, the researchers were able to overcome one of the main difficulties associated with printing collagen - preventing it from deforming. Collagen is the most abundant protein in human tissues, so the ability to bioprint it effectively will be important in creating organs other than the heart too.
"It is important to understand that there are many years of research yet to be done," added Feinberg. "But there should still be excitement that we're making real progress towards engineering functional human tissues and organs, and this paper is one step along that path."
A major challenge in creating fully functioning tissues and organs is being able to provide them with a system that can deliver an adequate blood supply and efficiently remove waste products. A team of scientists from Rice University recently designed an open-source bioprinting technology – SLATE (Stero-lithography apparatus for tissue engineering) – which enables the creation of complex vasculature.
The team demonstrated the abilities of the technology by bioprinting lung-mimicking air sacs which allowed movement of oxygen similar to gas exchange occurring in human lung alveolar air sacs. The technique can also be applied to bioprinting other tissues and structures such as bicuspid valves in the heart.
"With the addition of multivascular and intravascular structure, we're introducing an extensive set of design freedoms for engineering living tissue," Jordan Miller, Assistant Professor of Bioengineering at Rice University said in a press release detailing the work. "We now have the freedom to build many of the intricate structures found in the body."
Following on from research completed in 2016, a team from the Wyss Institute has recently created a 3-D vascularized proximal tubule model which more fully mimics the human kidney’s reabsorption function. In the model, perfusable tubules and blood vessels are printed adjacent to each other and are able to communicate. “We construct these living renal devices in a few days and they can remain stable and functional for months,” said first author Neil Lin, in a press release.
The work is part of the Wyss Institute’s 3D Organ Engineering Initiative, which brings together multidisciplinary researchers with the aim of developing bioengineered transplantable tissues and organs.
While these examples highlight the great developments that have been made in being able to accurately print functioning tissues, it is likely to be some time before it is possible to bioprint entire organs suitable for transplantation. Moving from the small, relatively simple tissue structures to large, complex complete organs will require further progress in areas such as vascular network integration.
Once the technical hurdles have been overcome and fully functioning organs can successfully be bioprinted, extensive safety testing and regulatory policies may also add to the timescale before patients are able to receive a bioprinted organ. Although bioprinting is unfortunately unlikely to help patients currently in need of an organ transplant, many are optimistic that it is now a case of when and not if bioprinted tissues and organs will be available and an alternative option to organ donation.