Tag Archives: Wake Forest Institute for Regenerative Medicine

Faster, cheaper, pseudo-organs (also known as organoids)

There’ve been any number of ‘organoid’ stories recently, here and elsewhere. This one is special due to a quasi extra-cellular matrix (cells have a type of skeletal structure known as an extra-cellular matrix or ECM). From a Sept. 11, 2015 news item on Azonano,

Scientists have developed a new technique that produces a user friendly, low cost, tissue-engineered pseudo-organ. The chip-based model produces a faithful mimic of the in vivo liver inside a scalable fluid-handling device, demonstrating proof of principle for toxicology tests and opening up potential use in drug testing and personalised medicine.

The work was done by researchers based at the Wake Forest Institute for Regenerative Medicine and the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences. They created a device architecture within which were a series of 3D liver cell constructs enclosed in a biopolymer that closely mimics the extra-cellular matrix (ECM). Surrounding the printed cells with this ECM – which the body uses to support cells in the liver – makes this model a more realistic model of the cells in vivo.

A Sept. 10, 2015 Institute of Physics (IOP) press release, which originated the news item, provides more details about the technology,

The technique uses photopatterning to produce defined 3D constructs in a microfluidic system to probe the construct quickly. “It’s basically scaled-down pluming” explains Adam Hall, an author on the paper. “This paper describes fairly hefty devices – a few mm – but we’re working to scale this down considerably.”

Collaboration proved to be the key to success; “The challenges were not too significant once Adam and I merged our areas of expertise.” adds Aleksander Skardal, another author on the paper. “With his background in devices and microfabrication, and my background in biomaterials and biofabrication, the two technologies integrated rather well.”

The 3D construct device offers a new tool in the development of drug treatments. At present, 2D testing in vitro doesn’t replicate the activity of the cells, and until now 3D systems have not provided adequate interactions of cells with the ECM, or offered particularly high-throughput testing.

This is where the combination of technologies has proven vital. “3D constructs are less effective if you can’t probe them quickly” continues Hall. “And without some important task, microfluidics are just a fun party trick.”

The researchers were also happy how quickly the techniques fell into place.

“The first time we attempted to perform the in situ photopatterning – it just worked” says Skardal. “Science isn’t always that easy, so we knew we might be onto something.”

“Yes – this was one of those rare occasions where things seemed to fall into place” adds Hall.

The researchers are now working to reduce the size of the system allowing for multiple constructs that could be tested individually. This would open potential usage in drug testing and personalised medicine.

“Imagine being able to put, for example, tumor cells from a patient on a chip and test different drug cocktails on them” they conclude. “You could determine the effectiveness and side effects of different treatments on an individual basis without endangering the patient.”

Here’s a link to and a citation for the paper,

In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device by Aleksander Skardal, Mahesh Devarasetty, Shay Soker, and Adam R Hall. Biofabrication, Volume 7, Number 3 DOI: 10.1088/1758-5090/7/3/032001 Published 11 September 2015

© 2015 IOP Publishing Ltd

This is an open access paper.

Printing new knee cartilage

I was reminded of the 1992 Olympics in Barcelona while reading the Nov. 22, 2012 news item on Nanowerk about printing cartilage for knees. Some years ago I knew a Canadian wrestler who’d participated in those games and he had a story about knee cartilage that featured amputation.

Apparently, wrestlers in earlier generations had knee surgeries that involved removal of cartilage for therapeutic purposes. Unfortunately, decades later, these retired wrestlers found that whatever cartilage had remained was now worn through and bones were grinding on bones causing such pain that more than one wrestler agreed to amputation. I never did check out the story but it rang true largely because I’d come across a similar story from a physiotherapist regarding  a shoulder joint and the consequences of losing cartilage in there (very, very painful).

It seems that scientists are now working on a solution for those of us unlucky enough to have damaged or worn through cartilage in our joints, from the Nov. 22, 2012 IOP science news release, (Institute of Physics) which originated the news item,

The printing of 3D tissue has taken a major step forward with the creation of a novel hybrid printer that simplifies the process of creating implantable cartilage.

The printer is a combination of two low-cost fabrication techniques: a traditional ink jet printer and an electrospinning machine. Combining these systems allowed the scientists to build a structure made from natural and synthetic materials. …

In this study, the hybrid system produced cartilage constructs with increased mechanical stability compared to those created by an ink jet printer using gel material alone. The constructs were also shown to maintain their functional characteristics in the laboratory and a real-life system.

The key to this was the use of the electrospinning machine, which uses an electrical current to generate very fine fibres from a polymer solution. Electrospinning allows the composition of polymers to be easily controlled and therefore produces porous structures that encourage cells to integrate into surrounding tissue.

In this study, flexible mats of electrospun synthetic polymer were combined, layer-by-layer, with a solution of cartilage cells from a rabbit ear that were deposited using the traditional ink jet printer. The constructs were square with a 10cm diagonal and a 0.4mm thickness.

The researchers tested their strength by loading them with variable weights and, after one week, tested to see if the cartilage cells were still alive.

The constructs were also inserted into mice for two, four and eight weeks to see how they performed in a real life system. After eight weeks of implantation, the constructs appeared to have developed the structures and properties that are typical of elastic cartilage, demonstrating their potential for insertion into a patient.

The researchers state that in a future scenario, cartilage constructs could be clinically applied by using an MRI scan of a body part, such as the knee, as a blueprint for creating a matching construct. A careful selection of scaffold material for each patient’s construct would allow the implant to withstand mechanical forces while encouraging new cartilage to organise and fill the defect.

The researchers’ article in the IOP science jouBiofrarnal, Biofabrication, is freely available for 30 days after its date of publication, Nov. 21, 2012. You do need to register with IOP science to gain access. Here’s the citation and a link,

Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications by Tao Xu, Kyle W Binder, Mohammad Z Albanna, Dennis Dice, Weixin Zhao, James J Yoo and Anthony Atala in 2013 Biofabrication 5 015001 doi:10.1088/1758-5082/5/1/015001

I believe all of the scientists involved in this bioprinting project are with the Wake Forest Institute for Regenerative Medicine.