Navigation Links
Precisely engineering 3-D brain tissues

CAMBRIDGE, MA -- Borrowing from microfabrication techniques used in the semiconductor industry, MIT and Harvard Medical School (HMS) engineers have developed a simple and inexpensive way to create three-dimensional brain tissues in a lab dish.

The new technique yields tissue constructs that closely mimic the cellular composition of those in the living brain, allowing scientists to study how neurons form connections and to predict how cells from individual patients might respond to different drugs. The work also paves the way for developing bioengineered implants to replace damaged tissue for organ systems, according to the researchers.

"We think that by bringing this kind of control and manipulation into neurobiology, we can investigate many different directions," says Utkan Demirci, an assistant professor in the Harvard-MIT Division of Health Sciences and Technology (HST).

Demirci and Ed Boyden, associate professor of biological engineering and brain and cognitive sciences at MIT's Media Lab and McGovern Institute, are senior authors of a paper describing the new technique, which appears in the Nov. 27 online edition of the journal Advanced Materials. The paper's lead author is Umut Gurkan, a postdoc at HST, Harvard Medical School and Brigham and Women's Hospital.

'Unique challenges'

Although researchers have had some success growing artificial tissues such as liver or kidney, "the brain presents some unique challenges," Boyden says. "One of the challenges is the incredible spatial heterogeneity. There are so many kinds of cells, and they have such intricate wiring."

Brain tissue includes many types of neurons, including inhibitory and excitatory neurons, as well as supportive cells such as glial cells. All of these cells occur at specific ratios and in specific locations.

To mimic this architectural complexity in their engineered tissues, the researchers embedded a mixture of brain cells taken from the primary cortex of rats into sheets of hydrogel. They also included components of the extracellular matrix, which provides structural support and helps regulate cell behavior.

Those sheets were then stacked in layers, which can be sealed together using light to crosslink hydrogels. By covering layers of gels with plastic photomasks of varying shapes, the researchers could control how much of the gel was exposed to light, thus controlling the 3-D shape of the multilayer tissue construct.

This type of photolithography is also used to build integrated circuits onto semiconductors a process that requires a photomask aligner machine, which costs tens of thousands of dollars. However, the team developed a much less expensive way to assemble tissues using masks made from sheets of plastic, similar to overhead transparencies, held in place with alignment pins.

The tissue cubes can be made with a precision of 10 microns, comparable to the size of a single cell body. At the other end of the spectrum, the researchers are aiming to create a cubic millimeter of brain tissue with 100,000 cells and 900 million connections.

Answering fundamental questions

Because the tissues include a diverse repertoire of brain cells, occurring in the same ratios as they do in natural brain tissue, they could be used to study how neurons form the connections that allow them to communicate with each other.

"In the short term, there's a lot of fundamental questions you can answer about how cells interact with each other and respond to environmental cues," Boyden says.

As a first step, the researchers used these tissue constructs to study how a neuron's environment might constrain its growth. To do this, they placed single neurons in gel cubes of different sizes, then measured the cells' neurites, long extensions that neurons use to communicate with other cells. It turns out that under these conditions, neurons get "claustrophobic," Demirci says. "In small gels, they don't necessarily send out as long neurites as they would in a five-times-larger gel."

In the long term, the researchers hope to gain a better understanding of how to design tissue implants that could be used to replace damaged tissue in patients. Much research has been done in this area, but it has been difficult to figure out whether the new tissues are correctly wiring up with existing tissue and exchanging the right kinds of information.

Another long-term goal is using the tissues for personalized medicine. One day, doctors may be able to take cells from a patient with a neurological disorder and transform them into induced pluripotent stem cells, then induce these constructs to grow into neurons in a lab dish. By exposing these tissues to many possible drugs, "you might be able to figure out if a drug would benefit that person without having to spend years giving them lots of different drugs," Boyden says.


Contact: Sarah McDonnell
Massachusetts Institute of Technology

Related biology technology :

1. Pioneering electrical engineering work recognized
2. Engineering plants for biofuels
3. New UCLA Engineering research center to revolutionize nanoscale electromagnetic devices
4. Three Hertz Foundation Fellows Receive Presidential Honors; Leaders in Applied Physical, Biological and Engineering Sciences
5. Two Blades Foundation licenses genome engineering technology to KWS
6. Bronstein, Gewirtz & Grossman, LLC Announces Investigation of American Oriental Bioengineering Inc.
7. Reverse engineering epilepsys miracle diet
8. Trinity College Dublins Neuroscience and Bioengineering Programmes Receive Postgraduate Course of the Year Awards
9. X-BODY BioSciences to Present Novel Methods of Selecting for Antibodies Against Targets on Live Cells at CHIs Protein Engineering Summit
10. Global Genetic Engineering Industry
11. Smart, self-healing hydrogels open far-reaching possibilities in medicine, engineering
Post Your Comments:
(Date:6/23/2016)... BEACH, Calif. , June 23, 2016  Blueprint ... new biological discoveries to the medical community, has closed ... co-founder Matthew Nunez . "We have ... us with the capital we need to meet our ... will essentially provide us the runway to complete validation ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... the Pennsylvania Convention Center and will showcase its product’s latest features from June ... be presenting a scientific poster on Disrupting Clinical Trials in The Cloud during ...
(Date:6/23/2016)... , June 22, 2016  Amgen (NASDAQ: ... of the QB3@953 life sciences incubator to ... health. The shared laboratory space at QB3@953 was created ... a key obstacle for many early stage organizations - ... of the sponsorship, Amgen launched two "Amgen Golden Ticket" ...
(Date:6/22/2016)... , June 22, 2016 Research and ... Global Markets" report to their offering. ... billion in 2014 from $29.3 billion in 2013. The market is ... of 13.8% from 2015 to 2020, increasing from $50.6 billion in ... projected product forecasts during the forecast period (2015 to 2020) are ...
Breaking Biology Technology:
(Date:6/16/2016)... , June 16, 2016 ... size is expected to reach USD 1.83 billion ... Grand View Research, Inc. Technological proliferation and increasing ... applications are expected to drive the market growth. ... , The development of advanced multimodal ...
(Date:6/9/2016)... June 9, 2016 Paris ... Teleste,s video security solution to ensure the safety of people ... during the major tournament Teleste, an international ... and services, announced today that its video security solution will ... to back up public safety across the country. The system ...
(Date:6/2/2016)... 2016 The Department of Transport Management ... 44 million US Dollar project, for the , ... Personalization, Enrolment, and IT Infrastructure , to ... and implementation of Identity Management Solutions. Numerous renowned international vendors ... Decatur was selected for the most compliant and ...
Breaking Biology News(10 mins):