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THE SINGAPORE MAGAZINE OF RESEARCH,
TECHNOLOGY AND EDUCATION
About Innovation
COVER STORY:
Biotechnology Brings Hope to Tissue Regeneration
Applying synthetic molecules in regenerative medicine may translate to the repair of spinal-cord injury, bone, and heart tissue.
by Lay Leng TAN

eople stricken by paralysis because of spinal-cord injury suffer a personal tragedy. Their plight was brought home by the high-profile case of Superman actor Christopher Reeve. Long an active sportsman, he was reduced to a helpless paraplegic by a fall from a horse and then died last year from complications of his condition.

Researchers worldwide are investigating various means to treat this terrible debilitating condition. A group of US scientists at Northwestern University believe their synthetic molecules could lead to regeneration of bodily tissue, including neurons. They have succeeded in fabricating molecules that promote differentiation of mouse embryonic cells into neurons and the suppression of cells known as astrocytes, a development that holds promise of reversing paralysis due to spinal-cord injury.

Samuel Stupp, Board of Trustees Professor of Materials Science and Engineering, Chemistry, and Medicine at the university, says that his team has created exciting new materials for regenerative medicine. By virtue of their chemical structure, the synthesised materials can interact with cells of the central nervous system in ways that may help prevent the formation of the scar tissue often linked to paralysis after spinal-cord injury.

Stupp, who also directs the university's Institute for BioNanotechnology in Medicine, reveals that his team has created bioactive extracellular matrices by which they can manipulate cell behaviour, starting with a key issue in regenerative medicine - controlling the differentiation of a cell.

Team members have discovered the material using self-assembly of a type of peptide amphiphile that forms nanofibres in biological environments. They achieved this combination, dubbed matrix nanotechnology, via molecular design using a family of smart molecules that self-assemble into a matrix as well as have the capacity to signal cells. The researchers programme the solution such that when they introduce the molecules in liquid into a biological environment, the molecules group themselves to form a functional structure - for instance, they cause cells to differentiate, migrate, or proliferate.

Relying on certain parameters of the platform strategy, the investigators search for relevant biological knowledge about proteins, functions, structures, and so on from different sources and incorporate it into their matrix technology. They then customise the information for specific organs and tissues. So far they have achieved encouraging results in bone and neurons.

In neurons they have designed a three-dimensional network of nanofibres as a scaffold and coaxed molecules to self-assemble into a specific sequence of amino acids known to promote neuron growth. The findings were published early 2004 in an online edition of Science.

Stupp enthuses about the implications of the nanoscale discovery. "We have uncovered a little gold mine in the sense that we have a strategy to create complex structures and therefore can manage many aspects of cell behaviour. These structures can trigger regeneration of tissues in ways not considered before."

Many venture capitalists and companies keen to tap the patented matrix technology have approached Northwestern University, which is cautiously evaluating the suitors to ensure that the courtship culminates in a marriage that bears fruit.

Stupp elaborates on the strict screening process: "We want to make sure we put the technology into the hands of someone who will really develop it and make a difference to humanity. It has enormous potential for a profound impact on people and on the economy since the platform could cover almost any field. You could develop strategies to regenerate heart tissue, repair bone, make cartilage, and cure diabetes or spinal-cord injuries. With such complex targets, companies need to be focused as they approach the end.

"This type of technology, straddling biology and nanote-chnology, will be interesting to develop well. It may require participation of different countries. Most likely a group, perhaps of investors, will create a startup that will license the technology, and I shall have an active role in this company to ensure the translation. This startup company can develop relationships with all kinds of individuals. Parties in Japan and Korea have expressed interest."

He expects that the company that can exploit this technology will be a 21st century pharmaceutical company - not a classic pharmaceutical, biotechnological, materials, or nanotechnology setup, but rather, a hybrid of these.

A company named Nanotope has been set up. It has closed its initial round of financing and is in discussions with biopharma companies to partner with. The startup is finalising an agreement with Northwestern University for exclusive worldwide rights to the technology for regenerative medicine, wound healing, and cancer therapy.

Stupp intends to translate the technology and get the product to clinical trial within five years or less. All the targets at which his team aims are things with no current therapy, such as spinal-cord injury, so conducting a clinical trial might be easier. Relying on successful preclinical work on animals, he feels confident of getting approval for human tests.

Some targets identified include the spinal cord, heart, bone, and cartilage. Another is diabetes. He envisions possible collaboration with hospitals and others outside the US. Besides regenerative medicine, the technology can apply to other diseases, like cancer.

"Our technology is comparable to stem cell technology; both can be combined to produce regenerative strategies. However, our technology can be effective even without stem cell technology as it is modular and versatile, applicable in cellular or acellular therapy. The work is about materials with biological activities because of their structures and their way of interacting with proteins in specific ways. We are thinking of using matrix and cell, or matrix, biotechnology, and cells."

Although Stupp works with stem cells himself, he notes that anything to do with cells will be more expensive, risky, and difficult to implement. However, he believes, at some stage the need for both matrix and cells will exist.

The multidisciplinary expert serves on a committee on interdisciplinary graduate research and education that advises the president of the National University of Singapore. He is impressed with Singapore's commitment to investment in the development of knowledge and high technology. He sees possible niches for the nation in the areas of advanced biology, nanotechnology, and informatics.

For more information contact Samuel Stupp at s-stupp@northwestern.edu

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