IBN scientists harness ultrasmall peptides to repair spinal disc damage

New ultrasmall peptides that can be used as building blocks for a wide range of regenerative applications such as spinal disc replacement and cartilage repair have been developed by scientists at the Institute of Bioengineering and Nanotechnology (IBN), the world's first bioengineering and nanotechnology research institute. These peptides spontaneously assemble in water to form hydrogels, which resemble collagen, a major component of connective tissues found in cartilage, ligaments, tendons, bone and skin.

IBN's latest discovery offers promise for orthopedic patients, such as those suffering from degenerative disc diseases. Degenerative disc disease is currently the predominant cause of disability amongst the adult population, affecting 85% of the population by the age of 50. It is a type of back pain that is caused by the wearing away of the nucleus pulposus, a jelly-like material in the spinal disc, which is made up of collagen fibers. The spinal disc helps to absorb vertical pressure and provides flexibility to the spinal column. There is a strong market demand for orthopedics and in particular for spinal replacement. The worldwide spine market has been growing at a compound annual growth rate of about 8-10% over the last seven years. [1]

The unique class of peptides developed by IBN has similar gel strength as the jelly-like material in the spinal disc. Dr Charlotte Hauser, IBN Team Leader and Principal Research Scientist elaborated, “There is a huge unmet clinical need for a prosthetic device that can inhibit or repair early-stage disc damage. Our biocompatible peptide hydrogels could be injected into the body to stimulate disc regeneration or used for artificial disc replacement. This peptide-based approach could offer an alternative to spinal surgery by delaying or even abolishing the need for invasive surgery. Our ultrasmall peptides can also be easily translated to clinical use because they are easy and cost-effective to produce.”

The IBN team comprising Dr Rensheng Deng, Prof Jackie Y. Ying, Dr Charlotte Hauser, Dr Eva Yihua Loo and Dr Archana Mishra (from left to right).

Published recently in the leading nanoscience and nanotechnology journal, Nano Today, IBN's self-assembling peptides imitate nature by forming ordered structures using molecular recognition. This self-assembly approach is emerging as an important new strategy in bioengineering because it allows the peptides to form easily into various structures such as membranes, micelles and gels. The essence of this ‘Lego’-like technology lies in the unique design of the peptide.

IBN's self-assembling peptides were rationally designed comprising only simple 3 to 7 amino acids, making them extremely small compared to conventional peptides, which usually require 16 to 32 amino acids. IBN's peptide molecule also contains a characteristic motif – a water-insoluble ‘tail’ and a water-soluble ‘polar head’. This amphiphilic property allows the random peptides to self-assemble into hydrogels with uniform and stable fibrous structures within minutes after coming into contact with water. Unlike existing hydrogels, IBN's process does not require any enzymes or chemical agents to link the fibers together.

Microscopic images revealed that the structure of IBN's peptide-derived hydrogel bears a striking resemblance to collagen fibers. Tests have demonstrated that IBN's hydrogels are mechanically strong, heat-resistant and biocompatible with a variety of human cells. With a high water content of up to 99.9%, these hydrogels have fibrous structures that look like porous honeycombs due to the large number of water-containing cavities. By changing the concentration of the peptide, the researchers were also able to control the stiffness of the hydrogels, making them suitable for use as biomaterials for tissue engineering applications in regenerative medicine, such as for the treatment of degenerative disc disease, skin replacement and stem cell-related therapies.

In a separate study published in the Proceedings of the National Academy of Sciences, the IBN scientists reported that the structure of the ultrasmall peptides closely resembled amyloid fibers, which are abnormal constructs that are the hallmark of many fatal neurodegenerative diseases such as Alzheimer's, Parkinson, as well as Type II Diabetes. This novel class of peptides can therefore also be used as an excellent model system for the development of drugs targeted at the prevention or control of amyloid fibers.

“IBN aims to create new biomaterial platforms based on nanotechnology. This unique class of ultrasmall peptides are biomimetic, and have excellent potential as cell culture substrates and tissue engineering scaffolds,” added Professor Jackie. Y. Ying, IBN Executive Director.

*[1] Global Spine Market Report: 2010 Edition – Market Research Report on Aarkstore Enterprise (September 2, 2010)

Figure 1: A field emission scanning electron microscopy (FESEM) image of the ultrasmall peptides that resemble collagen and amyloid fibers.

Figure 2: An FESEM image of the honeycomb-like porous microstructures of the peptide scaffolds, which enable the hydrogels to contain large amounts of water.

References:

A. Mishra, Y. Loo, R. Deng Y. J. Chuah, H. T. Heeb, J. Y. Ying and C. A. E. Hauser, “Ultrasmall Natural Peptides Self-Assemble to Strong Temperature-Resistant Helical Fibers in Scaffolds Suitable for Tissue Engineering,” Nano Today, 6 (2011) 232-239.

C. A. E. Hauser, R. Deng, A. Mishra, Y. Loo, U. Khoe, F. Zhuang, D. W. Cheong, A. Accardo, M. B. Sullivan, C. Riekel, J. Y. Ying and U. A. Hauser, “Natural Tri- to Hexapeptides Self-Assemble in Water to Amyloid β-Type Fibre Aggregates by Unexpected α-Helical Intermediate Structures,” Proceedings of the National Academy of Sciences, 108 (2011) 1361-1366.

About the Institute of Bioengineering and Nanotechnology

The Institute of Bioengineering and Nanotechnology (IBN) was established in 2003 and is spearheaded by its Executive Director, Professor Jackie Yi-Ru Ying, who has been on the Massachusetts Institute of Technology's Chemical Engineering faculty since 1992, and was among the youngest to be promoted to Professor in 2001.

In 2008, Professor Ying was recognized as one of “One Hundred Engineers of the Modern Era” by the American Institute of Chemical Engineers for her groundbreaking work on nanostructured systems, nanoporous materials and host matrices for quantum dots and wires.

Under her direction, IBN conducts research at the cutting-edge of bioengineering and nanotechnology. Its programs are geared towards linking multiple disciplines across engineering, science and medicine to produce research breakthroughs that will improve healthcare and our quality of life.

IBN's research activities are focused in the following areas:

Drug and Gene Delivery, where the controlled release of therapeutics involve the use of functionalized polymers, hydrogels and biologics for targeting diseased cells and organs, and for responding to specific biological stimuli.

Cell and Tissue Engineering, where biomimicking materials, stem cell technology, microfluidic systems and bioimaging tools are combined to develop novel approaches to regenerative medicine and artificial organs.

Biodevices and Diagnostics, which involve nanotechnology and microfabricated platforms for high-throughput biomarker and drug screening, automated biologics synthesis, and rapid disease diagnosis.

Pharmaceuticals Synthesis and Green Chemistry, which encompasses the efficient catalytic synthesis of chiral pharmaceuticals, and new nanocomposite materials for sustainable technology and alternative energy generation.

IBN's innovative research is aimed at creating new knowledge and intellectual properties in the emerging fields of bioengineering and nanotechnology to attract top-notch researchers and business partners to Singapore. Since 2003, IBN researchers have published over 680 papers in leading journals.

IBN also plays an active role in technology transfer and spinning off companies, linking the research institute and industrial partners to other global institutions. The Institute has a portfolio of over 720 patents/patent applications on its inventions, and welcomes industrial partners to collaborate on and co-develop its technologies. IBN has successfully commercialized 33 patents/patent applications.

IBN's current staff strength stands at over 170 scientists, engineers and medical doctors. With its multinational and multidisciplinary research staff, the institute is geared towards generating new biomaterials, devices, systems and processes to boost Singapore's economy in the medical technology, pharmaceuticals, chemicals, consumer products and clean technology sectors.

IBN is also committed to nurturing young talents. Besides the training of PhD students, IBN has a Youth Research Program (YRP) for students and teachers from secondary schools, junior colleges, polytechnics, and universities. Since its inception in October 2003, IBN's YRP has reached out to more than 48,000 students and teachers from 274 local and overseas schools and institutions.

For more information, please log on to: www.ibn.a-star.edu.sg