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Posted: Sep 12, 2011

Ultrasmall peptides harnessed to repair spinal disc damage

(Nanowerk News) 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.
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."
A field emission scanning electron microscopy image of the ultrasmall peptides that resemble collagen and amyloid fibers
Figure 1: A field emission scanning electron microscopy (FESEM) image of the ultrasmall peptides that resemble collagen and amyloid fibers.
Published recently in the leading nanoscience and nanotechnology journal, Nano Today ("Ultrasmall Natural Peptides Self-Assemble to Strong Temperature-Resistant Helical Fibers in Scaffolds Suitable for Tissue Engineering"), 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.
An FESEM image of the honeycomb-like porous microstructures of the peptide scaffolds
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.
In a separate study published in the Proceedings of the National Academy of Sciences ("Natural Tri- to Hexapeptides Self-Assemble in Water to Amyloid β-Type Fibre Aggregates by Unexpected α-Helical Intermediate Structures"), 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.
Source: Institute of Bioengineering and Nanotechnology
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