Regenerative medicine attempts to restore living tissue which has been lost or damaged. It is a highly interdisciplinary field which has only been made possible by the intersection of recent advances in stem cell therapy, bioengineering, and nanotechnology.
Nanofabrication techniques now allow researchers to create nanofibre scaffolds for regenerative therapies. The exact way this works depends on the nature of the tissue, but in general the scaffolds are used to guide the growth of new tissue, seeded using stem cells.
Figure 1. Stem cells can be used to regrow damaged tissue in many areas of the body. Nanoscale scaffolds can improve results of stem cell therapy by guiding this growth in the right direction. Image Credits: National Eye Institute.
Nanofibres for Regenerative Medicine
Most nanofibres which have been used in regenerative medicine research are produced using the electrospinning method. This is a well-established technique, which allows a degree of control over the properties of the resulting nanofibre sheets or meshes, and is suited to a wide range of natural and synthetic fibre materials.
Whilst nanofibres are well suited to use as biological scaffolds, they are only useful in their untreated state as a 2D support - the pores within the 3D nanofibre mesh are too small to support cell growth. Some research has investigated the use of porogens in the electrospinning process - dopants which trigger the formation of larger, micron-scale pores within the nanopore mesh.
Self-Assembling Peptide Nanofibres
Another type of nanofibre which has proved effective in regenerative medicine is made from peptides which spontaneously form stable networks of nanofibres. This is driven by interactions between hydrophobic and hydrophilic regions of the peptide chain.
These peptide nanofibres can be functionalized with specific terminals to add additional capabilities, such as receptor-binding sites or growth hormones.
In 2012, researchers from Johns Hopkins University reported success in using stem cells and nanofibre scaffolds to regrow damaged cartilage. The nanofibre scaffolds consisted of electrospun polymer fibres, with added chondroitin sulfate to help trigger growth.
The precise requirements for the nanofibre scaffold depend on the type of tissue which is being regrown. Below, some of the types of tissues which researchers have worked with are summarized.
Functionalized peptide nanofibres have been shown to assist the treatment of ischaemic heart disease, which is caused by fatty deposits in the coronary arteries. Stem cell treatments had previously been attempted, but the benefits werre unclear. Using self-assembled peptide nanofibres functionalized with insulin growth factor as a delivery method was shown to improve cardiac function.
Bone consists or a mineral matrix, embedded with a wide variety of biological structures. Stem cells grown on a nanofibre scaffold can be used to regenerate this complex structure successfully. The scaffold materials which give the best results are made from a mixture of collagen, nano-structured titanium, electro-spun silk fibres, and nanostructured hydroxyapatite (the calcium phosphate-based mineral which makes up much of bone's solid structure).
Deficiency of limbal stem cells, the reservoir of stem cells used for natural repairs to the cornea, is currently treated with a transplant of cultured stem cells on human amniotic membrane - silk or collagen-based scaffolds have been developed as potential alternatives.
This method is now also showing promise as a method of treating corneal injuries, using electrospun nanofibres as the carrier medium for the stem cells. Both limbal and mesenchymal stem cells have been shown to improve corneal healing, and reduce the local inflammatory reaction.
Neural Tissue Engineering
Rebuilding neural tissue is one of the biggest challenges to regenerative medicine. It has a very complex structure, and the environment tends to inhibit the tissue's natural capability to regenerate.
Scaffolds of polymer nanofibres with stem cells have been shown to prevent the formation of scar tissue in spinal injuries, preventing the "communication block" that can occur when the spinal cord is damaged.
Breakout Labs, the Thiel Foundations's research funding program, supports a number of biotech companies working in the field of stem cell research and regenerative medicine.
The newest addition to the roster, Bell Biosystems, is developing a technology to help track therapeutic stem cells in the body using MRI.
Nanoparticle Labels in Stem Cell Therapy
Nanotechnology has also provided valuable tools for stem cell research. Magnetic nanoparticles can be attached to the cells before they are transplanted into the body in cell therapy trials. They can then act as contrast agents, helping to track the cells in the body via MRI scans.
The most common nanoparticle contrast agents are superparamagnetic iron oxide nanoparticles. These typically consist of a crystalline core of iron oxide, with an inert polymer shell which prevents agglomeration of the particles and minimizes interactions with the cells. These nano contrast agents have been approved by the FDA, and are commercially available from a number of suppliers.
Superparamagnetic nanoparticles have been used successfully to track stem cell fate in the central nervous system, heart, liver, and kidneys.
Recent progress in the field of nanotechnology has allowed corresponding rapid progress in regenerative medicine, particularly in biocompatible nanoscaffolds and tissue engineering.
A great deal of ongoing research is leading towards complete reconstruction of damaged tissue, including the nervous system, bone, blood vessels, and potentially whole organs, by utilizing the tools and materials provided by nanotechnology in conjunction with stem cell therapy. This is just one more way in which nanotechnology is gradually transforming the world of medicine.
Sources and Further Reading
- "Functionalized Nanostructures with Applications in Regenerative Medicine" - M. Perán et al, International Journal of Molecular Sciences, 2012. DOI: 10.3390/ijms13033847
- "Nanotechnologies in Regenerative Medicine" - Š. Kubinová & Eva Syková, Minimally Invasive Therapy, 2010. DOI: 10.3109/13645706.2010.481398
- "Nanotechnology for Regenerative Medicine" - D. Khang et al, Biomed Microdevices, 2010. DOI: 10.1007/s10544-008-9264-6