“Unlike bone, cartilage does not grow back, and therefore clinical strategies to regenerate this tissue are of great interest,” said Samuel I. Stupp, the paper’s senior author, Board of Trustees Professor of Chemistry, Materials Science and Engineering, and Medicine, and director of the Institute for BioNanotechnology in Medicine (IBNAM).

Type II collagen is the major protein in articular cartilage, the smooth, white connective tissue that covers the ends of bones where they come together to form joints. The Northwestern gel is injected as a liquid to the area of the damaged joint, where it then self-assembles and forms a solid. This extracellular matrix, which mimics what cells usually see, binds by molecular design one of the most important growth factors for the repair and regeneration of cartilage. By keeping the growth factor concentrated and localized, the cartilage cells have the opportunity to regenerate.

In collaboration with Nirav A. Shah, M.D., a sports medicine orthopaedic surgeon who treats athletes of all levels and ages and is a former orthopaedic resident at Northwestern, the researchers implanted their nanofiber gel in an animal model with cartilage defects.

The animals were treated with microfracture, where tiny holes are made in the bone beneath the damaged cartilage to create a new blood supply to stimulate the growth of new cartilage. The researchers tested various combinations: microfracture alone; microfracture and the nanofiber gel with growth factor added; and microfracture and the nanofiber gel without growth factor added.

They found their technique produced much better results than the microfracture procedure alone and, more importantly, found that addition of the expensive growth factor was not required to get the best results. Instead, because of the molecular design of the gel material, growth factor already present in the body is enough to regenerate cartilage.

The matrix only needed to be present for a month to produce cartilage growth. The matrix, based on self-assembling molecules known as peptide amphiphiles, biodegrades into nutrients and is replaced by natural cartilage.

Their current research results are published in a paper titled Supramolecular Design of Self-assembling Nanofibers for Cartilage Regeneration.

“Basically, we have demonstrated that electric charges flowing through a mixture of an organic semiconductor and metallic nanoparticles can behave the same way as neurotransmitters through a synaptic connection in the brain,” said Dominique Vuillaume, a research director at CNRS and head of the Molecular Nanostructures & Devices group at the Institute for Electronics Microelectronics and Nanotechnology (IEMN).

In the development of new information processing strategies, one approach consists in mimicking the way biological systems such as neuron networks operate to produce electronic circuits with new features. In the nervous system, a synapse is the junction between two neurons, enabling the transmission of electric messages from one neuron to another and the adaptation of the message as a function of the nature of the incoming signal (plasticity). For example, if the synapse receives very closely packed pulses of incoming signals, it will transmit a more intense action potential. Conversely, if the pulses are spaced farther apart, the action potential will be weaker.

“This is a fundamental property of the synapse behavior called STP (short-term plasticity)” explains Vuillaume. “In our NOMFET, the presynaptic signal is the pulse voltage applied on the NOMFET and the output signal is the drain current. The holes – the charge carriers in the p-type organic semiconductor used here – trapped in the metallic nanoparticles play the role of the inhibited neurotransmitters. The number of trapped holes in the nanoparticles depends on the input spike voltage and the output signal, the current, is a decreasing function of the number of holes stored in these nanoparticles – because less holes are available to transmit the current through the NOMFET.”

In other words, the encapsulated gold nanoparticles, fixed in the channel of the transistor and coated with pentacene, have a memory effect that allows them to mimic the way a synapse works during the transmission of action potentials between two neurons. This property therefore makes the electronic component capable of evolving as a function of the system in which it is placed.

The potential application of this work is to increase the performances of neural-network computing circuits. Moreover, nanoparticles and molecules are nanosize objects suitable for nanodevice fabrication; they can be manipulated and assembled by low-cost, bottom-up, techniques (e.g., self-assembly); and they are prone to work on flexible, plastic, substrates.

Vuillaume points out that this later feature might be advantageous if we envision connecting artificial neuromorphic devices and circuits (based on the NOMEFT) with soft biological materials. However, he also notes that, even if this work reduces the number of electronic devices required to mimic a biological synapse, the high level of synapse-neuron connectivity in the brain requires the development of artificial neural networks computing circuits in 3D.

The Taxol-carrying nanoparticles engineered in Perez’s laboratory are modified so they carry the drug only to the cancer cells, allowing targeted cancer treatment without harming healthy cells. This is achieved by attaching a vitamin (folic acid) derivative that cancer cells like to consume in high amounts.

The process works like this.  Cancer cells in the tumor connect with the engineered nanoparticles via cell receptors that can be regarded as “doors” or “docking stations.”  The nanoparticles enter the cell and release their cargo of iron oxide, fluorescent dye and drugs, allowing dual imaging and treatment.

The nanoparticles also carry a fluorescent dye and an iron oxide magnetic core so their locations can be seen by optical imaging and magnetic resonance imaging (MRI). That allows a physician to see how the tumor is responding to the treatment.

The nanoparticles can be engineered without the drug and used as imaging (contrast) agents for cancer. If there is no cancer, the biodegradable nanoparticles will not bind to the tissue and will be eliminated by the liver. The iron oxide core will be utilized as regular iron in the body.

Perez has spent the past five years looking at ways nanotechnology can be used to help diagnose, image and treat cancer and infectious diseases. It’s part of the quickly evolving world of nanomedicine.

“Although the results from the cell cultures are preliminary, they are very encouraging,” Perez said.

A new chemistry called “click chemistry” was utilized to attach the targeting molecule (folic acid) to the nanoparticles. This chemistry allows for the easy and specific attachment of molecules to nanoparticles without unwanted side products. It also allows for the easy attachment of other molecules to nanoparticles to specifically seek out particular tumors and other malignancies.

“Our work is an important beginning, because it demonstrates an avenue for using nanotechnology not only to diagnose but also to treat cancer, potentially at an early stage,” Perez said.