Nanoscale scaffolds spur stem cells to cartilage repair

Scanning electron micrographs showing chondroitin sulfate (CS) and poly(vinyl alcohol)-methacrylate (PVA) nanofibers after electrospinning and processing to render the nanofiber scaffolds water-insoluble. Image by Jeannine Coburn/JHU first appeared in PNAS.

A spun 3-D scaffold of nanofibers did a better job of producing larger quantities of and a more durable type of the cartilage protein than flat, 2-D sheets of fibers did. 

Johns Hopkins tissue engineers have used tiny, artificial fiber scaffolds thousands of times smaller than a human hair to help coax stem cells into developing into cartilage, the shock-absorbing lining of elbows and knees that often wears thin from injury or age.

Reporting online June 4 in the Proceedings of the National Academy of Sciences, investigators say they have produced an important component of cartilage in both laboratory and animal models. While the findings are still years away from use in people, the researchers say the results hold promise for devising new techniques to help the millions who endure joint pain.

“Joint pain affects the quality of life of millions of people. Rather than just patching the problem with short-term fixes, like surgical procedures such as microfracture, we’re building a temporary template that mimics the cartilage cell’s natural environment, and taking advantage of nature’s signals to biologically repair cartilage damage,” says Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology and director of the Translational Tissue Engineering Center at the Johns Hopkins University School of Medicine. Elisseeff is also an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology.

Unlike skin, cartilage can’t repair itself when damaged. For the last decade, Elisseeff’s team has been trying to better understand the development and growth of cartilage cells called chondrocytes, while also trying to build scaffolding that mimics the cartilage cell environment and generates new cartilage tissue. This environment is a three-dimensional mix of protein fibers and gel that provides support to connective tissue throughout the body, as well as physical and biological cues for cells to grow and differentiate.

In the laboratory, the researchers created a nanofiber-based network using a process called electrospinning, which entails shooting a polymer stream onto a charged platform, and added chondroitin sulfate — a compound commonly found in many joint supplements — to serve as a growth trigger. After characterizing the fibers, they made a number of different scaffolds from either spun polymer or spun polymer plus chondroitin. They then used goat bone marrow-derived stem cells (a widely used model) and seeded them in various scaffolds to see how stem cells responded to the material.

Elisseeff and her team watched the cells grow and found that compared to cells growing without scaffold, these cells developed into more voluminous, cartilage-like tissue.

“The nanofibers provided a platform where a larger volume of tissue could be produced,” says Elisseeff, adding that three-dimensional nanofiber scaffolds were more useful than the more common nanofiber sheets for studying cartilage defects in humans.

The investigators then tested their system in an animal model. They implanted the nanofiber scaffolds into damaged cartilage in the knees of rats, and compared the results to damaged cartilage in knees left alone.

They found that the use of the nanofiber scaffolds improved tissue development and repair as measured by the production of collagen, a component of cartilage. The nanofiber scaffolds resulted in greater production of a more durable type of collagen, which is usually lacking in surgically repaired cartilage tissue. In rats, for example, they found that the limbs with damaged cartilage treated with nanofiber scaffolds generated a higher percentage of the more durable collagen (type 2) than those damaged areas that were left untreated.

“Whereas scaffolds are generally pretty good at regenerating cartilage protein components in cartilage repair, there is often a lot of scar tissue-related type 1 collagen produced, which isn’t as strong,” says Elisseeff. “We found that our system generated more type 2 collagen, which ensures that cartilage lasts longer.”

“Creating a nanofiber network that enables us to more equally distribute cells and more closely mirror the actual cartilage extracellular environment are important advances in our work and in the field. These results are very promising,” she says.

Other authors included Jeannine M. Coburn, Matthew Gibson, Sean Monagle and Zachary Patterson, all from The Johns Hopkins University.

From a press release by Audrey Huang.

 

INBT obtains funding for engineering and science missions

Johns Hopkins students helped develop a bicycle-powered grain mill in Tanzania.

Engineering Missions for Graduate Student Education and Local Innovation

Applications are now being accepted for Global Engineering Innovation projects designed to give Johns Hopkins’ graduate students and select undergraduates an opportunity to investigate and tackle engineering challenges in the developing world. Undergraduate and graduate opportunities are available. Application deadline is April 5, 2013.

An information session on the Global Engineering Innovation program will be held on April 12  at 6 p.m. in  room G40 (ground floor conference room) in the New Engineering Building.

Johns Hopkins Institute for NanoBioTechnology has obtained funding to support three engineering mission teams composed of two to four students at a variety of international host sites. Teams will be mentored by an engineering faculty and a faculty member from the host site. Budgets, time lines and project plans will be developed by the team members with assistance by the host site faculty member.

To be eligible to apply, undergraduate and graduate students should be science or engineering majors (other majors will be considered if a fit is evident based on application material). Teams can be predefined by the students prior to applying but each team member must submit all application material. We will attempt to keep predefined teams together but the final decision will be made by the coordination committee (we will add or remove members if we feel a better team composition can be made).

To apply for this unique opportunity, send the following items to Ashanti Edwards at ashanti@jhu.edu.

  • Your resume including any outreach experience (domestic or international) and any foreign language capability (not required)
  • A brief (300 words max.) statement of your interest in Global Engineering Innovation
  • The name and contact information of at least one referee, preferably your faculty research advisor (or academic advisor for undergraduate students)

After teams, mentors and challenges are defined, the team or team leader will travel to the site to further evaluate challenge and design constraints. After return to Baltimore, the teams will meet to further research the challenge and brainstorm potential solutions. The JHU School for Advanced International Studies (SAIS) will be consulted so that students will be aware of the social and political atmosphere that may impact utilization and potential distribution of the engineering solutions. By the end of the first year, the students will have designed a working prototype. The teams will then travel to the Global Site with their working prototype to test solution feasibility and modify as needed. If successful, potential avenues of translation will be investigated with advisory board members with relevant experience.