Posts Tagged ‘Johns Hopkins University’

Squishy knees and tissue engineering at Johns Hopkins

Tuesday, January 15th, 2013

Researchers at Johns Hopkins University School of Medicine’s Translational Tissue Engineering Center (TTEC) have developed a material (a kind of hydrogel) which they use with a new technique they’ve developed for growing new tissue and cartilage in knees. From the Jan. 15, 2013 news release on EurekAlert,

Proof-of-concept clinical trial in 18 patients shows improved tissue growth

In a small study, researchers reported increased healthy tissue growth after surgical repair of damaged cartilage if they put a “hydrogel” scaffolding into the wound to support and nourish the healing process. The squishy hydrogel material was implanted in 15 patients during standard microfracture surgery, in which tiny holes are punched in a bone near the injured cartilage. The holes stimulate patients’ own specialized stem cells to emerge from bone marrow and grow new cartilage atop the bone.

…

“Our pilot study indicates that the new implant works as well in patients as it does in the lab, so we hope it will become a routine part of care and improve healing,” says Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology and director of the Johns Hopkins University School of Medicine’s Translational Tissue Engineering Center (TTEC). Damage to cartilage, the tough-yet-flexible material that gives shape to ears and noses and lines the surface of joints so they can move easily, can be caused by injury, disease or faulty genes. Microfracture is a standard of care for cartilage repair, but for holes in cartilage caused by injury, it often either fails to stimulate new cartilage growth or grows cartilage that is less hardy than the original tissue.

Here are more details from the Johns Hopkins Jan. 15, 2013 news release,

Tissue engineering researchers, including Elisseeff, theorized that the specialized stem cells needed a nourishing scaffold on which to grow, but demonstrating the clinical value of hydrogels has “taken a lot of time,” Elisseeff says. By experimenting with various materials, her group eventually developed a promising hydrogel, and then an adhesive that could bind it to the bone.

After testing the combination for several years in the lab and in goats, with promising results, she says, the group and their surgeon collaborators conducted their first clinical study, in which 15 patients with holes in the cartilage of their knees received a hydrogel and adhesive implant along with microfracture. For comparative purposes, another three patients were treated with microfracture alone. After six months, the researchers reported that the implants had caused no major problems, and MRIs showed that patients with implants had new cartilage filling an average 86 percent of the defect in their knees, while patients with only microfracture had an average of 64 percent of the tissue replaced. Patients with the implant also reported a greater decrease in knee pain in the six months following surgery, according to the investigators.

The trial continues, has enrolled more patients and is now being managed by a company called Biomet. The trial is part of efforts to win European regulatory approval for the device.

In the meantime, Elisseeff says her team has begun developing a next-generation implant, one in which the hydrogel and adhesive will be combined in a single material. In addition, they are working on technologies to lubricate joints and reduce inflammation.

The study has been published in the AAAS’s (American Association for the Advancement of Science) Science Translational Medicine journal,

Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite

Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel

Sci Transl Med 9 January 2013:
Vol. 5 no. 167 pp. 167ra6DOI:10.1126/scitranslmed.3004838

This article is behind a paywall and for some reason the authors are listed only in the news release,

Jennifer Elisseeff, Blanka Sharma, Sara Fermanian, Matthew Gibson, Shimon Unterman, Daniel A. Herzka, Jeannine Coburn and Alexander Y. Hui of the Johns Hopkins School of Medicine; Brett Cascio of Lake Charles Memorial Hospital; Norman Marcus, a private practice orthopedic surgeon; and Garry E. Gold of Stanford University

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Repairing joints with nanoscale scaffolds and stem cells

Thursday, July 19th, 2012

Cartilage damage is a major problem for millions of people and chondroitin supplements are widely used to counteract the pain and damage since cartilage does not regrow. Until now.

Researchers at Johns Hopkins University have used chondroitin sulfate to create nanoscaffolds for growing new cartilage. From the July 17, 2012 news release on EurekAlert,

Unlike skin, cartilage can’t repair itself when damaged. For the last decade, Elisseeff’s [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] 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 3-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 3-dimensional nanofiber scaffolds were more useful than the more common nanofiber sheets for studying cartilage defects in humans.

They’ve also experimented with animal models,

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.

I wouldn’t rush out yet for new cartilage . It’s likely to be several years before this is available to people.

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Small boxes in your bloodstream

Tuesday, April 24th, 2012

The boxes in question self-assemble although why anyone would consider the image of small boxes in one’s bloodstream appealing escapes me. Well, we are talking about engineers and mathematicians so perhaps it’s understandable. From the April 23, 2012 news item on Nanowerk,

… now, interdisciplinary research by engineers at Johns Hopkins University in Baltimore, Md., and mathematicians at Brown University in Providence, R.I., has led to a breakthrough showing that higher order polyhedra can indeed fold up and assemble themselves.

“What is remarkable here is not just that a structure folds up on its own, but that it folds into a very precise, three-dimensional shape, and it happens without any tweezers or human intervention,” says David Gracias, a chemical and biomolecular engineer at Johns Hopkins. “Much like nature assembles everything from sea shells to gem stones from the bottom up, the idea of self-assembly promises a new way to manufacture objects from the bottom up.”

Here’s a video from the US National Science Foundation about the work being done by David Gracias and his colleague at Brown University, mathematician Govind Menon,

Miles O’Brien of the NSF’s Science Nation magazine notes in his April 23, 2012 article that there are many applications for these structures,

Imagine thousands of precisely structured, tiny, biodegradable, boxes rushing through the bloodstream en route to a sick organ. Once they arrive at their destination, they can release medicine with pinpoint accuracy. That’s the vision for the future. For now, the more immediate concern is getting the design of the structures just right so that they can be manufactured with high yields.

“Our process is also compatible with integrated circuit fabrication, so we envision that we can use it to put silicon-based logic and memory chips onto the faces of 3-D polyhedra. Our methodology opens the door to the creation of truly three-dimensional ‘smart’ and multi-functional particles on both micro- and nano- length scales,” says Gracias.

Here’s more about the structures themselves, as mentioned in the video and in O’Brien’s article,

Menon’s team at Brown began designing these tiny 3-D structures by first flattening them out. They worked with a number of shapes, such as 12-sided interconnected panels, which can potentially fold into a dodecahedron shaped container. “Imagine cutting it up and flattening out the faces as you go along,” says Menon. “It’s a two-dimensional unfolding of the polyhedron.”

And not all flat shapes are created equal; some fold better than others. “The best ones are the ones which are most compact. There are 43,380 ways to fold a dodecahedron,” notes Menon.

The researchers developed an algorithm to sift through all of the possible choices, narrowing the field to a few compact shapes that easily fold into 3-D structures. Menon’s team sent those designs to Gracias and his team at Johns Hopkins who built the shapes, and validated the hypothesis.

“We deposit a material in between the faces and the edges, and then heat them up, which creates surface tension and pulls the edges together, fusing the structure shut,” explains Gracias. “The angle between adjacent panels in a dodecahedron is 116.6 degrees and in our process, pentagonal panels precisely align at these remarkably precise angles and seal themselves; all on their own.”

As noted earlier, I’m not thrilled with the idea of tiny boxes in my bloodstream but, analogy aside, the medical applications are appealing. As for Gracias’ smart and multifunctional particles, I look forward to hearing more about them.

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3-D and self-assembly

Thursday, December 8th, 2011

Here’s an intriguing approach to self-assembly for manufacturing purposes from scientists at Brown and Johns Hopkins Universities, respectively. From the Dec. 7, 2011 news item on Nanowerk,

In a paper published in the Proceedings of National Academy of Sciences (“Algorithmic design of self-folding polyhedra”), researchers from Brown and Johns Hopkins University determined the best 2-D arrangements, called planar nets, to create self-folding polyhedra with dimensions of a few hundred microns, the size of a small dust particle. The strength of the analysis lies in the combination of theory and experiment. The team at Brown devised algorithms to cut through the myriad possibilities and identify the best planar nets to yield the self-folding 3-D structures. Researchers at Johns Hopkins then confirmed the nets’ design principles with experiments.

Here’s the magnitude of the problem these scientists were solving (from the news item),

Material chemists and engineers would love to figure out how to create self-assembling shells, containers or structures that could be used as tiny drug-carrying containers or to build 3-D sensors and electronic devices.

There have been some successes with simple 3-D shapes such as cubes, but the list of possible starting points that could yield the ideal self-assembly for more complex geometric configurations gets long fast. For example, while there are 11 2-D arrangements for a cube, there are 43,380 for a dodecahedron (12 equal pentagonal faces). Creating a truncated octahedron (14 total faces – six squares and eight hexagons) has 2.3 million possibilities.

Associate professor of applied mathematics at Brown University, Govind Menon, says (from the news item),

“The issue is that one runs into a combinatorial explosion. … How do we search efficiently for the best solution within such a large dataset? This is where math can contribute to the problem.”

Here’s how they solved the problem (from the news item),

 

“Using a combination of theory and experiments, we uncovered design principles for optimum nets which self-assemble with high yields,” said David Gracias, associate professor in of chemical and biomolecular engineering at Johns Hopkins and a co-corresponding author on the paper.

“In doing so, we uncovered striking geometric analogies between natural assembly of proteins and viruses and these polyhedra, which could provide insight into naturally occurring self-assembling processes and is a step toward the development of self-assembly as a viable manufacturing paradigm.”

“This is about creating basic tools in nanotechnology,” said Menon, co-corresponding author on the paper. “It’s important to explore what shapes you can build. The bigger your toolbox, the better off you are.” While the approach has been used elsewhere to create smaller particles at the nanoscale, the researchers at Brown and Johns Hopkins used larger sizes to better understand the principles that govern self-folding polyhedra.

The news item on Nanowerk features more details, a video of a self-assembling dodecahedron, and an image of various options for 2-D nets that can be used to create 3-D shapes.

“Using a combination of theory and experiments, we uncovered design principles for optimum nets which self-assemble with high yields,” said David Gracias, associate professor in of chemical and biomolecular engineering at Johns Hopkins and a co-corresponding author on the paper. “In doing so, we uncovered striking geometric analogies between natural assembly of proteins and viruses and these polyhedra, which could provide insight into naturally occurring self-assembling processes and is a step toward the development of self-assembly as a viable manufacturing paradigm.”
“This is about creating basic tools in nanotechnology,” said Menon, co-corresponding author on the paper. “It’s important to explore what shapes you can build. The bigger your toolbox, the better off you are.”
While the approach has been used elsewhere to create smaller particles at the nanoscale, the researchers at Brown and Johns Hopkins used larger sizes to better understand the principles that govern self-folding polyhedra.

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