Tag Archives: bone

Bone bio-patches from the University of Iowa

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Let’s take a look at the bone patch developed at the University Iowa,

Researchers at the University of Iowa have created a bio patch to regenerate missing or damaged bone. The patch has been shown to nearly fully regrow missing skull, seen in the image above. Image courtesy of Satheesh Elangovan. & University of Iowa

Researchers at the University of Iowa have created a bio patch to regenerate missing or damaged bone. The patch has been shown to nearly fully regrow missing skull, seen in the image above. Image courtesy of Satheesh Elangovan. & University of Iowa

A Nov. 7, 2013 news item on Nanowerk provides information explaining the bone bio-patch,

Researchers at the University of Iowa have created a bio patch to regenerate missing or damaged bone by putting DNA into a nano-sized particle that delivers bone-producing instructions directly into cells.

The bone-regeneration kit relies on a collagen platform seeded with particles containing the genes needed for producing bone. In experiments, the gene-encoding bio patch successfully regrew bone fully enough to cover skull wounds in test animals. It also stimulated new growth in human bone marrow stromal cells in lab experiments.

The study is novel in that the researchers directly delivered bone-producing instructions (using piece of DNA that encodes for a platelet-derived growth factor called PDGF-B) to existing bone cells in vivo, allowing those cells to produce the proteins that led to more bone production. Previous attempts had relied on repeated applications from the outside, which is costly, intensive, and harder to replicate consistently.

The Nov. 6, 2013 University of Iowa news piece, which originated the news item and was written by Richard C. Lewis, provides some insight from the researchers (Note: Links have been removed),

“We delivered the DNA to the cells, so that the cells produce the protein and that’s how the protein is generated to enhance bone regeneration,” explains Aliasger Salem, professor in the College of Pharmacy and a co-corresponding author on the paper, published in the journal Biomaterials. ”If you deliver just the protein, you have keep delivering it with continuous injections to maintain the dose. With our method, you get local, sustained expression over a prolonged period of time without having to give continued doses of protein.”

The researchers believe the patch has several potential uses in dentistry. For instance, it could be used to rebuild bone in the gum area that serves as the concrete-like foundation for dental implants. That prospect would be a “life-changing experience” for patients who need implants and don’t have enough bone in the surrounding area, says Satheesh Elangovan, assistant professor in the UI’s College of Dentistry and a joint first author, as well as co-corresponding author, on the paper. It also can be used to repair birth defects where there’s missing bone around the head or face.

“We can make a scaffold in the actual shape and size of the defect site, and you’d get complete regeneration to match the shape of what should have been there,” Elangovan says.

The news article goes on to provide details about how the bio-patch was created,

The team started with a collagen scaffold. The researchers then loaded the bio patch with synthetically created plasmids, each of which is outfitted with the genetic instructions for producing bone. They then inserted the scaffold on to a 5-millimeter by 2-millimeter missing area of skull in test animals. Four weeks later, the team compared the bio patch’s effectiveness to inserting a scaffold with no plasmids or taking no action at all.

The plasmid-seeded bio patch grew 44-times more bone and soft tissue in the affected area than with the scaffold alone, and was 14-fold higher than the affected area with no manipulation. Aerial and cross-sectional scans showed the plasmid-encoded scaffolds had spurred enough new bone growth to nearly close the wound area, the researchers report.

The plasmid does its work by entering bone cells already in the body – usually those located right around the damaged area that wander over to the scaffold. The team used a polymer to shrink the particle’s size (like creating a zip file, for example) and to give the plasmid the positive electrical charge that would make it easier for the resident bone cells to take them in.

“The delivery mechanism is the scaffold loaded with the plasmid,” Salem says. “When cells migrate into the scaffold, they meet with the plasmid, they take up the plasmid, and they get the encoding to start producing PDGF-B, which enhances bone regeneration.”

The researchers also point out that their delivery system is nonviral. That means the plasmid is less likely to cause an undesired immune response and is easier to produce in mass quantities, which lowers the cost.

“The most exciting part to me is that we were able to develop an efficacious, nonviral-based gene-delivery system for treating bone loss,” says Sheetal D’mello, a graduate student in pharmacy and a joint first author on the paper.

Elangovan and Salem next hope to create a bio platform that promotes new blood vessel growth– needed for extended and sustained bone growth.

Here’s a link to and a citation for the published paper,

The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor by Satheesh Elangovan, Sheetal R. D’Mello, Liu Hong, Ryan D. Ross, Chantal Allamargot, Deborah V. Dawson, Clark M. Stanford, Georgia K. Johnson, D. Rick Sumnerd,& Aliasger K. Salem. Biomaterials Volume 35, Issue 2, January 2014, Pages 737–747 DOI: 10.1016/j.biomaterials.2013.10.021

This paper is behind a paywall.

Diamonds in your teeth—for health reasons

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Scientists at the University of California at Los Angeles (UCLA) in collaboration with their colleagues at the NanoCarbon Research Institute (Japan) are investigating the possibility of using nanodiamonds to promote bone growth that supports dental implants. From the Sept.18, 2013 news item on ScienceDaily,

UCLA researchers have discovered that diamonds on a much, much smaller scale than those used in jewelry could be used to promote bone growth and the durability of dental implants.

Nanodiamonds, which are created as byproducts of conventional mining and refining operations, are approximately four to five nanometers in diameter and are shaped like tiny soccer balls. Scientists from the UCLA School of Dentistry, the UCLA Department of Bioengineering and Northwestern University, along with collaborators at the NanoCarbon Research Institute in Japan, may have found a way to use them to improve bone growth and combat osteonecrosis, a potentially debilitating disease in which bones break down due to reduced blood flow.

The Sept. 17,2013 UCLA news release by Brianna Deane (also on EurekAlert), which originated the news item, describes how osteonecrosis affects bones and the impact that this new technique using nanodiamonds could have on applications for regenerative medicine (Note: A link has been removed),

When osteonecrosis affects the jaw, it can prevent people from eating and speaking; when it occurs near joints, it can restrict or preclude movement. Bone loss also occurs next to implants such as prosthetic joints or teeth, which leads to the implants becoming loose — or failing.
Implant failures necessitate additional procedures, which can be painful and expensive, and can jeopardize the function the patient had gained with an implant. These challenges are exacerbated when the disease occurs in the mouth, where there is a limited supply of local bone that can be used to secure the prosthetic tooth, a key consideration for both functional and aesthetic reasons.
….
During bone repair operations, which are typically costly and time-consuming, doctors insert a sponge through invasive surgery to locally administer proteins that promote bone growth, such as bone morphogenic protein.
Ho’s team discovered that using nanodiamonds to deliver these proteins has the potential to be more effective than the conventional approaches. The study found that nanodiamonds, which are invisible to the human eye, bind rapidly to both bone morphogenetic protein  and fibroblast growth factor, demonstrating that the proteins can be simultaneously delivered using one vehicle. The unique surface of the diamonds allows the proteins to be delivered more slowly, which may allow the affected area to be treated for a longer period of time. Furthermore, the nanodiamonds can be administered non-invasively, such as by an injection or an oral rinse.
“We’ve conducted several comprehensive studies, in both cells and animal models, looking at the safety of the nanodiamond particles,” said Laura Moore, the first author of the study and an M.D.-Ph.D. student at Northwestern University under the mentorship of Dr. Ho. “Initial studies indicate that they are well tolerated, which further increases their potential in dental and bone repair applications.”
“Nanodiamonds are versatile platforms,” said Ho, who is also professor of bioengineering and a member of the Jonsson Comprehensive Cancer Center and the California NanoSystems Institute. “Because they are useful for delivering such a broad range of therapies, nanodiamonds have the potential to impact several other facets of oral, maxillofacial and orthopedic surgery, as well as regenerative medicine.”
Ho’s team previously showed that nanodiamonds in preclinical models were effective at treating multiple forms of cancer. Because osteonecrosis can be a side effect of chemotherapy, the group decided to examine whether nanodiamonds might help treat the bone loss as well. Results from the new study could open the door for this versatile material to be used to address multiple challenges in drug delivery, regenerative medicine and other fields.

Here’s a citation for and a link to the researchers’ published paper,

Multi-protein Delivery by Nanodiamonds Promotes Bone Formation by L. Moore, M. Gatica, H. Kim, E. Osawa, & D. Ho. Published online before print September 17, 2013, doi: 10.1177/0022034513504952 JDR September 17, 2013 0022034513504952

This paper is behind a paywall.

Massachusetts Institute of Technology and bony 3D printing

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Markus Buehler (last mentioned here in a Nov. 28, 2012 posting*, about spider silk and music) and his research team at the Massachusetts Institute of Technology (MIT) have been inspired by various biomaterials to create materials that resemble bone matter, from the June 17, 2013 news item on ScienceDaily,

Researchers working to design new materials that are durable, lightweight and environmentally sustainable are increasingly looking to natural composites, such as bone, for inspiration: Bone is strong and tough because its two constituent materials, soft collagen protein and stiff hydroxyapatite mineral, are arranged in complex hierarchical patterns that change at every scale of the composite, from the micro up to the macro.

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Now researchers at MIT have developed an approach that allows them to turn their designs into reality. In just a few hours, they can move directly from a multiscale computer model of a synthetic material to the creation of physical samples.

In a paper published online June 17 in Advanced Functional Materials, associate professor Markus Buehler of the Department of Civil and Environmental Engineering and co-authors describe their approach.

The June 17, 2013 MIT news release by Denise Brehm, which originated the news item, explains the researchers’ approach in more detail (Note: A link has been removed),

The collagen in bone is too soft and stretchy to serve as a structural material, and the mineral hydroxyapatite is brittle and prone to fracturing. Yet when the two combine, they form a remarkable composite capable of providing skeletal support for the human body. The hierarchical patterns help bone withstand fracturing by dissipating energy and distributing damage over a larger area, rather than letting the material fail at a single point.

“The geometric patterns we used in the synthetic materials are based on those seen in natural materials like bone or nacre, but also include new designs that do not exist in nature,” says Buehler, who has done extensive research on the molecular structure and fracture behavior of biomaterials. His co-authors are graduate students Leon Dimas and Graham Bratzel, and Ido Eylon of the 3-D printer manufacturer Stratasys. “As engineers we are no longer limited to the natural patterns. We can design our own, which may perform even better than the ones that already exist.”

The researchers created three synthetic composite materials, each of which is one-eighth inch thick and about 5-by-7 inches in size. The first sample simulates the mechanical properties of bone and nacre (also known as mother of pearl). This synthetic has a microscopic pattern that looks like a staggered brick-and-mortar wall: A soft black polymer works as the mortar, and a stiff blue polymer forms the bricks. Another composite simulates the mineral calcite, with an inverted brick-and-mortar pattern featuring soft bricks enclosed in stiff polymer cells. The third composite has a diamond pattern resembling snakeskin. This one was tailored specifically to improve upon one aspect of bone’s ability to shift and spread damage.

The scientists are hinting that they’ve improved on nature and that may be so but I recall reading similar suggestions in studies I’ve read about 19th and 20th century research. It seems to me that scientists have claimed to be improving on nature for quite some time.

Interestingly, the suggested application for this new material is not biomedical, from the news release,

According to Buehler, the process could be scaled up to provide a cost-effective means of manufacturing materials that consist of two or more constituents, arranged in patterns of any variation imaginable and tailored for specific functions in different parts of a structure. He hopes that eventually entire buildings might be printed with optimized materials that incorporate electrical circuits, plumbing and energy harvesting. “The possibilities seem endless, as we are just beginning to push the limits of the kind of geometric features and material combinations we can print,” Buehler says.

You can find a link to and a citation for the published paper at the end of the ScienceDaily June 17, 2013 news item.

* Date changed from 2013 to 2012 on June 4, 2014

Red River Valley clay turned into bones at North Dakota State University

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A May 30, 2013 news item on Nanowerk highlights the Katti Group’s (at North Dakota State University [NDSU], US) research using clay from the Red River Valley as scaffolding for tissue engineering projects involving bone. From the news item (Note: A link has been removed),

Weak bones, broken bones, damaged bones, arthritic bones. Whether damaged by injury, disease or age, your body can’t create new bone, but maybe science can. Researchers at North Dakota State University, Fargo, are making strides in tissue engineering, designing scaffolds that may lead to ways to regenerate bone. Published in the Journal of Biomedical Materials Research Part A (“Nanoclays mediate stem cell differentiation and mineralized ECM formation on biopolymer scaffolds”), the research of Dr. Kalpana Katti, Dr. Dinesh Katti and graduate student Avinash Ambre includes a novel method that uses nanosized clays to make scaffolds to mineralize bone minerals such as hydroxyapatite.

The North Dakota State University May 30, 2013 news release, which originated the news item, explains (Note: A link has been removed),

The NDSU research team’s 3-D mesh scaffold is comprised of degradable materials that are compatible to human tissue. Over time, the cells generate bone and the scaffold deteriorates. As indicated in the NDSU team’s published scientific research from 2008 to 2013, the nanoclays enhance the mechanical properties of the scaffold by enabling scaffold to bear load while bone generates. An interesting finding by the Katti group shows that the nanoclays also impart useful biological properties to the scaffold.

“The biomineralized nanoclays also impart osteogenic or bone-forming abilities to the scaffold to enable birth of bone,” said Dr. Kalpana Katti, Distinguished Professor of civil engineering at NDSU. “Although it would have been exciting to say that this finding had a ‘Eureka moment,’ this discovery was a methodical exploration of simulations and modeling, indicating that amino acid modified nanoclays are viable new nanomaterials,” said Katti. The work was initially published in the Journal of Biomacromolecules in 2005. The current research findings in 2013 point toward the potential use of nanoclays for broader applications in medicine.

The NDSU’s group most recent study in the Journal of Biomedical Materials Research Part A reports that nanoclays mediate human cell differentiation into bone cells and grow bone. The Katti research group uses amino acids, the building blocks of life, to modify clay structures and the modified nanoclays coax new bone growth. “Our current research studies underway involve the use of bioreactors that mimic fluid/blood flow in the human body during bone tissue regeneration,” said Dr. Kalpana Katti.

Here’s a citation for and a link to the Katti Group’s latest published paper (from the press release),

Nanoclays mediate stem cell differentiation and mineralized ECM formation on biopolymer scaffolds
Journal of Biomedical Materials Research Part A
Avinash H. Ambre, Dinesh R. Katti and Kalpana S. Katti Article first published online : 15 FEB 2013, DOI: 10.1002/jbm.a.34561

This paper is behind a paywall.

Mathematical healing of skin and bone

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Mathematics professor at Australia’s Queensland University of Technology (QUT), Graeme Pettet provides a fascinating perspective on skin and bone, from the April 23, 2012 news item by Alita Pashley on physorg.com,

Professor Graeme Pettet, a mathematician from QUT’s Institute of Health Biomedical Innovation (IHBI), said maths could be used to better understand the structure of skin and bones and their response to healing techniques, which will eventually lead to better therapeutic innovations.

“Mathematics is the language of any science so if there are spatial or temporal variations of any kind then you can describe it mathematically,” he said.

…

“Skin is very difficult to describe. It’s very messy and very complicated. In fact most of the descriptions that engineers and biologists use are schematic stories (diagrams),” he said.

“Once we understand the structure (of the skin) and how it develops we can begin to analyze how that development impacts upon healing in the skin and maybe also diseases of the skin.”

Professor Pettet said his research would, for the first time, formalise the theories about the way cells interact when healing.

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Professor Pettet is also working on applying similar techniques to figure out how to show how small, localised damage at the site of bone fractures can impact on healing.

Unfortunately, there isn’t much more in the way of detail either in the news item or on the Tissue Repair and Regeneration Research Program webpage.