Nav: Home

Replicating fetal bone growth process could help heal large bone defects

June 05, 2019

To treat large gaps in long bones, like the femur, which result from bone tumor removal or a shattering trauma, researchers at Penn Medicine and the University of Illinois at Chicago developed a process that partially recreates the bone growth process that occurs before birth. A bone defect of more than two centimeters is considered substantial, and current successful healing rates stand at 50 percent or less, with failure often resulting in amputation. The team hopes that their method, which they've developed in rodent models to mimic the process of rapid fetal bone growth, can substantially improve success rates. Their findings are published in Science Translational Medicine.

"When bones are originally formed in the embryo, they're first generated from cartilage, like a template," said senior author Joel Boerckel, PhD, an assistant professor of Orthopaedic Surgery and Bioengineering at the University of Pennsylvania. "In order to regenerate bone within defects that otherwise won't heal in grown people, we are seeking to recreate the embryonic bone development process."

To do that, the researchers' process begins with the delivery of specially engineered stem cells (called a condensation of mesenchymal cells) to the rodents' bone defect, which sparks endochondral ossification, the specific term for embryonic bone development.

But, the researchers note that a baby's movement in the womb is also an important factor in the process to develop new bone quickly. Therefore, the second step taken by the team to mimic bone development involved special orthopaedic plates that can be adjusted to vary the mechanical forces placed on the regenerating limbs. This allowed for some movement in the defect area that contributed to cartilage formation and blood vessel growth, key steps of endochondral ossification. Through this combination of development-like stem cell delivery and mechanical forces, bone regeneration was on par with current methods for healing defects, such as high doses of the growth factor, BMP-2, a potent protein that stimulates bone formation. However, this experimental process did not generate any of the typical adverse side effects, such as abnormal bone growth, that can result from using BMP-2.

While plates are currently used to fix serious defects, they keep the joints completely stiff and don't allow for mechanical loading. In this study, the researchers compared stiff plates to those that were "unlocked" to allow limited movement. While bone volume increased in bones that were always kept in the stiff plates, the plates that were unlocked generated far more bone growth as time went on.

"Very little has been known about how the mechanical environment in bone defects affects the capacity of transplanted cells to contribute to the regeneration of the defects," said senior author Eben Alsberg, PhD, the Richard and Loan Hill Professor of Bioengineering and Orthopaedics at the University of Illinois at Chicago. "In this work, we've shown how critically important mechanical forces are in this process when implanting stem cell condensation constructs."

Not only did the researchers look at plates that were unlocked, they also studied the differences that occurred when plates were unlocked. One set was unlocked about four weeks after they were put in place, while the others were unlocked immediately. At 12 weeks after the plates were put in place, the bone growth for plates unlocked a month in was triple that of the plates that remained stiff the entire time. For plates unlocked immediately, the bone growth was doubled what resulted from using stiff plates.

"While this work is in its early stages, it is possible that these finding could influence how non-healing bone defects are treated with respect to both fixation and other transplanted therapeutic strategies," said Alsberg.

Moving forward, the researchers feel that further preclinical studies will be required to determine how these this process and the findings therein can be used in clinic. Additionally, the long-term goal is to not only map development and regeneration processes for bones themselves, but other tissues where the potential for regeneration is limited, such as in cartilage for patients with osteoarthritis.

"Devices and techniques we develop out of this research could also influence the way we implement physical therapy after injury," Boerckel explained. "Our findings support the emerging paradigm of 'regenerative rehabilitation,' a concept that marries principles from physical therapy and regenerative medicine. Our goals are to understand how mechanical stimuli influence cell behavior to better impact patient outcomes without additional drugs or devices."
-end-
Funding for this study included support from the Naughton Foundation, the Indiana Clinical Translational Sciences Institute, the National Institutes of Health (grant no. UL1TR001108), the American Heart Association (16SDG31230034), the National Science Foundation (1435467), the NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases awards (R01AR066193, R01AR063194, R01AR069564), the NIH's Biomedical Imaging & Bioengineering award (R01EB023907), the NIH's National Institute of Dental and Craniofacial Research award (5F32DE024712), and the Ohio Biomedical Research Commercialization Program award (TECG20150782).

Other authors include lead authors Anna M. McDermott, of Penn, and Samuel Herberg, of SUNY Upstate Medical University; as well as Devon E. Mason and Joseph M. Collins, of Penn; Hope B. Pearson and James H. Dawahare, of the University of Notre Dame; Rui Tang, of Case Western Reserve University; Amit N. Patwa and Mark W. Grinstaff, of Boston University; and Daniel J. Kelly, of Trinity College, Dublin.

University of Pennsylvania School of Medicine

Related Cartilage Articles:

Changes in brain cartilage may explain why sleep helps you learn
The morphing structure of the brain's ''cartilage cells'' may regulate how memories change while you snooze, according to new research in eNeuro.
From the lab, the first cartilage-mimicking gel that's strong enough for knees
The thin, slippery layer of cartilage between the bones in the knee is magical stuff: strong enough to withstand a person's weight, but soft and supple enough to cushion the joint against impact, over decades of repeat use.
Little skates could hold the key to cartilage therapy in humans
Unlike humans and other mammals, the skeletons of sharks, skates, and rays are made entirely of cartilage and they continue to grow that cartilage throughout adulthood.
Can magnetic stem cells improve cartilage repair?
Cells equipped with superparamagnetic iron oxide nanoparticles (SPIOs) can be directed to a specific location by an external magnetic field, which is beneficial for tissue repair.
Common conditions keep many patients out of knee cartilage research studies
Issues like age or existing arthritis may preclude patients from participating in clinical studies for new therapies that could benefit them
Will MSC micropellets outperform single cells for cartilage regeneration?
Repair of cartilage injuries or defects is aided by the introduction of mesenchymal stem cells (MSCs), which can be incorporated into hydrogels to amplify their effects.
Exercise helps prevent cartilage damage caused by arthritis
Exercise helps to prevent the degradation of cartilage caused by osteoarthritis, according to a new study from Queen Mary University of London.
Cartilage could be key to safe 'structural batteries'
Your knees and your smartphone battery have some surprisingly similar needs, a University of Michigan professor has discovered, and that new insight has led to a 'structural battery' prototype that incorporates a cartilage-like material to make the batteries highly durable and easy to shape.
Potential arthritis treatment prevents cartilage breakdown
In an advance that could improve the treatment options available for osteoarthritis, MIT engineers have designed a new material that can administer drugs directly to the cartilage.
A hydrogel that adheres firmly to cartilage and meniscus
EPFL researchers have developed a hydrogel -- made up of nearly 90 percent water -- that naturally adheres to soft tissue like cartilage and the meniscus.
More Cartilage News and Cartilage Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: IRL Online
Original broadcast date: March 20, 2020. Our online lives are now entirely interwoven with our real lives. But the laws that govern real life don't apply online. This hour, TED speakers explore rules to navigate this vast virtual space.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Falling
There are so many ways to fall–in love, asleep, even flat on your face. This hour, Radiolab dives into stories of great falls.  We jump into a black hole, take a trip over Niagara Falls, upend some myths about falling cats, and plunge into our favorite songs about falling. Support Radiolab by becoming a member today at Radiolab.org/donate.