The bone matrix as it developed over time. (Scale bar: 5 mm.) Click here to enlarge image.
Image: PNAS et al.
Bones often come in complex, delicate shapes, making it hard to find matching natural replacements for them in patients suffering from injuries, diseases or birth defects. Now researchers have grown bone grafts in the exact shape of a desired bone, an advance that could help provide doctors with just what they need for face, skull and other skeletal reconstructions.
Although missing bone can be replaced by titanium, "there is no better substitute for lost tissue than living tissue," bioengineer Gordana Vunjak-Novakovic at Columbia University explains. "Although titanium is better than nothing—you need something to help bear loads—real bones also have bone marrow inside that has many important metabolic functions."
Patients also could rely on donated bones, but these run the risk of contamination and tissue rejection. Or surgeons can harvest bone from elsewhere in a patient's body and carve it to fit where they need to, "but this is very hard on patients," Vunjak-Novakovic says. "The damage at the site of harvest is major, and it takes long to regenerate this tissue, and patients often report doing so hurts much more and longer than the implant itself."
Instead, bioengineer Warren Grayson, along with Vunjak-Novakovic and their colleagues, grew their own grafts. They started with the temporomandibular joint, found at the point where the jaw meets the skull in front of the ear. "It was the greatest challenge we could think of, the most complex piece in the skull in terms of shape, based on surgeons we asked," she says. "If we can grow this piece, we think we can grow anything."
The temporomandibular joint, or TMJ, is also of growing clinical relevance, Vunjak-Novakovic adds. As many as roughly one out of four people experience symptoms of disorders involving the TMJ, such as pain in the chewing muscles and jaw stiffness as well as painful clicking, popping or grating in the joint.
The researchers first used real bone as a scaffold—"we know actual bones are ideal because they work in real life," Vunjak-Novakovic says. They stripped the knee joints of calves of all their cells with detergents and enzymes and then, based on digitized x-ray images from an anonymous patient, had machines carve them into cubic-centimeter-size human jaw joints.
They next seeded each scaffold with three million commercially available human mesenchymal stem cells, which can give rise to bone, cartilage, fat and other tissues. The cells, which lined the pores of the scaffold, were regularly fed with streams of nutrients, growth factors and oxygen in a bioreactor. The pattern and rate of this perfusion guides how the bone structure grows, just as blood does in vivo, and the physical stimulation of the cells provided by this flow is critical for proper growth.
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17 Comments
Add CommentThis is an absolutely fantastic breakthrough. As a TMJ disorder patient I can only begin to imagine how this could effect not only my life but the lives of thousands of other patients who have had to agree to less than ideal jaw implants to try and improve their function and pain levels. 3 years ago after many surgeries to try and save them, I had both of my jaw joints removed because they were, essentially, fused shut. I then had a custom joint replacement implanted which is made of titanium. I am only 27 years old, and I faced a lifetime of more surgeries because the titanium implants do not last. This breakthrough gives me hope that a permanent solution is closer than we ever thought. Congratulations to Vunjak-Novakovic, Grayson, their colleagues, and Columbia University. This has the potential to change so many lives!!
Reply | Report Abuse | Link to thisit is not a quick solution so it could not be used in emergencies, but i can see this becoming a common practice when 5 weeks is available. once they overcome the final hurtle of supplying blood to these grafts, i think this will be quickly adopted.
Reply | Report Abuse | Link to thisCongratulations and thank you from the many TMJ patients that will benefit from this scientific breakthrough!
Reply | Report Abuse | Link to thisThe TMJ Association, Ltd.
www.tmj.org
info@tmj.org
Maybe I can hang on if I know SOMEONE has perceived the importance of working on this - and actually done something.
Reply | Report Abuse | Link to thisHope. What a powerful word.
I want to expand briefly on my earlier comment about this amazing milestone that Warren Grayson, along with Gordana Vunjak-Novakovic, have achieved.
Reply | Report Abuse | Link to thisMy personal saga with TMJD began over 30 years ago. From 1981-1992 I was implanted with jaw joint implants to "cure" my TMJ, all of which were doomed to fail because there was no sound science behind them. I've also had a rib graft using two of my own ribs to try to reconstruct my jawbone & TMJs -that was a resounding failure.
After that surgery failed, my oral surgeon told me that my only option was total joint replacements made from titanium, or some other combination of metal and plastic, but that my chances for success were slim. I opted for no more surgery until there was some REAL hope on the horizon, a day I never thought I'd live to see, quite frankly.
And yet - here it is - HOPE - if not for me (and I still do have some), then for the thousands of younger patients who might otherwise be forced to endure multiple surgeries, re-operations, badly designed devices....lifetimes bereft of a light at the end of the tunnel. (Yes, I realize there is still much to be done in solving the vascularization problem.)
Congratulations on not only an astonishing achievement, but in focusing on a joint so badly neglected over the years in scientific research - the temporomandibular joint. You've provided concrete evidence that someone recognizes the need at a time when so many lack that basic force which keeps them going - HOPE. And you've proven successful treatment can be feasible if the science is done right. Obviously, the implications of your work expanding into other areas (skulls, faces, hips, knees, etc) are mind-boggling & exciting. But by tackling the TMJ first, you've taken on perhaps the most difficult joint on which to conduct your research.
I salute you with kudos & gratitude.
Betsy Burnam
with the flattened necrosis of my jaw joints, I'm not sure if it would work , but I am Hopeful (false hope is better than no hope) that the decision for nothing after the tephlon removal from the fossa , (and given the previous comments on failures) I may someday have "even jaw alignment" which I obtain through biofeedback, meditation, PT, massage, but does not last due to stress.
Reply | Report Abuse | Link to thisIn 1992 when the tephlon was removed , the nylon sheath that replaced the ligament and miniscus from 1986 locked jaw,was not different from "normal" tissue other than no miniscus. The surgeon said if he hadn't read the previous report he would not have realized how well the tissue regrew. He thought at first it was just a minisectomy previous surgery.
I am scheduled to have a total joint replacement next year. My jaw is fused and I have an 8 mil opening. I have gotten to the point that I have to have something done after 20 years of constant pain and suffering. Does any one know how much longer this will be? If it is a few years I can try and hold on.
Reply | Report Abuse | Link to thisI am scheduled to have a total joint replacement next year. My jaw is fused and I have an 8 mil opening. I have gotten to the point that I have to have something done after 20 years of constant pain and suffering. Does any one know how much longer this will be? If it is a few years I can try and hold on.
Reply | Report Abuse | Link to thisAlthough this is something that will probably not happen in the very near future, it is HOPE. I am 53 years old, just had my 10th surgery last week and am waiting on custom made bilateral joints as I write this. It will be number 11 and probably the last chance I have at a normal life. It is discouraging for sure but we don't have a lot of choices once surgery has been performed. I have had just about every possible procedure that can be done performed and this last one is my last chance. My body cannot withstand many more hours and hours of anesthesia and there is not a lot of bone left anymore for anyone to work with, so I pray this one works.I will keep you all in my prayers also. Sherry
Reply | Report Abuse | Link to thisThis is great news, better late than never. I recently had my 10th surgery and am awaiting my 11th in a few weeks for custom made bilateral joints. I have had just about every possible operation available and so am praying that this is the last one. I wish you all well and hope and pray for all of you that you get the results you deserve also. Sherry
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