Tissue Engineering for the TMJ’s

We all know someone who has arthritis, which is an inflammation that gradually destroys the structure of a joint.  Osteoarthritis, on the other hand, wears down the cartilage in the joints.  One of the major causes of pain for patients in the US is Osteoarthritis, and in fact over 20% of adults have this in their hip or knee.  Osteoarthritis is classified as a degenerative joint disease (DJD), meaning that the cartilage between the bones literally disintegrates. Treatments for DJD are extremely challenging, especially as people get older.

Total joint replacement procedures are generally successful in restoring joint function and can decrease (and potentially eliminate) pain.  There are downsides of joint replacements, as some of the prostheses can have a limited lifespan due to loosening, infection, and fractures in areas surrounding the bone. As an alternative treatment, tissue-engineering procedures have been progressing over the last two decades.  Even though there are challenges in producing a fully functional tissue, many advances have been made in regard to lab-created cartilage-like tissue, which can be created and then implanted.

As an expert in treating TMJ disorders, Dr. Klein has seen over 15,000 patients who are experiencing things like limited opening, pain on opening, limited movement to each side, clicking or popping noises, and a deviation in opening on the affected side. Unfortunately, the “typical” patient deals with these symptoms for years, not knowing that they even have a problem, and/or not knowing who to go to for help.

Because of the prevalence of TMJ disorders resulting from trauma, such as a car accident or sports injury, the temporomandibular joint is a primary target for tissue-engineering applications. Additionally, the small size of the TMJ minimizes difficulties/complications, as compared to larger joints.  Keep in mind that even though it is small, the complex shape of the TMJ must be preserved.  The temporomandibular joint is a structure made up of cartilage and bone. It is important that the geometry of the joint is carefully reconstructed to maintain the proper joint mechanics to ensure normal function.

tmj joint with osteoarthritis

Researchers have been investigating biological TMJ grafts, grown in-lab that could integrate with the tissues that are already there.  By remodeling the joint over time, this provides a life-long function for the patient, possibly eliminating the chances for a total joint replacement.  TMJ tissue engineering can improve the outcomes of patients suffering TMJ disorders, in addition to things like thinning of the disc.

In the 1960’s, doctors started using implants made of Teflon.  While these provided patients with immediate relief from symptoms and dysfunctions, the long-term effects were degraded implants and ultimately, failure.  In terms of bone regeneration, tissue engineering may improve restoration, giving surgeons the tools to regenerate the damaged structures of the TMJ completely. Challenges in this approach include the available selection of cells and growth factors that all work in unison.

Although there is no commercial, tissue-engineered product currently on the market for treating TMD, several studies have been performed toward the development of appropriate tools for engineering TMJ tissues.

tmj joint
tmj joint reconstruction

Testing for TMJ reconstruction has been most effective using the recipients’ own cells.  This helps to avoid risks of immune rejection and infectious disease transmission. To minimize the damage caused by biopsy, a small quantity of tissue from a single source would be used, and the cells would be expanded in vitro. 

A therapeutic approach would be necessary to reconstruct the precise architecture of the TMJs. An image-based, micro-printing approach has been used in studies to design the required external and internal geometries of the TMJs. This technique is known as solid free-form fabrication.  Using imaging-guided fabrication, researchers can shape a block of bone into the exact geometry of the TMJ being repaired.  Because cartilage and bone form under different environmental conditions, the formation of TMJ grafts requires a separate supply of bone and cartilage.

Cartilage provides load bearing and lubrication in our joints. When injured, cartilage has poor healing ability. Successful replacement of damaged cartilage will hinge on the ability to fix the mechanical and structural properties of the healthy native tissue before implantation.  The TMJ grafts can be implanted to determine the grafts’ ability to structurally and functionally replace the native joint.

tmj cartilage

An important future challenge is the engineering of shape-specific constructs that are likened to the specific dimensions of the TMJ tissues to be replaced. Most tissue engineering studies examine flat and relatively small newly formed tissues.  Since both the TMJ disc and the condyle have complex geometries, a scale-up approach will be needed that also considers shape conformity.

Tissue engineering is a rapidly evolving field with ongoing development. More studies are already in process and will continue until these techniques can be applied effectively to TMJ disorder. 

References:

Tissue engineered autologous cartilage-bone grafts for temporomandibular joint regeneration; Science Translational Medicine (2020). doi: 10.1126/scitranslmed.abb6683 O’Connell GD, Lima EG, Bian L, et al.

Toward engineering a biological joint replacement. J Knee Surg. 2012;25(3):187-196. doi:10.1055/s-0032-1319783 Grayson WL, Chao PH, Marolt D, Kaplan DL, Vunjak-Novakovic G.

Engineering custom-designed osteochondral tissue grafts. Trends Biotechnol. 2008;26(4):181-189. doi:10.1016/j.tibtech.2007.12.009 Weng Y, et al.

Tissue-engineered composites of bone and cartilage for mandible condylar reconstruction. J Oral Maxillofac Surg. 2001;59:185–190. Acri TM, Shin K, Seol D, et al.

Tissue Engineering for the Temporomandibular Joint. Adv Healthc Mater. 2019;8(2):e1801236. doi:10.1002/adhm.201801236 Vapniarsky N, Huwe LW, Arzi B, et al.

Tissue engineering toward temporomandibular joint disc regeneration. Sci Transl Med. 2018;10(446):eaaq1802. doi:10.1126/scitranslmed.aaq1802 Aryaei A, Vapniarsky N, Hu JC, Athanasiou KA.

Recent Tissue Engineering Advances for the Treatment of Temporomandibular Joint Disorders. Curr Osteoporos Rep. 2016;14(6):269-279. doi:10.1007/s11914-016-0327-y