Bio-functionalisation of a custom-made total temporomandibular joint prosthesis

General introduction
The temporomandibular joint (TMJ) plays a role in many functions such as mastication, swallowing, talking, facial expressions, breathing, airway support and even maintaining the correct pressure of the middle ear. The joint can perform both translative and rotational movements and subjected to more cyclic loading and unloading than any other joint in the body. As a result, temporomandibular disorders (TMDs) are far from rare.(1) A 2008 study by the National Health Interview Survey concluded that up to 5% of all Americans deal with TMD-related pain(2), and a study conducted by Janal et al.(3) reported that up to 10% of all female patients examined had a TMD. Despite this high prevalence, in most cases conservative therapy such as physiotherapy and pharmacotherapy will suffice as treatment. Yet in about 5 to 10%, symptoms persist, demanding a more invasive approach.(4,5) which can range from a simple arthrocentesis to ultimately total joint replacement surgery. (1,6)
TMJ anatomy
To better understand the function of the temporomandibular joint, as well as the total joint replacement (TJR) (procedure), a comprehensive knowledge of this diarthrosis’ anatomy is needed.
The TMJ is comprised of the head of the mandibular condyle and the temporal glenoid fossa. The condyle is an ovoid process at the superior part of the mandibular ramus. It has a convex form and is wider in the mediolateral sense (15-20 mm) than in the anteroposterior direction (8-10 mm), with the medial side of the condyle being directed more posteriorly compared to the lateral side. The articular surface of the condyle is located on the anterosuperior part of the condyle.(7)
Anteriorly of the tympanic plate, the articular temporal component can be found and shows several landmarks. Most anteriorly, the articular eminence and tubercle are located. The eminence has a strong incline, which becomes nearly horizontal towards the glenoid fossa, forming the preglenoid plane. The centrally located glenoid fossa is widest in the mediolateral direction, as the condyle is seated in this fossa. Posteriorly, an elevation is seen, forming the posterior articular ridge. This ridge laterally further increases in height, forming the post-glenoid process, which forms the posterior border of the joint.(7)
The temporal and condylar component are both separated by an oval-shaped biconcave fibrocartilaginous articular disc. This disc divides the joint in an larger upper and smaller inferior compartment, allowing for a rotational/hinge movement to occur in the inferior compartment, whilst a translational/gliding movement occurs in the upper compartment. The anterior and posterior part of the disc are quite a bit thicker at respectively 2 and 3mm compared to the center, where the disc measures about 1 mm. The posterior part, known as the bilaminar region, has an upper elastin and a lower fibrous layer, separated by connective tissue. The upper layer is connected to the post-glenoid process, preventing anterior displacement of the disc. The inferior layer fuses with the joint capsule below the condyle as to prevent the disc rotating over the condyle. The disc is also fixed to the medial and lateral pole of the condyle, to allow it to move together with the latter. Anteriorly, the disc is fixed to the fibrous capsule of the joint. This fibrous capsule surrounding the whole of the TMJ is called the articular capsule. Anteriorly, an opening in the capsule is seen, allowing the lateral pterygoid muscle (LPM) to pass through and insert itself onto the condyle and the anterior part of the disc. The inside of the capsule is lined with a synovial membrane, thus making the TMJ a synovial joint.(7,8)
Besides the capsule, the movements of TMJ are restricted by three main ligaments. The lateral ligament forms a part of the capsule and limits both the forward and posterior translation of the condyle, as well as the maximal lateral movement. The fibers originate from the articular tubercle and insert in the lateral side of the condyle and the condylar neck, as well as into the articular disc. The stylomandibular ligament, which inserts onto the mandibular angle and the posterior border, limits to protrusive movement of the mandible in case of more extreme movements. Lastly, the sphenomandibular ligament remains passive during movement of the lower jaw.(9)
There are four true mastication muscles which make direct contact with the TMJ. Three of these muscles help to close the mouth. The masseter muscle is the ‘main closer’ of the mouth, and is further aided by the medial pterygoid muscle, which could be seen as the counterpart to the masseter muscle, yet on the medial side of the mandible. The third muscle to help close the mouth, is the temporal muscle, which inserts onto the coronoid process. However, as mastication is more than rather just opening and closing, the lateral pterygoid muscle can be seen as vital to proper masticatory function. Whereas the superior belly of the LPM inserts into the disc, allowing proper disc movement, the inferior belly inserts into the condyle and allows for protrusion of the condyles when both side contract simultaneously, leading to the mouth opening. Additionally to allowing proper disc movement, the superior belly also participates in contralateral and protrusive moment. Despite this involvement of the superior belly, the inferior one is the principal muscle for laterotrusive movement. In case of a unilateral contraction, a laterotrusive movement will occur, which is extremely important for being able to properly chew. Important to note is that, with current TMJ TJR, the LPM’s function is not retained, thus losing the possibility of laterotrusive movement.(8–11)
Equally important for every surgeon to the structure of the joint are the main blood vessels and nerves surrounding the joint. The maxillary artery and superficial temporal artery provide the main vascularization to the joint. The superficial temporal artery is the terminal branch of the external carotid and can be found relatively superficially, posterolaterally to the condyle. It makes for a point of attention during a surgical exploration, especially when taking a pre-auricular approach. The maxillary artery branches from the external carotid as well, yet passes on the medial side of the mandible, between the ramus and the sphenomandibular ligament, below the sigmoid notch. This artery is important, as the arteria meningea media branches off at the level of the condyle and passes medially from it, risking being damaged when performing a condylectomy. Venous drainage is realized mainly through the pterygoid plexus and superficial temporal vein, as well as several other maxillary veins, forming the retromandibular vein.(12,13)
Aims and overview of the thesis
In 2019 Elledge et al.(26) reported on 27 different TMJ TJR being produced in over fifteen countries with only 2 of them being approved by the United States Food and Drug Administration (FDA). Twenty-two of these TJR applied a similar design to these 2 approved systems, yet still varied in the prosthetic materials that were used. Also, only 12 systems performed preclinical laboratory tests, yet none underwent in vivo testing before being implanted in human patients. The authors concluded that ‘Not all systems are equal in terms of design, material composition, preclinical laboratory testing, manufacturing methods, regulatory status, and reports of clinical outcomes.’
Thus, this doctoral thesis set out to develop and properly investigate a personalized TMJ prosthesis. The hypothesis is that it would be possible to develop a prosthesis that meets orthopedic standards in both wear properties and adverse tissue reactions. We also hypothesized that is possible to reinsert the LPM onto the prothesis, allowing for lateral condylar movement. Also, we aimed to further improve the per-operative and post-operative protocols that are currently in place, by evaluating the available literature and developing new guidelines or protocols.
General introduction
The first chapter provides a general introduction on the anatomy of the joint, its surgical indications, and approaches. The outline of the thesis is presented as well.
Part 1 Literature analysis and development
By better understanding the historic development of temporomandibular joint prosthetic systems with attention for the different materials and designs that were used, significant insights can be obtained in developing a new TMJR. By analyzing the challenges and complications that were encountered not only by engineers, but also by surgeons, the design of a new TMJR can also be influenced from a clinical point of view. This second chapter provides an extensive systematic review of the historical evolution of the prosthetic replacement of the joint, leading to several conclusions for future application.
Whereas the second chapter briefly touches the prosthetic materials that were used in both the past and present, the third chapter further elaborates on this topic by means of a narrative review. The importance of the use of biocompatible materials is evident, yet certain materials are clearly less suited for loading or articulation, compared to other materials, as their use nearly resulted in an abandonment of the prosthetic replacement of the TMJ. Thus, this chapter discusses the criteria that a biomaterial must meet, other than biocompatibility, to be considered suitable for implantation. An insight is also provided into both surface modification techniques to further improve on current materials, as well as potential future materials.
While at first, TMJ prostheses were stock implants, sometimes provided in different sizes, there was no possibility to deal with the patient’s specific anatomy. Through the development of computer-assisted design/ computer-assisted manufacturing (CAD-CAM) systems, patient-specific implants (PSI) were developed. In chapter four a meta-analysis is performed to compare both types of protheses, with special attention for functionality (maximal mouth opening), pain and diet, as well as possible confounders that might influence these results.
Part 2 Animal-model experiment
Using the data and conclusions from the literature analysis that was performed, a novel patient-specific implant was designed. To evaluate if the implant was suitable for human implantation and could meet orthopedic standards, an animal-model experiment using sheep was designed. The prosthesis was first implanted in one sheep, to evaluate the surgical procedure and to establish the standard procedure. Next, 6 sheep were implanted with a ‘regular’ prosthesis and 6 ewes were treated with a prosthesis that underwent surface modification on the condylar head. Ten months after implantation, the sheep were euthanized to evaluate the peri-articular tissues, as well as the implants themselves.
In the fifth chapter of this thesis the surface wear of both the condylar and fossa component are analyzed and discussed. Both a linear and volumetric wear analysis of the fossa was performed through optical scanning. The condylar surface was evaluated through scanning electron and confocal laser microscopy. The amount of wear between the two types of prosthetic systems was compared and the condylar surface smoothness was analyzed to determine the effect of the surface treatment. Lastly, the amount of wear that occurred was compared to the standards set in orthopedic surgery.
Following the wear analysis of the prosthetic components, the next chapter discusses a histological analysis of the peri-articular tissues that was performed to evaluate the amount of inflammation in the peri-articular tissues. The inflammatory response between both types of prostheses was also compared. The tissues were evaluated for the presence of chronic inflammation as well as ‘synovial-like interface membrane’ type I synovitis and type VI reactions.
Besides assuring suitability of implantation, based on wear properties, good osseointegration of the prosthetic system is needed as well. The last two chapters of the second part of this thesis discuss both the integration of the prosthetic system, as well as the integration of the reinserted LPM onto the condylar component. In chapter 7 a radiological analysis of the prosthetic system is performed, to first evaluate the integration of the LPM onto the condylar component. This led to the finding of four different radiological situations, based on which those sheep who showed (partial) bony integration were selected for further histological analysis in chapter 8, to determine if bony ingrowth within a scaffold at the condylar neck occurred. In both chapters the integration of the prosthetic components was also evaluated.
Part 3 Clinical application and protocols
Using the data and conclusions from the earlier chapters, the first chapter in the final part of this thesis discusses the development of the novel type of patient-specific, custom-made TMJ prosthesis, now applied for human implantation, using CAD-CAM, additive manufacturing and surface treatment. Eleven patients and a total of sixteen joints were treated using the TMJR and its function was evaluated the analysis of the early in vivo results, with attention for the reported pain and dietary scores, as well as the measured movements. In chapter ten, the prosthetic system is further adapted to not only restore the function of the TMJ, but also to restore segmental mandibular defects with occlusal abnormalities. A total of five patients and six joints were treated using the extended TMJR (eTMJR) and evaluated for at least one year. The chapter also focusses on problems that can occur during the implantation of an eTMJR.
Both chapters eleven and twelve focus on further improving the per-and postoperative protocols for a total mandibular joint replacement. Through a systematic review, the first chapter discusses the usefulness of a periprosthetic autologous fat graft (AFG), to prevent postoperative heterotopic bone formation, leading to an ankylotic joint and necessity for a surgical revision. Besides per-operative measures to ensure proper joint function, post-operative physiotherapy is important as well to keep the joint mobile. By use of a systematic review, physiotherapeutic treatments are analyzed. This chapter seeks to develop a new postoperative physiotherapy protocol which is thorough yet comprehensible for practitioners and supported by scientific evidence.
Discussion and summary
In Chapter 13 we discuss the general findings of the previous chapters and provide insight into future studies to further improve and support the developed TMJ prosthesis. The final chapter contains both Dutch and English summaries of this thesis.
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