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Chondrogenic effect of the perichondrium graft on the internal derangement and osteoarthritis of the temporomandibular joint of the rabbit
Journal of Cranio-Maxillo-Facial Surgery 39 (2011) 351e358
Contents lists available at ScienceDirect
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Chondrogenic effect of the perichondrium graft on the internal derangement and osteoarthritis of the temporomandibular joint of the rabbit Gaye Taylan Filinte*, Mithat Akan, Ilker Bilgic, Mustafa Karaca, Tayfun Akoz Dr. Lutfi Kirdar Kartal Education and Research Hospital, Plastic, Reconstructive and Aesthetic Surgery Clinic, Istanbul, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 30 April 2009 Accepted 14 September 2010
Internal derangement of the temporomandibular joint is usually defined as the disruption of the condyle and disc relationship. In addition to this description the other elements of the joint including the cartilage surface, synovial fluid, the ligaments and the bony surface itself demonstrate varying degrees of pathology in concordance with the stage of the internal derangement, as well. This study is designed to create an osteoarthritic model in the rabbit temporomandibular joint. A 2 2 mm defect was performed on the cartilage surface of the both condyles of each animal (n ¼ 30). The osteoarthritic changes were demonstrated by computerised tomography sections. The right joints of the animals constituted the control group and the left, the study group. At the time of the defect generation, a perichondrium graft from the animal’s ear was implanted onto the defect in the study group. The control group was left to heal secondarily. The joints of three randomized groups of 10 animals for each were inspected at the 4th, 6th, and 8th weeks. Cartilage regeneration and regression of the osteoarthritic changes were demonstrated in the study group both in the 6th and 8th week groups. However, the control group showed less cartilage regeneration and progression of the osteoarthritic changes in all weeks, with progression with time. The perichondrium graft has demonstrated chondrogenic effect on the condyle and this in turn changed the progression to internal derangement. Ó 2010 European Association for Cranio-Maxillo-Facial Surgery.
Keywords: Internal derangement Temporomandibular joint Perichondrium
1. Introduction Internal derangement of the temporomandibular joint refers to an abnormal relationship between the condyle and the disc. Various stages of internal derangement exist from painless click with no limitations in jaw opening to degenerative joint disease (Emshoff and Rudisch, 2004). The usual malposition of the disc is anteriorly in respect to the condyle. The exposed condyle surface faces the interior joint elements and becomes vulnerable to the osteoarthritic changes both by the changes in the synovial fluid components and by direct trauma. The cartilage composition of the surface of the condyle is fibrocartilage which is different from the other synovial joints with hyaline cartilage (Quinn, 1992). The fibrocartilage resists the shear forces in the joint. Because of the characteristics of the cartilage itself, the chondrocytes cannot produce new cartilage in areas of cartilage defects. Healing happens by fibrosis. The rabbit temporomandibular joint was used to study the regenerative capacity of the perichondrium graft in internal derangement of the joints. Thirty animals were used and both joints * Corresponding author. E-mail address: [email protected] (G. Taylan Filinte).
were included in the study. The internal derangement was mimicked by creating a defect on the condylar cartilage surface. The neochondrogenesis and the changes in the degenerative joint disease were followed at various intervals. Perichondrium grafts demonstrated new cartilage formation and decrease in the osteoarthritic changes in the joint. The unresponsiveness to conventional therapies in the management of temporomandibular joint internal derangement has led the researchers to look for alternative therapies. The role of the disc was quite significant until recently but, the other elements constituting the joint are involved in the degenerative process as well. The fibrocartilage plays a major role in the progression of the disease to degenerative joint disease. As demonstrated in the study, a perichondrium graft has reversed the osteoarthritic changes by neochondrogenesis. The promising results of this and many other studies may place neochondrogenesis as a substitute for the existing therapies in the future.
2. Materials and methods Thirty New Zealand male rabbits were included in the study. The animals were anesthetised with intramuscular ketamine
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hydrochloride and xylasine hydrochloride in doses of 40 mg/kg and 5 mg/kg respectively. The temporomandibular joint regions just posterior to the orbital cavities of the animals were shaved and cleaned with povidone iodine solutions bilaterally. The left joints of the animals were included in the study group (n ¼ 30 joints) and the right joints of the animals were included in the control group (n ¼ 30 joints). A 2e3 cm vertical incision between the posterior of the lateral orbital wall and the external acoustic meatus were performed. Incision of the joint capsule and superior retraction of the joint disc exposed the condylar head. The lateral orbital wall was osteotomised 2e3 mm from its posterior to increase condylar exposure. After traction of the condyle a 2 2 mm defect was created on the cartilage surface with the help of a blunt drill in both groups (Fig.1). The study group involved the following procedures; the ear on this side was cleaned and incised to expose the cartilage surface. Perichondrium was shaved using a scalpel. The perichondrium was placed into the defect (Fig. 2). Disc was returned to its normal position and the joint capsule was closed. In the control group the disc was returned to its normal position with the defect left empty and the joint capsule was closed afterwards (Fig. 3). The skin was sutured continuously with non absorbable sutures. Postoperative dressings were changed every 2 days and the sutures were removed at the 1st week. A postoperative soft diet regimen was used for both groups. Randomized animals were grouped into 3 with 10 animals for each. Each one of the three groups was examined macroscopically, histologically and with computerised tomography. The first group was examined at the 4th, the second at the 6th, and the third at the 8th weeks. The animals were euthanised with high dose intramuscular penthotal injection and the joints were removed. Statistical calculations were performed with GraphPad Prisma V.3 program for Windows.
2.3. Histopathological findings The same pathologist evaluated the specimens. The results were classified into three groups according to their similarities to normal cartilage; 1. Near-normal cartilage. 2. Fibro-hyaline cartilage. 3. Fibrosis. 2.3.1. 4th week The control group demonstrated fibrosis and fibro-hyaline cartilage (Fig. 13). The study group demonstrated similar cartilage (fibrosis and fibro-hyaline) with the control group (Fig. 14). 2.3.2. 6th week Cartilage regeneration was fibrosis and fibro-hyaline type in the control group (Fig. 15). Fibrosis amount was greater. The study group demonstrated less amount of fibrosis and increased amount of near-normal cartilage (Fig. 16). 2.3.3. 8th week Fibrosis type regeneration continued in the control group with similar amount of fibro-hyaline type. However no near-normal type cartilage was demonstrated (Fig. 17). The most amount of near-normal type cartilage was demonstrated in the study group at this week (Fig. 18). No fibrosis was demonstrated with varying amount of fibro-hyaline type cartilage. 3. Results The following results were demonstrated in the study;
2.1. Macroscopic findings 2.1.1. 4th week Both the control and the study group joints revealed sustained defects with depressed levels from the normal joint surface (Figs. 4 and 5). 2.1.2. 6th week Depressed level at the defect zone of the control group (Fig. 6), and near to normal level of the study group (Fig. 7). 2.1.3. 8th week Lesser defect compared to the earlier weeks but still depressed than the normal level in the control group. The same level and even more in some of the newly regenerated cartilage as the normal cartilage in the study group (Fig. 8). 2.2. Computerised tomography findings 2.2.1. 6th week Computerised tomography sections were evaluated after 6 weeks. The decreased joint space and irregularities on the condylar head was noticed in the control group (Fig. 9). The study group revealed normal joint space with no irregularities on the condylar head (Fig. 10). 2.2.2. 8th week Irregularities on the condylar head and the decreased joint space in the control group of the 8th week was similar to the findings of the 6th week control group. The decrease in the joint space was significant with subchondral sclerosis (Fig. 11). The study group revealed no subchondral sclerosis nor condylar irregularities. The joint space was normal (Fig. 12).
1. The control group demonstrated a depressed defect zone in all weeks macroscopically. However the study group showed increase of the defect level with increasing weeks. At the 8th week, all specimens demonstrated the same level with the normal cartilage. 2. The study group showed a statistically significant increase in cartilage regeneration after 6th week. The cartilage regeneration in the control group was less than the study group in all weeks. Near-normal cartilage formation was not observed in the control group in any weeks. The study group demonstrated the most amount of near-normal cartilage at the 8th week. 3. The control group demonstrated osteoarthritis in the computerised tomography sections after 6th week with slight osteoarthrosis at the 8th week. Osteoarthrosis was not observed in the study group in any weeks. 4. Chi square test was performed during the evaluation qualitative data. Kappa test was used inter-observer reliability. Statistical significance level was established at p < 0,005 (Tables 1 and 2). 4. Discussion Internal derangement of the temporomandibular joint is a progressive disease with different symptoms at different stages. It is usually quite disturbing in the patient’s daily life. Among the signs and symptoms of this disease are; preauricular pain, click in the joint, crepitation, irregular and limited joint movements (Arinci et al., 2005). All the structures of the joint involve the internal derangement. As a highly specialised joint, the temporomandibular joint has a leading role in craniofacial growth and function. Osteoarthritis of this joint is quite common. The general guidelines for osteoarthritis
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Fig. 4. The macroscopic view of the defect at the 4th week and control group. Fig. 1. The defect on the condylar head.
Fig. 5. The macroscopic view of the defect at the 4th week and study group.
Fig. 2. The perichondrium graft placed into the defect.
Fig. 3. The defect on the condylar head of the control group.
Fig. 6. Depressed level at the defect zone of the control group.
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of other joints can be applied to the temporomandibular joint as well. However every joint has a specialised function. As the knee joint is a load bearing joint, the TMJ bears shear forces. While osteoarthritis of the knee joint is usually observed at older ages, TMJ osteoarthritis is seen at a younger ages both in humans and animals (Meng et al., 2005). Biomechanical models of the TMJ aim to explain the aetiology of the osteoarthritis signs in the internally deranged joints. Models of perforated discs, discectomies, and displaced discs help to investigate the relation between the degenerative changes and internal derangement (Emshoff and Rudisch, 2004; Arinci et al., 2005; Meng et al., 2005; Ali and Sharawy, 1994; Axelsson et al., 1992; Berteretche et al., 2001; Bjornland and Haanaes, 1999; De Bont et al., 1986; Lang et al., 1993; Westesson and Rohlin, 1984). Which one is the cause and which one is the result? This close relationship is not understood as there is not one certain cause. Many authors suggest that disc
Fig. 7. Near to normal level of the study group.
displacement is a cause, a result and an accompanying sign of the osteoarthritis (Ishimaru and Goss, 1992; Luder, 1993; Stegenga, 2001; Stegenga et al., 1989). Cledes et al. have demonstrated that cartilage changes in a chemically performed osteoarthritis model of the rabbit TMJ, causes disc perforation. The close relationship between the joint structures explains the disc damage after cartilage defects, and cartilage degeneration after deplaced and perforated disc. This supports the theory supporting internal derangement as a cause, a result or an accompanying sign of the arthrosis (Cledes et al., 2006). The study of Sharawy et al. involving the rabbit TMJ has supported other studies claiming that anterior disc emplacement causes intracellular and extracellular changes of osteoarthritis (Sharawy et al., 2000). In this study they have split all the connections of the disc but the posterior ones and investigated the condyles with electron microscopy after 2 weeks. They have found that surgically caused anterior disc displacement caused ultrastructural changes on the condylar cartilage similar to osteoarthritis. The pathogenesis of the internal derangement has shifted from the disc displacement theory to the biochemical causes (Yeung et al., 2006). Classical therapies include disc repair and placement of the disc back to its original zone in patients unresponsive to conservative measures. Different therapies decreasing the symptoms and increasing the interincisive opening without changing the position of the disc have gained popularity nowadays (Dimitroulis et al., 1995). Among them are; arthroscopy, simple lysis and lavage, and increasing the hydraulic pressure in the upper joint space. TMJ arthrocentesis and lavage described by Nitzan is irrigation of the upper joint space under local anaesthesia. Significant decrease in pain after arthrocentesis has been observed (Dimitroulis et al., 1995). Yeung et al. have performed high molecular weight sodium hyaluronate injection to 27 patients with disc displacement. They have observed a significant decrease in pain intensity and increase in interincisive opening. There is not a consensus on how the sodium hyaluronate works, and it is not wrong to mention a mechanical effect. The slippery action of it on synovial surfaces and the damaged disc are among the other explanations. The slippery environment and the decreased friction coefficient are the probable causes of the increase in interincisive opening. The decrease in pain is mainly due to the analgesic, anti-inflammatory and slippery effect of hyaluronic acid (Yeung et al., 2006). Xinmin et al. have demonstrated that viscosupplementation (intraarticular sodium hyaluronate injection), avoids osteoarthritis of the TMJ and when applied with arthrocentesis, a synergy is observed. Their study involved 24 rabbits with intraarticular matrix metalloproteinase-1 injection to induce bilateral osteoarthritis of the TMJ.
Fig. 8. The control and the study group at the 8th week.
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Fig. 9. The arrow demonstrates the control group on the CT at the 6th week. Fig. 11. The arrow demonstrates the control group on the CT at the 8th week.
Fig. 10. The arrow demonstrates the study group on the CT at the 6th week.
Fig. 12. The arrow demonstrates the study group on the CT at the 8th week.
Arthrocentesis, viscosupplementation and their combinations were performed respectively to three randomized groups. They used one of the joints of each animal as the control. After 8 weeks they observed that arthrocentesis alone did not significantly alter the
osteoarthritic changes when compared to the control group. However, both the applications of viscosupplementation alone and with arthrocentesis, have demonstrated significant improvement in osteoarthritis compared to the control group (Xinmin and Jian, 2005).
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Fig. 13. The control group demonstrated fibrosis and fibro-hyaline cartilage at the 4th week.
Fig. 16. The study group demonstrated less amount of fibrosis and increased amount of near-normal cartilage at the 6th week.
Fig. 14. The study group demonstrated similar cartilage (fibrosis and fibro-hyaline) at the 4th week. Fig. 17. Fibrosis type regeneration continued in the control group with similar amount of fibro-hyaline type at the 8th week.
Fig. 15. Cartilage regeneration was fibrosis and fibro-hyaline type in the control group at the 6th week.
Fig. 18. The most amount of near-normal type cartilage was demonstrated in the study group at the 8th week.
G. Taylan Filinte et al. / Journal of Cranio-Maxillo-Facial Surgery 39 (2011) 351e358 Table 1 The number and quality of newly formed tissue according to the weeks between two groups.
4th week
6th week
8th week
Study group
Control group
Near-normal Fibro-hyaline Fibrosis
0 7 3
0.0% 70.0% 30.0%
0 3 7
0.0% 30.0% 70.0%
c2:3.20
Near-normal Fibro-hyaline Fibrosis
3 6 1
30.0% 60.0% 10.0%
0 4 6
0.0% 40.0% 60.0%
c2:6.97
Near-normal Fibro-hyaline Fibrosis
6 4 0
60.0% 40.0% 0.0%
0 4 6
0.0% 40.0% 60.0%
p ¼ 0.074
p ¼ 0.031
c2:12 p ¼ 0.002
Table 2 The number and quality of newly formed tissue according to the weeks between two groups. 4th week
6th week
8th week
Study group
Near-normal Fibro-hyaline Fibrosis
0 7 3
0% 70% 30%
3 6 1
30% 60% 10%
6 4 0
60% 40% 0%
c2:10.32 p ¼ 0.035
Control group
Near-normal Fibro-hyaline Fibrosis
0 3 7
0.0% 30% 70%
0 4 6
0.0% 40% 60%
4 6
40% 60%
c2:0.287 p ¼ 0.866
From this one may conclude that arthrocentesis does not improve pathological changes, instead it has a temporary action. Alpaslan et al. demonstrated the action of arthrocentesis comes from the elimination of inflammatory mediators away from the joint (Alpaslan et al., 2000). It does not improve the microstructure of the joint. The synergy of arthrocentesis and viscosupplementation when used together probably comes from the elimination of inflammatory mediators from the environment which allows the hyaluronate to act more permanently (Tanaka et al., 2002). Emshoff et al. have elucidated some theories about the aetiology of internal derangement. They have studied the magnetic resonance images of internal derangement, osteoarthrosis, effusion, and bone marrow oedema before and after arthrocentesis and hydraulic distension. Though many patients confirmed improvement in pain, the position of the disc had changed only in few. The magnetic resonance images of osteoarthrosis and internal derangement did not correlate with the increase in interincisive opening and significant decrease in pain. However, after treatment the MR images of bone marrow oedema, a secondary inflammatory sign, had improved significantly. These results ascertain the importance of the inflammatory events on internal derangement of increased stages (Emshoff et al., 2006). Few points can be addressed when all the studies are evaluated up to now; 1. Internal derangement is a progressive disease and is associated with osteoarthritis and osteoarthrosis especially at the advanced stages. 2. Clinical signs are usually unrelated to the disc position at the advanced stages. A question is raised at this point; can regeneration of the internal elements of the joint help to reverse the pathology of internal derangement? The articular cartilage is mainly composed of extracellular matrix, chondrocytes and water. Chondrocytes of the cartilage control the mechanism of extracellular matrix regeneration and degradation. Water is indispensable for the nourishment of avascular cartilage. The perichondrium is a fibrous vascular capsule surrounding the cartilage. Cartilage regeneration occurs both by means of mitosis of the chondrocytes into the cartilage matrix and by the cells of the deep layer of
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perichondrial connective tissue. Perichondrial connective tissue cells leave the perichondrium and become intracartilaginous chondrocytes while synthesizing matrix tissue. Chondrocytes have minute amount of regeneration capacity. Therefore, regeneration following trauma ends with fibrosis (Motoki and Mulliken, 1990). Many animal studies concerning cartilage repair have used full thickness cartilage defects up to 3 mm. These defects demonstrate healing spontaneously. Jackson et al. have investigated the healing characteristics of full thickness osteochondral defects with a diameter of 6 mm in the knee joints of goats. No healing was observed with time and bone resorption and cartilage loss was demonstrated after 12th week. They have classified the wide cartilage defects as “interaction zone” and proposed that biological and synthetic materials are required for healing to decrease the damage of this zone to the surrounding (Jackson et al., 2001). A cartilage defect of 2 mm was planned in this study to avoid “critical cartilage defect”. This in turn provided the standard conditions for healing especially for the control group. Many studies have been performed demonstrating new cartilage formation with free perichondrium grafts (Skoog and Johansson, 1976; Upton et al., 1981). Diaz-Flores et al. have demonstrated two types of cartilage formation after free autogenous perichondrium transfer (Diaz-Flores et al.,1988). While the new cartilage generating from the perichondrocytes of the inner perichondrium layer is classified as type 1, that newly generated from the undifferentiated perivascular mesenchymal cells from the graft bed is classified as type 2. Diaz-Flores et al. have shown that perivascular cells also aid in cartilage degeneration from the perichondrium graft (Diaz-Flores et al., 1991). Soft tissues around cartilage increase regeneration from the perichondrial cells with the help of perivascular cells. When there are limited cartilage donor sites, donor site morbidity is another challenge. Both perichondrial and periosteal grafts aid in cartilage formation. Ulutas et al. have created cartilage defects on the ear of the rabbit. They have placed perichondrium grafts, periosteal grafts and periosteal graft plus hyaluronan in three different groups with cartilage defects of 1 1 cm respectively and compared the difference in cartilage regeneration between the groups and the control group. While no difference in cartilage regeneration between the groups was observed, the control group demonstrated significant delay in cartilage regeneration. Hyaluronate had added no beneficial effect (Ulutas et al., 2005). Carranza-Bencano et al. have used free periosteal implants to the full thickness cartilage defects on medial femoral condyle of the rabbit. The control group has not demonstrated full regeneration while the study group showed statistically significant regeneration with the use of periosteal implants (Carranza-Bencano et al., 2000). 5. Conclusion The defect generated on the temporomandibular joint in this study simulated a form of internal derangement. Osteoarthritis and internal derangement have a close relationship based on the supposition that joint degeneration may cause late stage internal derangement. Various osteoarthritis models described before have been investigated and a cartilage defect was chosen for a model in this study. Histological, macroscopical and radiologic findings supported internal derangement in both joints. The second stage of the study aimed to find a therapeutic intervention to reduce degeneration. A perichondrium graft was chosen because of its characteristics in inducing cartilage regeneration. It caused little, if any, donor site morbidity. When the results are considered, cartilage regeneration was better in terms of quality and quantity when a perichondrium graft was used. The healing cartilage also decreased the signs of osteoarthritis in the joint. As an organic tissue and having various sources in the body, perichondrium grafts
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may have a place in the future as an alternative therapy in internal derangement. More studies are required to support this idea. References Ali AM, Sharawy MM: Histopathological changes in the rabbit craniomandibular joint associated with experimentally induced anterior disk displacement. J Oral Pathol Med 23: 364e374, 1994 Alpaslan C, Bilgihan A, Alpaslan GH, Guner BH, Ozgur YM, Erbas D: Effect of arthrocentesis and sodium hyaluronate injection on nitrite, nitrate, and thiobarbituric acid-reactive substance levels in the synovial fluid. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 89: 686e690, 2000 Arinci A, Ademoglu E, Aslan A, Turkoglu UM, Karabulut AB, Karan A: Molecular correlates of temporomandibular joint disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99: 666e670, 2005 Axelsson S, Holmlund A, Hjerpe A: An experimental model of osteoarthrosis in the temporomandibular joint of the rabbit. Acta Odontol Scand 50: 273e280, 1992 Berteretche MV, Foucart JM, Meunier A, Carpentier P: Histologic changes associated with experimental partial anterior disc displacement in the rabbit temporomandibular joint. J Orofac Pain 15: 306e319, 2001 Bjornland T, Haanaes HR: Discectomy of the temporomandibular joint: an experimental study in monkeys. J Craniomaxillofac Surg 27: 113e116, 1999 Carranza-Bencano A, Garcia-Paino L, Armas Pardon JR, Cayuela Dominguez A: Neochondrogenesis in repair of full-thickness articular cartilage defects using free autogenous periosteal grafts in the rabbit. A follow-up in six months. Osteoarthritis Cartilage 8: 351e358, 2000 Cledes G, Felizardo R, Foucart JM, Carpentier P: Validation of a chemical osteoarthritis model in rabbit temporomandibular joint: a compliment to biomechanical models. Int J Oral Maxillofac Surg 35: 1026e1033, 2006 De Bont LGM, Boering G, Liem RSB, Eulderink F, Westesson PL: Osteoarthritis and internal derangement of the temporomandibular joint: a light microscopic study. J Oral Maxillofac Surg 44: 634e643, 1986 Diaz-Flores L, Gutierrez R, Gonzalez P, Varela H: Inducible perivascular cells contribute to the neochondrogenesis in grafted perichondrium. Anat Rec 229: 1e8, 1991 Diaz-Flores L, Rodriguez E, Gayoso MJ, Gutierrez R: Growth of two types of cartilage after implantation of free autogeneic perichondrial grafts. Clin Orthop 234: 267e279, 1988 Dimitroulis G, Dolwick MF, Martinez A: Temporomandibular joint arthrocentesis and lavage fort he treatment of closed lock: a follow-up study. Br J Oral Maxillofac Surg 33: 23e26, 1995 Emshoff R, Gerhard S, Ennemoser T, Rudisch A: Magnetic resonance imaging findings of internal derangement, osteoarthrosis, effusion, and bone marrow edema before and after performance of arthrocentesis and hydraulic distension of the temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101: 784e790, 2006
Emshoff R, Rudisch A: Determining predictor variables for treatment outcomes of arthrocentesis and hydraulic distention of the temporomandibular joint. J Oral Maxillofac Surg 62: 816e823, 2004 Ishimaru JI, Goss AN: A model for osteoarthritis of the temporomandibular joint. J Oral Maxillofac Surg 50: 1191e1195, 1992 Jackson DW, Lalor PA, Aberman HM, Simon TM: Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study. J Bone Joint Surg Am 83-A: 1591e1592, 2001 Lang TC, Zimny ML, Vijayagopal P: Experimental temporomandibular joint disc perforation in the rabbit: a gross morphologic, biochemical, and ultrastructural analysis. J Oral Maxillofac Surg 51: 1115e1128, 1993 Luder HU: Articular degeneration and remodeling in human temporomandibular joints with normal and abnormal disc position. J Orofac Pain 7: 391e402, 1993 Meng J, Ma X, Ma D, Xu C: Microarray analysis of differential gene expression in temporomandibular joint condylar cartilage after experimentally induced osteoarthritis. Osteoarthritis Cartilage 13: 1115e1125, 2005 Motoki DS, Mulliken JB: The healing of bone and cartilage. Clin Plast Surg 17: 527e544, 1990 Quinn JH: Pain mediators and chondromalacia in internally deranged temporomandibular joints. In: Bell WH (ed.), Modern practice in orthognathic and reconstructive surgery, vol. 1. Philadelphia: W.B. Saunders, 471e475, 1992 Sharawy M, Ali AM, Choi WS, Larke V: Ultrastructural characterization of the rabbit mandibular condyle following experimental induction of anterior disk displacement. Cells Tissues Organs 167: 38e48, 2000 Skoog T, Johansson SH: The formation of articular cartilage from free perichondrial grafts. Plast Reconstr Surg 57: 1e6, 1976 Stegenga B, De Bont LGM, Boering G: Osteoarthritis as the cause of craniomandibular pain and dysfunction: a unifying concept. J Oral Maxillofac Surg 47: 249e256, 1989 Stegenga B: Osteoarthritis of the temporomandibular joint organ and its relationship to disc displacement. J Orofac Pain 15: 193e205, 2001 Tanaka N, Sakahashi H, Sato E, Hirose K, Ishima T, Ishii S: Intra-articular injection of high molecular weight hyaluronan after arthrocentesis as treatment for rheumatoid knees with joint effusion. Rheumatol Int 22: 151e154, 2002 Ulutas K, Menderes A, Karaca C, Ozkal S: Repair of cartilage defects with periosteal grafts. Br J Plast Surg 58: 65e72, 2005 Upton J, Sohn SA, Glowacki J: Neocartilage derived from transplanted perichondrium: what is it? Plast Reconstr Surg 68: 166e174, 1981 Westesson PL, Rohlin M: Internal derangement related to osteoarthrosis in temporomandibular joint autopsy specimens. Oral Surg Oral Med Oral Pathol 57: 17e22, 1984 Xinmin Y, Jian H: Treatment of temporomandibular joint osteoarthritis with viscosupplementation and arthrocentesis on rabbit model. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100: E35eE38, 2005 Yeung RWK, Chow RLK, Samman N, Chiu K: Short-term therapeutic outcome of intra-articular high molecular weight hyaluronic acid injection for nonreducing disc displacement of the temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102: 453e461, 2006
Contents lists available at ScienceDirect
Journal of Cranio-Maxillo-Facial Surgery journal homepage: www.jcmfs.com
Chondrogenic effect of the perichondrium graft on the internal derangement and osteoarthritis of the temporomandibular joint of the rabbit Gaye Taylan Filinte*, Mithat Akan, Ilker Bilgic, Mustafa Karaca, Tayfun Akoz Dr. Lutfi Kirdar Kartal Education and Research Hospital, Plastic, Reconstructive and Aesthetic Surgery Clinic, Istanbul, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 30 April 2009 Accepted 14 September 2010
Internal derangement of the temporomandibular joint is usually defined as the disruption of the condyle and disc relationship. In addition to this description the other elements of the joint including the cartilage surface, synovial fluid, the ligaments and the bony surface itself demonstrate varying degrees of pathology in concordance with the stage of the internal derangement, as well. This study is designed to create an osteoarthritic model in the rabbit temporomandibular joint. A 2 2 mm defect was performed on the cartilage surface of the both condyles of each animal (n ¼ 30). The osteoarthritic changes were demonstrated by computerised tomography sections. The right joints of the animals constituted the control group and the left, the study group. At the time of the defect generation, a perichondrium graft from the animal’s ear was implanted onto the defect in the study group. The control group was left to heal secondarily. The joints of three randomized groups of 10 animals for each were inspected at the 4th, 6th, and 8th weeks. Cartilage regeneration and regression of the osteoarthritic changes were demonstrated in the study group both in the 6th and 8th week groups. However, the control group showed less cartilage regeneration and progression of the osteoarthritic changes in all weeks, with progression with time. The perichondrium graft has demonstrated chondrogenic effect on the condyle and this in turn changed the progression to internal derangement. Ó 2010 European Association for Cranio-Maxillo-Facial Surgery.
Keywords: Internal derangement Temporomandibular joint Perichondrium
1. Introduction Internal derangement of the temporomandibular joint refers to an abnormal relationship between the condyle and the disc. Various stages of internal derangement exist from painless click with no limitations in jaw opening to degenerative joint disease (Emshoff and Rudisch, 2004). The usual malposition of the disc is anteriorly in respect to the condyle. The exposed condyle surface faces the interior joint elements and becomes vulnerable to the osteoarthritic changes both by the changes in the synovial fluid components and by direct trauma. The cartilage composition of the surface of the condyle is fibrocartilage which is different from the other synovial joints with hyaline cartilage (Quinn, 1992). The fibrocartilage resists the shear forces in the joint. Because of the characteristics of the cartilage itself, the chondrocytes cannot produce new cartilage in areas of cartilage defects. Healing happens by fibrosis. The rabbit temporomandibular joint was used to study the regenerative capacity of the perichondrium graft in internal derangement of the joints. Thirty animals were used and both joints * Corresponding author. E-mail address: [email protected] (G. Taylan Filinte).
were included in the study. The internal derangement was mimicked by creating a defect on the condylar cartilage surface. The neochondrogenesis and the changes in the degenerative joint disease were followed at various intervals. Perichondrium grafts demonstrated new cartilage formation and decrease in the osteoarthritic changes in the joint. The unresponsiveness to conventional therapies in the management of temporomandibular joint internal derangement has led the researchers to look for alternative therapies. The role of the disc was quite significant until recently but, the other elements constituting the joint are involved in the degenerative process as well. The fibrocartilage plays a major role in the progression of the disease to degenerative joint disease. As demonstrated in the study, a perichondrium graft has reversed the osteoarthritic changes by neochondrogenesis. The promising results of this and many other studies may place neochondrogenesis as a substitute for the existing therapies in the future.
2. Materials and methods Thirty New Zealand male rabbits were included in the study. The animals were anesthetised with intramuscular ketamine
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hydrochloride and xylasine hydrochloride in doses of 40 mg/kg and 5 mg/kg respectively. The temporomandibular joint regions just posterior to the orbital cavities of the animals were shaved and cleaned with povidone iodine solutions bilaterally. The left joints of the animals were included in the study group (n ¼ 30 joints) and the right joints of the animals were included in the control group (n ¼ 30 joints). A 2e3 cm vertical incision between the posterior of the lateral orbital wall and the external acoustic meatus were performed. Incision of the joint capsule and superior retraction of the joint disc exposed the condylar head. The lateral orbital wall was osteotomised 2e3 mm from its posterior to increase condylar exposure. After traction of the condyle a 2 2 mm defect was created on the cartilage surface with the help of a blunt drill in both groups (Fig.1). The study group involved the following procedures; the ear on this side was cleaned and incised to expose the cartilage surface. Perichondrium was shaved using a scalpel. The perichondrium was placed into the defect (Fig. 2). Disc was returned to its normal position and the joint capsule was closed. In the control group the disc was returned to its normal position with the defect left empty and the joint capsule was closed afterwards (Fig. 3). The skin was sutured continuously with non absorbable sutures. Postoperative dressings were changed every 2 days and the sutures were removed at the 1st week. A postoperative soft diet regimen was used for both groups. Randomized animals were grouped into 3 with 10 animals for each. Each one of the three groups was examined macroscopically, histologically and with computerised tomography. The first group was examined at the 4th, the second at the 6th, and the third at the 8th weeks. The animals were euthanised with high dose intramuscular penthotal injection and the joints were removed. Statistical calculations were performed with GraphPad Prisma V.3 program for Windows.
2.3. Histopathological findings The same pathologist evaluated the specimens. The results were classified into three groups according to their similarities to normal cartilage; 1. Near-normal cartilage. 2. Fibro-hyaline cartilage. 3. Fibrosis. 2.3.1. 4th week The control group demonstrated fibrosis and fibro-hyaline cartilage (Fig. 13). The study group demonstrated similar cartilage (fibrosis and fibro-hyaline) with the control group (Fig. 14). 2.3.2. 6th week Cartilage regeneration was fibrosis and fibro-hyaline type in the control group (Fig. 15). Fibrosis amount was greater. The study group demonstrated less amount of fibrosis and increased amount of near-normal cartilage (Fig. 16). 2.3.3. 8th week Fibrosis type regeneration continued in the control group with similar amount of fibro-hyaline type. However no near-normal type cartilage was demonstrated (Fig. 17). The most amount of near-normal type cartilage was demonstrated in the study group at this week (Fig. 18). No fibrosis was demonstrated with varying amount of fibro-hyaline type cartilage. 3. Results The following results were demonstrated in the study;
2.1. Macroscopic findings 2.1.1. 4th week Both the control and the study group joints revealed sustained defects with depressed levels from the normal joint surface (Figs. 4 and 5). 2.1.2. 6th week Depressed level at the defect zone of the control group (Fig. 6), and near to normal level of the study group (Fig. 7). 2.1.3. 8th week Lesser defect compared to the earlier weeks but still depressed than the normal level in the control group. The same level and even more in some of the newly regenerated cartilage as the normal cartilage in the study group (Fig. 8). 2.2. Computerised tomography findings 2.2.1. 6th week Computerised tomography sections were evaluated after 6 weeks. The decreased joint space and irregularities on the condylar head was noticed in the control group (Fig. 9). The study group revealed normal joint space with no irregularities on the condylar head (Fig. 10). 2.2.2. 8th week Irregularities on the condylar head and the decreased joint space in the control group of the 8th week was similar to the findings of the 6th week control group. The decrease in the joint space was significant with subchondral sclerosis (Fig. 11). The study group revealed no subchondral sclerosis nor condylar irregularities. The joint space was normal (Fig. 12).
1. The control group demonstrated a depressed defect zone in all weeks macroscopically. However the study group showed increase of the defect level with increasing weeks. At the 8th week, all specimens demonstrated the same level with the normal cartilage. 2. The study group showed a statistically significant increase in cartilage regeneration after 6th week. The cartilage regeneration in the control group was less than the study group in all weeks. Near-normal cartilage formation was not observed in the control group in any weeks. The study group demonstrated the most amount of near-normal cartilage at the 8th week. 3. The control group demonstrated osteoarthritis in the computerised tomography sections after 6th week with slight osteoarthrosis at the 8th week. Osteoarthrosis was not observed in the study group in any weeks. 4. Chi square test was performed during the evaluation qualitative data. Kappa test was used inter-observer reliability. Statistical significance level was established at p < 0,005 (Tables 1 and 2). 4. Discussion Internal derangement of the temporomandibular joint is a progressive disease with different symptoms at different stages. It is usually quite disturbing in the patient’s daily life. Among the signs and symptoms of this disease are; preauricular pain, click in the joint, crepitation, irregular and limited joint movements (Arinci et al., 2005). All the structures of the joint involve the internal derangement. As a highly specialised joint, the temporomandibular joint has a leading role in craniofacial growth and function. Osteoarthritis of this joint is quite common. The general guidelines for osteoarthritis
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Fig. 4. The macroscopic view of the defect at the 4th week and control group. Fig. 1. The defect on the condylar head.
Fig. 5. The macroscopic view of the defect at the 4th week and study group.
Fig. 2. The perichondrium graft placed into the defect.
Fig. 3. The defect on the condylar head of the control group.
Fig. 6. Depressed level at the defect zone of the control group.
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of other joints can be applied to the temporomandibular joint as well. However every joint has a specialised function. As the knee joint is a load bearing joint, the TMJ bears shear forces. While osteoarthritis of the knee joint is usually observed at older ages, TMJ osteoarthritis is seen at a younger ages both in humans and animals (Meng et al., 2005). Biomechanical models of the TMJ aim to explain the aetiology of the osteoarthritis signs in the internally deranged joints. Models of perforated discs, discectomies, and displaced discs help to investigate the relation between the degenerative changes and internal derangement (Emshoff and Rudisch, 2004; Arinci et al., 2005; Meng et al., 2005; Ali and Sharawy, 1994; Axelsson et al., 1992; Berteretche et al., 2001; Bjornland and Haanaes, 1999; De Bont et al., 1986; Lang et al., 1993; Westesson and Rohlin, 1984). Which one is the cause and which one is the result? This close relationship is not understood as there is not one certain cause. Many authors suggest that disc
Fig. 7. Near to normal level of the study group.
displacement is a cause, a result and an accompanying sign of the osteoarthritis (Ishimaru and Goss, 1992; Luder, 1993; Stegenga, 2001; Stegenga et al., 1989). Cledes et al. have demonstrated that cartilage changes in a chemically performed osteoarthritis model of the rabbit TMJ, causes disc perforation. The close relationship between the joint structures explains the disc damage after cartilage defects, and cartilage degeneration after deplaced and perforated disc. This supports the theory supporting internal derangement as a cause, a result or an accompanying sign of the arthrosis (Cledes et al., 2006). The study of Sharawy et al. involving the rabbit TMJ has supported other studies claiming that anterior disc emplacement causes intracellular and extracellular changes of osteoarthritis (Sharawy et al., 2000). In this study they have split all the connections of the disc but the posterior ones and investigated the condyles with electron microscopy after 2 weeks. They have found that surgically caused anterior disc displacement caused ultrastructural changes on the condylar cartilage similar to osteoarthritis. The pathogenesis of the internal derangement has shifted from the disc displacement theory to the biochemical causes (Yeung et al., 2006). Classical therapies include disc repair and placement of the disc back to its original zone in patients unresponsive to conservative measures. Different therapies decreasing the symptoms and increasing the interincisive opening without changing the position of the disc have gained popularity nowadays (Dimitroulis et al., 1995). Among them are; arthroscopy, simple lysis and lavage, and increasing the hydraulic pressure in the upper joint space. TMJ arthrocentesis and lavage described by Nitzan is irrigation of the upper joint space under local anaesthesia. Significant decrease in pain after arthrocentesis has been observed (Dimitroulis et al., 1995). Yeung et al. have performed high molecular weight sodium hyaluronate injection to 27 patients with disc displacement. They have observed a significant decrease in pain intensity and increase in interincisive opening. There is not a consensus on how the sodium hyaluronate works, and it is not wrong to mention a mechanical effect. The slippery action of it on synovial surfaces and the damaged disc are among the other explanations. The slippery environment and the decreased friction coefficient are the probable causes of the increase in interincisive opening. The decrease in pain is mainly due to the analgesic, anti-inflammatory and slippery effect of hyaluronic acid (Yeung et al., 2006). Xinmin et al. have demonstrated that viscosupplementation (intraarticular sodium hyaluronate injection), avoids osteoarthritis of the TMJ and when applied with arthrocentesis, a synergy is observed. Their study involved 24 rabbits with intraarticular matrix metalloproteinase-1 injection to induce bilateral osteoarthritis of the TMJ.
Fig. 8. The control and the study group at the 8th week.
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Fig. 9. The arrow demonstrates the control group on the CT at the 6th week. Fig. 11. The arrow demonstrates the control group on the CT at the 8th week.
Fig. 10. The arrow demonstrates the study group on the CT at the 6th week.
Fig. 12. The arrow demonstrates the study group on the CT at the 8th week.
Arthrocentesis, viscosupplementation and their combinations were performed respectively to three randomized groups. They used one of the joints of each animal as the control. After 8 weeks they observed that arthrocentesis alone did not significantly alter the
osteoarthritic changes when compared to the control group. However, both the applications of viscosupplementation alone and with arthrocentesis, have demonstrated significant improvement in osteoarthritis compared to the control group (Xinmin and Jian, 2005).
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Fig. 13. The control group demonstrated fibrosis and fibro-hyaline cartilage at the 4th week.
Fig. 16. The study group demonstrated less amount of fibrosis and increased amount of near-normal cartilage at the 6th week.
Fig. 14. The study group demonstrated similar cartilage (fibrosis and fibro-hyaline) at the 4th week. Fig. 17. Fibrosis type regeneration continued in the control group with similar amount of fibro-hyaline type at the 8th week.
Fig. 15. Cartilage regeneration was fibrosis and fibro-hyaline type in the control group at the 6th week.
Fig. 18. The most amount of near-normal type cartilage was demonstrated in the study group at the 8th week.
G. Taylan Filinte et al. / Journal of Cranio-Maxillo-Facial Surgery 39 (2011) 351e358 Table 1 The number and quality of newly formed tissue according to the weeks between two groups.
4th week
6th week
8th week
Study group
Control group
Near-normal Fibro-hyaline Fibrosis
0 7 3
0.0% 70.0% 30.0%
0 3 7
0.0% 30.0% 70.0%
c2:3.20
Near-normal Fibro-hyaline Fibrosis
3 6 1
30.0% 60.0% 10.0%
0 4 6
0.0% 40.0% 60.0%
c2:6.97
Near-normal Fibro-hyaline Fibrosis
6 4 0
60.0% 40.0% 0.0%
0 4 6
0.0% 40.0% 60.0%
p ¼ 0.074
p ¼ 0.031
c2:12 p ¼ 0.002
Table 2 The number and quality of newly formed tissue according to the weeks between two groups. 4th week
6th week
8th week
Study group
Near-normal Fibro-hyaline Fibrosis
0 7 3
0% 70% 30%
3 6 1
30% 60% 10%
6 4 0
60% 40% 0%
c2:10.32 p ¼ 0.035
Control group
Near-normal Fibro-hyaline Fibrosis
0 3 7
0.0% 30% 70%
0 4 6
0.0% 40% 60%
4 6
40% 60%
c2:0.287 p ¼ 0.866
From this one may conclude that arthrocentesis does not improve pathological changes, instead it has a temporary action. Alpaslan et al. demonstrated the action of arthrocentesis comes from the elimination of inflammatory mediators away from the joint (Alpaslan et al., 2000). It does not improve the microstructure of the joint. The synergy of arthrocentesis and viscosupplementation when used together probably comes from the elimination of inflammatory mediators from the environment which allows the hyaluronate to act more permanently (Tanaka et al., 2002). Emshoff et al. have elucidated some theories about the aetiology of internal derangement. They have studied the magnetic resonance images of internal derangement, osteoarthrosis, effusion, and bone marrow oedema before and after arthrocentesis and hydraulic distension. Though many patients confirmed improvement in pain, the position of the disc had changed only in few. The magnetic resonance images of osteoarthrosis and internal derangement did not correlate with the increase in interincisive opening and significant decrease in pain. However, after treatment the MR images of bone marrow oedema, a secondary inflammatory sign, had improved significantly. These results ascertain the importance of the inflammatory events on internal derangement of increased stages (Emshoff et al., 2006). Few points can be addressed when all the studies are evaluated up to now; 1. Internal derangement is a progressive disease and is associated with osteoarthritis and osteoarthrosis especially at the advanced stages. 2. Clinical signs are usually unrelated to the disc position at the advanced stages. A question is raised at this point; can regeneration of the internal elements of the joint help to reverse the pathology of internal derangement? The articular cartilage is mainly composed of extracellular matrix, chondrocytes and water. Chondrocytes of the cartilage control the mechanism of extracellular matrix regeneration and degradation. Water is indispensable for the nourishment of avascular cartilage. The perichondrium is a fibrous vascular capsule surrounding the cartilage. Cartilage regeneration occurs both by means of mitosis of the chondrocytes into the cartilage matrix and by the cells of the deep layer of
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perichondrial connective tissue. Perichondrial connective tissue cells leave the perichondrium and become intracartilaginous chondrocytes while synthesizing matrix tissue. Chondrocytes have minute amount of regeneration capacity. Therefore, regeneration following trauma ends with fibrosis (Motoki and Mulliken, 1990). Many animal studies concerning cartilage repair have used full thickness cartilage defects up to 3 mm. These defects demonstrate healing spontaneously. Jackson et al. have investigated the healing characteristics of full thickness osteochondral defects with a diameter of 6 mm in the knee joints of goats. No healing was observed with time and bone resorption and cartilage loss was demonstrated after 12th week. They have classified the wide cartilage defects as “interaction zone” and proposed that biological and synthetic materials are required for healing to decrease the damage of this zone to the surrounding (Jackson et al., 2001). A cartilage defect of 2 mm was planned in this study to avoid “critical cartilage defect”. This in turn provided the standard conditions for healing especially for the control group. Many studies have been performed demonstrating new cartilage formation with free perichondrium grafts (Skoog and Johansson, 1976; Upton et al., 1981). Diaz-Flores et al. have demonstrated two types of cartilage formation after free autogenous perichondrium transfer (Diaz-Flores et al.,1988). While the new cartilage generating from the perichondrocytes of the inner perichondrium layer is classified as type 1, that newly generated from the undifferentiated perivascular mesenchymal cells from the graft bed is classified as type 2. Diaz-Flores et al. have shown that perivascular cells also aid in cartilage degeneration from the perichondrium graft (Diaz-Flores et al., 1991). Soft tissues around cartilage increase regeneration from the perichondrial cells with the help of perivascular cells. When there are limited cartilage donor sites, donor site morbidity is another challenge. Both perichondrial and periosteal grafts aid in cartilage formation. Ulutas et al. have created cartilage defects on the ear of the rabbit. They have placed perichondrium grafts, periosteal grafts and periosteal graft plus hyaluronan in three different groups with cartilage defects of 1 1 cm respectively and compared the difference in cartilage regeneration between the groups and the control group. While no difference in cartilage regeneration between the groups was observed, the control group demonstrated significant delay in cartilage regeneration. Hyaluronate had added no beneficial effect (Ulutas et al., 2005). Carranza-Bencano et al. have used free periosteal implants to the full thickness cartilage defects on medial femoral condyle of the rabbit. The control group has not demonstrated full regeneration while the study group showed statistically significant regeneration with the use of periosteal implants (Carranza-Bencano et al., 2000). 5. Conclusion The defect generated on the temporomandibular joint in this study simulated a form of internal derangement. Osteoarthritis and internal derangement have a close relationship based on the supposition that joint degeneration may cause late stage internal derangement. Various osteoarthritis models described before have been investigated and a cartilage defect was chosen for a model in this study. Histological, macroscopical and radiologic findings supported internal derangement in both joints. The second stage of the study aimed to find a therapeutic intervention to reduce degeneration. A perichondrium graft was chosen because of its characteristics in inducing cartilage regeneration. It caused little, if any, donor site morbidity. When the results are considered, cartilage regeneration was better in terms of quality and quantity when a perichondrium graft was used. The healing cartilage also decreased the signs of osteoarthritis in the joint. As an organic tissue and having various sources in the body, perichondrium grafts
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