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Histological Evaluation of an 11-year-old Hydroxyapatite Ceramic Implant in Mandibular Bone
An 11-year-old Hydroxyapatite Ceramic Implant in Mandibular Bone Asian J Oral Maxillofac Surg 2003;15:142-145. CASE REPORTS
Histological Evaluation of an 11-year-old Hydroxyapatite Ceramic Implant in Mandibular Bone 1
Kenji Kurashina,1 Toshikazu Minemura,2 Hiroshi Kurita,1 Qiang Wu1 Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Japan 2 Department of Dentistry and Oral Surgery, Iida Municipal Hospital, Iida, Japan
Abstract: There are no detailed long-term histological studies of hydroxyapatite implanted in human bone tissue. This report is of histological and radiographic examination of a patient with mandibular bone implanted with hydroxyapatite ceramics after cyst ennucleation and a good clinical course for 10 years. The mandibular bone was resected 11 years after the initial operation because of infection. Histology of the retrieved mandibular bone revealed that bone tissue proliferated into interparticular spaces and attached to the hydroxyapatite ceramics surfaces in the non-infected portion and that hydroxyapatite ceramics disappeared with bone destruction in the infected portion. From the histological results, clinical findings, and chronological radiographic findings for 10 years, it was concluded that hydroxyapatite ceramics could maintain their favourable properties as a bone substitute in human bone for a long time. Key Words: Hydroxyapatite, Mandible
Introduction There are no reports of tissue response to hydroxyapatite ceramics (HACs) and long-term changes of HACs after implantation in the human body. However, a few reports on long-term experiments in dogs are available.1,2 For this reason, it would be interesting to investigate bone retrieved many years after reconstruction with HACs. This report is of a histological and radiographic examination of a segment of human mandibular bone that was reconstructed with HACs and has shown a good postoperative course for 10 years.
Case Report A 63-year-old Japanese man was referred with a follicular cyst of the mandible. Cyst enucleation using general anaesthesia was performed, and the bone defect was filled with 2 types of HAC, a porous HAC block and dense HAC particles. At the base of the defect, a trimmed HAC block (Bonetite, Mitsubishi Materials Co., Saitama, Japan) was placed Correspondence: Kenji Kurashina, Department of Dentistry and Oral Surgery, School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. Tel: (81 263) 372 675, Fax: (81 263) 372 676 E-mail: [email protected]
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to avoid pressure on the mandibular nerve, and HAC particles (Bonetite) were used to fill the remaining defect. Postoperatively, an alveolar ridge of adequate shape and consistency was obtained, and a dental prosthesis was worn without difficulty for 10 years. During the follow-up period, chronological radiographs showed no changes in the reconstructed area except for slight condensation of the HAC particles in the early stage and gradual osteogenic changes in the defect (Figure 1a). After 10 years, the patient presented to the department with pus and HAC particle discharge. Radiographs showed partial loss of HAC particles in the reconstructed alveolar ridge. Treatment by drainage, administration of antibiotics, and removal of infected HAC particles was successfully performed. Approximately 1 year after this episode, the patient returned with abscess formation in the submandibular region. Radiographs and computed tomography at that time revealed loss of a large quantity of HAC particles and destruction of the reconstructed mandibular bone (Figure 1b). He was treated by segmental resection of the infected portion of the mandible with immediate transplantation of autogenous iliac bone. Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
Kurashina, Minemura, Kurita, et al
a
b
Figure 1. Radiographs of the reconstructed mandible taken (a) 5 years after hydroxyapatite ceramic implantation and (b) just before resection 11 years after initial hydroxyapatite ceramic implantation. Arrows in (a) indicate a porous hydroxyapatite ceramic block placed at the bottom of the defect. Hydroxyapatite ceramic loss and bone destruction is noticed in (b).
Histological Examination The resected mandibular bone was sectioned into 5 pieces and fixed in 10% neutral formalin for 1 week, followed by dehydration and embedding in polyester resin (Rigolac, Ohken, Tokyo, Japan). Specimens were serially cut perpendicular to the long axis of the mandible and ground with an Exakt-micro grinding system (Exakt, Norderstedt, Germany) to approximately 20 microns. Most of the ground sections were stained with 5% toluidine blue and examined with a light microscope. Some sections were used for taking microradiographs or scanning electron micrographs. Sections from the most distal segment in the noninfected area of the resected mandible showed microscopically and microradiographically that HAC particles were scattered almost uniformly in the bone tissue. All particles appeared connected and fixed to each other by newly formed bone tissue which proliferated into interparticular spaces (Figures 2a and b). No inflammatory or phagocytic cell infiltration were recognised in the interparticular spaces. The contact between particles and bone was direct without intervening soft tissues (Figure 2c). The surface of the HAC particles was smooth without any signs of resorption and no small fragments of HAC were seen (Figure 2c). Tissues from infected parts showed destruction of bone tissue, loss of HAC particles, and granulation tissue formation (Figure 2d). Some particles were intermingled in the granulation tissue without any Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
contact with the remaining healthy bone tissue. Some sections showed porous HAC block that was partially embedded in the bone tissue (Figure 2e). In the nonaffected parts near the cortical bone, the same findings seen in the sections from the most distal segment were recognised, that is, normal bone invasion into interparticular spaces or HAC pores revealing direct contact with the HAC surfaces. Scanning electron microscopic (SEM) observation of the boundary between bone and the HACs showed that the contact was direct without intervening soft tissue. No resorption of HACs was detected in SEM observation (Figure 2f).
Discussion There are a few studies of HACs implanted in the human body, but they usually refer to materials retrieved after short-term implantation.3-5 It is therefore not clear whether HACs can maintain properties of biocompatibility and osteo-integrative ability in the long term, and few reports on the change of HACs after long-term implantation are available. The present report is useful because it describes findings in human mandibular bone reconstructed with HACs after a good clinical course for 10 years. The mandibular bone examined in this report was resected due to an osteomyelitis-like lesion (Figure 1b). The retrieved mandible was divided into 5 blocks to examine the cut surfaces macroscopically and it was found that the most distal part was not 143
An 11-year-old Hydroxyapatite Ceramic Implant in Mandibular Bone
a
b
c
d
e
f
Figure 2. (a) Histology of the non-infected part. Normal and mature bone invades the interparticular spaces, showing close contact to the hydroxyapatite ceramics (undecalcified section, 5% toluidine blue stain, original magnification x 10). (b) Microradiograph of the non-infected part. Bone invades into the space of the particles (white parts) and directly contacts them [original magnification x 10]. (c) Higher magnification view of the non-infected part. Bone tissue contacts directly with the surface of the HACs (asterisks) [undecalcified section, 5% toluidine blue stain, original magnification x 100]. (d) Histology of severely infected parts. Loss of hydroxyapatite ceramic particles and granulation tissue formation (right half) are seen [asterisk shows the mandibular canal; undecalcified section, 5% toluidine blue stain, original magnification x 10]. (e) Histology of severely infected part containing porous hydroxyapatite ceramic block (arrowheads), which is half surrounded by the bone tissue (bottom) [undecalcified section, 5% toluidine blue stain, original magnification x 10]. (f) Scanning electron micrograph of the hydroxyapatite ceramic particles (white) surrounded by the bone tissue (original magnification x 100, bar indicates 100 μm).
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Kurashina, Minemura, Kurita, et al
affected. This macroscopic feature is also shown in the radiographs (Figure 1b) and computed tomography scan performed immediately before the resection. Thus, it is reasonable to expect that this non-affected part mirrors the condition of the whole reconstructed area before infection. Indeed, the resected area had shown a uniform radiographical appearance during the initial 10-year follow up period (Figure 1a). Therefore, interest was mainly confined to the distal segment of the resected mandible. Light micrographs and microradiographs in the distal segment showed that HAC particles were surrounded by normal mature bone resembling normal cancellous bone (Figures 2a and b). The contact between bone tissue and HAC surfaces was direct without intervening fibrous tissues, both histologically and microradiographically (Figures 2b and c). HACs did not show any irregularities or depressions suggesting resorption. Tolerance of HACs by bone tissue, direct contact, and lack of resorption of HACs were also confirmed by the SEM studies (Figure 2f). As revealed by this examination, HACs remain in bone tissue for at least 10 years, indicating that almost no bone replacement can be expected. This is an interesting finding as it was expected that the HACs would be resorbed to some extent based on an in vitro study that revealed that they were soluble in a physiological saline solution.6 In conclusion, the HACs may be expected to maintain biocompatibility with bone tissue and integrate with it for at least 10 years when implanted in
Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
human mandibular bone. The HACs did not show any sign of resorption and were not replaced by bone tissue, although the composite of HACs and regenerated bone could constitute a functional mandible for 10 years.
References 1. Boyne P, Rethstein SS. Long-term study of hydroxyapatite implants in canine alveolar bone. J Oral Maxillofac Surg 1984;42:589-594. 2. Gumaer KJ, Sherer AD. Tissue response in dogs to dense hydroxylapatite implantation in the femur. J Oral Maxillofac Surg 1986;44:618-627. 3. Frank RM, Klewansky P, Hemmerle J, Tenenbaum H. Ultrastructural demonstration of the importance of crystal size of bioceramic powders implanted into human periodontal lesions. J Clin Periodontol 1991;18:669-680. 4. Ganeles J, Listgarten MA, Evian CI. Ultrastructure of duraapatite — periodontal tissue interface in human intrabony defects. J Periodontol 1985;57: 133-139. 5. van Blitterswijk CA, Hesseling SC, Grote JJ, Koerten HK, de Groot K. The biocompatibility of hydroxyapatite ceramic: a study of retrieved human middle ear implants. J Biomed Mater Res 1990;24:433-453. 6. Kurashina K, Yajima M, Takeda S, Yamazaki T, Minemura T, Kotani A, Takeuchi H, Ono M. Studies on the clinical use of ceramic materials : Experience of the use of hydroxyapatite ceramics in oral surgery [article in Japanese]. Jpn J Oral Maxillofac Surg 1985:31:2169-2178.
145
Histological Evaluation of an 11-year-old Hydroxyapatite Ceramic Implant in Mandibular Bone 1
Kenji Kurashina,1 Toshikazu Minemura,2 Hiroshi Kurita,1 Qiang Wu1 Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Japan 2 Department of Dentistry and Oral Surgery, Iida Municipal Hospital, Iida, Japan
Abstract: There are no detailed long-term histological studies of hydroxyapatite implanted in human bone tissue. This report is of histological and radiographic examination of a patient with mandibular bone implanted with hydroxyapatite ceramics after cyst ennucleation and a good clinical course for 10 years. The mandibular bone was resected 11 years after the initial operation because of infection. Histology of the retrieved mandibular bone revealed that bone tissue proliferated into interparticular spaces and attached to the hydroxyapatite ceramics surfaces in the non-infected portion and that hydroxyapatite ceramics disappeared with bone destruction in the infected portion. From the histological results, clinical findings, and chronological radiographic findings for 10 years, it was concluded that hydroxyapatite ceramics could maintain their favourable properties as a bone substitute in human bone for a long time. Key Words: Hydroxyapatite, Mandible
Introduction There are no reports of tissue response to hydroxyapatite ceramics (HACs) and long-term changes of HACs after implantation in the human body. However, a few reports on long-term experiments in dogs are available.1,2 For this reason, it would be interesting to investigate bone retrieved many years after reconstruction with HACs. This report is of a histological and radiographic examination of a segment of human mandibular bone that was reconstructed with HACs and has shown a good postoperative course for 10 years.
Case Report A 63-year-old Japanese man was referred with a follicular cyst of the mandible. Cyst enucleation using general anaesthesia was performed, and the bone defect was filled with 2 types of HAC, a porous HAC block and dense HAC particles. At the base of the defect, a trimmed HAC block (Bonetite, Mitsubishi Materials Co., Saitama, Japan) was placed Correspondence: Kenji Kurashina, Department of Dentistry and Oral Surgery, School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. Tel: (81 263) 372 675, Fax: (81 263) 372 676 E-mail: [email protected]
142
to avoid pressure on the mandibular nerve, and HAC particles (Bonetite) were used to fill the remaining defect. Postoperatively, an alveolar ridge of adequate shape and consistency was obtained, and a dental prosthesis was worn without difficulty for 10 years. During the follow-up period, chronological radiographs showed no changes in the reconstructed area except for slight condensation of the HAC particles in the early stage and gradual osteogenic changes in the defect (Figure 1a). After 10 years, the patient presented to the department with pus and HAC particle discharge. Radiographs showed partial loss of HAC particles in the reconstructed alveolar ridge. Treatment by drainage, administration of antibiotics, and removal of infected HAC particles was successfully performed. Approximately 1 year after this episode, the patient returned with abscess formation in the submandibular region. Radiographs and computed tomography at that time revealed loss of a large quantity of HAC particles and destruction of the reconstructed mandibular bone (Figure 1b). He was treated by segmental resection of the infected portion of the mandible with immediate transplantation of autogenous iliac bone. Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
Kurashina, Minemura, Kurita, et al
a
b
Figure 1. Radiographs of the reconstructed mandible taken (a) 5 years after hydroxyapatite ceramic implantation and (b) just before resection 11 years after initial hydroxyapatite ceramic implantation. Arrows in (a) indicate a porous hydroxyapatite ceramic block placed at the bottom of the defect. Hydroxyapatite ceramic loss and bone destruction is noticed in (b).
Histological Examination The resected mandibular bone was sectioned into 5 pieces and fixed in 10% neutral formalin for 1 week, followed by dehydration and embedding in polyester resin (Rigolac, Ohken, Tokyo, Japan). Specimens were serially cut perpendicular to the long axis of the mandible and ground with an Exakt-micro grinding system (Exakt, Norderstedt, Germany) to approximately 20 microns. Most of the ground sections were stained with 5% toluidine blue and examined with a light microscope. Some sections were used for taking microradiographs or scanning electron micrographs. Sections from the most distal segment in the noninfected area of the resected mandible showed microscopically and microradiographically that HAC particles were scattered almost uniformly in the bone tissue. All particles appeared connected and fixed to each other by newly formed bone tissue which proliferated into interparticular spaces (Figures 2a and b). No inflammatory or phagocytic cell infiltration were recognised in the interparticular spaces. The contact between particles and bone was direct without intervening soft tissues (Figure 2c). The surface of the HAC particles was smooth without any signs of resorption and no small fragments of HAC were seen (Figure 2c). Tissues from infected parts showed destruction of bone tissue, loss of HAC particles, and granulation tissue formation (Figure 2d). Some particles were intermingled in the granulation tissue without any Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
contact with the remaining healthy bone tissue. Some sections showed porous HAC block that was partially embedded in the bone tissue (Figure 2e). In the nonaffected parts near the cortical bone, the same findings seen in the sections from the most distal segment were recognised, that is, normal bone invasion into interparticular spaces or HAC pores revealing direct contact with the HAC surfaces. Scanning electron microscopic (SEM) observation of the boundary between bone and the HACs showed that the contact was direct without intervening soft tissue. No resorption of HACs was detected in SEM observation (Figure 2f).
Discussion There are a few studies of HACs implanted in the human body, but they usually refer to materials retrieved after short-term implantation.3-5 It is therefore not clear whether HACs can maintain properties of biocompatibility and osteo-integrative ability in the long term, and few reports on the change of HACs after long-term implantation are available. The present report is useful because it describes findings in human mandibular bone reconstructed with HACs after a good clinical course for 10 years. The mandibular bone examined in this report was resected due to an osteomyelitis-like lesion (Figure 1b). The retrieved mandible was divided into 5 blocks to examine the cut surfaces macroscopically and it was found that the most distal part was not 143
An 11-year-old Hydroxyapatite Ceramic Implant in Mandibular Bone
a
b
c
d
e
f
Figure 2. (a) Histology of the non-infected part. Normal and mature bone invades the interparticular spaces, showing close contact to the hydroxyapatite ceramics (undecalcified section, 5% toluidine blue stain, original magnification x 10). (b) Microradiograph of the non-infected part. Bone invades into the space of the particles (white parts) and directly contacts them [original magnification x 10]. (c) Higher magnification view of the non-infected part. Bone tissue contacts directly with the surface of the HACs (asterisks) [undecalcified section, 5% toluidine blue stain, original magnification x 100]. (d) Histology of severely infected parts. Loss of hydroxyapatite ceramic particles and granulation tissue formation (right half) are seen [asterisk shows the mandibular canal; undecalcified section, 5% toluidine blue stain, original magnification x 10]. (e) Histology of severely infected part containing porous hydroxyapatite ceramic block (arrowheads), which is half surrounded by the bone tissue (bottom) [undecalcified section, 5% toluidine blue stain, original magnification x 10]. (f) Scanning electron micrograph of the hydroxyapatite ceramic particles (white) surrounded by the bone tissue (original magnification x 100, bar indicates 100 μm).
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Kurashina, Minemura, Kurita, et al
affected. This macroscopic feature is also shown in the radiographs (Figure 1b) and computed tomography scan performed immediately before the resection. Thus, it is reasonable to expect that this non-affected part mirrors the condition of the whole reconstructed area before infection. Indeed, the resected area had shown a uniform radiographical appearance during the initial 10-year follow up period (Figure 1a). Therefore, interest was mainly confined to the distal segment of the resected mandible. Light micrographs and microradiographs in the distal segment showed that HAC particles were surrounded by normal mature bone resembling normal cancellous bone (Figures 2a and b). The contact between bone tissue and HAC surfaces was direct without intervening fibrous tissues, both histologically and microradiographically (Figures 2b and c). HACs did not show any irregularities or depressions suggesting resorption. Tolerance of HACs by bone tissue, direct contact, and lack of resorption of HACs were also confirmed by the SEM studies (Figure 2f). As revealed by this examination, HACs remain in bone tissue for at least 10 years, indicating that almost no bone replacement can be expected. This is an interesting finding as it was expected that the HACs would be resorbed to some extent based on an in vitro study that revealed that they were soluble in a physiological saline solution.6 In conclusion, the HACs may be expected to maintain biocompatibility with bone tissue and integrate with it for at least 10 years when implanted in
Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
human mandibular bone. The HACs did not show any sign of resorption and were not replaced by bone tissue, although the composite of HACs and regenerated bone could constitute a functional mandible for 10 years.
References 1. Boyne P, Rethstein SS. Long-term study of hydroxyapatite implants in canine alveolar bone. J Oral Maxillofac Surg 1984;42:589-594. 2. Gumaer KJ, Sherer AD. Tissue response in dogs to dense hydroxylapatite implantation in the femur. J Oral Maxillofac Surg 1986;44:618-627. 3. Frank RM, Klewansky P, Hemmerle J, Tenenbaum H. Ultrastructural demonstration of the importance of crystal size of bioceramic powders implanted into human periodontal lesions. J Clin Periodontol 1991;18:669-680. 4. Ganeles J, Listgarten MA, Evian CI. Ultrastructure of duraapatite — periodontal tissue interface in human intrabony defects. J Periodontol 1985;57: 133-139. 5. van Blitterswijk CA, Hesseling SC, Grote JJ, Koerten HK, de Groot K. The biocompatibility of hydroxyapatite ceramic: a study of retrieved human middle ear implants. J Biomed Mater Res 1990;24:433-453. 6. Kurashina K, Yajima M, Takeda S, Yamazaki T, Minemura T, Kotani A, Takeuchi H, Ono M. Studies on the clinical use of ceramic materials : Experience of the use of hydroxyapatite ceramics in oral surgery [article in Japanese]. Jpn J Oral Maxillofac Surg 1985:31:2169-2178.
145