Soft Tissue Integration of Hydroxyapatite-Coated Abutments for Bone Conduction Implants Anna Larsson, MD, DDS;* Marcus Andersson, PhD;† Stina Wigren, MSc;† Aldina Pivodic, MSc;‡ Mark Flynn, PhD;† Ulf Nannmark, DDS, PhD*
ABSTRACT Purpose: The protocol for bone conduction hearing implant surgery involves reduction of soft tissues around the abutment to minimize the risk of skin-related complications. The present investigation was undertaken to demonstrate that hydroxyapatite-coated abutments provide improved soft tissue integration compared with conventional (pure titanium) abutments and are suitable for use without surgical removal of subepidermal soft tissues. Materials and Methods: Forty-eight implants for bone conduction with two different types of abutments (test and control) were inserted in the skull parietal part of eight sheep. Test abutments had a hydroxyapatite-coated surface and a concave shape. Conventional titanium abutments were used as controls. A follow-up time of 4 weeks was used. Histomorphometric analyses of test and control samples were analyzed, and morphometric results were compared using mixed model analysis. Results: Histological assessment showed healthy soft tissues around the abutments with limited or no signs of inflammation. Hydroxyapatite-coated abutments showed intimate dermal adherence, while less close contact was noted for control abutments. Statistically significant differences in mean pocket depth (0.4 vs 1.6 mm, p = .0013) and epidermal downgrowth (0.6 vs 2.0 mm, p = .0003) between test and control abutments were recorded. Conclusion: The study confirms that hydroxyapatite-coated abutments resulted in a significant reduction in pocket depth and improved soft tissue integration compared with conventional titanium abutments, possibly by providing tight adherence at the interface. Statistically significant reduced pocket depth formation and epidermal downgrowth were recorded. KEY WORDS: bone-anchored hearing aid, hearing aids, hydroxyapatite, minimally invasive surgery
abutment and surrounding soft tissues,1,2 preventing the formation of deep epidermal pockets serving as reservoirs for bacteria. However, variable degrees of inflammation or infection around the abutment are not uncommon.3,4 Certain complications reported from bone conduction implant surgeries, such as flap necrosis and numbness and/or pain around the implant, are related to extensive tissue removal.5–7 In addition, soft tissue reduction has the cosmetic drawback of leaving a hair-free “divot” area around the abutment. Therefore, from both a medical and esthetic perspective, leaving the skin intact may provide significant advantages if soft tissue stability can be guaranteed. Percutaneous healing has been studied in different fields of medical devices, and epidermal migration due to lack of adherence between the implant surface and surrounding dermis/epidermis has been proposed to contribute to the limited longevity of skin-penetrating
INTRODUCTION Bone conduction hearing implants comprise of a percutaneous abutment, which couples the externally worn sound processor to an osseointegrated implant in the skull bone. Removal of subepidermal soft tissues around the skin-penetrating abutment has been a mandatory and effective procedure to maintain a healthy implant site by limiting movement between *Oral & Maxillofacial Surgery, Department of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; †Cochlear Bone Anchored Solutions AB, Mölnlycke, Sweden; ‡ Statistiska Konsultgruppen, Gothenburg, Sweden Corresponding Author: Dr. Anna Larsson, Oral & Maxillofacial Surgery, University of Gothenburg, Gothenburg S40530, Sweden; e-mail: [email protected] Level of Evidence: NA Animal studies and basic research. © 2015 Wiley Periodicals, Inc. DOI 10.1111/cid.12304
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devices.8 Authors have concluded that a successful percutaneous implant is made of a material that allows soft tissues to adhere to the surface, thus preventing epidermal migration.8–11 Histologic and electron microscopic analyses of clinical long-term percutaneous abutments for bone conduction implants by Holgers and colleagues12,13 revealed the presence of epithelial downgrowth and only weak mechanical adherence between the titanium surface and surrounding soft tissues. However, new studies have demonstrated that hydroxyapatite has the ability to firmly integrate with dermal tissues. While mostly used in endosseous applications for its osteoconductive properties, preclinical and clinical investigations have shown that hydroxyapatite outperforms other materials by providing firm adherence with dermis and limiting epidermal migration.14–16 The present study aimed at developing abutments for bone conduction hearing implants that can be used in conjunction with minimally invasive surgery. Larsson and colleagues17 have previously investigated four experimental abutment configurations – differing in material (titanium vs hydroxyapatite) and/or macroscopic design (rounded vs concave) – for their ability to integrate in soft tissue. Soft tissues were evaluated histologically at 1, 2, and 4 weeks of healing. It was concluded that hydroxyapatite enhanced soft tissue adherence compared with titanium abutments; the most stable soft tissue integration was achieved with hydroxyapatitecoated concave abutments. The aim of the present investigation was to confirm, using a statistically powered sample size, that the hydroxyapatite-coated abutment with a concave shape reduces soft tissue downgrowth and pocket formation compared with the conventional titanium abutment. MATERIALS AND METHODS The investigation was performed at the Laboratory of Experimental Biomedicine, University of Gothenburg (Göteborg, Sweden). The study complies with the international guidelines on the ethical use of animals and was approved by the Ethics Committee for Animal Research (Göteborg, Sweden). Abutments A total of 48 implants with abutments (24 test, 24 control) and eight animals were used in the study. The number of abutments and animals were based on statis-
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Figure 1 Test abutments had a hydroxyapatite-coated surface and a pronounced concavity at the lower portion (left). Standard titanium abutments were used as control (right). Both abutment types were equal in height and were premounted on 4-mm implants.
tical power calculations with 80%-degree power. The customized test abutments* had a hydroxyapatite layer (average thickness ∼80 μm, applied by plasma spray) covering the tissue-facing titanium surfaces and featured a concavity at the lower portion of the abutment. Standard titanium abutments with a rounded shape (Cochlear™ Baha BA300 Abutment 9 mm) were used as control (Figure 1). Each abutment was mounted on a 4-mm Cochlear Baha BI300 implant. All abutments were of equal height (9 mm). Abutments and implants were manufactured by Cochlear Bone Anchored Solutions AB (Mölnlycke, Sweden). Surgery The study included eight skeletally mature female black sheep (approximately 50 kg in weight). Before study started, the animals were housed for 2 weeks for acclimatization. At the day of surgery, following premedication intramuscular with Dexdomitor 0.015 mg/kg (Orion Pharma, Sollentuna, Sweden), general anesthesia (PropoVet 0.2 ml/kg, Orion Pharma) was given intravenous until effect. The animals were intubated and kept at a mean alveolar concentration of 1.5 MAC with isoflurane (Isoba, Intervet, Sollentuna, Sweden). When stable conditions for blood pressure, pulse, and oxygenation were obtained, Antisedan 0.075 mg/kg (Orion Pharma) was given to reverse the Dexdomitor effect. Temgesic 0.02 mg/kg (Schering-Plough, Brussels, Belgium) was also given i.v. slowly to maintain analgesic effect after surgery. *Later named Cochlear Baha BA400 Abutment.
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Trimming of hair, washing with antibacterial iodine solution, and sterile draping of the surgical site were carried out. Local anesthesia was administered via injection of 5 ml Marcain 0.5% (Astra Zeneca, Södertälje, Sweden). A 4- to 6-cm straight incision was placed bilaterally superior–posterior from the orbital rim and caudal– preauricular to the ear. Bleeding was controlled with bipolar diathermy but was used with caution. A periosteal flap was elevated, and implants with a premounted test or control abutment were inserted using the one-stage surgical procedure recommended by the manufacturer. Implant insertion was performed to a pre-set torque of 25 Ncm. Where necessary, insertion was interrupted before reaching 25 Ncm. Implant stability was verified by resonance frequency analysis (Osstell ISQ, Osstell, Göteborg, Sweden). Three implants were placed bilaterally in the incision line, approximately 5 to 10 mm apart. Test and control abutments were placed according to an alternating scheme. After implantation, the sites were rinsed with saline solution and the skin edges repositioned. No soft tissue reduction was performed. To ensure good adaptation between the abutment and surrounding skin, a biopsy punch was sometimes used to sculpture the wound edges before suturing the soft tissue around the abutments with resorbable sutures (Monocryl 4/0, Johnson & Johnson, Sollentuna, Sweden); the same procedure was followed for test and control abutments. Spray dressing (OpSite, Smith & Nephew, Hull, England) was applied on the skin; no other wound dressing was used.
concentrations and subsequently infiltrated and polymerized in heat-curing resin (LR White, Sigma-Aldrich Sweden AB Stockholm, Sweden). Embedded blocks were cut in half along the long axis of the implant, perpendicular to the primary incision. Sections (approximately 20 μm thick) were prepared for light microscopy using a cutting and grinding machine (Exakt Apparatebau, Hamburg, Germany) according to the technique described by Donath and Breuner,18 and stained with hematoxylin/eosin. Descriptive histological examination and morphometric measurements were performed with a Nikon Eclipse 80i microscope (BergmanLabora, Danderyd, Sweden) and Easy Image 2000 analysis software (Tekno Optik AB, Huddinge, Sweden) using ×4 to ×60 lenses. Histomorphometric measurements were obtained from the left and right side of the abutment (1) pocket depth (PD), (2) epidermal downgrowth (EDG), (3) length of soft tissue-to-abutment contact (S/A), and (4) soft tissue height (STH) (Figure 2). Statistical Analysis A mixed model analysis with implant and animal as fixed effects, allowing for adjustment of within animal
Postoperative Care After surgery, the animals were extubated and allowed to wake up in solitude. After full recovery, the animals were placed in stables and were allowed food and water ad libitum. Complimentary analgesics (Metacam, Boehringer, Malmö, Sweden) were administered during the first 3 to 7 days if needed. During follow-up, the animals received daily care by trained staff. After 4 weeks, the animals were euthanized with an overdose of pentobarbital sodium (Omnidea, Stockholm, Sweden). The implants and abutments were removed en bloc with surrounding soft and hard tissues and processed for histology. Histology Samples were fixated in 4% paraformaldehyde in 0.1 M phosphate buffer, dehydrated in increasing ethanol
Figure 2 Schematic illustration of histomorphometric measurements: pocket depth (PD), defined as the vertical distance between the highest point of surrounding soft tissue (uppermost layer of the dermis) and the first point of contact between epidermis and abutment surface; epidermal downgrowth (EDG), that is, vertical distance between the highest point of surrounding soft tissue (uppermost layer of the dermis) and the last point of contact between epidermis and abutment; length of soft tissue-to-abutment contact (S/A), that is, length of the part of the abutment in contact with soft tissue; and soft tissue height (STH), that is, vertical distance between the highest point of surrounding soft tissue (uppermost layer of the dermis) and the bone level.
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TABLE 1 Histological Measurements per Abutment Type Device Type Measurement
Pocket depth Epidermal downgrowth Length of soft tissue-to-abutment contact Soft tissue height
Test
Control
p Value
441.1 (162.3) 649.1 (141.5) 1,180.8 (148.5) 4,915.8 (175.7)
1,633.7 (169.1) 2,019.2 (147.4) 710.0 (154.7) 5,208.7 (183.0)
.0013 .0003 .0621 .2817
The values represent least square means (standard error). All values are given in micrometers.
correlation, was used for comparisons between test and control abutments. The mean value of measurements performed at the left and right side of each abutment were used in the analysis; implant loss and nonvalid data due to artifacts were considered as missing data and were not imputed. Two-sided significance tests were conducted at a 5% significance level.
were recorded for test and control abutments, respectively, the difference being statistically significant (p = .0013). Similarly, test abutments presented significantly lower EDG than control abutments, 0.6 versus 2.0 mm (p = .0003). A tendency to a difference in the measured S/A, in favor of the test abutment (p = .062), was also noted. There was no significant difference in total STH between test and control samples (p = .28).
RESULTS Animal surgery proceeded uneventfully. The thickness of the cortical plate varied between approximately 2 and 4 mm (assessed visually) and was sufficient to obtain satisfactory implant stability. All implants were rotationally stable. Similar implant stability quotient (ISQ) values were recorded for test and control implants (least square mean ISQ of 49.1 vs 49.6, p = .78). The soft tissues were sutured in close contact with the abutments, and firm adaptation was achieved. All implant sites healed satisfactorily. No signs of local infection and/or tissue overgrowth were noted around any of the abutments at any time. During the course of the study, six implants were lost due to trauma; one animal lost all three implants from one side of the head (one test, two control), one animal lost the left and right anterior implants (one test, one control), and one animal lost one posterior implant (one control). Quantitative Histology The soft tissue facing test abutments was characterized by close dermal adherence and minimal EDG and limited pockets. Control samples presented less intimate contact between abutment surface and dermis, often accompanied by significant epidermal migration and pocket formation. The results of the histological measurements are presented in Table 1. Mean PDs of 0.4 versus 1.6 mm
DISCUSSION The present investigation compares histologically soft tissue stability and tissue-abutment interface between hydroxyapatite-coated abutments and conventional titanium abutments for bone conduction hearing implants, placed without removal of subepidermal soft tissues. The study demonstrated significant improvements in soft tissue integration with the hydroxyapatite-coated abutment in terms of an intimate dermal junction and statistically significant reductions in EDG and pocket formation compared with the titanium abutment. The study confirmed the results from earlier presented data.17 The stronger integration of the hydroxyapatitecoated abutment is expected to positively affect clinical long-term soft tissue stability when used in bone conduction implant surgery without soft tissue reduction. The present study used the same sheep model that proved successful in the preceding animal investigation.17 In both studies, surgical invasiveness was minimized by accessing the bone via a small incision through the skin before inserting an implant with premounted abutment and carefully suturing the full-thickness soft tissue edges closely around the abutment. While the former animal study evaluated soft tissue integration at different time points during healing – 1 to 4 weeks – the present study adopted a 4-week study period to focus solely on completely healed soft tissue. Acknowledging
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the limitations of experimental research, the chosen animal model is judged to provide clinically relevant information as sheep present soft tissue anatomy (e.g., thickness, mobility, and composition) and healing characteristics resembling humans. Sheep and goats have been used previously in percutaneous research.10,11,19 However, one drawback of placing percutaneous implants in the skull of sheep is their natural headbutting behavior, which presumably led to six traumatic implant losses in the present investigation. The hydroxyapatite-coated samples are clearly distinguishable from the controls; hence, a blinded histological assessment was not possible. However, the measurements were performed using a predefined instruction in order to maintain consistency between samples. All measurements were also reviewed and compared with the histological sample by at least two other authors. The measurements chosen for the evaluation – EDG, PD and S/A – are deemed to be of clinical importance as they jointly provide a good picture of the stability of the soft tissue-to-abutment connection. To guarantee the long-term success of different types of percutaneous implants, researchers have concluded that EDG along the percutaneous implant surface must be controlled8,10 as it may eventually cause failure by marsupialization.8 Epidermal migration may also result in a separation between epidermis and implant surface ultimately leading to the formation of deep epidermal pockets. Epidermal PD should be kept to a minimum as deep pockets may serve as reservoirs for bacteria and jeopardize long-term peri-implant soft tissue health. The S/A is a measure of the total length/area of the abutment in direct contact with the surrounding tissues and provides a high-level indication of the extent of soft tissue integration. Studies have shown that epidermal migration can be effectively suppressed if the underlying dermis forms a stable junction with the implant surface.10,11 While titanium does not integrate with soft tissues,12,13 percutaneous hydroxyapatite implants have repeatedly proven to provide intimate adherence with the surrounding tissues.10,11,15,16 In the present investigation, only weak adherence was noted between dermis and titanium abutments, while dermal connective tissue cells adhered tightly to the hydroxyapatite surface. The stronger adherence to the hydroxyapatite-coated abutments translated into a 68% reduction in epidermal migration (p = .0003) and 73% lower mean PDs (p = .0013) com-
pared with the standard titanium abutments, and the total S/A was 66% longer for hydroxyapatite-coated concave samples (p = .062). Although hydroxyapatite has repeatedly proven to integrate well in living tissues, the underlying mechanisms remain an area of investigation. The ability of extracellular matrix proteins, such as fibronectin and vitronectin, to specifically bind to hydroxyapatite in an orientation that favors subsequent cell attachment to the proteins20 has been proposed to be a part of the explanation. The higher roughness of the hydroxyapatite surface may also contribute to the improved tissue adherence due to a larger surface area and a topography that may promote surface cell interactions. Ultrastructural analyses of the tissue-abutment interface are required to elucidate the mechanisms involved in soft tissue integration of percutaneous hydroxyapatite implants. Until recently, abutments for percutaneous bone conduction implants have exclusively been made of titanium. As the titanium surface lacks the ability to provide a stable soft tissue-to-abutment connection, the recommended surgical procedure has always advocated thorough removal of subepidermal tissues to create “a stress-free interface between the percutaneous implant and the epidermal tissues.”1 This approach has been successful in stabilizing the tissues around the abutment and limiting pocket formation to maintain a healthy implant site. However, in addition to increasing surgical invasiveness, extensive soft tissue removal has cosmetic and medical disadvantages. While published evidence remains limited, surgeons have attempted bone conduction hearing implant surgery without soft tissue reduction using standard titanium abutments and have reported promising outcomes.5–7 However, the results from the present investigation provide evidence that hydroxyapatite abutments may be more suitable for this purpose as they provide adherence with soft tissues, which is expected to improve longterm stability of the skin. CONCLUSION The present investigation confirms that hydroxyapatitecoated abutments significantly improve soft tissue integration compared with standard titanium abutments, statistically significantly reduced PD and EDG, by providing an intimate soft tissue-to-surface contact. The demonstrated improvements in soft tissue stability suggest that percutaneous bone conduction hearing
Hydroxyapatite-Coated Abutments
implant surgery may no longer require extensive subepidermal tissue reduction to maintain a healthy implant site if a hydroxyapatite-coated abutment is used. A minimally invasive surgical technique is expected to provide significant medical and cosmetic advantages to the patient. REFERENCES 1. Tjellström A. Percutaneous implants in clinical practice. CRC Crit Rev Biocompat 1985; 1:205–228. 2. de Wolf MJ, Hol MK, Huygen PL, Mylanus EA, Cremers CW. Clinical outcome of the simplified surgical technique for BAHA implantation. Otol Neurotol 2008; 29:1100–1108. 3. Dun CA, Faber HT, de Wolf MJ, Mylanus EA, Cremers CW, Hol MK. Assessment of more than 1,000 implanted percutaneous bone conduction devices: skin reactions and implant survival. Otol Neurotol 2012; 33:192–198. 4. Hobson JC, Roper AJ, Andrew R, Rothera MP, Hill P, Green KM. Complications of bone-anchored hearing aid implantation. J Laryngol Otol 2010; 124:132–136. 5. Hultcrantz M. Outcome of the bone-anchored hearing aid procedure without skin thinning: a prospective clinical trial. Otol Neurotol 2011; 32:1134–1139. 6. Hawley K, Haberkamp TJ. Osseointegrated hearing implant surgery: outcomes using a minimal soft tissue removal technique. Otolaryngol Head Neck Surg 2013; 148:653–657. 7. Lanis A, Hultcrantz M. Percutaneous osseointegrated implant surgery without skin thinning in children: a retrospective case review. Otol Neurotol 2013; 34:715–722. 8. von Recum AF. Applications and failure modes of percutaneous devices: a review. J Biomed Mater Res 1984; 18:323– 336. 9. von Recum AF, Park JB. Permanent percutaneous devices. Crit Rev Bioeng 1981; 5:37–77. 10. Pendegrass CJ, Goodship AE, Price JS, Blunn GW. Nature’s answer to breaching the skin barrier: an innovative development for amputees. J Anat 2006; 209:59–67.
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11. Smith TJ, Galm A, Chatterjee S, et al. Modulation of the soft tissue reactions to percutaneous orthopaedic implants. J Orthop Res 2006; 24:1377–1383. 12. Holgers KM, Thomsen P, Ericson LE, Tjellström A, Bjursten LM. Morphological evaluation of clinical long-term percutaneous titanium implants. Int J Oral Maxillofac Implants 1994; 9:689–697. 13. Holgers KM, Thomsen P, Tjellström A, Ericson LE. Electron microscopic observations on the soft tissue around clinical long-term percutaneous titanium implants. Biomaterials 1995; 16:83–90. 14. Aoki H, Akao M, Shin Y, Tsuzi T, Togawa T. Sintered hydroxyapatite for a percutaneous device and its clinical application. Med Prog Technol 1987; 12:213–220. 15. Shin Y, Akao M. Tissue reactions to various percutaneous materials with different surface properties and structures. Artif Organs 1997; 21:995–1001. 16. Oyane A, Hyodo K, Uchida M, Sogo Y, Ito A. Preliminary in vivo study of apatite and laminin-apatite composite layers on polymeric percutaneous implants. J Biomed Mater Res B Appl Biomater 2011; 97:96–104. 17. Larsson A, Wigren S, Andersson M, Ekeroth G, Flynn M, Nannmark U. Histologic evaluation of soft tissue integration of experimental abutments for bone anchored hearing implants using surgery without soft tissue reduction. Otol Neurotol 2012; 33:1445–1451. 18. Donath K, Breuner G. A method for the study of undecalcified bones and teeth with attached soft tissues. The Sage-Schliff (sawing and grinding) technique. J Oral Pathol 1982; 11:318–326. 19. Pendegrass CJ, Goodship AE, Blunn GW. Development of a soft tissue seal around bone-anchored transcutaneous amputation prostheses. Biomaterials 2006; 27:4183–4191. 20. Kilpadi KL, Chang PL, Bellis SL. Hydroxylapatite binds more serum proteins, purified integrins, and osteoblast precursor cells than titanium or steel. J Biomed Mater Res 2001; 57:258–267.
ABSTRACT Purpose: The protocol for bone conduction hearing implant surgery involves reduction of soft tissues around the abutment to minimize the risk of skin-related complications. The present investigation was undertaken to demonstrate that hydroxyapatite-coated abutments provide improved soft tissue integration compared with conventional (pure titanium) abutments and are suitable for use without surgical removal of subepidermal soft tissues. Materials and Methods: Forty-eight implants for bone conduction with two different types of abutments (test and control) were inserted in the skull parietal part of eight sheep. Test abutments had a hydroxyapatite-coated surface and a concave shape. Conventional titanium abutments were used as controls. A follow-up time of 4 weeks was used. Histomorphometric analyses of test and control samples were analyzed, and morphometric results were compared using mixed model analysis. Results: Histological assessment showed healthy soft tissues around the abutments with limited or no signs of inflammation. Hydroxyapatite-coated abutments showed intimate dermal adherence, while less close contact was noted for control abutments. Statistically significant differences in mean pocket depth (0.4 vs 1.6 mm, p = .0013) and epidermal downgrowth (0.6 vs 2.0 mm, p = .0003) between test and control abutments were recorded. Conclusion: The study confirms that hydroxyapatite-coated abutments resulted in a significant reduction in pocket depth and improved soft tissue integration compared with conventional titanium abutments, possibly by providing tight adherence at the interface. Statistically significant reduced pocket depth formation and epidermal downgrowth were recorded. KEY WORDS: bone-anchored hearing aid, hearing aids, hydroxyapatite, minimally invasive surgery
abutment and surrounding soft tissues,1,2 preventing the formation of deep epidermal pockets serving as reservoirs for bacteria. However, variable degrees of inflammation or infection around the abutment are not uncommon.3,4 Certain complications reported from bone conduction implant surgeries, such as flap necrosis and numbness and/or pain around the implant, are related to extensive tissue removal.5–7 In addition, soft tissue reduction has the cosmetic drawback of leaving a hair-free “divot” area around the abutment. Therefore, from both a medical and esthetic perspective, leaving the skin intact may provide significant advantages if soft tissue stability can be guaranteed. Percutaneous healing has been studied in different fields of medical devices, and epidermal migration due to lack of adherence between the implant surface and surrounding dermis/epidermis has been proposed to contribute to the limited longevity of skin-penetrating
INTRODUCTION Bone conduction hearing implants comprise of a percutaneous abutment, which couples the externally worn sound processor to an osseointegrated implant in the skull bone. Removal of subepidermal soft tissues around the skin-penetrating abutment has been a mandatory and effective procedure to maintain a healthy implant site by limiting movement between *Oral & Maxillofacial Surgery, Department of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; †Cochlear Bone Anchored Solutions AB, Mölnlycke, Sweden; ‡ Statistiska Konsultgruppen, Gothenburg, Sweden Corresponding Author: Dr. Anna Larsson, Oral & Maxillofacial Surgery, University of Gothenburg, Gothenburg S40530, Sweden; e-mail: [email protected] Level of Evidence: NA Animal studies and basic research. © 2015 Wiley Periodicals, Inc. DOI 10.1111/cid.12304
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devices.8 Authors have concluded that a successful percutaneous implant is made of a material that allows soft tissues to adhere to the surface, thus preventing epidermal migration.8–11 Histologic and electron microscopic analyses of clinical long-term percutaneous abutments for bone conduction implants by Holgers and colleagues12,13 revealed the presence of epithelial downgrowth and only weak mechanical adherence between the titanium surface and surrounding soft tissues. However, new studies have demonstrated that hydroxyapatite has the ability to firmly integrate with dermal tissues. While mostly used in endosseous applications for its osteoconductive properties, preclinical and clinical investigations have shown that hydroxyapatite outperforms other materials by providing firm adherence with dermis and limiting epidermal migration.14–16 The present study aimed at developing abutments for bone conduction hearing implants that can be used in conjunction with minimally invasive surgery. Larsson and colleagues17 have previously investigated four experimental abutment configurations – differing in material (titanium vs hydroxyapatite) and/or macroscopic design (rounded vs concave) – for their ability to integrate in soft tissue. Soft tissues were evaluated histologically at 1, 2, and 4 weeks of healing. It was concluded that hydroxyapatite enhanced soft tissue adherence compared with titanium abutments; the most stable soft tissue integration was achieved with hydroxyapatitecoated concave abutments. The aim of the present investigation was to confirm, using a statistically powered sample size, that the hydroxyapatite-coated abutment with a concave shape reduces soft tissue downgrowth and pocket formation compared with the conventional titanium abutment. MATERIALS AND METHODS The investigation was performed at the Laboratory of Experimental Biomedicine, University of Gothenburg (Göteborg, Sweden). The study complies with the international guidelines on the ethical use of animals and was approved by the Ethics Committee for Animal Research (Göteborg, Sweden). Abutments A total of 48 implants with abutments (24 test, 24 control) and eight animals were used in the study. The number of abutments and animals were based on statis-
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Figure 1 Test abutments had a hydroxyapatite-coated surface and a pronounced concavity at the lower portion (left). Standard titanium abutments were used as control (right). Both abutment types were equal in height and were premounted on 4-mm implants.
tical power calculations with 80%-degree power. The customized test abutments* had a hydroxyapatite layer (average thickness ∼80 μm, applied by plasma spray) covering the tissue-facing titanium surfaces and featured a concavity at the lower portion of the abutment. Standard titanium abutments with a rounded shape (Cochlear™ Baha BA300 Abutment 9 mm) were used as control (Figure 1). Each abutment was mounted on a 4-mm Cochlear Baha BI300 implant. All abutments were of equal height (9 mm). Abutments and implants were manufactured by Cochlear Bone Anchored Solutions AB (Mölnlycke, Sweden). Surgery The study included eight skeletally mature female black sheep (approximately 50 kg in weight). Before study started, the animals were housed for 2 weeks for acclimatization. At the day of surgery, following premedication intramuscular with Dexdomitor 0.015 mg/kg (Orion Pharma, Sollentuna, Sweden), general anesthesia (PropoVet 0.2 ml/kg, Orion Pharma) was given intravenous until effect. The animals were intubated and kept at a mean alveolar concentration of 1.5 MAC with isoflurane (Isoba, Intervet, Sollentuna, Sweden). When stable conditions for blood pressure, pulse, and oxygenation were obtained, Antisedan 0.075 mg/kg (Orion Pharma) was given to reverse the Dexdomitor effect. Temgesic 0.02 mg/kg (Schering-Plough, Brussels, Belgium) was also given i.v. slowly to maintain analgesic effect after surgery. *Later named Cochlear Baha BA400 Abutment.
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Trimming of hair, washing with antibacterial iodine solution, and sterile draping of the surgical site were carried out. Local anesthesia was administered via injection of 5 ml Marcain 0.5% (Astra Zeneca, Södertälje, Sweden). A 4- to 6-cm straight incision was placed bilaterally superior–posterior from the orbital rim and caudal– preauricular to the ear. Bleeding was controlled with bipolar diathermy but was used with caution. A periosteal flap was elevated, and implants with a premounted test or control abutment were inserted using the one-stage surgical procedure recommended by the manufacturer. Implant insertion was performed to a pre-set torque of 25 Ncm. Where necessary, insertion was interrupted before reaching 25 Ncm. Implant stability was verified by resonance frequency analysis (Osstell ISQ, Osstell, Göteborg, Sweden). Three implants were placed bilaterally in the incision line, approximately 5 to 10 mm apart. Test and control abutments were placed according to an alternating scheme. After implantation, the sites were rinsed with saline solution and the skin edges repositioned. No soft tissue reduction was performed. To ensure good adaptation between the abutment and surrounding skin, a biopsy punch was sometimes used to sculpture the wound edges before suturing the soft tissue around the abutments with resorbable sutures (Monocryl 4/0, Johnson & Johnson, Sollentuna, Sweden); the same procedure was followed for test and control abutments. Spray dressing (OpSite, Smith & Nephew, Hull, England) was applied on the skin; no other wound dressing was used.
concentrations and subsequently infiltrated and polymerized in heat-curing resin (LR White, Sigma-Aldrich Sweden AB Stockholm, Sweden). Embedded blocks were cut in half along the long axis of the implant, perpendicular to the primary incision. Sections (approximately 20 μm thick) were prepared for light microscopy using a cutting and grinding machine (Exakt Apparatebau, Hamburg, Germany) according to the technique described by Donath and Breuner,18 and stained with hematoxylin/eosin. Descriptive histological examination and morphometric measurements were performed with a Nikon Eclipse 80i microscope (BergmanLabora, Danderyd, Sweden) and Easy Image 2000 analysis software (Tekno Optik AB, Huddinge, Sweden) using ×4 to ×60 lenses. Histomorphometric measurements were obtained from the left and right side of the abutment (1) pocket depth (PD), (2) epidermal downgrowth (EDG), (3) length of soft tissue-to-abutment contact (S/A), and (4) soft tissue height (STH) (Figure 2). Statistical Analysis A mixed model analysis with implant and animal as fixed effects, allowing for adjustment of within animal
Postoperative Care After surgery, the animals were extubated and allowed to wake up in solitude. After full recovery, the animals were placed in stables and were allowed food and water ad libitum. Complimentary analgesics (Metacam, Boehringer, Malmö, Sweden) were administered during the first 3 to 7 days if needed. During follow-up, the animals received daily care by trained staff. After 4 weeks, the animals were euthanized with an overdose of pentobarbital sodium (Omnidea, Stockholm, Sweden). The implants and abutments were removed en bloc with surrounding soft and hard tissues and processed for histology. Histology Samples were fixated in 4% paraformaldehyde in 0.1 M phosphate buffer, dehydrated in increasing ethanol
Figure 2 Schematic illustration of histomorphometric measurements: pocket depth (PD), defined as the vertical distance between the highest point of surrounding soft tissue (uppermost layer of the dermis) and the first point of contact between epidermis and abutment surface; epidermal downgrowth (EDG), that is, vertical distance between the highest point of surrounding soft tissue (uppermost layer of the dermis) and the last point of contact between epidermis and abutment; length of soft tissue-to-abutment contact (S/A), that is, length of the part of the abutment in contact with soft tissue; and soft tissue height (STH), that is, vertical distance between the highest point of surrounding soft tissue (uppermost layer of the dermis) and the bone level.
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TABLE 1 Histological Measurements per Abutment Type Device Type Measurement
Pocket depth Epidermal downgrowth Length of soft tissue-to-abutment contact Soft tissue height
Test
Control
p Value
441.1 (162.3) 649.1 (141.5) 1,180.8 (148.5) 4,915.8 (175.7)
1,633.7 (169.1) 2,019.2 (147.4) 710.0 (154.7) 5,208.7 (183.0)
.0013 .0003 .0621 .2817
The values represent least square means (standard error). All values are given in micrometers.
correlation, was used for comparisons between test and control abutments. The mean value of measurements performed at the left and right side of each abutment were used in the analysis; implant loss and nonvalid data due to artifacts were considered as missing data and were not imputed. Two-sided significance tests were conducted at a 5% significance level.
were recorded for test and control abutments, respectively, the difference being statistically significant (p = .0013). Similarly, test abutments presented significantly lower EDG than control abutments, 0.6 versus 2.0 mm (p = .0003). A tendency to a difference in the measured S/A, in favor of the test abutment (p = .062), was also noted. There was no significant difference in total STH between test and control samples (p = .28).
RESULTS Animal surgery proceeded uneventfully. The thickness of the cortical plate varied between approximately 2 and 4 mm (assessed visually) and was sufficient to obtain satisfactory implant stability. All implants were rotationally stable. Similar implant stability quotient (ISQ) values were recorded for test and control implants (least square mean ISQ of 49.1 vs 49.6, p = .78). The soft tissues were sutured in close contact with the abutments, and firm adaptation was achieved. All implant sites healed satisfactorily. No signs of local infection and/or tissue overgrowth were noted around any of the abutments at any time. During the course of the study, six implants were lost due to trauma; one animal lost all three implants from one side of the head (one test, two control), one animal lost the left and right anterior implants (one test, one control), and one animal lost one posterior implant (one control). Quantitative Histology The soft tissue facing test abutments was characterized by close dermal adherence and minimal EDG and limited pockets. Control samples presented less intimate contact between abutment surface and dermis, often accompanied by significant epidermal migration and pocket formation. The results of the histological measurements are presented in Table 1. Mean PDs of 0.4 versus 1.6 mm
DISCUSSION The present investigation compares histologically soft tissue stability and tissue-abutment interface between hydroxyapatite-coated abutments and conventional titanium abutments for bone conduction hearing implants, placed without removal of subepidermal soft tissues. The study demonstrated significant improvements in soft tissue integration with the hydroxyapatite-coated abutment in terms of an intimate dermal junction and statistically significant reductions in EDG and pocket formation compared with the titanium abutment. The study confirmed the results from earlier presented data.17 The stronger integration of the hydroxyapatitecoated abutment is expected to positively affect clinical long-term soft tissue stability when used in bone conduction implant surgery without soft tissue reduction. The present study used the same sheep model that proved successful in the preceding animal investigation.17 In both studies, surgical invasiveness was minimized by accessing the bone via a small incision through the skin before inserting an implant with premounted abutment and carefully suturing the full-thickness soft tissue edges closely around the abutment. While the former animal study evaluated soft tissue integration at different time points during healing – 1 to 4 weeks – the present study adopted a 4-week study period to focus solely on completely healed soft tissue. Acknowledging
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the limitations of experimental research, the chosen animal model is judged to provide clinically relevant information as sheep present soft tissue anatomy (e.g., thickness, mobility, and composition) and healing characteristics resembling humans. Sheep and goats have been used previously in percutaneous research.10,11,19 However, one drawback of placing percutaneous implants in the skull of sheep is their natural headbutting behavior, which presumably led to six traumatic implant losses in the present investigation. The hydroxyapatite-coated samples are clearly distinguishable from the controls; hence, a blinded histological assessment was not possible. However, the measurements were performed using a predefined instruction in order to maintain consistency between samples. All measurements were also reviewed and compared with the histological sample by at least two other authors. The measurements chosen for the evaluation – EDG, PD and S/A – are deemed to be of clinical importance as they jointly provide a good picture of the stability of the soft tissue-to-abutment connection. To guarantee the long-term success of different types of percutaneous implants, researchers have concluded that EDG along the percutaneous implant surface must be controlled8,10 as it may eventually cause failure by marsupialization.8 Epidermal migration may also result in a separation between epidermis and implant surface ultimately leading to the formation of deep epidermal pockets. Epidermal PD should be kept to a minimum as deep pockets may serve as reservoirs for bacteria and jeopardize long-term peri-implant soft tissue health. The S/A is a measure of the total length/area of the abutment in direct contact with the surrounding tissues and provides a high-level indication of the extent of soft tissue integration. Studies have shown that epidermal migration can be effectively suppressed if the underlying dermis forms a stable junction with the implant surface.10,11 While titanium does not integrate with soft tissues,12,13 percutaneous hydroxyapatite implants have repeatedly proven to provide intimate adherence with the surrounding tissues.10,11,15,16 In the present investigation, only weak adherence was noted between dermis and titanium abutments, while dermal connective tissue cells adhered tightly to the hydroxyapatite surface. The stronger adherence to the hydroxyapatite-coated abutments translated into a 68% reduction in epidermal migration (p = .0003) and 73% lower mean PDs (p = .0013) com-
pared with the standard titanium abutments, and the total S/A was 66% longer for hydroxyapatite-coated concave samples (p = .062). Although hydroxyapatite has repeatedly proven to integrate well in living tissues, the underlying mechanisms remain an area of investigation. The ability of extracellular matrix proteins, such as fibronectin and vitronectin, to specifically bind to hydroxyapatite in an orientation that favors subsequent cell attachment to the proteins20 has been proposed to be a part of the explanation. The higher roughness of the hydroxyapatite surface may also contribute to the improved tissue adherence due to a larger surface area and a topography that may promote surface cell interactions. Ultrastructural analyses of the tissue-abutment interface are required to elucidate the mechanisms involved in soft tissue integration of percutaneous hydroxyapatite implants. Until recently, abutments for percutaneous bone conduction implants have exclusively been made of titanium. As the titanium surface lacks the ability to provide a stable soft tissue-to-abutment connection, the recommended surgical procedure has always advocated thorough removal of subepidermal tissues to create “a stress-free interface between the percutaneous implant and the epidermal tissues.”1 This approach has been successful in stabilizing the tissues around the abutment and limiting pocket formation to maintain a healthy implant site. However, in addition to increasing surgical invasiveness, extensive soft tissue removal has cosmetic and medical disadvantages. While published evidence remains limited, surgeons have attempted bone conduction hearing implant surgery without soft tissue reduction using standard titanium abutments and have reported promising outcomes.5–7 However, the results from the present investigation provide evidence that hydroxyapatite abutments may be more suitable for this purpose as they provide adherence with soft tissues, which is expected to improve longterm stability of the skin. CONCLUSION The present investigation confirms that hydroxyapatitecoated abutments significantly improve soft tissue integration compared with standard titanium abutments, statistically significantly reduced PD and EDG, by providing an intimate soft tissue-to-surface contact. The demonstrated improvements in soft tissue stability suggest that percutaneous bone conduction hearing
Hydroxyapatite-Coated Abutments
implant surgery may no longer require extensive subepidermal tissue reduction to maintain a healthy implant site if a hydroxyapatite-coated abutment is used. A minimally invasive surgical technique is expected to provide significant medical and cosmetic advantages to the patient. REFERENCES 1. Tjellström A. Percutaneous implants in clinical practice. CRC Crit Rev Biocompat 1985; 1:205–228. 2. de Wolf MJ, Hol MK, Huygen PL, Mylanus EA, Cremers CW. Clinical outcome of the simplified surgical technique for BAHA implantation. Otol Neurotol 2008; 29:1100–1108. 3. Dun CA, Faber HT, de Wolf MJ, Mylanus EA, Cremers CW, Hol MK. Assessment of more than 1,000 implanted percutaneous bone conduction devices: skin reactions and implant survival. Otol Neurotol 2012; 33:192–198. 4. Hobson JC, Roper AJ, Andrew R, Rothera MP, Hill P, Green KM. Complications of bone-anchored hearing aid implantation. J Laryngol Otol 2010; 124:132–136. 5. Hultcrantz M. Outcome of the bone-anchored hearing aid procedure without skin thinning: a prospective clinical trial. Otol Neurotol 2011; 32:1134–1139. 6. Hawley K, Haberkamp TJ. Osseointegrated hearing implant surgery: outcomes using a minimal soft tissue removal technique. Otolaryngol Head Neck Surg 2013; 148:653–657. 7. Lanis A, Hultcrantz M. Percutaneous osseointegrated implant surgery without skin thinning in children: a retrospective case review. Otol Neurotol 2013; 34:715–722. 8. von Recum AF. Applications and failure modes of percutaneous devices: a review. J Biomed Mater Res 1984; 18:323– 336. 9. von Recum AF, Park JB. Permanent percutaneous devices. Crit Rev Bioeng 1981; 5:37–77. 10. Pendegrass CJ, Goodship AE, Price JS, Blunn GW. Nature’s answer to breaching the skin barrier: an innovative development for amputees. J Anat 2006; 209:59–67.
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