153
Titanium Endosseous Tissue Interface: A Literature Review Timothy
G.
Donley* and
Implant-Soft
William B. Gillette^
Background information about normal periodontal anatomy and titanium used in endosseous implant fabrication is provided. Literature is reviewed concerning epithelial and connective tissue attachment to titanium. Information about the adequacy of cell attachment to implants, possible mechanisms of cell attachment formation, and the effect of implant surface properties on attachment is presented. A chemical attachment between titanium implant surface oxide layer and epithelium has been demonstrated in vitro and in vivo. This attachment is mediated by a glycoprotein similar to that seen between epithelium and natural tooth surfaces. While only minimal histological evidence exists, connective tissue fibers adjacent to titanium implanted surfaces may bring the tissue in tight apposition to the implant without an absolute biologic attachment between the implant and connective tissue. Alteration of the titanium surface morphology may selectively enhance the attachment of either epithelial cells or fibroblasts, theoretically enhancing the formation of a biologic seal between the implanted titanium surface and its adjacent tissue. A greater understanding of the mechanisms of attachment and of the factors which enhance the integrity of the biologic seal between implant and soft tissues should permit an improved prognosis for functioning titanium implants. / Periodontol
1991; 62:153-160.
Key Words: Epithelial attachment; connective tissue; titanium; biocompatible materials; dental
implants.
In the natural dentition, the junctional epithelium (JE) is believed to provide a seal at the base of a periodontal sulcus against penetration of periodontally pathologic chemical and bacterial substances. Disruption of this seal and/or lysis of the connective tissue fibers inserted into root cementum apical to the JE leads to rapid migration of the crevicular epithelium forming a pathologic pocket.1 As no cementum or fiber insertion is reported on the surface of titanium transmucosal abutments, an epithelial perimucosal seal may provide the only barrier against pathologic insults to deeper tissues. Destruction of the integrity of the perimucosal titanium surface seal could conceivably lead to extension of the pathologic pocket to the osseous structures. Concern over breakdown between oral soft tissues adjacent to implanted materials with apical epithelial migration to the ultimate point of implant exfoliation exists in the literature.2-5 Here, we review the literature concerning the nature of the titanium endosseous implant-soft tissue interface. »Private
practice, Pittsburgh,
tRichard L. Roudebush,
anapolis, IN. The opinions and
PA. Veterans Administration Medical
Center, Indi-
assertations contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Veterans Administration.
BACKGROUND Periodontal Anatomy In the natural dentition, the dento-gingival junction consists of keratinized gingival epithelium, non-keratinized sulcular or crevicular epithelium, and JE all supported by collagen fiber bundles in a connective tissue.6 The connective tissue fibers connect the tooth cementum to the surrounding alveolar bone and gingiva. At the electron microscopic level, cell-mediated hemidesmosomes attach the JE to natural tooth surfaces via a basal lamina7-8 (Fig. 1). With endosseous implants, epithelium and connective tissue are interfaced with titanium rather than tooth structures. The similarity of the attachment between soft tissues and the natural dentition and that between soft tissues and titanium endosseous implant surfaces will depend, in part, on the nature of the titanium surface.3 Titanium Implants Many oral implants of various designs are made of titanium in either its surgically pure or alloyed form. A high degree of biocompatibility, strength, and corrosion resistance make these metals ideal for oral implants. Surgically pure titanium also contains trace amounts of elements which mark-
J Periodontol 1991
TITANTIUM IMPLANT SOFT TISSUE INTERFACE: A REVIEW
154
TOOTH
LAMINA
STRUCTURE
DENSA
_J f
LAMINA RARA INTERNA
Figure
1:
tween an
LAMINA
LUC|DA
Diagram of the basal lamina-hemidesmosomal attachment beepithelial cell and a natural tooth sutface at the electron micro-
scopic level.
edly improve the mechanical properties of pure titanium.9 In its alloyed form titanium is most commonly mixed with
6% aluminum and 4% vanadium (TÌ-6A1-4V).9 The aluminum increases the strength and decreases the weight of the alloy. The vanadium acts as an aluminum scavenger presumably preventing the formation of corrosion promoting Ti-Al compounds.9 The surface properties of an implant relate directly to the success of implant procedures.10-" Within a millisecond of exposure to air, a 10 to 100 angstrom thick oxide layer forms on a cut surface of pure titanium. Passivity refers to an oxidized layer that does not break down under physiological conditions.9 While exposure to air produces this oxide layer, U.S. manufactured titanium oral implant materials are passivated using a nitric acid bath as required by the United States Food and Drug Administration. On a titanium oral implant surface considerable variation in surface oxide properties with a variable oxygen content can be expected with different machining conditions.10-" Surgically pure titanium or titanium alloy implant surfaces (with titanium concentrations of 85% to 95%) apparently maintain this oxide layer without significant breakdown or corrosion under physiologic conditions.9-" It is the relatively thick titanium oxide layer that determines the implant-tissue interaction, not the metal itself.10-" IMPLANT-SOFT TISSUE INTERFACE Historical Review In 1952, Loechler and Mueller12 described the gingival and connective tissues in microscopic sections from a transgingival post of a Vitallium* (cobalt-chromium-molybdenum alloy) subperiosteal implant as being essentially the same as that around normal teeth. Bodine and Mohammed13 in 1970 reported on a detailed histologie study of a subperiosteal implant removed from a *Austenal Dental Inc.,
Chicago,
IL.
February
patient following 12 years of functioning. An epitheliallined crevice surrounding the abutment was infiltrated with plasma cells and lymphocytes. The connective tissue directly in contact with the submerged implant metal consisted of flattened compressed fibers and cells with elongated nuclei which they termed "typical implant connective tissue." James14-15 provided indirect evidence of an adhesion between epithelial cells and metal implant surfaces. He inserted one-piece Vitallium implants with posts protruding above the bone level in dogs. After 21 days of healing, mucopolysaccharides suggestive of an epithelial attachment were observed at the base of the implant sulcus. Collagen fibers in the lamina propria of the connective tissue were oriented perpendicular to the implant surface. He concluded that evidence supported the theory of an epithelial attachment at the base of an implant sulcus similar to that found
in the natural dental sulcus. James and Schultz5 presented the first in vivo ultrastructural evidence of hemidesmosomal and basal lamina formation between regenerated junctional epithelial cells and a Vitallium implant. Using transmission electron microscopy and a monkey model, they noted a narrow band of amorphous material immediately adjacent to the implant space which resembled a basal lamina with both a lamina densa and lamina lucida. Poorly defined hemidesmosomes were observed. Listgarten and Lai16 in 1975 demonstrated similar findings using epoxy methylmethacrylate dental implants in monkeys. Hemidesmosomes appeared to develop by 2 weeks. Swope and James17 later placed one piece, partially exposed, Vitallium root form implants sequentially into monkeys to determine more precisely the time period required for hemidesmosomes to develop following intraoral implant placement. Electron microscopy of block sections revealed hemidesmosomes beginning to form after 2 days and being well established by 3 days. McKinney et al.2 more recently published scanning and transmission electron micrographs from an analysis of sapphire (single crystalline alpha-aluminum oxide) endosseous implants removed from dogs. Numerous dense hemidesmosomal like structures were observed on epithelial pseudopodia at intervals along the epithelial cell membrane adjacent to the implant. Higher resolution reportedly confirmed the presence of a well-ordered basal lamina in association with the cell membrane hemidesmosomes. They referred to the area between regenerating crevicular epithelium of the gingiva and the implant surface as the biological seal. Crevicular epithelium was reported to be similar in all respects to that around natural teeth. Epithelium proceeded downward in the gingival sulcus as a nonkeratinized structure. The authors suggested that the described, well-ordered seal could develop at the tissue interface of any implanted material.
Epithelial Attachment
to Titanium Baumhammers et al.18 in 1978 used scanning electron microscopy to examine the in vitro 5-day growth of human
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epithelial cells on tooth enamel, glass, Vitallium, titanium, and vitreous carbon. Cells grew and adapted equally well
to all tested surfaces and were similar whether the tested
surfaces were smooth or roughened by sandblasting. They cautioned that epithelial growth on similar substances in vivo could be affected by factors inherent to the intraoral environment such as plaque, saliva, inflammation, crevicular fluid, and possibly corrosion. In a recent experiment by Kasten et al.,19 75,000 cells/ ml of gingival epithelial cells were seeded onto differently prepared titanium and hydroxyapatite implant surfaces. Human gingival cells reportedly adhered three times more frequently to hydroxyapatite than to titanium type implant surfaces. Gould et al.20 in 1981 reported on the attachment of epithelial cells to titanium in vitro. They grew porcine oral tissue epithelial cells on thin films of titanium alloy embedded in epoxy resin. Electron microscopy of adherent cells often showed clear evidence of hemidesmosomal attachments between themselves and the titanium surface. Material having the appearance of basal lamina was identifiable in these regions. Epithelial cells were suggested to attach to titanium surfaces in much the same manner as they attach to natural tooth surfaces. Jansen et al.21 more recently studied the ultrastructure of guinea pig epithelial attachment to gold, titanium, carbon, apatite, and polystyrene substrates. Their findings disputed those of Gould et al.,20 noting hemidesmosomal-like attachments only on apatite and polystyrene but not on metallic or carbon surfaces. Differences in cell populations, culture conditions, or treatment of titanium substrates may have influenced the differing results. They proposed the existence of a yet unknown property of the substrate which determined the nature and structure of epithelial contact with the substrate. James22,23 reviewed his earlier research and concluded that a JE adjacent to implanted surfaces shows histochemical characterizations similar to that of the JE attached to natural teeth. Epithelium adjacent to implants stains positive with Periodic-acid Schiff technique indicating that it produces acid Polysaccharides with properties capable of providing adhesion between the implant surface and the JE. Connective Tissue Attachment to Titanium
James22,23 further proposed that circumferential connective
tissue fibers could be expected to surround an implant post in a manner similar to circumferential fibers in the dental gingiva. Fibers would also extend from the alveolar crest to the implant JE providing a functional arrangement. Dmytryk et al.24 recently presented results from a study which assessed the ability of tissue culture fibroblasts to attach and colonize on the surface of pure titanium dental implants following instrumentation of the implant surface with curets of dissimilar composition. Surfaces treated with plastic and titanium curets showed greater numbers of attached cells than stainless steel curet treated surfaces. Scan-
DONLEY,
GILLETTE
155
electron microscopic analysis suggested that fibroblasts adherent to the implant surfaces treated with plastic and titanium curets were more typical of fibroblasts in a favorable culture condition. These in vitro results theoretically suggest that implant maintenance could affect tissue attach-
ning
ment
integrity.
Hobo et al.25 reviewed the literature published by Branemark's group and proposed that deep within the gingival crevice, collagen fibers could be expected to form a tight cuff around the implant abutment. A 2 mm connective tissue band was suggested to attach tightly to the abutment surface and act as a resistant barrier. While a band of connective tissue may bring the tissue in tight apposition to the implant a lack of an absolute biologic attachment between the implant and surrounding connective tissue elements has been suggested.3 The thickness and orientation of the collagen fibers may depend upon the functional load placed upon the implant.3 In Vivo Studies Gould and Brunette26 reported in vivo findings similar to their previously reviewed in vitro report.20 Wire films of titanium were again prepared and in this study implanted into three sites of marginal gingival tissue in a human subject. The tissue encapsulated wire implants were removed after 4 weeks and analyzed for epithelial cell adherence. At epithelial-titanium interfaces there was clear evidence of hemidesmosomes as well as material consistent with basal lamina. Hansson, et al.27 and Albrektsson, et al.28 reported on the structural aspects of the interface between tissue and titanium implants based on information from analysis of an unnamed number of non-alloyed titanium implants removed from humans after reported successful clinical function up to 7 years. Additional information about the experimentation was not provided. They reported that submucosal connective tissue around titanium dental implants contained fibroblasts as the dominant cell type with macrophages and scattered lymphocytes. Bundles of collagen filaments and fibrils, often observed approaching the implant, always had a proteoglycan layer 20 nm thick between fibrils and cells from the metal oxide surface of the titanium. There was no evidence of toxic or reactive responses. The authors suggested that connective tissue accepted titanium rather than isolating it as a foreign body. Epithelial cells coronal to the connective tissue portions were attached to titanium via hemidesmosomes. Reportedly there were no signs of inflammatory reactions in analyzed epithelial areas. From these clinical reports the authors concluded that epithelial cells apparently do adhere to titanium surfaces forming a long-lasting and presumably biomechanical resistant attachment to the implants in vivo. While additional histological information concerning implant-soft tissue interfaces seems necessary, the technical difficulty in demonstrating these junctions is substantial.3,29
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TITANTIUM IMPLANT SOFT TISSUE INTERFACE: A REVIEW
Implant-Tissue Architecture Two distinct interfaces have been described with dental implants: 1) the perimucosal interface where soft tissue meets the implant and 2) the endosteal interface where bone meets the implant.30 At the perimucosal interface crevicular epithelium, supported by connective tissue, forms the implantsoft tissue interface. The reviewed literature suggests that a portion of the crevicular epithelial cells adjacent to a titanium implant can be expected to form a hemidesmosomal type attachment to the implant surface. While the attachment may not always be clinically detectable, attached epithelium should be histologically evident along the implant. The transgingival abutment to implant fixture junction has been described as corresponding to the cemento-enamel junction in the natural dentition.25 However, this may not be so. The theoretically possible relationships between the attached portion of epithelium and the implant surfaces can be classified as diagrammed in Figure 2. The attached epithelium can extend along the abutment surface without approaching the abutment to fixture junction, the apical extent of the attached epithelium can be located at the abutment to fixture junction, the attached epithelium can trans-
February
1991
gress the junction, or the entire attached epithelium can be located on the fixture apical to the junction. The frequency of these relationships in vivo is unknown. The implanttissue architecture probably depends on tissue location at the time of abutment placement and other factors. Tissue architecture may change over time. How Cell Attachment Occurs In 1981 Lavelle31 theorized that cellular adhesions to an implant surface would depend on whether the implant surface was protein coated of serum or salivary origin. Mucosal cell interaction with protein components adsorbed onto the implant's cervical region would influence the subsequent behavior of cellular adhesions. McKinney et al.32 more recently furthered this theory of how epithelial cells attach to implant surfaces. Using dogs, they reported that regenerated crevicular gingiva around ceramic dental implants developed junctional epithelial organelle and cellular architecture that was similar to the structures between natural teeth and tissues. In formation of the attachment complex, the authors proposed that increased vesicles noted in the JE cells adjacent to the implant
Figure 2: Diagram of the possible architectural relationships between titanium implant surfaces and soft tissues. A portion of the crevicular epithelium adjacent to titanium implants conform an attachment to the implant surface. Shown are the gingival epithelium (GE), connective tissue (CT), alveolar bone (AB), and the crevicular epithelium (unlabeled arrow). A: the attached epithelium can extend along the abutment surface without approaching the abutment-fixture junction; B: the apical extent of the attached epithelium can be located at the abutment fixture junction; C: the attached epithelium can transgress the junction; or D: the entire attached epithelium can be located along the fixture apical to the junction.
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surface secreted products which included laminin, an extracellular glycoprotein component of the lamina lucida. This laminin was probably responsible for adhesion of the epithelial cells to other collagenous components of the basal lamina. They further theorized that fibroblasts produce glycosaminoglycans during healing which may coat the implant surface. Additionally, fibroblasts and endothelial cells, present in the healing wound extracellular matrix, produce fibronectin, a glycoprotein found in the lamina densa. This fibronectin, which binds to collagen and glycosaminoglycans, may represent the "glue" between the implant biomaterial and the type IV collagen of the lamina densa. Meffert reviewed the literature33-35 and suggested that the junctional hemidesmosomal attachment may not be predictable in a metallic system. He suggested that a temporary chemical alteration in the implant surface at the time of surgical placement could potentially influence the cell types involved in the healing response following placement. He noted that collagen and fibronectin, suggested to potentially promote fibroblastic proliferation and attachment to the implant surface, were actually found to retard healing when applied to the implant surface. More favorable results were reported using bovine collagen on titanium alloy to enhance fibroblastic activity in vitro. Fibroblast attachment was measurably better to smooth surgical titanium, but better cell orientation was noted on porous, roughened titanium surfaces. Meffert also suggested that laminin, using the rationale of guided tissue regeneration, may allow the implant wound to be preferentially populated with more desirable cells, theoretically resulting in enhanced tissue attachment to the implant surface. Effect of Titanium Surface Configuration on ImplantTissue Interface The integrity of the implant-soft tissue seal may depend on the surface configuration of the titanium.3-10 Lavelle31 suggested that oral mucosal adhesion onto an implant surface would depend upon the chemistry and form of the cervical region of the implant surface. His preference for the most favorable cell adhesion was a smooth, inert implant surface. He suggested that the ideal implant material for soft tissue cell adhesion would be polished titanium. Differences in implant surface sterilization methods may affect the implant-tissue interfaces.36 Other aspects of implant material preparation may affect tissue attachment. Melcher37 recently summarized considerations of the biological processes that occur in the implant tissue bed immediately following placement. He theorized that biocompatible implant material substrates and geometrical configurations may be more hospitable for attachment of one cell type than for another. He further proposed that determining such biocompatibilities could allow for design of an implant with differing materials and surface configurations. Ideally, such a design could encourage desired cell types to migrate and attach to their respective surfaces; e.g., epithelial cells could be influenced to migrate and
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attach to the cervical regions of the implant while fibroblasts could be restricted to the implant portion located adjacent to the lamina propria of the gingiva. He proposed that research is needed to discover substances that would be selectively hospitable for desired cell types. Brunette et al.38 examined cultured expiants of human gingiva on titanium-coated silicon which was fabricated using a mask-etching technique, creating a surface of uniform and well defined titanium grooves measuring 115 µ at the depth and 165 µ at the top of each groove. When epithelial cells were plated as suspensions, the cells were oriented along the long axis of the groove. Similarly, cellular migration followed the grooves. Where the grooved portion of the surface ended, the cells fanned out in a more typical configuration. They suggested that a surface similar to that used experimentally could be used clinically. It could be aligned at right angles to the long axis of a dental implant, impeding apical migration of the epithelium and thus encouraging a healthy implant-tissue interface. Toth et al.1" reviewed the literature and similarly proposed that microscopic grooves placed in the implant surface could orient the growth of both fibroblasts and epithelial cells. Inuoe, et al.39 studied the effect of the surface geometry of titanium alloy on the orientation of fibroblasts. They cultured human gingival fibroblasts onto titanium discs with smooth and porous surfaces. Unlike on the smooth discs, cells that migrated onto the porous discs had no recognizable preferred orientation. The authors speculated that the surface texture could determine the nature of the implanttissue attachment. Lowenberg et al.40 in 1987 used a similar design to study the attachment of human gingival fibroblasts to titanium alloy discs, human root slices, and zirconium alloy discs. Results suggested that titanium alloy was as hospitable to the initial attachment of fibroblasts as control demineralized root slices. Within the titanium discs, cell attachment was better to a smooth surface but orientation was more favorable on a porous surface. Meffert et al.41 summarized results from a recent study by some of the same authors, Block, Kent, and Kay,42 which suggested that following insertion of smooth titanium implants in dogs, JE migrated apically with marked inflammatory infiltration. After 4 months, a cleavage of soft tissue with deep epithelial invagination was noted adjacent to the smooth titanium surface. A hydroxyapatite coated, porous titanium surface did not demonstrate as much apical migration of the JE. Déporter et al.43-44 placed implants into dogs to examine the effect of a porous coating on the titanium alloy implant surface. The implant fixture consisted of a sintered, porous endosseous portion. Four to 8 weeks later a transgingival component with a porous subgingival portion and a machined smooth coronal portion was attached. The porous portion of the transgingival component was intended to permit gingival attachment by fibrous connective tissue ingrowth into the pores. The smooth portion was intended to
158
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TITANTIUM IMPLANT SOFT TISSUE INTERFACE: A REVIEW
3A: Scanning electron micrograph of a titanium implant fixture and abutment. Blocked area is the fixture-abutment junction. (Original
Figure
magnification
20, 15KV).
facilitate plaque control. Fixed bridges were subsequently placed between sets of two implants. Frequent exposure of the porous transgingival portion with subsequent inflammation and implant failure led to early termination of the study. Despite the fact that the porous transgingival portion facilitated plaque retention and encouraged an inflammatory reaction, the authors noted some evidence of gingival connective tissue attachment into the transgingival collar. Schroeder et al.45 reported in 1981 on experiments begun 7 years previously which investigated the reactions of connective tissue and epithelium to perforated hollow cylinder shaped titanium implants. Fixtures inserted into monkeys had a polished titanium post protruding from the gingival surface immediately after placement. The submerged surface had been flame-sprayed with titanium powder providing a rough surface with pores 25 to 100 µ in size. After 8 to 12 weeks two adjacent abutments were joined by gold bridges and allowed to function for 6 to 20 months. Analysis of fixtures removed from areas of immobile mucosa without apparent marginal inflammation demonstrated connective tissue with fibers inserted functionally at 90° into the plasma sprayed neck portion of the implant to such a degree that application of tensile strength dislodged particles of the sprayed surface rather than detach the fibers from the rough surface. Epithelium was observed at portions along the sprayed
February
3B: Higher power view of the seam between the fixture and abutThe dimensions of this seam can exceed the average width of an epithelial cell or fibroblast (bar represents average epithelial cell or fibroblast width). (Original magnification x 300, 15KV).
Figure ment.
titanium surface. Here, the surface titanium particles were embedded in an amorphous, finely granular surface whose ultrastructure corresponded to that of a thickened basal lamina. Microvilli of the adjacent epithelial cells projected into the basal lamina in a hemidesmosomal like arrangement. The authors concluded that epithelium in addition to connective tissue might function to resist the mechanical loads imposed by the implants. The effect of the microscopic seam between an implant abutment and fixture on tissue adherence has not been documented. The dimensions of this seam can exceed the average width of an epithelial cell or fibroblast (Fig. 3). The precise dimensions of the connective tissue, junctional and crevicular epithelium, while well established adjacent to natural tooth surfaces,46 have not been well established adjacent to implants. A greater understanding of factors which affect the implant-soft tissue interface will permit the design, fabrication and insertion of implant fixtures which enhance the formation of a biologic seal between tissues and the implant surface.
Adequacy of the Seal
TenCate29 suggested that oral mucosa possessed all the nec-
essary qualities to form a junction with any structure piercing it. He theorized that attachment of tissues to implant
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surfaces was not as much an issue as the adequacy of the seal provided at the implant-soft tissue interface. Adell et al.47 and Lekholm et al.48 reported only minimal inflammation clinically and histologically in longitudinal and cross-sectional human studies of the marginal tissue reactions at titanium implants. They proposed that the epithelial seal was viable and adequate in function. Changes similar to those seen with Periodontitis in the natural dentition were reportedly not observed around the implant fixtures. TenCate29 reviewed an unpublished report by Lindhe which indicated that the implant junctional epithelium apparently differed slightly from the dental JE in that signs of inflammation normally observed in the natural dentition (widened intercellular space and increased mitotic activity) were not observable in the JE adjacent to implant surfaces. The mechanism of plaque-induced inflammation around implant fixtures was suggested to be totally different than that at natural teeth.30 Yet, characteristics of the implant sulci appear to be similar to the periodontal sulci with respect to crevicular fluid flow and microflora.49 Sanz et al.50 recently studied the histological and ultrastructural characteristics of human soft tissues adjacent to implants. Light microscopy sections of connective tissue demonstrated an inflammatory infiltrate the degree of which correlated with clinical findings of deeper probing depths. Examination of the epithelium showed transmigration of leukocytes and the presence of bacteria between the cells. It was suggested that the peri-implant soft tissue environment reacts against plaque bacteria similarly as in human periodontal disease. The pathogenesis of disease around implants has not been well investigated.3 Enhancing the integrity of the biologic seal should result in greater tissue resistance to inflammatory insults, thus improving the prognosis of functioning implants. CONCLUSION Attachment between epithelium and titanium has been demonstrated in vitro and in vivo. While the precise nature and mechanism of this attachment is not known, an attachment between the implant abutment surface oxide layer and the adjacent epithelium frequently occurs. This attachment is mediated by a glycoprotein similar to that seen between epithelium and natural tooth surfaces. While only minimal histological evidence exists, connective tissue fibers adjacent to titanium implanted surfaces may bring the tissue in tight apposition to the implant without an absolute biologic attachment. The architecture of the tissues adjacent to titanium implant surfaces depends partly on the implant surface configuration. Alteration of the titanium surface morphology may selectively enhance the attachment of either epithelial cells or fibroblasts, theoretically enhancing the formation of a biologic seal between the implanted titanium surface and its adjacent tissue.
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A greater understanding of the mechanisms of attachment and of the factors which enhance the integrity of the biologic seal between implant and soft tissues should permit an improved prognosis for functioning titanium implants.
Acknowledgments Dr. Jean Schoknecht, Supervisor of Electron Microscopy, and the Department of Periodontics at Indiana University
gratefully acknowledged for their use of the scanning electron microscope (Amray 1000A-NSF PCM 800 5911). Gratitude is expressed to Mr. David Gregory at the Medical Media School of
Dentistry
are
expert assistance with and the
Service, Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, for his preparation of the illustrations. REFERENCES 1. Schluger S, Yuodelis R, Page RC, Johnson RH. In: Periodontal Diseases, 2nd ed. Philadelphia: Lea and Febiger; 1990:207-211. 2. McKinney RV, Stefiik DE, Koth DL. Evidence for a biological seal at the implant-tissue interface. In: McKinney RV, Lemons JE, eds. The Dental Implant Clinical and Biological Response of Oral Tissues. Littleton: PSG Publishing Company; 1985; 25-56. 3. Stallard RE. The periodontal implant junction. In: McKinney RV,
4.
5.
6. 7.
8.
9.
10. 11. 12.
Lemons JE, eds. The Dental Implant Clinical and Biological Response of Oral Tissues. Littleton NJ: PSG Publishing Company, 1985; 131-142. Kent JN, DeLong P, Homsy CA, Hends EC. Intraosseous dental implants: Nature of the interface../ Am Dent Assoc 1974; 89:11421151. James RA, Schultz RL. Hemidesmosomes and the adhesion of junctional epithelial cells to metal implants. A preliminary report. Oral Impiantai 1974; 4:294-302. Bhaskar SN, ed. Orban's Oral Histology and Embryology. 9th ed. St. Louis: The CV Mosby Company; 1980:310-330. Listgarten MA. Electron microscopic study of the dentogingival junction of man. Am J Anat 1966; 119:147-154. Schroeder HE, Listgarten MA. Fine structure of the developing epithelial attachment of human teeth. In: Wolsky A, ed. Monographs in Developmental Biology, vol. 2. Basel, Switzerland: S. Karger; 1971:6978. Parr GR, Gardner LK, Toth RW. Titanium: The mystery metal of implant dentistry. Dental materials aspects. ./ Prosthet Dent 1985; 54:410-414. Toth RW, Parr GR. Gardner LK. Soft tissue response to endosseous titanium oral implants. J Prosthet Dent 1985; 54:564-567. Kasemo B. Biocompatibility of titanium implants: Surface science aspects../ Prosthet Dent 1983; 49:832-837. Loechler PS, Mueller MW. Successful implant dentures. Northwest
Dent 1952; 31:134-139. 13. Bodine
14.
15.
RL, Mohammed CI. Implant denture histology: Gross and microscopic studies of a human mandible with a 12-year subperiosteal implant denture. Dent Clin North Am 1970; 14:145-159. James R. A histopathological study of the nature of the epithelium surrounding implant posts. Part I../ Oral Implantai 1972; 3:105-122. James R. A histopathological study of the nature of the epithelium surrounding implant posts. Part II. ./ Oral Implantai 1973; 3:137159.
Listgarten MA,
Lai CH. Ultrastructure of the intact interface between endosseous epoxy resin dental implant and the host tissue. J Biol Buccale 1975; 3:13-28. 17. Swope EM, James RA. A longitudinal study on hemidesmosome 16.
an
J Periodontol 160
18.
19.
20.
21.
22. 23. 24.
25.
26.
27.
28. 29.
TITANTIUM IMPLANT SOFT TISSUE INTERFACE: A REVIEW formation at the dental implant-tissue interface../ Oral Implanto! 1981; 9:412-422. Baumhammers A, Langkamp HH, Matta RK, Kilbury K. Scanning electron microscopy of epithelial cells grown on enamel, glass and implant materials. J Periodontol 1978; 49:592-597. Kasten FH, Soileau KM and Meffert RM. Quantitative evaluation of human gingival epithelial cell attachment to implant surfaces in vitro. Int J Periodontics Restorative Dent 1990; 10:68-79. Gould TRL, Brunette DM, Westbury L. The attachment mechanisms of epithelial cells to titanium in vitro. / Periodont Res 1981; 16:61 16. Jansen JA, DeWijn JR, Wolters-Lutgerhorst ML, VanMullem PJ. Ultrastructural study of epithelial cell attachment to implant materials. J Dent Res 1985; 64:891-896. James RA. The support systems and the pergingival defense mechanism of oral implants. J Oral Implantai 1976; 6:270-279. James RA. Peri-implant considerations. Dent Clin North Am 1980; 24:415-420. Dmytryk J, Fox S, Moriarty J. The effects of scaling titanium implant surfaces with metal and plastic instruments on cell attachment. J Periodontol 1990:61;491-496. Hobo S, Ichida E, Garcia LT. Osseointegration and Occlusa! Rehabilitation. Chicago: Quintessence Publishing Company; 1989:3354. Gould TRL, Brunette DM. Ultrastructural study of the attachment of human gingiva to titanium in vivo. J Prosthet Dent 1984; 52:418420. Hansson HA, Albrektsson T, Branemark PI. Structural aspects of the interface between tissue and titanium implants. J Prosthet Dent 1983; 50:108-113. Albrektsson T, Branemark PI, Hansson HA, Lindstrom J. Osseointegrated titanium implants. Acta Orthop Scand 1981; 52:155-170. TenCate AR. The gingival junction. In: Branemark PI, Zarb GA, Albrektsson T, eds. Tissue Integrated Prosthesis. Chicago: Quintessence
Publishing Company; 1985;145-153.
30. Brunski J, Hipp JA, El-Wakad M. Dental implant design: Biomechanics and interfacial tissues. J Oral Implantai 1986; 12:365-377. 31. Lavelle CLB. Mucosal seal around endosseous dental implants. J Oral
32.
Implantai 1981; 9:357-371. McKinney RV, Stefiik DE, Koth
DL. Evidence for a junctional epithelial attachment to ceramic dental implants: A transmission electron microscopic study. J Periodontol 1985; 56:579-591. 33. Meffert RM. The soft tissue interface in dental implantology. lmplantologist 1986; 5:55-58. 34. Meffert RM. Periodontal implications of endosseous implants. In: Schluger S, Yuodelis R, Page RC, Johnson RH. Periodontal Diseases. 2nd ed. Philadelphia: Lea and Febiger; 1990; 70,7-731. 35. Meffert RM. Implant therapy. In: Nevins M, Becker W, Kornman K. Proceedings of the World Workshop in Clinical Periodontics. Chicago: American Academy of Periodontology; 1989; Section VIII, pg 1-10.
February 1991 36. Doundoulakis JH. Surface analysis of titanium after sterilization: Role in implant-tissue interface and bioadhesion. / Prosthet Dent 1987;
58:471-478. 37. Melcher AH.
Summary of biological plantai 1988; 5(2):31-32.
considerations. Int J Oral Im-
38. Brunette M, Kenner GS, Gould TRL. Grooved titanium surfaces orient growth and migration of cells from human gingival explants. J Dent Res 1983; 62:1045-1048. 39. Inoue T, Cox JE, Pillar RM, Melcher AH. Effect of the surface geometry of smooth and porous-coated titanium alloy on the orientation of fibroblasts in vitro. / Biomed Mater Res 1987; 21:107-126. 40. Lowenberg BF, Pilliar RM, Aubin JE, Férnie GR, Melcher AH. Migration, attachment and orientation of human gingival fibroblasts to root slices, naked and porous-surface titanium alloy discs and zircalloy 2 discs in vitro. / Dent Res 1987: 66; 1000-1005. 41. Meffert RM, Block MS, Kent JN. What is osseointegration? Int J Periodontics Restorative Dent 1987; 7(4):8-21. 42. Block MS, Kent JN, Kay JF. Evaluation of hydroxylapatite-coated titanium dental implants in dogs. J Oral Maxillofac Surg 1987; 45:601607. 43. DePorter DA, Friedland , Watson PA, et al. A clinical and radiographic assessment of a porous-surfaces, titanium alloy dental implant system in dogs. J Dent Res 1986; 65:1071-1077. 44. DePorter DA. Watson PA, Pilliar RM, Howley TP, Winslow J. A histological evaluation of a functional endosseous, porous-surfaced, titanium alloy dental implant system in the dog. / Dent Res 1988; 67:1190-1195. 45. Schroeder A, Van der Zypen E, Stuch H. Sutter F. The reaction of bone, connective tissue and epithelium to endosteal implants with titanium-sprayed surfaces. J Maxillofac Surg 1981; 9:15-25. 46. Garguilo A, Wentz F. Orban B. Dimensions and relations of the dento-gingival junction in humans. / Periodontol 1961; 32:261-267. 47. Adell R, Lekholm U, Rockler B, et al. Marginal tissue reactions at osseointegrated titanium fixtures. (I) A 3-year longitudinal prospective study. Int J Oral Maxillofac Surg 1986; 15:39-52. 48. Lekholm U, Adell R. Lindhe J, et al. Marginal tissue reactions at osseointegrated titanium fixtures. (II) A cross-sectional retrospective study. Int J Oral Maxillofac Surg 1986; 15:53-61. 49. Apse P, Ellen RP, Overall CM, Zarb GA. Microbiota and crevicular fluid collagenase activity in the osseointegrated dental implant sulcus. A comparison of sites in edentulous and partially edentulous patients. J Periodont Res 1989; 24:96-105. 50. Sanz M, Alandez J, Van Steenberghe D, Quirynen M, Newman M, Flemmig T. Histological and ultrastructural characteristics of periimplant gingival tissues. Presented at Academy of Periodontology Annual Meeting October 25, 1989, Washington, DC. Send reprint requests to: Dr. Timothy G. Donley, Associated Specialists, 110 Fort Couch Rd., Pittsburgh, PA 15241. Accepted for publication August 6, 1990.
Dental
Titanium Endosseous Tissue Interface: A Literature Review Timothy
G.
Donley* and
Implant-Soft
William B. Gillette^
Background information about normal periodontal anatomy and titanium used in endosseous implant fabrication is provided. Literature is reviewed concerning epithelial and connective tissue attachment to titanium. Information about the adequacy of cell attachment to implants, possible mechanisms of cell attachment formation, and the effect of implant surface properties on attachment is presented. A chemical attachment between titanium implant surface oxide layer and epithelium has been demonstrated in vitro and in vivo. This attachment is mediated by a glycoprotein similar to that seen between epithelium and natural tooth surfaces. While only minimal histological evidence exists, connective tissue fibers adjacent to titanium implanted surfaces may bring the tissue in tight apposition to the implant without an absolute biologic attachment between the implant and connective tissue. Alteration of the titanium surface morphology may selectively enhance the attachment of either epithelial cells or fibroblasts, theoretically enhancing the formation of a biologic seal between the implanted titanium surface and its adjacent tissue. A greater understanding of the mechanisms of attachment and of the factors which enhance the integrity of the biologic seal between implant and soft tissues should permit an improved prognosis for functioning titanium implants. / Periodontol
1991; 62:153-160.
Key Words: Epithelial attachment; connective tissue; titanium; biocompatible materials; dental
implants.
In the natural dentition, the junctional epithelium (JE) is believed to provide a seal at the base of a periodontal sulcus against penetration of periodontally pathologic chemical and bacterial substances. Disruption of this seal and/or lysis of the connective tissue fibers inserted into root cementum apical to the JE leads to rapid migration of the crevicular epithelium forming a pathologic pocket.1 As no cementum or fiber insertion is reported on the surface of titanium transmucosal abutments, an epithelial perimucosal seal may provide the only barrier against pathologic insults to deeper tissues. Destruction of the integrity of the perimucosal titanium surface seal could conceivably lead to extension of the pathologic pocket to the osseous structures. Concern over breakdown between oral soft tissues adjacent to implanted materials with apical epithelial migration to the ultimate point of implant exfoliation exists in the literature.2-5 Here, we review the literature concerning the nature of the titanium endosseous implant-soft tissue interface. »Private
practice, Pittsburgh,
tRichard L. Roudebush,
anapolis, IN. The opinions and
PA. Veterans Administration Medical
Center, Indi-
assertations contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Veterans Administration.
BACKGROUND Periodontal Anatomy In the natural dentition, the dento-gingival junction consists of keratinized gingival epithelium, non-keratinized sulcular or crevicular epithelium, and JE all supported by collagen fiber bundles in a connective tissue.6 The connective tissue fibers connect the tooth cementum to the surrounding alveolar bone and gingiva. At the electron microscopic level, cell-mediated hemidesmosomes attach the JE to natural tooth surfaces via a basal lamina7-8 (Fig. 1). With endosseous implants, epithelium and connective tissue are interfaced with titanium rather than tooth structures. The similarity of the attachment between soft tissues and the natural dentition and that between soft tissues and titanium endosseous implant surfaces will depend, in part, on the nature of the titanium surface.3 Titanium Implants Many oral implants of various designs are made of titanium in either its surgically pure or alloyed form. A high degree of biocompatibility, strength, and corrosion resistance make these metals ideal for oral implants. Surgically pure titanium also contains trace amounts of elements which mark-
J Periodontol 1991
TITANTIUM IMPLANT SOFT TISSUE INTERFACE: A REVIEW
154
TOOTH
LAMINA
STRUCTURE
DENSA
_J f
LAMINA RARA INTERNA
Figure
1:
tween an
LAMINA
LUC|DA
Diagram of the basal lamina-hemidesmosomal attachment beepithelial cell and a natural tooth sutface at the electron micro-
scopic level.
edly improve the mechanical properties of pure titanium.9 In its alloyed form titanium is most commonly mixed with
6% aluminum and 4% vanadium (TÌ-6A1-4V).9 The aluminum increases the strength and decreases the weight of the alloy. The vanadium acts as an aluminum scavenger presumably preventing the formation of corrosion promoting Ti-Al compounds.9 The surface properties of an implant relate directly to the success of implant procedures.10-" Within a millisecond of exposure to air, a 10 to 100 angstrom thick oxide layer forms on a cut surface of pure titanium. Passivity refers to an oxidized layer that does not break down under physiological conditions.9 While exposure to air produces this oxide layer, U.S. manufactured titanium oral implant materials are passivated using a nitric acid bath as required by the United States Food and Drug Administration. On a titanium oral implant surface considerable variation in surface oxide properties with a variable oxygen content can be expected with different machining conditions.10-" Surgically pure titanium or titanium alloy implant surfaces (with titanium concentrations of 85% to 95%) apparently maintain this oxide layer without significant breakdown or corrosion under physiologic conditions.9-" It is the relatively thick titanium oxide layer that determines the implant-tissue interaction, not the metal itself.10-" IMPLANT-SOFT TISSUE INTERFACE Historical Review In 1952, Loechler and Mueller12 described the gingival and connective tissues in microscopic sections from a transgingival post of a Vitallium* (cobalt-chromium-molybdenum alloy) subperiosteal implant as being essentially the same as that around normal teeth. Bodine and Mohammed13 in 1970 reported on a detailed histologie study of a subperiosteal implant removed from a *Austenal Dental Inc.,
Chicago,
IL.
February
patient following 12 years of functioning. An epitheliallined crevice surrounding the abutment was infiltrated with plasma cells and lymphocytes. The connective tissue directly in contact with the submerged implant metal consisted of flattened compressed fibers and cells with elongated nuclei which they termed "typical implant connective tissue." James14-15 provided indirect evidence of an adhesion between epithelial cells and metal implant surfaces. He inserted one-piece Vitallium implants with posts protruding above the bone level in dogs. After 21 days of healing, mucopolysaccharides suggestive of an epithelial attachment were observed at the base of the implant sulcus. Collagen fibers in the lamina propria of the connective tissue were oriented perpendicular to the implant surface. He concluded that evidence supported the theory of an epithelial attachment at the base of an implant sulcus similar to that found
in the natural dental sulcus. James and Schultz5 presented the first in vivo ultrastructural evidence of hemidesmosomal and basal lamina formation between regenerated junctional epithelial cells and a Vitallium implant. Using transmission electron microscopy and a monkey model, they noted a narrow band of amorphous material immediately adjacent to the implant space which resembled a basal lamina with both a lamina densa and lamina lucida. Poorly defined hemidesmosomes were observed. Listgarten and Lai16 in 1975 demonstrated similar findings using epoxy methylmethacrylate dental implants in monkeys. Hemidesmosomes appeared to develop by 2 weeks. Swope and James17 later placed one piece, partially exposed, Vitallium root form implants sequentially into monkeys to determine more precisely the time period required for hemidesmosomes to develop following intraoral implant placement. Electron microscopy of block sections revealed hemidesmosomes beginning to form after 2 days and being well established by 3 days. McKinney et al.2 more recently published scanning and transmission electron micrographs from an analysis of sapphire (single crystalline alpha-aluminum oxide) endosseous implants removed from dogs. Numerous dense hemidesmosomal like structures were observed on epithelial pseudopodia at intervals along the epithelial cell membrane adjacent to the implant. Higher resolution reportedly confirmed the presence of a well-ordered basal lamina in association with the cell membrane hemidesmosomes. They referred to the area between regenerating crevicular epithelium of the gingiva and the implant surface as the biological seal. Crevicular epithelium was reported to be similar in all respects to that around natural teeth. Epithelium proceeded downward in the gingival sulcus as a nonkeratinized structure. The authors suggested that the described, well-ordered seal could develop at the tissue interface of any implanted material.
Epithelial Attachment
to Titanium Baumhammers et al.18 in 1978 used scanning electron microscopy to examine the in vitro 5-day growth of human
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epithelial cells on tooth enamel, glass, Vitallium, titanium, and vitreous carbon. Cells grew and adapted equally well
to all tested surfaces and were similar whether the tested
surfaces were smooth or roughened by sandblasting. They cautioned that epithelial growth on similar substances in vivo could be affected by factors inherent to the intraoral environment such as plaque, saliva, inflammation, crevicular fluid, and possibly corrosion. In a recent experiment by Kasten et al.,19 75,000 cells/ ml of gingival epithelial cells were seeded onto differently prepared titanium and hydroxyapatite implant surfaces. Human gingival cells reportedly adhered three times more frequently to hydroxyapatite than to titanium type implant surfaces. Gould et al.20 in 1981 reported on the attachment of epithelial cells to titanium in vitro. They grew porcine oral tissue epithelial cells on thin films of titanium alloy embedded in epoxy resin. Electron microscopy of adherent cells often showed clear evidence of hemidesmosomal attachments between themselves and the titanium surface. Material having the appearance of basal lamina was identifiable in these regions. Epithelial cells were suggested to attach to titanium surfaces in much the same manner as they attach to natural tooth surfaces. Jansen et al.21 more recently studied the ultrastructure of guinea pig epithelial attachment to gold, titanium, carbon, apatite, and polystyrene substrates. Their findings disputed those of Gould et al.,20 noting hemidesmosomal-like attachments only on apatite and polystyrene but not on metallic or carbon surfaces. Differences in cell populations, culture conditions, or treatment of titanium substrates may have influenced the differing results. They proposed the existence of a yet unknown property of the substrate which determined the nature and structure of epithelial contact with the substrate. James22,23 reviewed his earlier research and concluded that a JE adjacent to implanted surfaces shows histochemical characterizations similar to that of the JE attached to natural teeth. Epithelium adjacent to implants stains positive with Periodic-acid Schiff technique indicating that it produces acid Polysaccharides with properties capable of providing adhesion between the implant surface and the JE. Connective Tissue Attachment to Titanium
James22,23 further proposed that circumferential connective
tissue fibers could be expected to surround an implant post in a manner similar to circumferential fibers in the dental gingiva. Fibers would also extend from the alveolar crest to the implant JE providing a functional arrangement. Dmytryk et al.24 recently presented results from a study which assessed the ability of tissue culture fibroblasts to attach and colonize on the surface of pure titanium dental implants following instrumentation of the implant surface with curets of dissimilar composition. Surfaces treated with plastic and titanium curets showed greater numbers of attached cells than stainless steel curet treated surfaces. Scan-
DONLEY,
GILLETTE
155
electron microscopic analysis suggested that fibroblasts adherent to the implant surfaces treated with plastic and titanium curets were more typical of fibroblasts in a favorable culture condition. These in vitro results theoretically suggest that implant maintenance could affect tissue attach-
ning
ment
integrity.
Hobo et al.25 reviewed the literature published by Branemark's group and proposed that deep within the gingival crevice, collagen fibers could be expected to form a tight cuff around the implant abutment. A 2 mm connective tissue band was suggested to attach tightly to the abutment surface and act as a resistant barrier. While a band of connective tissue may bring the tissue in tight apposition to the implant a lack of an absolute biologic attachment between the implant and surrounding connective tissue elements has been suggested.3 The thickness and orientation of the collagen fibers may depend upon the functional load placed upon the implant.3 In Vivo Studies Gould and Brunette26 reported in vivo findings similar to their previously reviewed in vitro report.20 Wire films of titanium were again prepared and in this study implanted into three sites of marginal gingival tissue in a human subject. The tissue encapsulated wire implants were removed after 4 weeks and analyzed for epithelial cell adherence. At epithelial-titanium interfaces there was clear evidence of hemidesmosomes as well as material consistent with basal lamina. Hansson, et al.27 and Albrektsson, et al.28 reported on the structural aspects of the interface between tissue and titanium implants based on information from analysis of an unnamed number of non-alloyed titanium implants removed from humans after reported successful clinical function up to 7 years. Additional information about the experimentation was not provided. They reported that submucosal connective tissue around titanium dental implants contained fibroblasts as the dominant cell type with macrophages and scattered lymphocytes. Bundles of collagen filaments and fibrils, often observed approaching the implant, always had a proteoglycan layer 20 nm thick between fibrils and cells from the metal oxide surface of the titanium. There was no evidence of toxic or reactive responses. The authors suggested that connective tissue accepted titanium rather than isolating it as a foreign body. Epithelial cells coronal to the connective tissue portions were attached to titanium via hemidesmosomes. Reportedly there were no signs of inflammatory reactions in analyzed epithelial areas. From these clinical reports the authors concluded that epithelial cells apparently do adhere to titanium surfaces forming a long-lasting and presumably biomechanical resistant attachment to the implants in vivo. While additional histological information concerning implant-soft tissue interfaces seems necessary, the technical difficulty in demonstrating these junctions is substantial.3,29
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TITANTIUM IMPLANT SOFT TISSUE INTERFACE: A REVIEW
Implant-Tissue Architecture Two distinct interfaces have been described with dental implants: 1) the perimucosal interface where soft tissue meets the implant and 2) the endosteal interface where bone meets the implant.30 At the perimucosal interface crevicular epithelium, supported by connective tissue, forms the implantsoft tissue interface. The reviewed literature suggests that a portion of the crevicular epithelial cells adjacent to a titanium implant can be expected to form a hemidesmosomal type attachment to the implant surface. While the attachment may not always be clinically detectable, attached epithelium should be histologically evident along the implant. The transgingival abutment to implant fixture junction has been described as corresponding to the cemento-enamel junction in the natural dentition.25 However, this may not be so. The theoretically possible relationships between the attached portion of epithelium and the implant surfaces can be classified as diagrammed in Figure 2. The attached epithelium can extend along the abutment surface without approaching the abutment to fixture junction, the apical extent of the attached epithelium can be located at the abutment to fixture junction, the attached epithelium can trans-
February
1991
gress the junction, or the entire attached epithelium can be located on the fixture apical to the junction. The frequency of these relationships in vivo is unknown. The implanttissue architecture probably depends on tissue location at the time of abutment placement and other factors. Tissue architecture may change over time. How Cell Attachment Occurs In 1981 Lavelle31 theorized that cellular adhesions to an implant surface would depend on whether the implant surface was protein coated of serum or salivary origin. Mucosal cell interaction with protein components adsorbed onto the implant's cervical region would influence the subsequent behavior of cellular adhesions. McKinney et al.32 more recently furthered this theory of how epithelial cells attach to implant surfaces. Using dogs, they reported that regenerated crevicular gingiva around ceramic dental implants developed junctional epithelial organelle and cellular architecture that was similar to the structures between natural teeth and tissues. In formation of the attachment complex, the authors proposed that increased vesicles noted in the JE cells adjacent to the implant
Figure 2: Diagram of the possible architectural relationships between titanium implant surfaces and soft tissues. A portion of the crevicular epithelium adjacent to titanium implants conform an attachment to the implant surface. Shown are the gingival epithelium (GE), connective tissue (CT), alveolar bone (AB), and the crevicular epithelium (unlabeled arrow). A: the attached epithelium can extend along the abutment surface without approaching the abutment-fixture junction; B: the apical extent of the attached epithelium can be located at the abutment fixture junction; C: the attached epithelium can transgress the junction; or D: the entire attached epithelium can be located along the fixture apical to the junction.
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surface secreted products which included laminin, an extracellular glycoprotein component of the lamina lucida. This laminin was probably responsible for adhesion of the epithelial cells to other collagenous components of the basal lamina. They further theorized that fibroblasts produce glycosaminoglycans during healing which may coat the implant surface. Additionally, fibroblasts and endothelial cells, present in the healing wound extracellular matrix, produce fibronectin, a glycoprotein found in the lamina densa. This fibronectin, which binds to collagen and glycosaminoglycans, may represent the "glue" between the implant biomaterial and the type IV collagen of the lamina densa. Meffert reviewed the literature33-35 and suggested that the junctional hemidesmosomal attachment may not be predictable in a metallic system. He suggested that a temporary chemical alteration in the implant surface at the time of surgical placement could potentially influence the cell types involved in the healing response following placement. He noted that collagen and fibronectin, suggested to potentially promote fibroblastic proliferation and attachment to the implant surface, were actually found to retard healing when applied to the implant surface. More favorable results were reported using bovine collagen on titanium alloy to enhance fibroblastic activity in vitro. Fibroblast attachment was measurably better to smooth surgical titanium, but better cell orientation was noted on porous, roughened titanium surfaces. Meffert also suggested that laminin, using the rationale of guided tissue regeneration, may allow the implant wound to be preferentially populated with more desirable cells, theoretically resulting in enhanced tissue attachment to the implant surface. Effect of Titanium Surface Configuration on ImplantTissue Interface The integrity of the implant-soft tissue seal may depend on the surface configuration of the titanium.3-10 Lavelle31 suggested that oral mucosal adhesion onto an implant surface would depend upon the chemistry and form of the cervical region of the implant surface. His preference for the most favorable cell adhesion was a smooth, inert implant surface. He suggested that the ideal implant material for soft tissue cell adhesion would be polished titanium. Differences in implant surface sterilization methods may affect the implant-tissue interfaces.36 Other aspects of implant material preparation may affect tissue attachment. Melcher37 recently summarized considerations of the biological processes that occur in the implant tissue bed immediately following placement. He theorized that biocompatible implant material substrates and geometrical configurations may be more hospitable for attachment of one cell type than for another. He further proposed that determining such biocompatibilities could allow for design of an implant with differing materials and surface configurations. Ideally, such a design could encourage desired cell types to migrate and attach to their respective surfaces; e.g., epithelial cells could be influenced to migrate and
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attach to the cervical regions of the implant while fibroblasts could be restricted to the implant portion located adjacent to the lamina propria of the gingiva. He proposed that research is needed to discover substances that would be selectively hospitable for desired cell types. Brunette et al.38 examined cultured expiants of human gingiva on titanium-coated silicon which was fabricated using a mask-etching technique, creating a surface of uniform and well defined titanium grooves measuring 115 µ at the depth and 165 µ at the top of each groove. When epithelial cells were plated as suspensions, the cells were oriented along the long axis of the groove. Similarly, cellular migration followed the grooves. Where the grooved portion of the surface ended, the cells fanned out in a more typical configuration. They suggested that a surface similar to that used experimentally could be used clinically. It could be aligned at right angles to the long axis of a dental implant, impeding apical migration of the epithelium and thus encouraging a healthy implant-tissue interface. Toth et al.1" reviewed the literature and similarly proposed that microscopic grooves placed in the implant surface could orient the growth of both fibroblasts and epithelial cells. Inuoe, et al.39 studied the effect of the surface geometry of titanium alloy on the orientation of fibroblasts. They cultured human gingival fibroblasts onto titanium discs with smooth and porous surfaces. Unlike on the smooth discs, cells that migrated onto the porous discs had no recognizable preferred orientation. The authors speculated that the surface texture could determine the nature of the implanttissue attachment. Lowenberg et al.40 in 1987 used a similar design to study the attachment of human gingival fibroblasts to titanium alloy discs, human root slices, and zirconium alloy discs. Results suggested that titanium alloy was as hospitable to the initial attachment of fibroblasts as control demineralized root slices. Within the titanium discs, cell attachment was better to a smooth surface but orientation was more favorable on a porous surface. Meffert et al.41 summarized results from a recent study by some of the same authors, Block, Kent, and Kay,42 which suggested that following insertion of smooth titanium implants in dogs, JE migrated apically with marked inflammatory infiltration. After 4 months, a cleavage of soft tissue with deep epithelial invagination was noted adjacent to the smooth titanium surface. A hydroxyapatite coated, porous titanium surface did not demonstrate as much apical migration of the JE. Déporter et al.43-44 placed implants into dogs to examine the effect of a porous coating on the titanium alloy implant surface. The implant fixture consisted of a sintered, porous endosseous portion. Four to 8 weeks later a transgingival component with a porous subgingival portion and a machined smooth coronal portion was attached. The porous portion of the transgingival component was intended to permit gingival attachment by fibrous connective tissue ingrowth into the pores. The smooth portion was intended to
158
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TITANTIUM IMPLANT SOFT TISSUE INTERFACE: A REVIEW
3A: Scanning electron micrograph of a titanium implant fixture and abutment. Blocked area is the fixture-abutment junction. (Original
Figure
magnification
20, 15KV).
facilitate plaque control. Fixed bridges were subsequently placed between sets of two implants. Frequent exposure of the porous transgingival portion with subsequent inflammation and implant failure led to early termination of the study. Despite the fact that the porous transgingival portion facilitated plaque retention and encouraged an inflammatory reaction, the authors noted some evidence of gingival connective tissue attachment into the transgingival collar. Schroeder et al.45 reported in 1981 on experiments begun 7 years previously which investigated the reactions of connective tissue and epithelium to perforated hollow cylinder shaped titanium implants. Fixtures inserted into monkeys had a polished titanium post protruding from the gingival surface immediately after placement. The submerged surface had been flame-sprayed with titanium powder providing a rough surface with pores 25 to 100 µ in size. After 8 to 12 weeks two adjacent abutments were joined by gold bridges and allowed to function for 6 to 20 months. Analysis of fixtures removed from areas of immobile mucosa without apparent marginal inflammation demonstrated connective tissue with fibers inserted functionally at 90° into the plasma sprayed neck portion of the implant to such a degree that application of tensile strength dislodged particles of the sprayed surface rather than detach the fibers from the rough surface. Epithelium was observed at portions along the sprayed
February
3B: Higher power view of the seam between the fixture and abutThe dimensions of this seam can exceed the average width of an epithelial cell or fibroblast (bar represents average epithelial cell or fibroblast width). (Original magnification x 300, 15KV).
Figure ment.
titanium surface. Here, the surface titanium particles were embedded in an amorphous, finely granular surface whose ultrastructure corresponded to that of a thickened basal lamina. Microvilli of the adjacent epithelial cells projected into the basal lamina in a hemidesmosomal like arrangement. The authors concluded that epithelium in addition to connective tissue might function to resist the mechanical loads imposed by the implants. The effect of the microscopic seam between an implant abutment and fixture on tissue adherence has not been documented. The dimensions of this seam can exceed the average width of an epithelial cell or fibroblast (Fig. 3). The precise dimensions of the connective tissue, junctional and crevicular epithelium, while well established adjacent to natural tooth surfaces,46 have not been well established adjacent to implants. A greater understanding of factors which affect the implant-soft tissue interface will permit the design, fabrication and insertion of implant fixtures which enhance the formation of a biologic seal between tissues and the implant surface.
Adequacy of the Seal
TenCate29 suggested that oral mucosa possessed all the nec-
essary qualities to form a junction with any structure piercing it. He theorized that attachment of tissues to implant
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surfaces was not as much an issue as the adequacy of the seal provided at the implant-soft tissue interface. Adell et al.47 and Lekholm et al.48 reported only minimal inflammation clinically and histologically in longitudinal and cross-sectional human studies of the marginal tissue reactions at titanium implants. They proposed that the epithelial seal was viable and adequate in function. Changes similar to those seen with Periodontitis in the natural dentition were reportedly not observed around the implant fixtures. TenCate29 reviewed an unpublished report by Lindhe which indicated that the implant junctional epithelium apparently differed slightly from the dental JE in that signs of inflammation normally observed in the natural dentition (widened intercellular space and increased mitotic activity) were not observable in the JE adjacent to implant surfaces. The mechanism of plaque-induced inflammation around implant fixtures was suggested to be totally different than that at natural teeth.30 Yet, characteristics of the implant sulci appear to be similar to the periodontal sulci with respect to crevicular fluid flow and microflora.49 Sanz et al.50 recently studied the histological and ultrastructural characteristics of human soft tissues adjacent to implants. Light microscopy sections of connective tissue demonstrated an inflammatory infiltrate the degree of which correlated with clinical findings of deeper probing depths. Examination of the epithelium showed transmigration of leukocytes and the presence of bacteria between the cells. It was suggested that the peri-implant soft tissue environment reacts against plaque bacteria similarly as in human periodontal disease. The pathogenesis of disease around implants has not been well investigated.3 Enhancing the integrity of the biologic seal should result in greater tissue resistance to inflammatory insults, thus improving the prognosis of functioning implants. CONCLUSION Attachment between epithelium and titanium has been demonstrated in vitro and in vivo. While the precise nature and mechanism of this attachment is not known, an attachment between the implant abutment surface oxide layer and the adjacent epithelium frequently occurs. This attachment is mediated by a glycoprotein similar to that seen between epithelium and natural tooth surfaces. While only minimal histological evidence exists, connective tissue fibers adjacent to titanium implanted surfaces may bring the tissue in tight apposition to the implant without an absolute biologic attachment. The architecture of the tissues adjacent to titanium implant surfaces depends partly on the implant surface configuration. Alteration of the titanium surface morphology may selectively enhance the attachment of either epithelial cells or fibroblasts, theoretically enhancing the formation of a biologic seal between the implanted titanium surface and its adjacent tissue.
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A greater understanding of the mechanisms of attachment and of the factors which enhance the integrity of the biologic seal between implant and soft tissues should permit an improved prognosis for functioning titanium implants.
Acknowledgments Dr. Jean Schoknecht, Supervisor of Electron Microscopy, and the Department of Periodontics at Indiana University
gratefully acknowledged for their use of the scanning electron microscope (Amray 1000A-NSF PCM 800 5911). Gratitude is expressed to Mr. David Gregory at the Medical Media School of
Dentistry
are
expert assistance with and the
Service, Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, for his preparation of the illustrations. REFERENCES 1. Schluger S, Yuodelis R, Page RC, Johnson RH. In: Periodontal Diseases, 2nd ed. Philadelphia: Lea and Febiger; 1990:207-211. 2. McKinney RV, Stefiik DE, Koth DL. Evidence for a biological seal at the implant-tissue interface. In: McKinney RV, Lemons JE, eds. The Dental Implant Clinical and Biological Response of Oral Tissues. Littleton: PSG Publishing Company; 1985; 25-56. 3. Stallard RE. The periodontal implant junction. In: McKinney RV,
4.
5.
6. 7.
8.
9.
10. 11. 12.
Lemons JE, eds. The Dental Implant Clinical and Biological Response of Oral Tissues. Littleton NJ: PSG Publishing Company, 1985; 131-142. Kent JN, DeLong P, Homsy CA, Hends EC. Intraosseous dental implants: Nature of the interface../ Am Dent Assoc 1974; 89:11421151. James RA, Schultz RL. Hemidesmosomes and the adhesion of junctional epithelial cells to metal implants. A preliminary report. Oral Impiantai 1974; 4:294-302. Bhaskar SN, ed. Orban's Oral Histology and Embryology. 9th ed. St. Louis: The CV Mosby Company; 1980:310-330. Listgarten MA. Electron microscopic study of the dentogingival junction of man. Am J Anat 1966; 119:147-154. Schroeder HE, Listgarten MA. Fine structure of the developing epithelial attachment of human teeth. In: Wolsky A, ed. Monographs in Developmental Biology, vol. 2. Basel, Switzerland: S. Karger; 1971:6978. Parr GR, Gardner LK, Toth RW. Titanium: The mystery metal of implant dentistry. Dental materials aspects. ./ Prosthet Dent 1985; 54:410-414. Toth RW, Parr GR. Gardner LK. Soft tissue response to endosseous titanium oral implants. J Prosthet Dent 1985; 54:564-567. Kasemo B. Biocompatibility of titanium implants: Surface science aspects../ Prosthet Dent 1983; 49:832-837. Loechler PS, Mueller MW. Successful implant dentures. Northwest
Dent 1952; 31:134-139. 13. Bodine
14.
15.
RL, Mohammed CI. Implant denture histology: Gross and microscopic studies of a human mandible with a 12-year subperiosteal implant denture. Dent Clin North Am 1970; 14:145-159. James R. A histopathological study of the nature of the epithelium surrounding implant posts. Part I../ Oral Implantai 1972; 3:105-122. James R. A histopathological study of the nature of the epithelium surrounding implant posts. Part II. ./ Oral Implantai 1973; 3:137159.
Listgarten MA,
Lai CH. Ultrastructure of the intact interface between endosseous epoxy resin dental implant and the host tissue. J Biol Buccale 1975; 3:13-28. 17. Swope EM, James RA. A longitudinal study on hemidesmosome 16.
an
J Periodontol 160
18.
19.
20.
21.
22. 23. 24.
25.
26.
27.
28. 29.
TITANTIUM IMPLANT SOFT TISSUE INTERFACE: A REVIEW formation at the dental implant-tissue interface../ Oral Implanto! 1981; 9:412-422. Baumhammers A, Langkamp HH, Matta RK, Kilbury K. Scanning electron microscopy of epithelial cells grown on enamel, glass and implant materials. J Periodontol 1978; 49:592-597. Kasten FH, Soileau KM and Meffert RM. Quantitative evaluation of human gingival epithelial cell attachment to implant surfaces in vitro. Int J Periodontics Restorative Dent 1990; 10:68-79. Gould TRL, Brunette DM, Westbury L. The attachment mechanisms of epithelial cells to titanium in vitro. / Periodont Res 1981; 16:61 16. Jansen JA, DeWijn JR, Wolters-Lutgerhorst ML, VanMullem PJ. Ultrastructural study of epithelial cell attachment to implant materials. J Dent Res 1985; 64:891-896. James RA. The support systems and the pergingival defense mechanism of oral implants. J Oral Implantai 1976; 6:270-279. James RA. Peri-implant considerations. Dent Clin North Am 1980; 24:415-420. Dmytryk J, Fox S, Moriarty J. The effects of scaling titanium implant surfaces with metal and plastic instruments on cell attachment. J Periodontol 1990:61;491-496. Hobo S, Ichida E, Garcia LT. Osseointegration and Occlusa! Rehabilitation. Chicago: Quintessence Publishing Company; 1989:3354. Gould TRL, Brunette DM. Ultrastructural study of the attachment of human gingiva to titanium in vivo. J Prosthet Dent 1984; 52:418420. Hansson HA, Albrektsson T, Branemark PI. Structural aspects of the interface between tissue and titanium implants. J Prosthet Dent 1983; 50:108-113. Albrektsson T, Branemark PI, Hansson HA, Lindstrom J. Osseointegrated titanium implants. Acta Orthop Scand 1981; 52:155-170. TenCate AR. The gingival junction. In: Branemark PI, Zarb GA, Albrektsson T, eds. Tissue Integrated Prosthesis. Chicago: Quintessence
Publishing Company; 1985;145-153.
30. Brunski J, Hipp JA, El-Wakad M. Dental implant design: Biomechanics and interfacial tissues. J Oral Implantai 1986; 12:365-377. 31. Lavelle CLB. Mucosal seal around endosseous dental implants. J Oral
32.
Implantai 1981; 9:357-371. McKinney RV, Stefiik DE, Koth
DL. Evidence for a junctional epithelial attachment to ceramic dental implants: A transmission electron microscopic study. J Periodontol 1985; 56:579-591. 33. Meffert RM. The soft tissue interface in dental implantology. lmplantologist 1986; 5:55-58. 34. Meffert RM. Periodontal implications of endosseous implants. In: Schluger S, Yuodelis R, Page RC, Johnson RH. Periodontal Diseases. 2nd ed. Philadelphia: Lea and Febiger; 1990; 70,7-731. 35. Meffert RM. Implant therapy. In: Nevins M, Becker W, Kornman K. Proceedings of the World Workshop in Clinical Periodontics. Chicago: American Academy of Periodontology; 1989; Section VIII, pg 1-10.
February 1991 36. Doundoulakis JH. Surface analysis of titanium after sterilization: Role in implant-tissue interface and bioadhesion. / Prosthet Dent 1987;
58:471-478. 37. Melcher AH.
Summary of biological plantai 1988; 5(2):31-32.
considerations. Int J Oral Im-
38. Brunette M, Kenner GS, Gould TRL. Grooved titanium surfaces orient growth and migration of cells from human gingival explants. J Dent Res 1983; 62:1045-1048. 39. Inoue T, Cox JE, Pillar RM, Melcher AH. Effect of the surface geometry of smooth and porous-coated titanium alloy on the orientation of fibroblasts in vitro. / Biomed Mater Res 1987; 21:107-126. 40. Lowenberg BF, Pilliar RM, Aubin JE, Férnie GR, Melcher AH. Migration, attachment and orientation of human gingival fibroblasts to root slices, naked and porous-surface titanium alloy discs and zircalloy 2 discs in vitro. / Dent Res 1987: 66; 1000-1005. 41. Meffert RM, Block MS, Kent JN. What is osseointegration? Int J Periodontics Restorative Dent 1987; 7(4):8-21. 42. Block MS, Kent JN, Kay JF. Evaluation of hydroxylapatite-coated titanium dental implants in dogs. J Oral Maxillofac Surg 1987; 45:601607. 43. DePorter DA, Friedland , Watson PA, et al. A clinical and radiographic assessment of a porous-surfaces, titanium alloy dental implant system in dogs. J Dent Res 1986; 65:1071-1077. 44. DePorter DA. Watson PA, Pilliar RM, Howley TP, Winslow J. A histological evaluation of a functional endosseous, porous-surfaced, titanium alloy dental implant system in the dog. / Dent Res 1988; 67:1190-1195. 45. Schroeder A, Van der Zypen E, Stuch H. Sutter F. The reaction of bone, connective tissue and epithelium to endosteal implants with titanium-sprayed surfaces. J Maxillofac Surg 1981; 9:15-25. 46. Garguilo A, Wentz F. Orban B. Dimensions and relations of the dento-gingival junction in humans. / Periodontol 1961; 32:261-267. 47. Adell R, Lekholm U, Rockler B, et al. Marginal tissue reactions at osseointegrated titanium fixtures. (I) A 3-year longitudinal prospective study. Int J Oral Maxillofac Surg 1986; 15:39-52. 48. Lekholm U, Adell R. Lindhe J, et al. Marginal tissue reactions at osseointegrated titanium fixtures. (II) A cross-sectional retrospective study. Int J Oral Maxillofac Surg 1986; 15:53-61. 49. Apse P, Ellen RP, Overall CM, Zarb GA. Microbiota and crevicular fluid collagenase activity in the osseointegrated dental implant sulcus. A comparison of sites in edentulous and partially edentulous patients. J Periodont Res 1989; 24:96-105. 50. Sanz M, Alandez J, Van Steenberghe D, Quirynen M, Newman M, Flemmig T. Histological and ultrastructural characteristics of periimplant gingival tissues. Presented at Academy of Periodontology Annual Meeting October 25, 1989, Washington, DC. Send reprint requests to: Dr. Timothy G. Donley, Associated Specialists, 110 Fort Couch Rd., Pittsburgh, PA 15241. Accepted for publication August 6, 1990.
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