Aspects of oral implant technology and osseointegration

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Aspects of oral implant technology and osseointegration


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Publication Doctoral Thesis
Doctoral Thesis, comprehensive summary
Title Aspects of oral implant technology and osseointegration
Author Rezende de Jesus, Rainde Naiara
Date 2019
English abstract
Implant rehabilitation of edentulous patients is a predictable treatment with high long-term survival rates (90-95%) reported for the major dental implant systems after 5-10 years in function. Throughout recent years, different materials, implant surface technologies, macrodesigns, and surgical techniques have been developed to enhance osseointegration and lessen treatment timeframes, for example allowing immediate or early functional loading in patients with reduced bone density. In regards with implant surface properties, hydrophilicity ensures a more rapid coverage of the implant surface with blood and biological fluids, and a faster blood clot formation; this, in combination with the synergistic effect of micro- and/or nanotopography of the implant surface, lead to faster resolution of inflammation and positive modulation of osteogenesis, in turn enhancing the rate and quality of bone-to-implant contact (BIC). Specifically, a novel modification of sandblasted, dual acid-etched surface (SAE) implants to increase hydrophilicity (SAE-HD) has been suggested to enhance osseointegration during the early healing period in a preclinical in vivo model of rabbit tibia in comparison to the hydrophobic SAE surface. However, its histomorphometrical parameters of osseointegration and biomechanical properties have not been investigated in large animal platforms of low- and high-density bone. Furthermore, there is limited knowledge regarding the possible combined modulatory impact of implant macrogeometry and surface hydrophilicity on osteoclastogenesis. In regards with the surgical technique for implant installation, contemporary practice dictates that the implant site is prepared slightly narrower than the implant diameter as per standard (i.e. there is slight mismatch of the inner and outer implant diameter in relation to the drilled bone walls with the implant threads engaging with the bone in the pursuit of high primary implant stability, as measured by maximum insertion torque values (ITV). However, excessive lateral compression of highly-dense trabecular bone and thick cortex has been shown to cause microdamage and necrosis, triggering extensive interfacial bone remodeling, which in turn negatively affects the biomechanical competence of the implant site throughout the healing period. Recently, an oversized drilling technique has been proposed, where the final drill for site preparation has similar or slightly larger diameter than that of the inner implant diameter; this creates closed “healing chambers” between the inner implant diameter and the surgically instrumented bone wall. It is suggested that in spite of low ITV achieved with this surgical approach, the osteoconductive properties of modified implant surfaces positively modulate host-to-implant interactions and enhance osseointegration. However, research to date appears remarkably controversial on this topic, while studies reporting on marginal peri-implant bone levels (MBL) of highly dense bone are limited. The general aim of the present thesis was to evaluate the possible impact of aspects of current oral implant technology, i.e. surface hydrophilicity, implant macrogeometry, and surgical preparation of the implant recipient site, on implant osseointegration. Specifically, it was hypothesized that: • Implants with a chemically modified micro-rough surface would achieve higher BIC and interfacial shear strength in comparison to hydrophobic implants. • Oversized implant recipient sites, by applying sequential profiling and/or tapping of the bone, would promote higher amount and better quality of osseointegration in comparison to undersized-drilled sites. In study I and II, histomorphometrical parameters (BIC and relative peri-implant bone density [BD]) and biomechanical properties (removal torque value [RTV], removal energy, and connection stiffness]) at SAE (control) and SAE-HD (test) implants were assessed at early stages of osseointegration. Two pairs of SAE and SAE-HD implants, of same microgeometry, were installed bilaterally in the proximal tibia of six Beagle dogs and assessed after 2 and 4 weeks of healing. In study I, histomorphometrical parameters were analyzed on non-decalcified sections. In study II, the removal torque test (RTQ) was conducted on a Shimadzu universal testing machine. Results showed that BIC, BD, RTV, and removal energy increased with time in both SAE and SAE-HD implants. No significant differences were observed between the two groups for any of the evaluated parameters and at any observation time-point but a slight increase over time during the early osseointegration period. In study III, the influence of the implant thread design (trapezoidal vs. triangular threads) and surface hydrophilicity (SAE-HD vs. SAE) on osteoclast (OC) differentiation, activation, and survival was evaluated in vitro in a model of RAW 264.7 cells. Titanium disks with SAE or SAE-HD surface and different macrodesign, comprising of trapezoidal (HLX) or triangular threads (TMX) were used: HLX/SAE-HD, HLX-SAE, TMX/SAE-HD, and TMX/SAE. RAW264.7 macrophages were seeded on the disks, differentiated to OC by RANKL treatment and cultured for 5 days. OC differentiated on polystyrene plates were used as positive controls [CCPC (+)]. OC differentiation and viability were assessed by enzymatic TRAP activity and MTT assays. Expression levels of various OC-related genes were measured at the mRNA level by qPCR. SAE-HD surfaces negatively modulate macrophage/osteoclast viability. Specifically, SAE-HD with triangular threads increases the cellular pro-inflammatory status, while surface hydrophilicity and macrodesign do not seem to have a distinct impact on OC differentiation and activation in vitro in a model of RAW 264.7 cells. In study IV, the current evidence on the effects of oversized surgical preparation of the implant site in terms of biomechanical properties (ISQ, ITV, and RTV) and biological parameters of osseointegration (BIC and BD) was systematically assessed in preclinical animal studies. Electronic databases were searched for preclinical in vivo controlled studies reporting on drilling techniques according to the relative implant-final drill discrepancy (IDD; mm), defined herein as the dimensional mismatch between the outer implant diameter and the bone wall in the implantation bed: (1) control ≥ 0.2 mm (press-fit/standard to undersized implant drilling technique); (2) test OD = 0.0 – 0.1 mm (oversized drilling technique to achieve either nearly or precisely similar dimension between the bone defect and the implant outer diameter); and (3) test GAP ≤ –0.1 mm (oversized drilling technique presenting a gap between the bone defect and the implant outer diameter). Random effects meta-analyses were performed for the outcomes ITV, RTV, BIC, and BD at different healing periods. Evidence from 12 studies indicate that oversized surgical preparation of the implant site appears to minimize marginal bone resorption characterized by fast rates of new bone formation in the healing chambers through an intramembranous-type healing mode. However, in terms of biological and biomechanical parameters of osseointegration, oversized implant sites does not seem to provide any additional benefit compared to narrower implant sites, neither at the time of implant placement nor during the early healing period, yielding comparable results at the late post-operative period in different experimental animal models. In study V, the effect of oversized surgical preparation of the implant site on histomorphometrical parameters of osseointegration (BIC and BD) and marginal peri-implant bone level (MBL) of tapered implants with a progressive thread geometry was evaluated following 12 weeks in vivo in the mandible of minipigs. Ten implants with hydrophilic surface (SAE-HD) were inserted in the edentulous mandible of each of 5 female minipigs, by applying different drilling protocols (standard [SD, control] vs. oversized [OD, test]). SD included a 3-step series of drills without profiling of the cortical bone (IDD = 0.3 mm). OD included a 5-step series of drills and profiling of the cortical bone which resulted, respectively, in two IDD along the implant axis: (1) IDD = 0.1 mm in the 8-mm central apical length of the osteotomy; and (2) IDD = 0.0 mm in the 3.5-mm coronal length. Maximum ITV was recorded and non-submerged healing was allowed for 12 weeks (n = 5). Oversized surgical preparation of the implant site yielded low ITV at tapered implants with a progressive thread geometry, but enhanced osseointegration and peri-implant bone density, and preserved better the MBL.
Swedish abstract
Behandling med käkbensförankrade tandimplantat är en vanlig metod för att ersätta förlorade tänder hos helt och partiellt tandlösa patienter. Trots att implantatbehandling uppvisar en långsiktigt hög lyckande- och överlevnadsfrekvens (90–95% efter 10 år) så förekommer implantatförluster och marginal benförlust kring implantaten under det första året efter insättning och/eller belastning, vilket kan försämra det estetiska resultatet. För att förhindra tidiga implantatförluster och/eller den marginala benremodelleringen görs olika modifieringar av de topografiska, fysikaliska och kemiska egenskaperna hos implantatytorna i syfte att påskynda och öka benbildningen i kontakt med implantatet (bone-to-implant contact [BIC]). Till exempel uppvisar en hydrofil yta med moderat råhet (höjdavvikelser på omkring 1.5 µm) en snabbare beläggning av blod jämfört med en hydrofob yta, vilket i sin tur påverkar den tidiga läkningen genom migrering och differentiering av benbildande osteoblaster. En annan metod som föreslagits för att förbättra osseointegrationen (beninläkningen) och den marginala bennivån kring implantaten är att öka primärtstabiliteten, d.v.s. den initiala mekaniska fixeringen i käkbenet. Implantatets primärstabilitet påverkas av bentätheten, implantatets design (d.v.s. utformning och gängdesign) och det använda borrprotokollet vid preparation av implantatsätet. Standardborrprotokollen innebär att ostetomien (borrhålet) är mindre än implantatets diameter (”relative implant-final drill discrepancy” [IDD]; 0.2 – 0.5 mm). Studier har visat att en underdimensionerad osteotomi, d.v.s. (IDD > 0.5 mm), kan förbättra osseointegrationen. Samtidigt har överdriven kompression av marginalt ben med hög täthet visat sig orsaka marginal bennekros, vilket ökar benresorptionen och risken för tidig implantatförlust. I gengäld har ”överdimensionering” av osteotomien, antingen med exakt samma dimension som implantatet eller med IDD ≤ –0.1 mm större än implantatet uppvisat kontroversiella resultat. Det primära syftet med avhandlingen var att utvärdera olika aspekter av nuvarande oralimplantatteknologi och dess effekter på osseointegrationen. I delarbete I och II utvärderades hos djur den biologiska responsen (BIC och relativ bendensitet [BD], studie I) och de biomekaniska egenskaperna (maximala momentvärdena vid implantatinsättning [RTV], borttagningsenergi och implantatanslutnings-styvhet, studie II]) på. Resultaten visade att BIC, BD, RTV och borttagningsenergin ökade med tiden i både hydrofoba- och hydrofila-ytor. Emellertid observerades inga signifikanta skillnader mellan de två grupperna avseende de utvärderade parametrarna vid någon av observationstidpunkterna. I delarbete III utvärderades påverkan av implantatsgängans design och ytvätbarhet på osteoklasternas differentiering, aktivering och överlevnad in vitro. Titandiskar framställdes med hydrofoba- och hydrofila-ytor och med gängor bestående av kvadratiska, trapezoid- och stödgeometri (progressiv gänggeometri) eller dubbel-triangulära geometri. Med molekylära analyser mättes osteoklasternas differentiering och livskraft, vidhäftning och morfologi samt expressionsnivåer av olika relaterade gener. Hydrofila ytor modulerade negativt makrofag/osteoklast livskraft. Specifikt ökar hydrofila ytor med dubbel-triangulära gängdesign den cellulära proinflammatoriska responsen, medan hydrofoba ytor och implantatsgängans design inte verkar ha någon tydlig inverkan på osteoklasternas differentiering, aktivering eller överlevnad. I delarbete IV utvärderades de biomekaniska och biologiska effekterna av överdimensionerad, standard och underdimensionerad osteotomi genom en systematisk litteraturöversikt. Utfallet av ITV, RTV, BIC och BD vid olika läkningsperioder testades statistiskt för att upptäcka signifikanta skillnader. Resultat från 12 studier tyder på att överdimensionerade osteotomi verkar minska den marginala benresorptionen, kännetecknad av snabbare och ökad benbildning i de ihåliga utrymmena. Emellertid uppvisar överdimensionerade osteotomier inte vid någon observationstidpunkt några ytterligare fördelar av de mätta osseointegrationsparametrarna jämfört med standardtillvägagångssättet eller underdimensionerade osteotomier. I delarbete V utvärderades, hos djur, den biologiska responsen (BIC och relativ bendensitet [BD]) och MBL av överdimensionerad osteotomi (OD) på avsmalnande implantat med en progressiv gänggeometri i jämförelse med det standard tillvägagångssättet (SD) efter en läkningsperiod på 12 veckor. SD inkluderade ett borrprotokoll med 3-stegsserie av borrar, medan OD omfattade en 5-stegsserie. Även om OD gav ett lågt ITV vid avsmalnande implantat med hydrofil yta så förbättrades osseointegrationen och bendensiteten och MBL bevarades bättre. Sammanfattningsvis indikerar denna avhandling: • Att hydrofila och hydrofoba implantat med en moderat ytråhet uppvisar likartad potential för framgångsrik osseointegration med starka biomekaniska egenskaper. • Att hydrofilicitet modulerar negativ makrofag/osteoklast livskraft, men varken vätbarhet eller gängdesign verkar ha en distinkt påverkan på osteoklast differentiering, aktivering och överlevnad in vitro. • Att överdimensionerad osteotomi uppvisar en stor heterogenicitet och kontrovers när det gäller dess eventuellt positiva effekter på osseointegrationen jämfört med en standard osteotomi, men vid tillfällen av tätt och tjockt marginalt ben förbättrade överdimensionerade osteotomier osseointegrationen och bentätheten jämfört med standardtillvägagångssättet, samt bevarade bättre den marginala bennivån.
DOI (link to publisher's fulltext.)
Publisher Malmö University, Faculty of Odontology
Series/Issue Doctoral dissertation in odontology;
ISBN 9789178770090
Language eng (iso)
Subject biomaterials
oral implants
surface topography
surface roughness
surface energy
surface wettability
implant body
thread design
surgical protocol
oversized drilling
bone-to-implant contact
bone density
primary implant stability
insertion torque
removal torque
removal energy
connection stiffness
RAW264.7 cells
gene expression
Research Subject Categories::ODONTOLOGY
Included papers
  1. de Jesus RNR, Stavropoulos A, Oliveira MTF, Soares PBF, Moura CCG, Zanetta-Barbosa D. Histomorphometric evaluation of a dual acid-etched vs. a chemically modified hydrophilic dual acid-etched implant surface. An experimental study in dogs. Clinical Oral Implants Research. 2017,28(5): 551-557. doi: 10.1111/clr.12833.

  2. de Jesus RNR, Carrilho E, Antunes PV, Ramalho A, Moura CCG, Stavropoulos A, Zanetta-Barbosa D. Interfacial biomechanical properties of a dual acid-etched versus a chemically modified hydrophilic dual ac-id-etched implant surface: an experimental study in Beagles. International Journal of Implant Dentistry. 2018,4(1): 1-10. doi: 10.1186/s40729-018-0139-1.

  3. de Jesus RNR, Tsatsanis C, Moura CCG, Zanetta-Barbosa D, Stavropoulos A. III. Differential modulation of osteoclastogenesis by macrogeometrically designed hydrophobic and chemically modified hydrophilic titanium surfaces. (Submitted)

  4. de Jesus RNR, Pandis N, Zanetta-Barbosa D, Stavropoulos A. Oversized surgical preparation of the implant site: systematic review and meta-analysis of preclinical studies. (In manuscript)

  5. de Jesus RNR, Serafeim P, Zanetta-Barbosa D, Stavropoulos A. Effect of an oversized implant site preparation on osseointegration of submerged tapered titanium implants: a study in the minipig mandible. (In manuscript)

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