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- Alenezi, Ali
(författare)
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On enhancement of bone formation using local drug delivery systems
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Despite that many reports have confirmed the long-term clinical success rates associated with implant treatment, implant failure to achieve and maintain osseointegration still occurs in many cases. Local and sustained drug release at the bone-implant interface is one of the strategies that have been suggested to improve the osseointegration. The local drug release could help avoiding the risks usually associated with systemic administration, such as high drug dose or the loss of drug bioavailability. Aims: To map out the most commonly used chemical compounds and drug delivery systems used in animal experiments for implant research (Study I). Furthermore, to develop a new surface coating designed for medical devices and implants, and to examine the drug release mechanism from the coating using near infrared light (NIR) as an external stimulus (Study II). In addition, we examined the release of clarithromycin from PLGA microspheres within beta-tricalcium phosphate (β-TCP), and evaluated their osteogenic effect in a calvaria defect model in vivo (Study III). In Study IV, we evaluated the local release of strontium ranelate (Sr-ranelate) from implant surface coated with mesoporous titania films, and investigated if the local release of Sr-ranelate could improve bone formation around implants in an animal model. Materials and Methods: The articles included in the present thesis consist of four different studies. For Study I, an electronic search was done in three databases (PubMed, Scopus, Embase) to map out the most commonly used methods for local drug and chemical compound delivery to implant sites, and to assess their influence on bone response. Meta-analyses were performed for the outcome of bone-to-implant contact (BIC). In Study II, PNIPAAm-AAm polymers were synthesized at different compositions. The polymers were then incorporated with gold nanorods (GNRs) since these rods at predetermined aspect ratio can absorb NIR light to generate heat within the polymeric layer to initiate a drug release. The volume-phase transition behavior for the polymers was analyzed using differential scanning calorimetry (DSC). The GNRs-incorporated PNIPAAm was characterized using scanning electron microscopy (SEM) and quartz crystal microbalance with dissipation monitoring (QCM-D). The release behavior using phenol as drug model was investigated upon NIR irradiation using UV/VIS spectroscopy. In addition, the antibacterial behavior of polymer layers loaded with vancomycin was examined against Staphylococcus epidermidis. In Study III, four bone defects (5 mm of diameter) were created in the calvaria of New Zealand White rabbits (n = 21, n= 7/time point). The defects were randomly designated to four groups. Group 1: no augmentation (sham), Group 2: β-TCP, Group 3: β-TCP with 0.12 mg clarithromycin, and Group 4: β-TCP with 6.12 mg PLGA microspheres loaded with 0.12 mg clarithromycin. After 2, 4, and 12 weeks of healing, bone regeneration was evaluated using micro-computed tomography (µCT) and histology. In Study IV, mini-screw titanium implants were coated with mesoporous TiO2 films using Pluronic (P123) with or without poly propylene glycol (PPG) to create films with two different pore sizes. The implants were then incorporated with Sr-ranelate. SEM evaluation was performed to visualize the mesoporous TiO2 films and determine the pore size. The absorption and release kinetics of Sr-ranelate from mesoporous TiO2 films were evaluated by QCM-D. For the in vivo experiment, mini-screw titanium implants with or without Sr-ranelate were inserted in rats’ tibia bone to evaluate bone formation after 2 and 6 weeks. Results: In the systematic review (Study I), sixty-one studies met the inclusion criteria. Calcium phosphate (CaP), bisphosphonates (BPs), and bone morphogenetic proteins (BMPs) were the most commonly used chemical compounds. There were two main methods for local drug delivery at the bone-implant interface: (1) directly from an implant surface by coating or immobilizing techniques, and (2) the local application of drugs to the implant site, using carriers. There was a statistically significant increase in BIC for both local drug delivery methods (p= .02 and p < .0001, respectively) when compared to controls. There was a statistically significant increase in BIC when CaP (p= .0001) and BMPs (p= .02) were either coated into implants or delivered to the implant site, in comparison to when drugs were not used. The difference was not significant for the use of BPs (p= .15). In Study II, the DSC analyses showed that PNIPAAm-AAm containing 10% acrylamide had an appropriate phase transition temperature of 42◦C. SEM images showed that the surface coating consisted of a 200 nm thick uniform polymer layer. The QCM-D analysis coupled with in situ NIR irradiation demonstrated a dramatic shift in frequency that was attributed to mass being released from the surface upon irradiation. This mass release correlated well with the drug release profile as determined using UV/VIS spectroscopy with phenol as a model drug. For Study III, clarithromycin release from PLGA microspheres revealed sustained release for around 4 weeks with 50% release during the first week. Histologically, new bone formation was evident at 2 and 4 weeks of healing in all groups and bone formation increased as a function of healing time. At 12 weeks, Group 4 (β-TCP with PLGA microspheres loaded with clarithromycin) showed significantly higher amount of newly formed bone compared to Group 1 (sham). The µCT showed that Group 4 expressed significantly higher bone formation compared to Group 1 at all time points. In Study IV, the SEM images showed TiO2 films with porous structures covering the entire surface with pore sizes determined to be 6 nm for P123 and 7.2 nm for P123-PPG. The QCM-D analysis revealed an absorption of 3300 ng/cm2 of Sr-ranelate on the 7.2 nm TiO2 films, which was about 3 times more than the observed amount on the 6 nm TiO2 films (1200 ng/cm2). The histomorphometric analyses revealed higher percentages of bone implant contact (BIC) and bone area (BA) for implants with Sr-ranelate compared to implants in the control group after 2 and 6 weeks of healing. However, these differences were found not to be significant (BIC with a p-value of 0.43 after 2 weeks and 0.172 after 6 weeks), (BA with a p-value of 0.503 after 2 weeks, and 0.088 after 6 weeks). The mean BIC and BA values within the same group showed significant increase among all groups after comparing 2 and 6 weeks. Conclusions: Most studies assessing local drug/chemical compound release systems in implants evaluated the influence of the use of BPs, CaP, and BMPs on bone healing. The use of local chemical compound delivery systems around implants could significantly improve implant osseointegration in animal models (Study I). In addition, on demand-release of the antibiotic agent vancomycin from the coating induced by NIR light resulted in a clear inhibition zone around a coated substrate in a bacteria culture test, thereby providing proof of concept of the developed drug delivery system (Study II). The in vivo findings showed that β-TCP with clarithromycin-loaded microspheres can enhance bone formation in bone defects (Study III). Meanwhile, the in vivo findings on Sr-ranelate study (Study IV) could not confirm the positive effects of Sr-ranelate on implant incorporation in bone made by other authors.
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| 3. |
- Braian, Michael
(författare)
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Digital dentistry : studies on the trueness and precision of additive manufacturing and intraoral scanning
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Artificial designs and features usually control production workflowsin the industry. The operator has the freedom to adapt designs toachieve the desired function; when the operator is satisfied, massproduction of the two objects is possible. The production workflowfor prosthetic restorations in dentistry is a fairly complicatedprocedure that requires several well-controlled processes, and eachunit is individually adapted to one unique situation. The aim of thefinal restoration is to replace damaged or missing soft and hard tissue,and to restore function, phonetics and aesthetics. The restoration hashigh material property requirements in order to withstand high forces,thermal changes, aging and humidity. If the fit of the reconstructionis insufficient there is a high probability for clinical failures rangingfrom inflammatory processes to reconstruction fractures. Thegrading of perfect, sufficient and insufficient fit is unknown althoughthe definition clinically acceptable fit has been used to describe andcontrol a reconstruction that is well seated and controllable by the clinician. Study I in this thesis focuses on the clearance (play) betweendifferent implant components in order to achieve a threshold value forhow accurate the production in dentistry needs to be. We found thatmetallic components on external hex connections have a clearanceof approximately 50 μm.Not only is every case individually designed and manufactured,but the receiving intraoral part also needs to be replicated into anextraoral part ahead of production, a procedure that has been possiblewith different impression materials. Subsequently, the production goes through a series of controlled compensations to fit the intraoralsituation. The conventional workflow starts by the selection of animpression tray, ranging from custom-made trays to plastic stocktrays. The ideal trays are rigid, thereby minimising flexure during theimpression taking. There are several types of impression materialswith different properties regarding setting time, volume changes andmechanical properties. The next step in the conventional workflowis the casting of the impression. There are various types of gypsumproducts utilised in dentistry, and they require different amounts ofwater. The differences depend on the shape and compactness of thecrystals. Type IV dental stone gypsum is often used in reconstructivedentistry with a typical setting expansion of 0.10%. For the partialdigital workflow the same volume changes can be seen for theconventional impression, the stone model production and the dieprocessing. In order to design the intended construction digitallyinstead of using wax, the model needs to be digitised in an extraoral scanner, also known as desktop scanner.The fully digital workflow consists of a direct digitisation of the oralcavity utilising intraoral scanning devices. All intraoral scanners havethe same goal, to digitise the size, shape and surface of a physicalobject into a geometrical virtual shape. This acquisition needs to berepeatable, reproducible and accurate. The IOS manufacturers tryto achieve these goals with different hardware and software setups.Study IV focuses on the acquisition accuracy of five different intraoralscanners for the digitisation of edentulous and dentated models. Theresults suggest that the devices had lower accuracy for the digitisationof the edentulous models when compared to the dentated model.Furthermore, Study IV presented observations suggesting that fullarchscans had lower accuracy when compared to shorter arch scanson both models. For the cross-arch measurements on the edentulousscans, the trueness values ranged from 6 μm to 193 μm, and, for the shorter arch measurements, the results ranged from 2 μm to 103 μm.For the dentated cast, the cross-arch trueness values ranged from6 μm to 150 μm, and, for the shorter arch measurements, the resultsranged from 4 μm to -56 μm.The digitised file is then utilised as a virtual model by a computeraideddesigner in order to virtually design the intended reconstruction.The designed file is then manufactured utilising computer-aidedmanufacturing, which can be performed either by a subtractivemachine (milling) or by additive systems (3D printing). Study II andStudy III explore the production tolerances for producing polymericand metallic objects from additive systems. Study III also containeda subtractive group. The results from these two studies suggest thatall tested additive systems for producing polymeric objects were, onaverage, 500 μm to
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| 5. |
- González Arribas, Elena
(författare)
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Flexible and transparent biological electric power sources based on nanostructured electrodes
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Portabel medicinteknisk utrustning framträder alltmer som en av de mest lovande metoderna för vårdövervakning och personlig behandling. Förebyggande vård och hantering av kroniska sjukdomar är resurskrävande och en överföring av det konventionella sjukhuscentrerade sjukvårdssystemet till ett individcentrerat vårdsystem skulle vara samhällsekonomiskt gynnsam. I ett sådant scenario representerar bärbara mätenheter en teknik för övervakning av patienter på ett icke-invasivt och lättanvänt sätt. Denna teknik har möjlighet att tillhandahålla långsiktiga hälsostatusövervakningar och förmedla realtidsdata som läkare kan analysera för att ge patienterna återkoppling utan att behöva träffa patienterna lika ofta. Dessutom är många utan kroniska sjukdomar också intresserade av att övervaka kroppens hälsotillstånd för att förhindra sjukdomar och uppnå en högre livskvalitet. Dagens bärbara enheter integrerar elektronik med låg strömförbrukning och trådlös teknik, s.k. ”low power wireless technology”, för att överföra information från enheten till en mottagare. Elektronik behöver tillförlitliga strömkällor för att säkerställa funktionen, och biologiska kraftkällor är särskilt lämpliga alternativ att använda i bärbara enheter, eftersom de har hög prestanda när de används under fysiologiska förhållanden. Olika biologiska kraftkällor har tillverkats och testats i denna avhandling. Materialen som används för att tillverka dem är transparenta och flexibla. Dessa två egenskaper bidrar starkt till användarvänligheten och ökar därmed benägenheten att använda sådana kraftkällor. De biologiska kraftkällorna omvandlar kemisk energi till elektrisk energi genom att oxidera glukos och reducera syre under förhållanden som liknar dem som föreligger i mänsklig tårvätska. Detta arbete bidrar till att öka kunskapen om flexibla, transparenta och nanostrukturerade material som används för tillverkning av biologiska kraftkällor.
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| 6. |
- Hallström, Hadar
(författare)
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On prevention and treatment of peri-implant inflammation
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focuses on prevention and treatment of biological complications around dental implants.BackgroundAn increasing number of individuals have restorations that are anchored to the jaws by dental implants. Modern-day implants are a Swedish invention that became available to patients in the 1970s. Implant restorations are common and several patients have had their implants for more than twenty years. The long-time survival rate is good, but as with all treatments, complications do occur. These complications can be technical problems, like fractures of the framework, discolouring and wear of the prosthesis, or fractures of the actual implant. Biological complications appear initially as peri-implant mucositis (PiM) which is a bacterially induced inflammation of the soft tissue around an implant. PiM may progress into peri-implantitis (Pi) that involves the implant supporting bone and can ultimately lead to loss of the implant. The prevalence of complications has been debated. Depending on patient population and definition used, the prevalence has been reported in the range of 19-65% for PiM and 1-47% for Pi. Treatment of peri-implant diseases consists of reinforcement of the patients’ oral hygiene, non-surgical mechanical therapy and incases with bone loss adjacent to the implant surgical interventions may be needed. Irrespective of treatment method complete resolution of the diseases is rare and even though no evidence exists that the use of antibiotics improves the treatment outcome antibiotics are often prescribed. Frequent use of antibiotics is a main contributor to the development of bacterial resistance that has developed into a serious global problem. Probiotics are live bacteria that inadequate doses are beneficial to the host and under certain circumstances have demonstrated abilities to hamper inflammations.AimsThe aim of the thesis was to clarify whether 1) probiotics administered in lozenges can prevent or lower the inflammatory reaction to plaque accumulation, 2) if the use of probiotics as an adjunct to mechanical treatment of peri-implant mucositis has a beneficiary effect, and 3) if systemically administered antibiotics given as additive enhance the outcome following the treatment of peri-implant mucositis and peri-implantitis.MethodsFour studies were designed to fulfil the aim:· a placebo controlled cross-over study testing whether probiotics can prevent or lower the inflammatory response to a bacterial challenge.· a placebo controlled RCT study evaluating whether probiotics given as an additive to mechanical treatment of peri-implant mucositis provides any benefits.· a RCT study evaluating whether systemically administered antibiotics given as an additive to mechanical treatment of periimplant mucositis are beneficial.· a RCT study evaluating whether systemically administered antibiotics given as an additive to surgical treatment of periimplantitis are beneficial.Clinical, microbiological, and immunological parameters were used to analyse study outcomes.Results· Daily probiotic lozenges had no significant effect on the inflammatory response in an experimental gingivitis model compared to placebo.· Daily probiotic lozenges as additive to oral hygiene instructions and mechanical debridement had no significant effect on the clinical, microbiological, or immunological outcome in the treatment of peri-implant mucositis compared to placebo.· Systemically administered antibiotics as additive to oral hygiene instructions and mechanical debridement had no significant effect on the clinical or microbiological outcome in the treatment of peri-implant mucositis.· Systemically administered antibiotics as additive to oral hygiene instructions and surgical mechanical debridement had no significant effect on the clinical or microbiological outcome in the treatment of peri-implantitis.ConclusionsNeither probiotics containing Lactobacillus reuteri or Azithromycin have any major effect on the treatment outcome of periimplant mucositis or peri-implantitis when given as additive to conventional treatment. The use of daily lozenges containing Lactobacillus reuteri yields no benefits when it comes to preventing gingivitis under experimental gingivitis conditions.
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| 7. |
- Milosavljevic, Aleksandar
(författare)
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Periodontal treatment strategies in general dentistry
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Periodontal diseases, such as gingivitis and chronic periodontitis,are infectious diseases that are common in the adult population. InSweden, treatment is mostly provided in general dentistry by generaldental practitioners (GDPs) and dental hygienists (DHs). Thecare chain also comprises periodontists since they act as consultantsto the GDPs and DHs. Several studies have explored how cliniciansjudge, diagnose, and treat patients with different diseasesbut no previous study has explored how patients, with commonlyoccurring periodontal conditions in a population, are diagnosedand treated in general dentistry. Therefore the overall aim of thethesis was to study the treatment strategies applied by general dentistryclinicians to patients with common periodontal conditions.This thesis is based on five studies, where study I-IV are based on aquestionnaire and conducted using a quantitative approach while study V is based on in-depth interviews and conducted using aqualitative approach. The questionnaire in study I-IV comprised four simulated patientcases with different periodontal conditions. These four cases representthe periodontal status of the majority of middle-aged patientspresented in a general dentistry practice: 1) Generalised bone lossbut minimal signs of inflammation (well-maintained), 2) Generalisedbone loss and signs of inflammation (periodontitis), 3) Negligiblebone loss and minimal signs of inflammation (healthy), and4) Negligible bone loss but with signs of inflammation (gingivitis).The clinicians who participated in the studies were asked to judge each patient case as healthy or diseased, propose a diagnosis, evaluatetreatment needs, propose a treatment plan, and assess theprognosis.In study I, GDPs and DHs were combined in one group as generaldentistry clinicians (GDCs) and compared as to their judgement,proposed diagnosis and proposed treatment. Key findings: Three ofthe four patient cases was each judged as healthy by some GDCsand as diseased by others. The difference in judgement did not influencethe GDCs’ intention to treat or their proposed treatmentmeasures but did influence the estimated number of treatment sessions. In study II, GDCs were compared as to their prognostic assessment,treatment goals and estimation of treatment extent in termsof more or less treatment assigned to a given patient case in comparisonto the other patient cases (healthy patient case excluded).Key finding: The majority of GDCs was in general pessimistic intheir prognostic assessment and anticipated that all patient caseswere to experience a deterioration of their periodontal condition.The most common treatment goal, irrespective of the patient case,was to improve oral health awareness. The periodontitis patientcase was estimated to need the most treatment; slightly more thanthe gingivitis and the well-maintained patient cases where a similartreatment extent was estimated. In Study III, dental students (DSs) from Paris (DSP) and Malmö(DSM) were compared to each other as to judgement, diagnosis,treatment plans, and prognostic assessment. This was done in orderto discover if difference in educational background might influenceDSs’ treatment strategies. Key finding: The majority of bothgroups of DSs judged all the patient cases as diseased. DSPs proposedperiodontitis as a diagnosis more readily and estimated ahigher risk for disease progression in patient cases with no obviousbone loss (healthy and gingivitis patient cases). DSPs also recommendedmore treatment measures and estimated longer treatmenttime for all the patient cases than DSMs. In study IV, periodontists were primarily compared amongst eachother and secondly to GDPs as to their judgement, diagnosis, proposedtreatment plans, and prognostic assessment. Key findings:Both periodontists and GDPs varied in their judgement and proposeddiagnosis. The difference in periodontists’ judgement influencedtheir intention to treat and prognostic assessment. The GDPsintended to treat three out of four patient cases (except the periodontitispatient case) more often and were more pessimistic in theirprognostic assessment of patient cases with negligible bone lossthan the periodontists. In Study V, the phenomenon of lived experience of performing aperiodontal treatment in the context of general dentistry was describedby analysing interviews from three different DHs using thedescriptive phenomenological psychological method. Key finding:The periodontal treatment is perceived more as a standardisedworkflow than as an individually tailored treatment. The patients’oral hygiene and self-awareness are experienced as crucial partswhile the mechanical infection control is perceived as successfulbut sometimes difficult to perform. The DHs are experiencing aneed to be supportive of the patient but are sometimes doubtful ofthe patient’s ability to achieve and maintain a positive change inoral health behaviour.
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| 8. |
- Stocchero, Michele
(författare)
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On Influence Of Undersized Implant Site On Implant Stability And Osseointegration
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of dental implants for the rehabilitation of edentulous areas is an established treatment, showing high success rates. Primary stability is one of the pre-requisites for osseointegration, and it is ensured by the mechanical interlocking at the bone to implant interface. Current procedures have changed from the original protocols, towards a reduction of treatment time. Nowadays, the achievement of a great magnitude of primary stability is demanded in clinical practice, since there is a trend to load the implant immediately or in the early stages after implant insertion. Aiming on this, several modifications have been introduced, such as more aggressive implant design, modified surfaces and novel surgical techniques. Undersized drilling preparation is one of the most commonly adopted protocols during the implant surgery. This technique creates an osteotomy that is consistently smaller than the implant diameter, so that a tight interfacial contact and compression is created. Clinically this is perceived with an increase of the insertion torque value (ITV). Albeit commonly performed, several aspects of undersized drilling are still not well investigated. It was hypothesized that a great magnitude of compression at the implant insertion would generate tissue damage and may trigger a negative bone response during the healing time. This could lead to an impairment of bone material properties, a decrease of stability and marginal bone loss. Based on a clinical need, the general aim of this thesis was a more consistent understanding of the effects of an undersized drilling osteotomy. Study I aimed to provide the current evidence based on the literature on biomechanical, biologic and clinical outcomes. An electronic and a manual search were undertaken including in vitro, animal, and clinical studies in which an undersized drilling protocol was compared with a non-undersized drilling protocol. 29 studies met the inclusion criteria, including 14 biomechanical, 7 biologic, 6 biologic and biomechanical, and 2 clinical. A meta-analysis was not performed. Several studies showed that implants inserted with an undersized drilling approach reached a significantly higher ITV than conventional drilling in low-density substrates, while this effect is less evident in denser substrates. Similar long-term bone-toimplant contact (BIC) was achieved between implants inserted with undersized and non-undersized protocols. Results in the short term were inconclusive. Clinical studies did not show negative outcomes for undersized drilling in low-density bone, although clinical evidence was sparse. In study II, clinical outcomes were evaluated with a retrospective design, which included 87 patients treated with 188 implants inserted with an adapted drilling protocol according to the surgeon’s perception of bone quality. ITV and Marginal bone loss (MBL) between implant placement and permanent restoration was calculated. ITV differed significantly based on mandible/maxilla, bone quality, implant diameter, and drilling protocol. Median MBL was 0.05 mm (0.00; 0.24). A significant difference was found between the mandible and maxilla and between drilling protocols. In particular, significantly higher MBL was found in the undersized drilling protocol. Multiple regression models were built to test the effect of independent variables on the outcomes. ITV was influenced by bone quality and implant diameter. MBL was influenced by bone quality, implant diameter, ITV, and the interaction between bone quality and ITV. It was estimated that MBL was greater with increased bone density and ITV. Study III aimed to evaluate in vivo the extent of cortical bone remodeling and the bone integration of implants placed after different drilling protocols. Forty-eight implants were inserted into the sheep mandible following two drilling protocols: undersized preparation and non‐undersized preparation. Healing time was set at 5 and 10 weeks. Removal torque (RTQ) was measured and the peri-implant bone was scanned using a micro-computed tomography (μ‐CT). Bone volume density (BV/TV) was calculated in pre‐determined hollow cylinders. Total BIC and newly‐formed BIC (newBIC) and Bone Area Fraction Occupancy (BAFO) was measured. Results showed that, at 5 weeks of healing, significantly greater RTQ value was present for the undersized group, while non-undersized group presented greater values of BV/TV, newBIC and BAFO. No differences were noted at 10 weeks. The purpose of study IV was to assess bone material properties and to predict the strain/stress distribution on cortical bone using a multiscale in silico model. Two types of micro-scale bone structures were assessed: cortical bone models with resorption cavities and without resorption cavities, following undersized and non-undersized drilling protocols respectively. In a macro-scale model, oblique load of 100N was simulated. Maximum principal stress/strain, and shear stress/ strain were calculated. Bone with resorption cavities presented anisotropic material properties. Compared to bone without cavities, greater maximum values of Maximum principal stress/strain was calculated, both in macro- and micro-scale models. These values were located at the implant neck area and in the proximity of cavities respectively. Greater values of shear stress/strain were found in the test along the mandibular longitudinal plane. In summary, this thesis suggested that undersized drilling technique can cause negative effects in the cortical bone. The literature indicated that undersized drilling technique is effective in increasing the ITV in low-density bone. However, ITV is mostly influenced by bone quality, rather than drilling protocol. Furthermore, high ITV can induce greater bone resorption in dense bone. Cortical bone has the capability to maintain high levels of rotational stability at undersized sites in the early phases of healing, despite the great amount of micro-damage. From a biologic point of view, this procedure causes a reduced apposition of newly formed bone at the interface and it initiates an intense bone resorption activity in the surrounding tissue. This creates a temporary porosity into cortical bone, reducing the volume of peri-implant mineralized tissue. Intra-cortical resorption cavities caused an impairment of material properties and compromised mechanical behavior. This bone model is more prone to micro-damage and to a delayed healing process. Therefore, avoiding early loading protocols is recommended. Future clinical studies should focus on the longer-term outcome of undersized drilling, since the current clinical evidence is insufficient.
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