Effect of bisphosphonates on anodized and heat-treated titanium surfaces: an animal experimental study

Background: Recent investigations reported that osseointegration of titanium implants can be significantly reinforced with a nanostructure treated with anodic oxidation and heat treatment. This experimental study investigates the effect of bisphosphonates on the nanotubular implant surface in rats. Methods: Thirty‐six titanium implants were divided into three groups: 1) machine‐turned (MT), 2) anodized and heat‐treated (AH), and 3) anodized and heat‐ and bisphosphonate‐treated (AHB) groups. The 36 implants were randomly placed in both tibias of 18 male Wistar rats. After 2 and 4 weeks, the levels of osseointegration of the implants were evaluated by a removal torque test and microcomputerized tomography (μCT). Peri‐implant bone tissue on the extracted region was examined for the expression of type I collagen and osteocalcin. Results: The AHB group showed the highest removal torque at 2 and 4 weeks (13.92 ± 1.51 Ncm and 18.10 ± 2.15 Ncm, respectively) followed, in order, by the AH group (11.63 ± 1.58 Ncm at 2 weeks and 14.80 ± 2.34 Ncm at 4 weeks) and MT group (4.30 ± 0.76 Ncm at 2 weeks and 6.20 ± 1.33 Ncm at 4 weeks) with statistically significant differences between the MT and other two groups at both time points. μCT images also revealed a denser appearance around implants in the AHB group than in the other groups. Levels of type I collagen and osteocalcin expression were similar between the MT and AH groups; however, the values were significantly higher in the AHB group compared to the other groups, which were 220.85% ± 71.09% and 363.04% ± 100.21%, respectively (P <0.05). Conclusion: Within the limits of this experiment, it was concluded that surface loading with bisphosphonates significantly improved the degree of osseointegration of titanium implants with a nanostructure.     

全身应用催产素对骨质疏松大鼠种植体骨结合的影响

目的 探讨骨质疏松大鼠全身应用催产素对种植体骨结合的影响。方法 20只大鼠平均分成对照组和实验组,接受双侧卵巢切除术以建立骨质疏松模型。12周后,在每只大鼠的双侧股骨远中干骺端各植入1枚种植体,同时接受催产素全身用药,实验组皮下注射催产素（每天1 mg•kg-1）,对照组注射生理盐水。用药4周后,观察8周,手术取出大鼠胫骨和带有种植体的股骨,采用显微CT和组织学染色观察大鼠胫骨的骨质疏松情况,用显微CT、组织学观察和推出试验评价骨结合效果。结果 实验组与对照组相比,胫骨样本的骨小梁增多、密集,交织成网状,骨质疏松模型成功建立。实验组种植体周围的相对骨体积分数为0.35%±0.06%,骨结合率为67.25%±9.06%,最大推出力为（70.32±10.91） N,对照组的相对骨体积分数、骨结合率和最大推出力分别为0.11%±0.02%、43.25%±7.01%、（21.65±4.36） N,实验组较对照组均明显增加（P<0.05）。结论 全身应用催产素可拮抗骨质疏松的负面影响,促进种植体愈合,对纯钛种植体的骨结合具有正向影响。     

Characterization of five different implant surfaces and their effect on osseointegration: a study in dogs

Background: Chemical modification of implant surface is typically associated with surface topographic alterations that may affect early osseointegration. This study investigates the effects of controlled surface alterations in early osseointegration in an animal model. Methods: Five implant surfaces were evaluated: 1) alumina‐blasting, 2) biologic blasting, 3) plasma, 4) microblasted resorbable blasting media (microblasted RBM), and 5) alumina‐blasting/acid‐etched (AB/AE). Surface topography was characterized by scanning electron microscopy and optical interferometry, and chemical assessment by x‐ray photoelectron spectroscopy. The implants were placed in the radius of six dogs, remaining 2 and 4 weeks in vivo. After euthanization, specimens were torqued‐to‐interface failure and non‐decalcified‐processed for histomorphologic bone–implant contact, and bone area fraction–occupied evaluation. Statistical evaluation was performed by one‐way analysis of variance (P <0.05) and post hoc testing by the Tukey test. Results: The alumina‐blasting surface presented the highest average surface roughness and mean root square of the surface values, the biologic blasting the lowest, and AB/AE an intermediate value. The remaining surfaces presented intermediate values between the biologic blasting and AB/AE. The x‐ray photoelectron spectroscopy spectra revealed calcium and phosphorus for the biologic blasting and microblasted RBM surfaces, and the highest oxygen levels for the plasma, microblasted RBM, and AB/AE surfaces. Significantly higher torque was observed at 2 weeks for the microblasted RBM surface (P <0.04), but no differences existed between surfaces at 4 weeks (P >0.74). No significant differences in bone–implant contact and bone area fraction–occupied values were observed at 2 and 4 weeks. Conclusion: The five surfaces were osteoconductive and resulted in high degrees of osseointegration and biomechanical fixation.     

Influence of involuntary cigarette smoke inhalation on osseointegration: a systematic review and meta-analysis of preclinical studies

There are no studies that have systematically reviewed the influence of involuntary cigarette smoke inhalation (ICSI) on the stability of implants. The aim of the present study was to perform a systematic review and meta-analysis of preclinical studies that assessed the influence of involuntary cigarette smoke inhalation ICSI on osseointegration. Indexed databases (PubMed, Google-Scholar, Scopus, EMBASE, and Web of Knowledge) were searched till September 2017. Titles and abstracts of studies identified using the above-described protocol were independently screened by 2 authors. Full-texts of studies judged by title and abstract to be relevant were independently evaluated for the stated eligibility criteria. Nine studies were included. Six studies showed that ICSI compromised bone area contact around implants. In 4 studies, peri-implant bone mineral density was significantly higher in the control group than among subjects exposed to ICSI. For the effects of ICSI on the osseointegration of dental implants, significant differences could be observed for bone-to-implant contact for test subjects in cancellous (Z = ?4.08, p < 0.001) and cortical bone (Z = ?4.31, p < 0.001) respectively. ICSI may negatively influence osseointegration of dental implants. It is imperative to educate patients about the negative effects of passive smoking on dental and systemic health.     

Effect of antiangiogenic targeted chemotherapy on the osseointegration of titanium implants in rabbits

Patients with cancer have recently been treated with more advanced targeted chemotherapies that have greater specificity towards the cancer cells and fewer side effects. However, the periods of treatment take longer than those of traditional cytotoxic treatments. The aim of this study was to examine the effect of antiangiogenic targeted chemotherapy on the osseointegration of titanium implants. Fourteen white New Zealand rabbits were allocated randomly into two groups of seven: the placebo control group and the Avastin^® group. Animals in the Avastin^® group had five doses of bevacizumab intraperitoneally (3 mg/kg/week). The first was given two days before the implant was inserted and the remaining four were given weekly for four weeks. One titanium implant was inserted in the right distal femoral condyle of each rabbit. Osseointegration of the implants was measured using microcomputed tomography (CT) and histomorphometric evaluation. Both of these showed less osseointegration in the Avastin^® group than in the controls. The pharmacological inhibition of angiogenesis by bevacizumab may negatively affect the osseointegration of titanium implants in rabbits.     

Early osseointegration to hydrophilic and hydrophobic implant surfaces in humans

Objective: To evaluate the rate and degree of osseointegration at chemically modified moderately rough, hydrophilic (SLActive) and moderately rough, hydrophobic (SLA) implant surfaces during early phases of healing in a human model. Material and methods: The devices used for this study of early healing were 4 mm long and 2.8 mm in diameter and had either an SLActive chemically modified or a moderately rough SLA surface configuration. These devices were surgically installed into the retro‐molar area of 49 human volunteers and retrieved after 7, 14, 28 and 42 days of submerged healing. A 5.2‐mm‐long specially designed trephine with a 4.9 mm inside diameter, allowing the circumferential sampling of 1 mm tissue together with the device was applied. Histologic ground sections were prepared and histometric analyses of the tissue components (i.e. old bone, new bone, bone debris and soft tissue) in contact with the device surfaces were performed. Results: All device sites healed uneventfully. All device surfaces were partially coated with bone debris. A significant fraction of this bone matrix coating became increasingly covered with newly formed bone. The process of new bone formation started already during the first week in the trabecular regions and increased gradually up to 42 days. The percentage of direct contact between newly formed bone and the device (bone‐to‐implant contact) after 2 and 4 weeks was more pronounced adjacent to the SLActive than to the SLA surface (14.8% vs. 12.2% and 48.3% vs. 32.4%, respectively), but after 42 days, these differences were no longer evident (61.6% vs. 61.5%). Conclusion: While healing showed similar characteristics with bone resorptive and appositional events for both SLActive and SLA surfaces between 7 and 42 days, the degree of osseointegration after 2 and 4 weeks was superior for the SLActive compared with the SLA surface. To cite this article :
Lang NP, Salvi GE, Huynh‐Ba G, Ivanovski S, Donos N, Bosshardt DD. Early osseointegration to hydrophilic and hydrophobic implant surfaces in humans.
Clin. Oral Impl. Res. 22 , 2011; 349–356. doi: 10.1111/j.1600‐0501.2011.02172.x     

Guided tissue regeneration ensures osseointegration of dental implants placed into extraction sockets. An experimental study in monkeys.

The aim of the present study was to explore the possibility of achieving osseointegration of dental titanium implants, inserted into alveoli immediately after tooth extraction, by covering the recipient site with a teflon membrane. In each of 7 monkeys, mucoperiosteal flaps were raised on the buccal and palatal aspects of the maxillary molars in both sides of the jaw. The second molars were then extracted and self tapping titanium implants of the screw type (Astra® Dental Implants) were inserted into the sockets of the largest roots. In the coronal portion of the sockets, a void was always present between the implant and the socket walls. In one side of the jaw, a membrane (Gore‐;Tex Aug‐mentation Material@) was adjusted to cover the implant. The implant in the other side of the jaw served as control and was only covered by the tissue flaps. Microscopic analysis after 3 months of healing revealed that soft tissue was facing the coronal portion of the implants to a varying degree in the control side, while osseointegration was consistently observed to the top of the membrane‐covered implants which remained submerged throughout the experimental period. The results suggest that the membrane techniaue can secure complete osseointegration of implants inserted immediately into extraction sockets.     

A comprehensive and critical review of dental implant placement in diabetic animals and patients

OBJECTIVES: A thorough and exhaustive analysis of the available studies concerning placement of endosseous dental implants in diabetic subjects has not been previously published. The aim of the present study was to perform a comprehensive and critical review of experimental and clinical studies published in the international peer-reviewed literature in the English language regarding endosseous implant installation in diabetic subjects and to draw evidence-based conclusions on the effectiveness and predictability of dental implant therapy in diabetic patients. MATERIAL AND METHODS: Literature search for articles published up to and including March 2005 in the English language was performed with a personal computer (PC) using The National Library Of Medicine (http://www.ncbi.nlm.nih.gov/PubMed) and Cochrane Oral Health Group databases. Search strategy included a specific series of terms and key words. The reference lists of identified publications, relevant texts and previous workshops were also scanned. Data sources also included several hand-searched journals and contact with experts, when it was considered appropriate. Search was conducted independently by the three reviewers (S. K., I. K. K., I. F.). At the first phase of selection the titles and abstracts and at the second phase full papers were screened independently by the three reviewers. Disagreement regarding inclusion of full papers was resolved by discussion among the reviewers. RESULTS: The search provided 227 potentially relevant titles and abstracts. At the first phase of evaluation, 199 publications were rejected based on title and abstract. At the second phase, the full text of the remaining 28 publications was retrieved for more detailed evaluation. These publications included 11 experimental studies and 16 clinical studies (one clinical study corresponded to two publications). Finally, 11 experimental and eight clinical studies were accepted. Clinical studies included four prospective and four retrospective studies. Because of the limited number of available studies and their heterogeneity, focusing on a specific predefined question to be answered by a systematic review was not feasible and therefore no meta-analysis was planned. CONCLUSION: Within the limits of the existing investigations, experimental studies seem to reveal an impaired bone healing response to implant placement in diabetic animals compared with non-diabetic controls, both quantitatively and qualitatively. The majority of clinical studies tend to indicate that diabetes is no contraindication for implant placement, on condition that it remains under metabolic control. However, definitive guidelines with objective criteria, such as type and duration of diabetes and glucosylated hemoglobin levels, need to be established in the future.     

Implant osseointegration in the irradiated mandible. A comparative study in dogs with a microradiographic and histologic assessment

This research focuses on the effects of radiotherapy on the osseointegration of dental implants placed before or after radiotherapy in 11 male beagles. After the extraction of all mandibular premolars 1st and 2nd molars, three dogs were implanted without radiotherapy (Control group), four dogs were irradiated 4 weeks after implantation (IrA group) and four dogs were irradiated 8 weeks before implantation (IrB group). Eight implants were placed in each dog, in an alternating pattern: four nonsubmerged ITI Bonefit titanium plasma spray-coated and four submerged Steri-Oss hydroxyapatite-coated. The irradiated dogs received 4.3 Gy daily for 10 days. Two different fluorescent markers were administered at the time of implantation and of irradiation. The dogs were sacrificed 6 months after implantation, i.e. 5 months after radiotherapy for the IrA group and 8 months for the IrB group. Each mandible was submitted to histological and microradiographic analysis. Bone formation occurred around 85 of the 88 implants and consisted mostly of the successive deposit of woven and lamellar bone. Both irradiated groups showed obvious bone remodeling in alveolar bone as well as in the basilar part of the mandible. Nevertheless, in the IrA group, the resorption phenomena predominated over osteogenesis. The balance between these two opposite processes seemed to be restored 8 months after the end of radiotherapy (IrB group). In spite of focal lesions of radiation-specific bone destruction emphasized in some irradiated dogs, we conclude from our results that osseointegration of dental implants is possible in irradiated bone tissue.     

Bone apposition around two different sandblasted, large-grit and acid-etched implant surfaces at sites with coronal circumferential defects: an experimental study in dogs

Objective: The study was designed to evaluate bone apposition around SLA (sandblasted, large-grit and acid-etched) implants compared with modified SLA (modSLA) ones at sites with different sizes of circumferential gaps.
Material and methods: All mandibular premolars and first molars of six beagle dogs were extracted. After a healing period of 3 months, three 10-mm-long implants were inserted in each side of the mandible. One implant was inserted with a 0.5-mm and one with a 1-mm gap between the implants and bone around the coronal 5 mm of the implants. The third implant was inserted without a gap as a control. The dogs were sacrificed respectively at weeks 2, 4 and 8 after implant placement for histological and histomorphometric analyses.
Results: The histomorphometric results showed similar pattern of bone apposition for the two surfaces. At 2 and 4 weeks of healing, the percentage of newly formed bone-to-implant contact (BIC%), new bone fill (NBF%) and the distance between the most coronal position of BIC and the defect bottom (B–D) were significantly higher for modSLA ( P <0.05). At 8 weeks of healing, this difference was not significant ( P >0.05). With regard to the defect size, the histological analyses showed no significant differences between the two defect sizes at all time points ( P >0.05).
Conclusion: Significantly more bone apposition was found for the modSLA surface than for the SLA surface at early stage of healing, indicating that modSLA surface may enhance bone apposition in coronal circumferential defects at non-submerged implants. Gap size within 1 mm may not need any kind of regenerative procedures.     

Type 2 diabetes has minimal effect on osseointegration of titanium implants in Psammomys obesus

Objectives: Dental implants are routinely used with high success rates in generally healthy individuals. In contrast, their use in patients with uncontrolled diabetes mellitus (DM) remains controversial as altered bone healing around implants has been reported. The majority of reports addressing the issue of osseointegration of implants in animals were performed in β‐cell cytotoxic‐induced Type I diabetes. In this study, we assessed the osseointegration of implants in Gerbil Psammomys obesus, a model of nutritionally induced Type 2 DM. Materials and methods: Titanium implants were inserted into the tibial medullary space of 140 male diabetic and control animals. One, 2, 4, and 8 weeks after implantation the tibias were removed for histomorphometric evaluation, which included trabecular bone volumes (TBV) and osseointegration. Results: Two weeks following implantation, diabetic animals had slightly less mature bone when compared with control animals. This distinction was not present 4 weeks after implantation. Interestingly, no correlation was found between ossetointegration or TBV and glucose and insulin levels. Furthermore, no difference in osseointegration and TBV values was seen between the groups. The heterogeneity of serum glucose and insulin levels in this model and the possible role of insulin in bone metabolism are discussed. Conclusions: No significant difference in osseointegration and TBV was seen between diabetic and control P. obesus, a model of nutritionally induced Type 2 DM.