Osteoinductive implants: the mise-en-scène for drug-bearing biomimetic coatings

In orthopaedic and dental implantology, novel tools and techniques are being sought to improve the regeneration of bone tissue. Numerous attempts have been made to enhance the osteoconductivity of titanium prostheses, including modifications in their surface properties and coating with layers of calcium phosphate. The technique whereby such layers are produced has recently undergone a revolutionary change, which has had profound consequences for their potential to serve as drug-carrier systems. Hitherto, calcium phosphate layers were deposited upon the surfaces of metal implants under highly unphysiological physical conditions, which precluded the incorporation of proteinaceous osteoinductive drugs. These agents could only be adsorbed, superficially, upon preformed layers. Such superficially adsorbed molecules are released too rapidly within a biological milieu to be effective in their osteoinductive capacity. Now, it is possible to deposit calcium phosphate layers under physiological conditions of temperature and pH by the so-called biomimetic process, during which bioactive agents can be coprecipitated. Since these molecules are integrated into the inorganic latticework, they are released gradually in vivo as the layer undergoes degradation. This feature enhances the capacity of these coatings to act as a carrier system for osteogenic agents.

Prognostic clinical and radiological parameters for immediate facial nerve function following vestibular schwannoma surgery

OBJECTIVE: The paper aims to define the parameters available before surgery which could predict immediate facial nerve function after excision of a vestibular schwannoma (VS). METHODS: Ninety-nine patients with VS operated consecutively by a single surgeon using an identical surgical technique have been evaluated retrospectively. Data were collected regarding patients' sex, age at onset of symptoms and at surgery, initial symptoms, neurological status at presentation, early post-operative neurological status and complications. The main radiological parameters included in the study were tumour extension pattern, diameters, shape, and volume, as well as extent of bony changes of the internal auditory canal. RESULTS: As the tumour stage and volume increase, facial nerve function is worse after surgery (p < 0.001 and p < 0.05, respectively). Concomitantly, larger extra-meatal tumour diameters in three dimensions (sagittal, coronal and axial) led to worse function (p < 0.01). Anterior and/or caudal tumour extension (p = 0.001 and p = 0.004, respectively) had more significant correlation than posterior and/or cranial extension (p = 0.022 and p = 0.353, respectively). Polycyclic VS had the worst prognosis, followed by the tumours with oval shape. The extent of intra-meatal tumour growth does not correlate with immediate facial nerve outcome. The different angles, lengths and diameters of the internal auditory channel showed no significant correlation with facial nerve outcome. Patients with headache as an initial symptom and those with gait instability and/or pre-operative poor facial nerve function had significantly worse immediate facial nerve outcome. CONCLUSION: Our data suggests that the analysis of the radiological and neurological patient data prior to surgery could give reliable clues regarding the immediate post-operative facial nerve function.

The use of extraoral implants for distal-extension removable dentures: a clinical evaluation up to 8 years

PURPOSE: This retrospective study reports the clinical outcome following placement of extraoral implants in severely resorbed posterior ridges to support distal-extension removable dentures. MATERIAL AND METHODS: Consecutively treated patients with partially or completely edentulous ridges, with available bone height in the posterior region of 6 mm or less, were included in the study. Implants originally intended for extraoral use (Straumann) were placed in second molar regions and allowed to heal for 4 to 6 months before abutment connection. At recall appointments, the peri-implant hard and soft tissues were evaluated. Complications with implant components, as well as mechanical and structural failures of the prostheses, were recorded. Two-year survival rates were calculated and life table analyses undertaken. RESULTS: Twenty-nine patients (19 women and 10 men; average age 61.2 years, range, 44 to 75 years) were included in the study. Forty-seven extraoral implants in 26 patients were placed in the second molar site of the mandible. Two extraoral implants in 2 patients failed during the osseointegration phase, yielding an 8-year cumulative success rate of 91.8%. The mean distance from the extraoral implants to the most distal tooth/implant was 28.1 mm (range, 16.7 to 39.2 mm). Twenty-three extraoral implants were restored with magnets, 18 with ball anchors, and 4 with conical cylinders. Replacement of abutments and retention elements was necessary in 2 patients. Four abutments in 2 patients were disconnected from the restorations. CONCLUSIONS: Within the limits of the employed research design, extraoral implants may be used successfully to provide support for distal-extension removable dentures in severely resorbed posterior alveolar ridges.

Long-term outcomes of dental implants with a titanium plasma-sprayed surface: a 20-year prospective case series study in partially edentulous patients

BACKGROUND Long-term studies of ≥10 years are important milestones to get a better understanding of potential factors causing implant failures or complications. PURPOSE The present study investigated the long-term outcomes of titanium dental implants with a rough, microporous surface (titanium plasma sprayed [TPS]) and the associated biologic and technical complications in partially edentulous patients with fixed dental prostheses over a 20-year follow-up period. MATERIALS AND METHODS Sixty-seven patients, who received 95 implants in the 1980s, were examined with well-established clinical and radiographic parameters. Based on these findings, each implant was classified as either successful, surviving, or failed. RESULTS Ten implants in nine patients were lost during the observation period, resulting in an implant survival rate of 89.5%. Radiographically, 92% of the implants exhibited crestal bone loss below 1 mm between the 1- and 20-year follow-up examinations. Only 8% yielded peri-implant bone loss of >1 mm and none exhibited severe bone loss of more than 1.8 mm. During the observation period, 19 implants (20%) experienced a biologic complication with suppuration. Of these 19 implants, 13 implants (13.7%) had been treated and were successfully maintained over the 20-year follow-up period. Therefore, the 20-year implant success rate was 75.8 or 89.5% depending on the different success criteria. Technical complications were observed in 32%. CONCLUSION The present study is the first to report satisfactory success rates after 20 years of function of dental implants with a TPS surface in partially edentulous patients.

Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth

Although vascular endothelial growth factor (VEGF) has been described as a potent angiogenic stimulus, its application in therapy remains difficult: blood vessels formed by exposure to VEGF tend to be malformed and leaky. In nature, the principal form of VEGF possesses a binding site for ECM components that maintain it in the immobilized state until released by local cellular enzymatic activity. In this study, we present an engineered variant form of VEGF, alpha2PI1-8-VEGF121, that mimics this concept of matrix-binding and cell-mediated release by local cell-associated enzymatic activity, working in the surgically-relevant biological matrix fibrin. We show that matrix-conjugated alpha2PI1-8-VEGF121 is protected from clearance, contrary to native VEGF121 mixed into fibrin, which was completely released as a passive diffusive burst. Grafting studies on the embryonic chicken chorioallantoic membrane (CAM) and in adult mice were performed to assess and compare the quantity and quality of neovasculature induced in response to fibrin implants formulated with matrix-bound alpha2PI1-8-VEGF121 or native diffusible VEGF121. Our CAM measurements demonstrated that cell-demanded release of alpha2PI1-8-VEGF121 increases the formation of new arterial and venous branches, whereas exposure to passively released wild-type VEGF121 primarily induced chaotic changes within the capillary plexus. Specifically, our analyses at several levels, from endothelial cell morphology and endothelial interactions with periendothelial cells, to vessel branching and network organization, revealed that alpha2PI1-8-VEGF121 induces vessel formation more potently than native VEGF121 and that those vessels possess more normal morphologies at the light microscopic and ultrastructural level. Permeability studies in mice validated that vessels induced by alpha2PI1-8-VEGF121 do not leak. In conclusion, cell-demanded release of engineered VEGF121 from fibrin implants may present a therapeutically safe and practical modality to induce local angiogenesis.

Evaluation of Dietary Laidlomycin Propionate and Synovex Plus Implants for Enhancing Performance of Feedlot Steers

One hundred fifty crossbred yearling steers with an average weight of 876 pounds were used in a 111-day experiment. Steers received either 1) no implant and no ionophore, 2) Synovex Plus¨ and no ionophore, 3) Cattlyst¨ and no implant, 4) Synovex Plus¨ and Cattlyst¨, or 5) Revalor S¨ and Rumensin¨. Implanting steers with ) Synovex Plus¨ increased gain and improved feed efficiency compared with control steers. Compared with steers not implanted, steers implanted with Synovex Plus¨ had heavier carcasses and larger ribeye areas, but similar fat thickness and yield grades. Feeding Cattlyst¨ alone did not increase gain or improve feed conversion, but there was some improvement in feedlot performance when Cattlyst¨ was fed to steers implanted with Synovex Plus¨. Steers implanted with Synovex Plus¨ and fed Cattlyst¨ had superior gains to steers implanted with Revalor S¨ and fed Rumensin¨.

Evaluation of Synovex Plus, Synovex S and Revalor S Implants in Feedlot Steers

One hundred forty-four crossbred yearling steers with an average weight of 841 pounds were used in a 116- day experiment. Steers received either 1) no implant, 2) Synovex S¨, 3) Revalor S¨, or 4) Synovex Plus¨. All implanted groups consumed more feed and gained faster and more efficiently than non-implanted steers. There were no significant differences in gain, feed intake or feed efficiency among implanted groups, though steers with the estrogen + trenbolone acetate combination implants were numerically superior to those implanted with Synovex S¨. There were no differences in feedlot performance between the two combination implants. Implants increased carcass weight with no significant effects on fat thickness or carcass quality grades. The combination implants containing trenbolone acetate increased ribeye area and increased masculinity of the carcasses. These results indicate Synovex Plus¨ is an effective implant for finishing steers.

Soft and hard tissue histologic dimensions around dental implants in the canine restored with smaller-diameter abutments: a paradigm shift in peri-implant biology

PURPOSE To evaluate the biologic width dimensions around implants with nonmatching implant-abutment diameters. MATERIALS AND METHODS Five canines had their mandibular premolars and first molars removed bilaterally and replaced with 12 implants that had nonmatching implant-abutment diameters. On one side, six implants were placed in a submerged surgical approach, and the other side utilized a nonsubmerged approach. Two of the implants on each side were placed either 1 mm above, even with, or 1 mm below the alveolar crest. Two months later, gold crowns were attached, and the dogs were sacrificed 6 months postloading. Block sections were processed for histologic and histomorphometric analyses. RESULTS The bone level, connective tissue length, epithelial dimension, and biologic width were not significantly different when the implants were initially placed in a submerged or nonsubmerged surgical approach. The bone level was significantly different around implants placed 1 mm above the crest compared to implants placed even with or 1 mm below the alveolar crest. The connective tissue dimension was not different for any implant level placement. The epithelial dimension and biologic width were significantly greater for implants placed 1 mm below the alveolar crest compared to implants placed even with or 1 mm above the alveolar crest. For five of six implant placements, connective tissue covered the implant/abutment interface. CONCLUSIONS This study reveals a fundamental change in the biologic response to implants with nonmatching implant-abutment diameters. Unlike implants with matching implant-abutment diameters, the connective tissue extended coronally past the interface (microgap). This morphologic tissue alteration represents a significant change in the biologic reaction to implant-abutment interfaces and suggests that marginal inflammation is eliminated or greatly reduced in these implant designs.

Bone healing around titanium implants in two rat colitis models

OBJECTIVE Crohn's disease is a chronic inflammatory process that has recently been associated with a higher risk of early implant failure. Herein we provide information on the impact of colitis on peri-implant bone formation using preclinical models of chemically induced colitis. METHODS Colitis was induced by intrarectal instillation of 2,4,6-trinitro-benzene-sulfonic-acid (TNBS). Colitis was also induced by feeding rats dextran-sodium-sulfate (DSS) in drinking water. One week after disease induction, titanium miniscrews were inserted into the tibia. Four weeks after implantation, peri-implant bone volume per tissue volume (BV/TV) and bone-to-implant contacts (BIC) were determined by histomorphometric analysis. RESULTS Cortical histomorphometric parameters were similar in the control (n = 10), DSS (n = 10) and TNBS (n = 8) groups. Cortical BV/TV was 92.2 ± 3.7%, 92.0 ± 3.0% and 92.6 ± 2.7%. Cortical BIC was 81.3 ± 8.8%, 83.2 ± 8.4% and 84.0 ± 7.0%, respectively. No significant differences were observed when comparing the medullary BV/TV and BIC (19.5 ± 6.4%, 16.2 ± 5.6% and 15.4 ± 9.0%) and (48.8 ± 12.9%, 49.2 ± 6.2 and 41.9 ± 11.7%), respectively. Successful induction of colitis was confirmed by loss of body weight and colon morphology. CONCLUSIONS The results suggest bone regeneration around implants is not impaired in chemically induced colitis models. Considering that Crohn's disease can affect any part of the gastrointestinal tract including the mouth, our model only partially reflects the clinical situation.