Biofunctionalization of dental abutments by a zinc/chitosan/gelatin coating to optimize fibroblast behavior and antibacterial properties.

Tightly sealed peri-implant gingival tissue provides a barrier against oral bacterial invasion, protecting the alveolar bone and maintaining long-term implant survival. To investigate if zinc can enhance the integration between peri-implant gingival tissue and abutment surface, we herein present novel zinc/chitosan/gelatin (Zn/CS/Gel) coatings prepared using the electrophoretic deposition (EPD) technique. The effect of these coatings on human gingival fibroblasts (hGFs) was investigated by culturing these cells on top of the EPD coatings. Surface characterization demonstrated that Zn2+ were released in a sustained and pH-responsive manner. The preclinical cell culture evaluation of these coatings indicated that the zinc-containing coatings enhanced cell migration, adhesion and collagen secretion of hGFs. Moreover, the zinc-containing coatings exhibited antibacterial efficacy by inhibiting the growth of Porphyromonas gingivalis and reducing attachment of Staphylococcus aureus. Notably, zinc-free CS/Gel coatings prevented attachment of P. gingivalis as well. The coatings were also shown to be cytocompatible with epithelial cells and osteoblasts, which are other relevant cell types which surround dental implants after clinical placement. Based on our findings, it can be concluded that Zn-containing coatings hold promise to enhance the adhesion of gingival tissue to the implant surface, which may potentially contribute to the formation of a robust peri-implant soft sealing counteracting bacterial invasion.

Smaller radioulnar window is associated with a distal biceps tendon rupture in patients with limited forearm rotation: a 3-dimensional computed tomography comparison study of proximal impingement caused by radial tuberosity hypertrophy-a single-center case series.

BACKGROUND: It has been suggested that hypertrophy of the radial tuberosity may result in impingement leading to either a lesion of the distal biceps tendon or rotational impairment. Two previous studies on hypertrophy of the radial tuberosity had contradictory results and did not examine the distance between the radius and ulna: the radioulnar window. Therefore, this comparative cohort study aimed to investigate the radioulnar window in healthy subjects and compare it with that in subjects with either nontraumatic-onset rotational impairment of the forearm or nontraumatic-onset distal biceps tendon ruptures with rotational impairment of the forearm by use of dynamic 3-dimensional computed tomography measurements to attain a comprehensive understanding of the underlying etiology of distal biceps tendon ruptures. We hypothesized that a smaller radioulnar window would increase the risk of having a nontraumatic-onset distal biceps tendon rupture and/or rotational impairment compared with healthy individuals. METHODS: This study measured the distance between the radius and ulna at the level of the radial tuberosity using entire-forearm computed tomography scans of 15 patients at the Amphia Hospital between 2019 and 2022. Measurements of healthy subjects were compared with those of subjects who had nontraumatic-onset rotational impairment of the forearm and subjects who had a nontraumatic-onset distal biceps tendon rupture with rotational impairment of the forearm. The Wilcoxon signed rank test was used for individual comparisons, and the Mann-Whitney U test was used for group comparisons. RESULTS: A significant difference was found between the radioulnar window in the forearms of the subjects with a distal biceps tendon rupture (mean, 1.6 mm; standard deviation 0.2 mm) and the radioulnar window in the forearms of the healthy subjects (mean, 4.8 mm; standard deviation, 1.4 mm; P = .018). A trend toward smaller radioulnar windows in the rotational impairment groups was also observed, although it was not significant (P > .05). CONCLUSIONS: The radioulnar window in the forearms of the subjects with a distal biceps tendon rupture with rotational impairment was significantly smaller than that in the forearms of the healthy subjects. Therefore, patients with a smaller radioulnar window have a higher risk of rupturing the distal biceps tendon. Nontraumatic-onset rotational impairment of the forearm may also be caused by a similar mechanism. Future studies are needed to further evaluate these findings.

A novel ex vivo perfusion-based mandibular pig model for dental product testing and training.

BACKGROUND: A translational ex vivo perfusion-based mandibular pig model was developed as an alternative to animal experiments, for initial assessment of biomaterials in dental and maxillofacial surgery and training. This study aimed to assess the face and content validity of the novel perfusion-based model. METHODS: Cadaveric porcine heads were connected to an organ assist perfusion device for blood circulation and tissue oxygenation. Dental professionals and dental trainees performed a surgical procedure on the mandibula resembling a submandibular extraoral incision to create bone defects. The bone defects were filled and covered with a commercial barrier membrane. All participants completed a questionnaire using a 5-point Likert scale to assess the face and content validity of the model. Validation data between the two groups of participants were compared with Mann-Whitney U test. RESULTS: Ten dental professionals and seven trainees evaluated the model for face and content validity. Participants reported model realism, with a mean face validity score of 3.9 ± 1.0 and a content validity of 4.1 ± 0.8. No significant differences were found for overall face and content validity between experts and trainees. CONCLUSION: We established face and content validity in a novel perfusion-based mandibular surgery model. This model can be used as an alternative for animal studies evaluating new biomaterials and related dental and maxillofacial surgical procedural training.

Surface Engineering for Dental Implantology: Favoring Tissue Responses Along the Implant.

Dental implants represent an illustrative example of successful medical devices used in increasing numbers to aid (partly) edentulous patients. Particularly in spite of the percutaneous nature of dental implant systems, their clinical success is remarkable. This clinical success is at least partly related to the effective surface treatment of the artificial dental root, providing appropriate physicochemical properties to achieve osseointegration. The demographic changes in the world, however, with a rapidly increasing life expectancy and an increase in patients suffering from comorbidities that affect wound healing and bone metabolism, make that the performance of dental implants requires continuous improvement. An additional factor endangering the clinical success of dental implants is peri-implantitis, which affects both the soft and hard tissue interactions with dental implants. In this study, we shed light on the optimization of dental implant surfaces through surface engineering. Depending on the region along the artificial dental root, different properties of the surface are required to optimize prevailing tissue response to facilitate osseointegration, improve soft tissue attachment, and exert antibacterial efficacy. As such, surface engineering represents an important tool for assuring the continued future success of dental implants. Impact Statement Dental implants represent a common treatment modality nowadays for the replacement of lost teeth or fixation of prosthetic devices. This review provides a detailed overview of the role of surface engineering for dental implants and their components to optimize tissue responses at the different regions along the artificial dental root. The surface properties steering immunomodulatory processes, facilitating osseointegration, and rendering antibacterial efficacy (at both artificial root and abutment region) are described. The review finally concludes that surface engineering provides a tool to warrant that dental implants will remain future proof in more challenging applications, including an aging patient population and comorbidities that affect bone metabolism and wound healing.

Tailoring Copper-Doped Bioactive Glass/Chitosan Coatings with Angiogenic and Antibacterial Properties.

Implant coatings are frequently applied to modulate tissue response and delivery of drugs. Copper (Cu)-containing coatings on dental implant abutments have been proposed to improve soft tissue integration and reduce the risk for peri-implant infections. However, precise control over Cu loading and release kinetics remains a major challenge. In this study, we introduced a bottom-up coating deposition method based on nanoparticle assembly to allow for local release of Cu ions from implant surfaces. We first doped mesoporous bioactive glass (MBG) nanoparticles with various amounts of Cu. Subsequently, we suspended these Cu-doped MBG (Cu-MBG), Cu-free MBG nanoparticles, or mixtures thereof in chitosan solution and prepared a series of composite coatings on commercially pure titanium disks as model surfaces for transmucosal components of bone implants through electrophoretic deposition (EPD). By changing the Cu-MBG:MBG ratio of the composite coatings, we controlled the Cu release kinetics without changing other coating properties. Human gingival fibroblasts proliferated on the composite coatings except for coatings with the highest amount of Cu, which inhibited their proliferation. The migration rate of human umbilical vein endothelial cells cultured on the composite coatings was highest on coatings containing equal amounts of Cu-MBG and Cu-free MBG. Antibacterial tests confirmed that Cu-containing coatings reduced the growth of Porphyromonas gingivalis up to fivefold compared with uncoated implants. In conclusion, our data indicate that the EPD method is suitable to deposit nanoparticle-based coatings onto dental implants, which enhance endothelial cell migration and reduce bacterial growth. Impact statement Precise control over the release of therapeutic agents remains a major challenge for implant coatings. In this study, we introduce a simple and cost-effective way to tune the release of angiogenic and antibacterial copper ions using the electrophoretic deposition technique. Due to the flexibility and mild processing conditions of this technique, our method can also be used to incorporate other therapeutic agents onto implant surfaces.

A Mini-Pig Mandibular Defect Model for Evaluation of Craniomaxillofacial Bone Regeneration.

Craniomaxillofacial bone defects represent a clinical challenge in the fields of maxillofacial surgery and (implant) dentistry. Regeneration of these bone defects requires the application of bone graft materials that facilitate new bone formation in a safe, reliable, and predictive manner. In addition to autologous bone graft, several types of (synthetic) bone substitute materials have become clinically available, and still major efforts are focused on improving such bone substitute materials by optimizing their properties. Given the regulatory necessity to evaluate the performance of new bone substitute materials for craniomaxillofacial bone regeneration in a large animal model with similarity to human bone before clinical application, we here describe a mini-pig mandibular bone defect model that allows for the creation of multiple (critical-size) bone defects within the mandibular body of a single animal. As examples of bone substitute materials, we utilize both the clinically used BioOss granules and an experimental calcium phosphate cement for filling the created defects. Regarding the latter, its advantages are the injectable application within the defect site, in which the material rapidly sets, and the tailorable degradation properties via the inclusion of hydrolytically degrading polymeric particles. For both bone substitute materials, we show the suitability of the bone defect model to assess bone regeneration via histology and micro-computed tomography. Impact statement Given the regulatory necessity to evaluate the performance of new bone substitute materials for craniomaxillofacial bone regeneration in a large animal model with similarity to the human bone before clinical application, we here describe a mini-pig mandibular bone defect model that allows for the creation of multiple (critical-size) bone defects within the mandibular body of a single animal that can be used for the evaluation of the bone regenerative capacity of new bone grafting materials as well as tissue-engineered products for alveolar bone regeneration.

Evaluation of Collagen Membranes Coated with Testosterone and Alendronate to Improve Guided Bone Regeneration in Mandibular Bone Defects in Minipigs.

OBJECTIVES: The purpose of the present in vivo study was to evaluate whether pericard collagen membranes coated with ancillary amounts of testosterone and alendronate in a poly-lactic glycolic acid (PLGA) carrier as compared to uncoated membranes will improve early bone regeneration. MATERIAL AND METHODS: In each of 16 minipigs, four standardized mandibular intraosseous defects were made bilaterally. The defects were filled with Bio-Oss® granules and covered with a non-coated or coated membrane. Membranes were spray-coated with 4 layers of PLGA containing testosterone and alendronate resulting in 20, 50 or 125 µg/cm2 of testosterone and 20 µg/cm2 alendronate (F20, F50, F125). Non-coated membranes served as controls (F0). Animals were sacrificed at 6 and 12 weeks after treatment. Qualitative and quantitative histological evaluations of bone regeneration were performed. Differences between groups were assessed by paired Student's t-test. RESULTS: Light microscopical analysis showed new bone formation that was in close contact with the Bio-Oss® surface without an intervening non-mineralized tissue layer. Histomorphometric analysis of newly formed bone showed a significant 20% increase in area in the F125 coated membrane treated defects (40 [SD 10]%) compared to the F0 treated defects after 6 weeks (33 [SD 10]%, P = 0.013). At week 12, the total percentage of new bone was increased compared to week 6, but no increase in newly formed bone compared to F0 was observed. CONCLUSIONS: The data from this in vivo study indicate that F125 collagen membranes coated with testosterone and alendronate resulted in superior bone formation (+24%) when normalized to control sites using uncoated membranes.

Osteophilic properties of bone implant surface modifications in a cassette model on a decorticated goat spinal transverse process.

UNLABELLED: This study comparatively evaluated the osteophilic capacity of 17 different surface modifications (i.e. fourteen different chemical modifications via ceramic coatings and three different physical modifications via surface roughness) for titanium (Ti) surfaces. All surface modifications were subjected to physico-chemical analyses and immersion in simulated body fluid (SBF) for coating stability assessment. Subsequently, a bone conduction chamber cassette model on the goat transverse process was used for comparative in vivo analysis based on bone responses to these different surface modifications after twelve weeks. Histological and histomorphometrical analyses in terms of longitudinal bone-to-implant contact percentage (BIC%), relative bone area (BA%) were investigated within each individual channel and maximum bone height (BH). Characterization of the surface modifications showed significant differences in surface chemistry and surface roughness among the surface modifications. Generally, immersion of the coatings in SBF showed net uptake of calcium by thick coatings (>50µm; plasma-sprayed and biomimetic coatings) and no fluctuations in the SBF for thin coatings (<50µm). The histomorphometrical data set demonstrated that only plasma-sprayed CaP coatings performed superiorly regarding BIC%, BA% and BH compared to un-coated surfaces, irrespective of surface roughness of the latter. In conclusion, this study demonstrated that the deposition of plasma-sprayed CaP coating with high roughness significantly improves the osteophilic capacity of titanium surfaces in a chamber cassette model. STATEMENT OF SIGNIFICANCE: For the bone implant market, a large number of surface modifications are available on different types of (dental and orthopedic) bone implants. As the implant surface provides the interface at which the biomaterial interacts with the surrounding (bone) tissue, it is of utmost importance to know what surface modification has optimal osteophilic properties. In contrast to numerous earlier studies on bone implant surface modifications with limited number of comparison surfaces, the manuscript by van Oirschot et al. describes the data of in vivo experiments using a large animal model that allows for direct and simultaneous comparison of a large variety of surface modifications, which included both commercially available and experimental surface modifications for bone implants. These data clearly show the superiority of plasma-sprayed hydroxyapatite coatings regarding bone-to-implant contact, bone amount, and bone height.

Comparison of different surface modifications for titanium implants installed into the goat iliac crest.

OBJECTIVES: This in vivo study with implants installed in the goat iliac crest was performed to determine whether the biological and mechanical properties of the bone-to-implant interface are influenced by (i) the type of implant anchorage (i.e., mono- vs. bicortical placement), and (ii) the presence of a bioactive hydroxyapatite (HA) or composite HA/bioactive glass (BG) coatings. MATERIALS AND METHODS: A total of 96 titanium (Ti) implants w/- coatings (Ti, Ti-HA & Ti-HABG; n = 8) were mono- or bicortically placed in the iliac crest of eight goats. At installation and after 4 weeks, implant stability was determined using insertion and removal torque testing (ITQ & RTQ). The peri-implant bone response was histologically and histomorphometrically evaluated by means of bone-to-implant contact (BIC%) and bone area (BA%). RESULTS: Monocortical implants demonstrated significantly lower RTQ values in comparison to ITQ values, whereas for bicortical implant placement RTQ and ITQ were similar. Further, mean RTQ values for monocortical implants were significantly lower in comparison to bicortical implants. Histomorphometrical evaluation demonstrated higher BIC% and BA% for bicortical implants compared to monocortical implants. For bicortical implants, BA% in the inner peri-implant region (0-500 µm) was significantly higher compared to the middle (500-1000 µm) and outer (1000-1500 µm) region. Also, a significant correlation was observed for monocortical implants between RTQ and BIC% and BA%. For surface modifications, no significant differences were found in ITQ and RTQ, for neither mono- nor bicortical implants. Histomorphometrically, HABG-coated implants demonstrated significantly higher BIC% compared to GAE surfaces for both mono- and bicortical implants. Bicortical HA-coated implants revealed significant higher BA% in the inner peri-implant region (0-500 µm) in comparison to bicortical GAE implants. CONCLUSIONS: This study demonstrated that bicortical implant placement beneficially affects implant stability during the early phase of osseointegration. A significant correlation between removal torque and bone-to-implant contact and bone area for monocortical implants was observed, but not for bicortical implants. Therefore, histomorphometrical data should be interpreted with caution to predict the biomechanical implant fixation of bone implants over time. Regarding surface modifications, in the present implantation model, the addition of BG to an RF magnetron sputtered HA coating enhanced the biological behavior of the coating compared to grit-blasted/acid-etched implants.

Tuning the degradation rate of calcium phosphate cements by incorporating mixtures of polylactic-co-glycolic acid microspheres and glucono-delta-lactone microparticles.

Calcium phosphate cements (CPCs) are frequently used as synthetic bone graft materials in view of their excellent osteocompatibility and clinical handling behavior. Hydroxyapatite-forming CPCs, however, degrade at very low rates, thereby limiting complete bone regeneration. The current study has investigated whether degradation of apatite-forming cements can be tuned by incorporating acid-producing slow-resorbing poly(D,L-lactic-co-glycolic) acid (PLGA) porogens, fast-resorbing glucono-delta-lactone (GDL) porogens, or mixtures thereof. The physicochemical, mechanical, and degradation characteristics of these CPC formulations were systematically analyzed upon soaking in phosphate-buffered saline (PBS). In parallel, various CPC formulations were implanted intramuscularly and orthotopically on top of the transverse process of goats followed by analysis of the soft tissue response and bone ingrowth after 12 weeks. In vitro degradation of GDL was almost completed after 2 weeks, as evidenced by characterization of the release of gluconic acid, while PLGA-containing CPCs released glycolic acid throughout the entire study (12 weeks), resulting in a decrease in compression strength of CPC. Extensive in vitro degradation of the CPC matrix was observed upon simultaneous incorporation of 30% PLGA-10% GDL. Histomorphometrical evaluation of the intramuscularly implanted samples revealed that all CPCs exhibited degradation, accompanied by an increase in capsule thickness. In the in vivo goat transverse process model, incorporation of 43% PLGA, 30% PLGA-5% GDL, and 30% PLGA-10% GDL in CPC significantly increased bone formation and resulted in higher bone height compared with both 10% GDL and 20% GDL-containing CPC samples.

In vivo evaluation of bioactive glass-based coatings on dental implants in a dog implantation model.

OBJECTIVES: Although titanium is commonly used as a favorable bone implant material due to its mechanical properties, its bioactive and osteoconductive capacity is relatively low. Calcium phosphate ceramics, predominantly hydroxyapatite (HA), have been frequently used for coating purposes to improve the bioactive properties. In view of the suggested osteopromotive capacity of bioactive glasses (BGs), this study aimed to evaluate the effect of BG incorporation into HA coatings on implant performance in terms of bone contact and bone area. MATERIALS AND METHODS: A total of 48 screw-type titanium implants with magnetron sputter coatings containing different ratios of HA and BG (HA, HABGLow, and HABGHigh; n = 8) were placed into the mandible of 16 Beagle dogs. After 4 and 12 weeks, their performance was evaluated histologically and histomorphometrically. Peri-implant bone area percentage (BA%) was determined in three zones (inner, 0-500 µm; middle, 500-1000 µm; and outer, 1000-1500 µm). Additionally, bone-to-implant contact (BIC%) and first bone-implant contact (1st BIC) were assessed for each sample. RESULTS: After 4 weeks, bone-to-implant contact for the HA- and HABGLow-coated groups was significantly higher (P < 0.05) than for the HABGHigh coatings. Mean values for overall BA% showed comparable values for both the HABGLow (58.3%)- and HABGHigh (56.3%)-coated groups. Data suggest that the relative BA around the HA-coated implants (67.8%) was higher, although this was only significant compared to the HABGHigh group. After 12 weeks, all three groups showed similar bone-to-implant contact and no differences in BA were found. CONCLUSIONS: The incorporation of BG into HA sputter coatings did not enhance the performance of a dental implant in implantations sites with good bone quality and quantity. On the contrary, coatings containing high concentrations of BG resulted in inferior performance during the early postimplantation healing phase.

Long-term survival of calcium phosphate-coated dental implants: a meta-analytical approach to the clinical literature.

BACKGROUND: Calcium phosphate ceramic coatings have the potential to compensate for challenging bone conditions such as delayed or impaired bone healing and low bone quantity or density. Thus, the increasing universal prevalence of subjects with such challenging bone conditions might be paralleled by an enhanced global use of calcium phosphate ceramic-coated dental implants. However, it is speculated that the long-term clinical survival of calcium phosphate-coated dental implants might be adversely affected by coating delamination. OBJECTIVE: The aims of the current review were (1) to systematically appraise and (2) to meta-analyse long-term survival data of calcium phosphate-coated dental implants in clinical trials. MATERIALS AND METHODS: An extensive search in the electronic databases of the National Library of Medicine (http://www.ncbi.nlm.nih.gov), The Cochrane Central Register of Controlled Trials and the ISI Web of Knowledge, was carried out for articles published between January 2000 and November 2011 to identify randomized controlled clinical trials, prospective clinical trials as well as retrospective analysis of cases (RA) presenting survival data on the topic of calcium phosphate-coated dental implants. Only publications in English were considered, and the search was narrowed to studies in humans with a follow-up of at least 5 years only. Furthermore, the reference lists of related review articles and publications selected for inclusion in this review were systematically screened. The primary outcome variable was percentage annual failure rate (AFR), and the secondary outcome variable was percentage cumulative survival rate (CSR). RESULTS: The electronic search in the database of the National Library of Medicine, The Cochrane Central Register of Controlled Trials and the ISI Web of Knowledge, resulted in the identification of 385 titles. These titles were initially screened by the two independent reviewers for possible inclusion, resulting in 29 publications suitable for further consideration. Screening the abstracts led to 20 full-text articles. From these articles, 15 reports were excluded. Finally, five of these original research reports could be selected for evaluation. No additional publications were identified by manual search. Thus, a total of five articles were included for analysis. Meta-analysis revealed that neither AFRs of calcium phosphate-coated dental implants increased progressively nor that long-term CSRs for calcium phosphate-coated dental implants were inferior to survival rates of noncoated implants. CONCLUSION: We conclude that (1) published long-term survival data for calcium phosphate-coated dental implants are very limited, (2) AFRs of calcium phosphate-coated dental implants do not increase progressively, and (3) long-term CSRs for calcium phosphate-coated dental implants are comparable to survival rates of noncoated implants.

Biological response to titanium implants coated with nanocrystals calcium phosphate or type 1 collagen in a dog model.

OBJECTIVE: The current study aimed to evaluate the osteogenic potential of electrosprayed organic and non-organic surface coatings in a gap-implant model over 4 and 12 weeks of implantation into the dog mandible. MATERIAL AND METHODS: Sixteen Beagle dogs received experimental titanium implants in the mandible 3 months after removal of left premolars (P2, P3 and P4). Three types of implants were installed in each animal: non-coated implant, nano-CaP coated implant and implant with type 1 collagen coating. Both micro-CT and histomorphometry were used to evaluate peri-implant bone response after implantation periods of 4 and 12 weeks. The bone area percentage was assessed histomorphometrically in three different zones (inner: 0-300 µm; middle: 300-600 µm; and outer: 600-1000 µm) around the implant surface. Bone-bridging of the gap was also calculated for each sample. RESULTS: Four weeks after implantation, nano-CaP and collagen-coated implants showed significantly higher bone volume (BV) in the inner zone compared with non-coated implants (P < 0.05 and P < 0.01). After 12 weeks, histomorphometric analysis showed comparable amounts of BV between all experimental groups. Also, no significant difference was found in the BV, as measured using micro-CT, between the implant groups. Absolute bone ingrowth measurements were highest for collagen-coated implants, but these differences were not significant. CONCLUSION: The obtained data failed to provide a consistent favourable effect on bone formation of the collagen coating over 3 months of implantation. It is concluded that the source of the collagen as well as the limited osseous environment overshadowed a possible effect of the applied implant surface modifications. Similarly, the tested nano-apatite surface coating did not improve peri-implant bone ingrowth into a gap-implant model.