Theory of Planned Behavior applied to the choice of food with preservatives by owners and for their dogs.

Many pet owners make food choices for their pets that are similar to those they make for themselves, and food characteristics such as the presence of preservatives can influence this decision. The Theory of Planned Behavior (TPB) is a tool used to predict intentions and behavior and can be an important indicator for the pet food industry. The aim of this study was to investigate pet owner behavior regarding food with or without preservatives, based on the behavior prediction of TPB. A questionnaire was distributed with questions related to direct (attitude, subjective norms, and perceived behavioral control) and indirect (behavioral beliefs, normative beliefs, and intentions) measures for the analysis of TPB. For the statistical analysis the structural equation modeling (SEM) was used. The correlation between owner behavior and the behavior imposed on their dog's diet was evaluated by paired T test or paired Wilcoxon test according to variables' adherence or not to normality, respectively. A total of 1,021 answers were evaluated after the inclusion and exclusion criteria were applied. The results indicated that TPB was effective in predicting the intentions (r2 = 0.58 for dogs and r2 = 0.59 for owners) and behavior (r2 = 0.58 for dogs and r2 = 0.57 for owners) regarding the intake of diets without preservatives. It was observed that owners are more concerned with the diet of their dogs than their own and they believe that the intake of preservatives can be prejudicial to the health of their dogs (p<0.001). However, owners trust more in pet food manufacturers than human food manufacturers (p<0.001). Therefore, it can be concluded that TPB can be an important tool to understand consumer behavior towards their dog food, and that the industry should intensify its approach on safety of preservatives in pet food, since many owners still believe they can be prejudicial to dogs.

A Synergic Strategy: Adipose-Derived Stem Cell Spheroids Seeded on 3D-Printed PLA/CHA Scaffolds Implanted in a Bone Critical-Size Defect Model.

Bone critical-size defects and non-union fractures have no intrinsic capacity for self-healing. In this context, the emergence of bone engineering has allowed the development of functional alternatives. The aim of this study was to evaluate the capacity of ASC spheroids in bone regeneration using a synergic strategy with 3D-printed scaffolds made from poly (lactic acid) (PLA) and nanostructured hydroxyapatite doped with carbonate ions (CHA) in a rat model of cranial critical-size defect. In summary, a set of results suggests that ASC spheroidal constructs promoted bone regeneration. In vitro results showed that ASC spheroids were able to spread and interact with the 3D-printed scaffold, synthesizing crucial growth factors and cytokines for bone regeneration, such as VEGF. Histological results after 3 and 6 months of implantation showed the formation of new bone tissue in the PLA/CHA scaffolds that were seeded with ASC spheroids. In conclusion, the presence of ASC spheroids in the PLA/CHA 3D-printed scaffolds seems to successfully promote bone formation, which can be crucial for a significant clinical improvement in critical bone defect regeneration.

Histomorphometric evaluation, SEM, and synchrotron analysis of the biological response of biodegradable and ceramic hydroxyapatite-based grafts: from the synthesis to the bed application.

This study aimed to analyze the physicochemical and histological properties of nanostructured hydroxyapatite and alginate composites produced at different temperatures with and without sintering and implanted in rabbit tibiae. Hydroxyapatite-alginate (HA) microspheres (425-600 µm) produced at 90 and 5 °C without (HA90 and HA5) or with sintering at 1000 °C (HA90S and HA5S) were characterized and applied to evaluate thein vitrodegradation; also were implanted in bone defects on rabbit's tibiae (n= 12). The animals were randomly divided into five groups (blood clot, HA90S, HA5S, HA90, and HA5) and euthanized after 7 and 28 d. X-ray diffraction and Fourier-transform infrared analysis of the non-sintered biomaterials showed a lower crystallinity than sintered materials, being more degradablein vitroandin vivo. However, the sinterization of HA5 led to the apatite phase's decomposition into tricalcium phosphate. Histomorphometric analysis showed the highest (p< 0.01) bone density in the blood clot group, similar bone levels among HA90S, HA90, and HA5, and significantly less bone in the HA5S. HA90 and HA5 groups presented higher degradation and homogeneous distribution of the new bone formation onto the surface of biomaterial fragments, compared to HA90S, presenting bone only around intact microspheres (p< 0.01). The elemental distribution (scanning electron microscope and energy dispersive spectroscopy andµXRF-SR analysis) of Ca, P, and Zn in the newly formed bone is similar to the cortical bone, indicating bone maturity at 28 d. The synthesized biomaterials are biocompatible and osteoconductive. The heat treatment directly influenced the material's behavior, where non-sintered HA90 and HA5 showed higher degradation, allowing a better distribution of the new bone onto the surface of the biomaterial fragments compared to HA90S presenting the same level of new bone, but only on the surface of the intact microspheres, potentially reducing the bone-biomaterial interface.

Magnetic Nanoparticles for Therapy and Diagnosis in Nanomedicine.

Magnetic nanoparticles (MNPs) have been widely used for their potential applications, mainly for the diagnosis and/or therapy (theranostic) of several diseases in the field of nanomedicine, as passive contrast agents, through the opsonization process, or active contrast agents, after their functionalization and the subsequent capture of the signal using various techniques such as magnetic resonance imaging (MRI), optical imaging, nuclear imaging, and ultrasound [...].

Nano-hydroxyapatite radiolabeled with radium dichloride [223Ra] RaCl2 for bone cancer targeted alpha therapy: In vitro assay and radiation effect on the nanostructure.

The use of targeted alpha therapy (TAT) for bone cancer is increasing each year. Among the alpha radionuclides, radium [223Ra]Ra+2 is the first one approved for bone cancer metastasis therapy. The development of novel radiopharmaceutical based on [223Ra]Ra+2 is essential to continuously increase the arsenal of new TAT drugs. In this study we have developed, characterized, and in vitro evaluated [223Ra] Ra-nano-hydroxyapatite. The results showed that [223Ra] Ra-nano-hydroxyapatite has a dose-response relationship for osteosarcoma cells and a safety profile for human fibroblast cells, corroborating the application as a radiopharmaceutical.

Evaluating Hydroxyapatite, Gold Nanoparticles, and Graphene-Copper as Bimodal Agents for X-ray and Computed Tomography.

A global need exists for new and more effective contrast agents for computed tomography and traditional X-ray modalities. Among the few options available nowadays, limitations imposed by industrial production, performance, and efficacy restrict the use and reduce the potential of both imaging techniques. The use of nanomaterials as new contrast agents for X-ray and computed tomography is an innovative and viable way to increase the options and enhance performance. In this study, we evaluated eight nanomaterials: hydroxyapatite doped with zinc (Zn-HA 10%); hydroxyapatite doped with strontium (Sr-HA 10%); hydroxyapatite without thermal treatment (HA 282 STT); thermally treated hydroxyapatite (HA 212 500 °C and HA 01.256 CTT 1000 °C); hydroxyapatite microspheres (HA microspheres); gold nanoparticles (AuNP); and graphene oxide doped with copper (Cu-GO). The results showed that for both imaging modalities; HA microspheres were the best option, followed by hydroxyapatite thermally treated at 1000 °C. The nanomaterials with the worst results were hydroxyapatite doped with zinc (Zn-HA 10%), and hydroxyapatite doped with strontium (Sr-HA 10%). Our data demonstrated the potential of using nanomaterials, especially HA microspheres, and hydroxyapatite with thermal treatment (HA 01.256 CTT 1000 °C) as contrast agents for X-ray and computed tomography.

Rescued Cats Prefer to Scratch Fabrics Commonly Used to Cover Upholstered Furniture.

Preference responses of cats for scratching fabrics commonly used on furniture were evaluated during four consecutive days in three Non-Governmental Organizations (NGOs) that rescue companion animals. Cats were grouped and their choices were registered at a group level (no individual identification). Daily choices for chenille, suede, synthetic leather, or waterproof grosgrain fabrics were evaluated for the cats' groups. A preference for chenille and non-preference for synthetic leather and waterproof grosgrain was found, independent of the NGO. In conclusion, although not using chenille does not assure that cats stop scratching furniture - especially if no other option to scratch is available - synthetic leather and waterproof grosgrain seem to be less attractive fabrics for these animals. Further studies are needed to investigate whether these findings apply to cats in a home scenario, when just one or a few individuals are usually present and only one type of fabric covering furniture is commonly available. Although we did not investigate the effect of providing scratching posts for these animals, we recommend such posts are available in the environment as scratching behavior is important to cats.

Embryotoxicity and visual-motor response of functionalized nanostructured hydroxyapatite-based biomaterials in zebrafish (Danio rerio).

Hydroxyapatite (HA) is a biomaterial widely used in biomedical applications. Many studies have shown that ionic substituents can be incorporated into HA to produce a mineral composition more similar to natural bone tissue with more favorable biological characteristics for application in bone regeneration. However, its potentially toxic effects need to be evaluated before full approval for human use. For this purpose, an embryotoxicity test was performed on zebrafish according to OECD guideline 236. Zebrafish embryos were exposed to 1 or 3 microspheres of alginate containing nanoparticles of HA and carbonate (CHA), strontium (SrHA), and zinc-substituted HA (ZnHA) from 4 to 120 h post-fertilization (hpf). Lethality and developmental endpoints were evaluated. In addition, larval behavior at 168 hpf was also analyzed to observe whether biomaterials adversely affect optomotor and avoidance responses (neurotoxicity), as well as the oxidative stress pattern through qPCR. After 120 h exposure to all microspheres with different patterns of crystallinity, porosity, nanoparticle size, surface area, and degradation behavior, there was no mortality rate greater than 20%, indicating the non-embryotoxic character of these biomaterials. All experimental groups showed positive optomotor and avoidance responses, which means that embryo exposure to the tested biomaterials had no neurotoxic effects. Furthermore, larvae exposed to one SrHA microsphere showed a better optomotor response than the control. Furthermore, the biomaterials did not change the pattern of mRNA levels of genes related to oxidative stress even after 120 hpf. The growing number of new HA-based biomaterials produced should be accompanied by increased studies to understand the biosafety of these compounds, especially in alternative models, such as zebrafish embryos. These results reinforce our hypothesis that ion-substituted HA biomaterials do not impose toxicological effects, cause development and neuromotor impairment, or increase oxidative stress in zebrafish embryos being useful for medical devices and in the process of bone regeneration.

Does Melatonin Associated with Nanostructured Calcium Phosphate Improve Alveolar Bone Repair?

Background and objectives: Calcium phosphates have been widely used as bone substitutes, but their properties are limited to osteoconduction. The association of calcium phosphates with osteoinductive bioactive molecules has been used as a strategy in regenerative medicine. Melatonin has been studied due to its cell protection and antioxidant functions, reducing osteoclastic activity and stimulating newly formed bone. This study aimed to evaluate the effect of topical application of melatonin associated with nanostructured carbonated hydroxyapatite microspheres in the alveolar bone repair of Wistar rats through histological and histomorphometric analysis. Materials and Methods: Thirty female Wistar rats (300 g) were used, divided randomly into three experimental groups (n = 10), G1: nanostructured carbonated hydroxyapatite microspheres associated with melatonin gel (CHA-M); G2: nanostructured carbonated hydroxyapatite (CHA); G3: blood clot (without alveolar filling). The animals were euthanized after 7 and 42 days of the postoperative period and processed for histological and histomorphometric evaluation. Kruskal-Wallis and Dunn's post-test were applied to investigate statistical differences between the groups at the same time point for new bone and connective tissue variables. Mann-Whitney was used to assess statistical differences between different time points and in the biomaterial variable. Results: Results showed a greater volume of residual biomaterial in the CHA-M than the CHA group (p = 0.007), and there were no significant differences in terms of newly formed bone and connective tissue between CHA and CHA-M after 42 days. Conclusions: This study concluded that both biomaterials improved alveolar bone repair from 7 to 42 days after surgery, and the association of CHA with melatonin gel reduced the biomaterial's biodegradation at the implanted site but did not improve the alveolar bone repair.

The Influence of rhBMP-7 Associated with Nanometric Hydroxyapatite Coatings Titanium Implant on the Osseointegration: A Pre-Clinical Study.

Background: Bioceramic nanometer coatings have been regarded as potential substitutes for plasma-sprayed hydroxyapatite coatings, and the association with bone morphogenetic protein (BMP) is an attempt to achieve faster osseointegration to hasten oral rehabilitation. Objective: This study aimed to investigate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) on the osseointegration of titanium implants coated with a thin film surface of hydroxyapatite (HA). Methods: Two implants (n = 24) were placed in each white New Zealand rabbits' femur (n = 6). Implants were placed in the right femur after standard instrumentation (A and B) and in the left femur after an over-instrumentation (C and D), preventing bone-implant contact. The distal implants were installed associated with rhBMP-7 (groups B [regular instrumentation] and D [over-instrumentation]) and, also, in the absence of without BMP (control groups A [regular instrumentation] and C [over-instrumentation]). After 4 weeks, the animals were euthanized. The bone blocks containing the implants were embedded in methyl methacrylate and sectioned parallel to the long axis of the implant, which were analyzed by image segmentation. The data were analyzed using a nonparametric statistical method. Results: We observed that Group A had a mean bone formation of 35.6% compared to Group B, which had 48.6% (p > 0.05). Moreover, this group showed 28.3% of connective tissue compared to Group A, with 39.3%. In the over-instrumented groups, rhBMP-7 (Group D) showed an enhanced and significant increase in bone formation when compared with the group without rhBMP-7 (Group C). Conclusion: We concluded that the association of rhBMP-7 to thin nanostructure HA-coated implants promoted greater new bone area than the same implants in the absence of rhBMP-7, mainly in cases of over-instrumented implant sites.

The Use of Hydroxyapatite Loaded with Doxycycline (HADOX) in Dentoalveolar Surgery as a Risk-Reduction Therapeutic Protocol in Subjects Treated with Different Bisphosphonate Dosages.

Medication-related osteonecrosis of the jaw (MRONJ) is considered as a severe adverse side effect of specific drugs such as anti-resorptive and anti-angiogenic medications. Evidence suggests that MRONJ is linked to invasive dental procedures, mainly dentoalveolar surgery. Several preventive strategies to minimize the risk of developing MRONJ have been investigated. However, no investigation has been attempted to evaluate the therapeutic effect of local drug-delivery technology as a preventive strategy protocol. The aim of this study is to evaluate the efficacy of hydroxyapatite-containing doxycycline (HADOX) in rats with high-risk MRONJ development. All the rats used in this study were divided into seven groups. Six groups of rats out of seven were exposed to two different doses of antiresorptive drug therapy for four weeks before undergoing an upper incisor extraction. After 28 days, all the animals were euthanized, and the bone blocks were processed for histological and histomorphometrical evaluation. The histomorphometric analysis confirmed that newly formed bone (NFB) was present in all groups, with significant differences. NFB in the HADOX group treated with zoledronic acid at 4% showed (28.38; C.I. 22.29-34.48), which represents a significant increase compared to HA (15.69; C.I. 4.89-26.48) (p = 0.02). A similar pattern was observed in the HADOX group treated with zoledronic acid 8% ZA treatment (p = 0.001). Conclusions: HADOX did not inhibit any bone repair and reduced early inflammatory response. Hence, HADOX could promote bone healing in patients undergoing antiresorptive drug therapy.

Trabecular architecture during the healing process of a tibial diaphysis defect.

The adaptation of trabecular bone microstructure to mechanical loads has been intensively investigated. However, loading-unrelated aspects of trabecular architecture remain unclear. We used synchrotron radiation-based X-ray microtomography to study the 3D microarchitecture of newly formed trabecular tissue in a defect produced in the cortical region of the rat tibia diaphysis, in the absence (7, 14, and 21 days) or the presence (21 days) of carbonated hydroxyapatite/alginate (cHA) microspheres. This work provides the first evidence that the woven bone trabecular network, formed during the healing process, displays a well-organized 3D microarchitecture consisting of nodes with 3 (3-N), 4 (4-N) and 5 (5-N) connecting trabeculae, with a mean relative abundance of (3-N)/(4-N)/(5-N) = 66/24/7, for the analyzed periods. The measured inter-trabecular angles (ITA) distribution presented a Gaussian profile, with mean value at 115° for 3-N nodes, and 105° for 4-N nodes, close to the angles of idealized 3D regular structures (120° and 109.5°, respectively). Changes in the dispersion of ITA distribution suggested that a highly symmetric trabecular fabric organized under tensegrity principles is formed early during the bone healing process. Post-implantation, cHA disaggregated into multiple fragments (~20-400 µm), stimulating osteoconduction and bone growth toward the interior of the medullary cavity. The presence of biomaterials in bone defects affected the trabecular dimensions; however, it did not interfere with the formation of geometrical motifs with topological parameters similar to those found in the sham-defects. STATEMENT OF SIGNIFICANCE: The trabecular bone microstructure enables the tissue to meet the necessary mechanical and functional demands. However, the process of trabecular microarchitecture formation during healing, in the absence or presence of a bone graft, is not yet well understood. This work demonstrated that, from the beginning of its formation in cortical bone defects, the woven-bone trabecular network is spatially organized according to the principle of tensegrity. This microarchitecture is comprised of highly symmetric geometric motifs and is an intrinsic characteristic of trabecular growth, regardless of hierarchical scale or mechanical stimulation. The addition of a biodegradable nanostructured calcium phosphate graft did not disrupt trabecular microarchitecture; however, graft biodegradation should be controlled to optimize the reproduction of intrinsic trabecular motifs throughout the defect.

Nanostructured Carbonated Hydroxyapatite Associated to rhBMP-2 Improves Bone Repair in Rat Calvaria.

Many biomaterials are used for Bone Morphogenetic Proteins (BMPs) delivery in bone tissue engineering. The BMP carrier system's primary function is to hold these growth factors at the wound's site for a prolonged time and provide initial support for cells to attach and elaborate the extracellular matrix for bone regeneration. This study aimed to evaluate the nanostructured carbonated hydroxyapatite microspheres (nCHA) as an rhBMP-2 carrier on rats calvaria. A total of fifteen male Wistar rats were randomly divided into three groups (n = 5): clot (control group), rhBMP-2 associated with collagen membrane (COL/rhBMP-2) or associated with the microspheres (nCHA/rhBMP-2). After 45 days, the calvaria defect samples were evaluated through histological, histomorphometric, and SR-µCT analyses to investigate new-formed bone and connective tissue volume densities. The descriptive histological analysis showed that nCHA/rhBMP-2 improved bone formation compared to other groups. These results were confirmed by histomorphometric and SR-µCT analysis that showed substantially defect area filling with a higher percentage of newly formed (36.24 ± 6.68) bone than those with the COL/rhBMP-2 (0.42 ± 0.40) and Clot (3.84 ± 4.57) (p < 0.05). The results showed that nCHA is an effective carrier for rhBMP-2 encouraging bone healing and an efficient alternative to collagen membrane for rhBMP-2 delivery.

Fabrication and characterization of remineralizing dental composites containing hydroxyapatite nanoparticles.

The aim of this study was to fabricate and characterize dental composites containing hydroxyapatite nanoparticles (HApNPs). Four dental composites were produced from the same organic matrix (70 wt% Bis-GMA and 30 wt% TEGDMA), with partial replacement of BaBSi particles (65 wt%) by HApNPs in the following concentrations (wt%): E0 (0) - control, E10 (10), E20 (20) and E30 (30). Ca2+ and PO43- release was evaluated in solutions with different pHs (4, 5.5, and 7) using atomic emission spectroscopy with microwave-induced nitrogen plasma while the enamel remineralization potential was evaluated in caries-like enamel lesions induced by S. mutans biofilm using micro-CT. The following properties were characterized: degree of conversion (DC%), microhardness (KHN), flexural strength (FS), elastic modulus (EM) and translucency (TP). The higher the HApNPs content, the higher the Ca2+ and PO43- release. The ions release was influenced by pH (4 > 5.5 > 7) (p < 0.05). All composites loaded with HApNPs were able to remineralize the enamel (E30 = E20 > E10) (p < 0.05). Contrarily, E0 was not able of recovering the enamel mineral loss. E0 and E10 presented highest DC%, while E20 and E30 showed similar and lowest DC%. KHN and FS were decreased with the addition of HApNPs, while EM was not influenced by the incorporation of HApNPs. E10 presented statistically similar TP to E0, while this property decreased for E20 and E30 (p < 0.05). Incorporation of HApNPs into dental composites promoted enamel remineralization, mainly at potentially cariogenic pH (= 4), while maintained their overall performance in terms of physicomechanical properties.

The role of apoptosis associated speck-like protein containing a caspase-1 recruitment domain (ASC) in response to bone substitutes.

The apoptosis-associated Speck-like protein containing a caspase-1 recruitment domain (ASC), present in inflammasomes, regulates inflammation events and is involved in osteogenic phenotype. Nevertheless, its function in bone repair induced by bone substitute biomaterials is unclear. This study aimed to unveil the role of ASC on osteoprogenitor and tissue response to stoichiometric-hydroxyapatite (HA), nanostructured carbonated-hydroxyapatite (CHA), and CHA containing 5% Strontium (SrCHA), characterized previously by XRD, uXRF-SR, and FTIR spectroscopy implants. Thereafter, conditioned media by the biomaterials were used later to treat pre-osteoblasts and an osteogenic stimulus was shown in response to the materials, with higher expression of Runx2, Osterix, ALP, and Collagen 1a1 genes, with significant involvement of inflammatory-related genes. Thus, to better address the involvement of inflammasome, primary cells obtained from both genotypes [Wild-Type (WT) and ASC Knockout (ASC-KO) mice] were subjected to conditioned media up to 7 days, and our data reinforces both HA and CHA induces lower levels of alkaline phosphatase (ALP) than SrCHA, considering both genotypes (p < 0.01), and ASC seems contribute with osteogenic stimulus promoted by SrCHA. Complimentarily, the biomaterials were implanted into both subcutaneous and bone defects in tibia. Histological analysis on 28 days after implantation of biomaterials into mice's subcutaneous tissue revealed moderate inflammatory response to them. Both histomorphometry and µCT analysis of tibias indicated that the biomaterials did not reverse the delay in bone repair of ASC KO, reinforcing the involvement of ASC on bone regeneration and bone de novo deposition. Also, the bone density in CHA was >2-fold higher in WT than ASC-KO samples. HA was virtually not resorbed throughout the experimental periods, in opposition to CHA in the WT group. CHA reduced to half-area after 28 days, and the bone deposition was higher in CHA for WT mice than HA. Taken together, our results show that biomaterials did not interfere with the healing pattern of the ASC KO, but CHA promoted higher bone deposition in the WT group, probably due to its greater biodegradability. These results reinforce the importance of ASC during bone de novo deposition and healing.

Periodontal esthetic surgery to improve a natural smile: Report case with 2-year follow-up.

The objective in this case report is to present a correction of excessive gingival exposure performed through periodontal esthetic surgery, using clinical crown lengthening and lip repositioning. The patient reported discomfort when smiling due to excessive gingival exposure, and clinical and photographic examinations of the patient showed vertical maxillary growth as the main diagnosis. In the digital smile design, the possibility of crown lengthening observed for teeth - upper left and right central incisors and upper left lateral incisor. A lip-repositioning procedure was also planned. An incision was performed at the mucogingival junction, and a parallel incision was realized at the top of the alveolar mucosa. Afterward, the incised gingival band was removed through vertical incisions in the planned border area. The muscular area was preserved. A simple suture was made, with the approach of the gingival margins around the surgical area. The crown-lengthening procedure was performed with the flapless technique. After 2-year follow-up, the periodontal esthetic surgery, comprising crown lengthening and lip repositioning, was noninvasive and can thus serve as an interesting alternative treatment for excessive exposure of the gingival smile, as it results in a harmonious and natural smile.

Owners Frequently Report that They Reward Behaviors of Dogs by Petting and Praising, Especially When Dogs Respond Correctly to Commands and Play with Their Toys.

We characterized the reward patterns of dogs' owners for the expression of desired behaviors of their pets through a questionnaire made available online on a social media page for 7 days (responses from over 66,676 owners). The questions were related to the type and frequency of rewards that pet owners applied and what specific dogs' behaviors were rewarded. Desired behaviors of dogs were frequently reported to be rewarded. Responding correctly to commands and playing with their own toys were behaviors reported to be rewarded more frequently by owners than eliminating in appropriate places, a behavior perceived commonly just later. Moreover, owners reported that they rewarded more frequently by petting and praising the dogs and less frequently by applying a combination of giving both food and toys to their dogs. Thus, dog owners commonly reward desired behaviors by petting and prasing the dogs, most likely because it is the most convenient reward to use. Moreover, rewarding is more common when dogs express desired behaviors more immediately perceived by owners, which has welfare implications for these companion animals.

Doxycycline containing hydroxyapatite ceramic microspheres as a bone-targeting drug delivery system.

Drug delivery technology is a promising way to enhance the therapeutic efficacy of drugs. The purpose of this study is to evaluate the physical and chemical properties of hydroxyapatite ceramic microspheres loaded with doxycycline (HADOX), their effects on in vitro osteoblast viability, and their antimicrobial activity, and to determine the effects of DOX on the healing of rat sockets after tooth extraction. The internal microsphere porosity was sensitive to the treatment used to adsorb DOX onto microsphere surface; HA microspheres without DOX presented 26% of pores, whereas HADOX0.15 microspheres presented 52.0%. An initial drug release of 49.15 µg/ml was observed in the first 24 hr. The minimal inhibitory concentration (MIC) tested against Enterococcus faecalis demonstrated that bacterial growth was inhibited for up to 7 days. Results of cell viability and cell proliferation did not indicate statistical differences in the metabolic activity of HADOX samples relative to HA without DOX microspheres (p > .05). After 1 week, a discreet inflammation reaction was observed in the control group, and after 6 weeks, newly-formed bone was observed in the HADOX0.15 (p < .05). The HADOX did not interfere in the bone repair and controlled the early inflammatory response. HADOX could be a promising biomaterial to promote bone repair in infected sites.

Randomized Controlled Clinical Trial of Nanostructured Carbonated Hydroxyapatite for Alveolar Bone Repair.

The properties of the biodegradation of bone substitutes in the dental socket after extraction is one of the goals of regenerative medicine. This double-blind, randomized, controlled clinical trial aimed to compare the effects of a new bioabsorbable nanostructured carbonated hydroxyapatite (CHA) with a commercially available bovine xenograft (Bio-Oss®) and clot (control group) in alveolar preservation. Thirty participants who required tooth extraction and implant placement were enrolled in this study. After 90 days, a sample of the grafted area was obtained for histological and histomorphometric evaluation and an implant was installed at the site. All surgical procedures were successfully carried out without complications and none of the patients were excluded. The samples revealed a statistically significant increase of new bone formation (NFB) in the CHA group compared with Bio-Oss® after 90 days from surgery (p < 0.05). However, the clot group presented no differences of NFB compared to CHA and Bio-Oss®. The CHA group presented less amount of reminiscent biomaterial compared to Bio-Oss®. Both biomaterials were considered osteoconductors, easy to handle, biocompatible, and suitable for alveolar filling. Nanostructured carbonated hydroxyapatite spheres promoted a higher biodegradation rate and is a promising biomaterial for alveolar socket preservation before implant treatment.

Microspheres of alginate encapsulated minocycline-loaded nanocrystalline carbonated hydroxyapatite: therapeutic potential and effects on bone regeneration.

Background and objective: Tetracycline and its derivatives, combined with calcium phosphates, have been proposed as a delivery system to control inflammatory processes and chronic infections. The objective of this study was to evaluate the microspheres of alginate encapsulated minocycline-loaded nanocrystalline carbonated hydroxyapatite (CHAMINO) as a biomimetic device to carry out target-controlled drug delivery for alveolar bone repair. Methods: CHAMINO microspheres were implanted in a rat central incisor socket after 7 and 42 days. New bone was formed in both groups between 7 and 42 days of implantation. However, the bone growth was significantly higher for the CHAMINO microspheres. Results: The minocycline (MINO) loading capacity of the nanocrystaline carbonated hydroxyapatite (CHA) nanoparticles was 25.1±2.2 µg MINO/mg CHA for adsorption over 24 hrs. The alginate microspheres containing minocycline-loaded CHA were biologically active and inhibited the Enterococcus faecalis culture growth for up to seven days of the MINO release. An osteoblastic cell viability assay based on the resazurin reduction was conducted after the cells were exposed to the CHAMINO powder and CHAMINO microspheres. Thus, it was found that the alginate extracts encapsulated the minocycline-loaded CHA microspheres and did not affect the osteoblastic cell viability, while the minocycline-doped CHA powder reduced the cell viability by 90%. Conclusion: This study concluded that the alginate microspheres encapsulating the minocycline-loaded nanocrystalline carbonated hydroxyapatite exhibited combined antibacterial activity against Enterococcus faecalis with cytocompatibility and osteoconduction properties. The significant improvement in the new bone formation after 42 days of implantation suggests that the CHAMINO microsphere has potential in clinical applications of bone regeneration.