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.

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.

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.

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.

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.

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.

Influence of the geometry of nanostructured hydroxyapatite and alginate composites in the initial phase of bone repair1.

PURPOSE: To analyze, histomorphologically, the influence of the geometry of nanostructured hydroxyapatite and alginate (HAn/Alg) composites in the initial phase of the bone repair. METHODS: Fifteen rats were distributed to three groups: MiHA - bone defect filled with HAn/Alg microspheres; GrHA - bone defect filled with HAn/Alg granules; and DV - empty bone defect; evaluated after 15 days postoperatively. The experimental surgical model was the critical bone defect, ≅8.5 mm, in rat calvaria. After euthanasia the specimens were embedded in paraffin and stained with hematoxylin and eosin, picrosirius and Masson-Goldner's trichrome. RESULTS: The histomorphologic analysis showed, in the MiHA, deposition of osteoid matrix within some microspheres and circumjacent to the others, near the bone edges. In GrHA, the deposition of this matrix was scarce inside and adjacent to the granules. In these two groups, chronic granulomatous inflammation was noted, more evident in GrHA. In the DV, it was observed bone neoformation restricted to the bone edges and formation of connective tissue with reduced thickness in relation to the bone edges, throughout the defect. CONCLUSION: The geometry of the biomaterials was determinant in the tissue response, since the microspheres showed more favorable to the bone regeneration in relation to the granules.

Does the association of blood-derived growth factors to nanostructured carbonated hydroxyapatite contributes to the maxillary sinus floor elevation? A randomized clinical trial.

OBJECTIVE: The combination of calcium phosphate with blood-derived growth factors (BDGF) has been widely used in bone regeneration procedures although its benefits are still unclear. The purpose of this study was to evaluate whether or not BDGF improves the efficacy of a modified carbonated calcium phosphate biomaterial in sinus floor augmentation. MATERIAL AND METHODS: Ten patients underwent 20 sinus floor augmentation procedures using nanostructured carbonated hydroxyapatite (cHA) microspheres alone or associated with BDGF in a randomized controlled clinical trial. The in vitro release of growth factors was assessed by an elution assay. Bone grafts were randomly implanted in the right and left maxillary sinuses of each participant, associated either with a 0.9% saline solution or BDGF. Bone gain was evaluated through cone beam tomography after 180 days. RESULTS: Nine women and one man composed the sample. The blood-derived concentrates were able to release high levels of growth factors and cytokines. A significant clinical advantage was observed in the use of the BDGF after fibrin polymerization around the biomaterial microspheres, optimizing the surgical procedures, thereby reducing the time and displacement, and improving the adaptation of the biomaterial in the maxillary sinus. No synergistic effect was observed in bone formation when cHA was associated with BDGF (p > 0.05). CONCLUSION: Equivalent new bone formation was observed for cHA in the presence or absence of the BDGF concentrate in bilateral sinus floor elevation after 6 months. Blood-derived growth factors did not improve bone repair when associated with calcium phosphate in sinus lift procedures.

Influence of the geometry of nanostructured hydroxyapatite and alginate composites in the initial phase of bone repair

Abstract Purpose: To analyze, histomorphologically, the influence of the geometry of nanostructured hydroxyapatite and alginate (HAn/Alg) composites in the initial phase of the bone repair. Methods: Fifteen rats were distributed to three groups: MiHA - bone defect filled with HAn/Alg microspheres; GrHA - bone defect filled with HAn/Alg granules; and DV - empty bone defect; evaluated after 15 days postoperatively. The experimental surgical model was the critical bone defect, ≅8.5 mm, in rat calvaria. After euthanasia the specimens were embedded in paraffin and stained with hematoxylin and eosin, picrosirius and Masson-Goldner's trichrome. Results: The histomorphologic analysis showed, in the MiHA, deposition of osteoid matrix within some microspheres and circumjacent to the others, near the bone edges. In GrHA, the deposition of this matrix was scarce inside and adjacent to the granules. In these two groups, chronic granulomatous inflammation was noted, more evident in GrHA. In the DV, it was observed bone neoformation restricted to the bone edges and formation of connective tissue with reduced thickness in relation to the bone edges, throughout the defect. Conclusion: The geometry of the biomaterials was determinant in the tissue response, since the microspheres showed more favorable to the bone regeneration in relation to the granules.

Adult Stem Cells Spheroids to Optimize Cell Colonization in Scaffolds for Cartilage and Bone Tissue Engineering.

Top-down tissue engineering aims to produce functional tissues using biomaterials as scaffolds, thus providing cues for cell proliferation and differentiation. Conversely, the bottom-up approach aims to precondition cells to form modular tissues units (building-blocks) represented by spheroids. In spheroid culture, adult stem cells are responsible for their extracellular matrix synthesis, re-creating structures at the tissue level. Spheroids from adult stem cells can be considered as organoids, since stem cells recapitulate differentiation pathways and also represent a promising approach for identifying new molecular targets (biomarkers) for diagnosis and therapy. Currently, spheroids can be used for scaffold-free (developmental engineering) or scaffold-based approaches. The scaffold promotes better spatial organization of individual spheroids and provides a defined geometry for their 3D assembly in larger and complex tissues. Furthermore, spheroids exhibit potent angiogenic and vasculogenic capacity and serve as efficient vascularization units in porous scaffolds for bone tissue engineering. An automated combinatorial approach that integrates spheroids into scaffolds is starting to be investigated for macro-scale tissue biofabrication.

Nano-Hydroxyapatite Doped with Ho-166 as Drug Delivery System for Bone Cancer Therapy and Diagnosis: Developing a Theragnostic Radiopharmaceuticals.

BACKGROUND: The use of nanobiomaterials is increasing each day. Among the immense variety of nanomaterials developed and studied the hydroxyapatite is one of the most ones. OBJECTIVE: In this study we developed and tested nano-hydroxyapatite dopped with Ho-166 for bone cancer. RESULTS: The results showed that the nano-hydroxyapatite dopped with Ho-166 has a great affinity for the bone. CONCLUSION: The pre-clinical studies support the use as a nano-radiopharmaceuticals for bone cancer treatment and diagnosis.

Histomorphometric evaluation of strontium-containing nanostructured hydroxyapatite as bone substitute in sheep.

The aim of this study is to evaluate the biocompatibility and osteoconductivity in surgical defects of sheep tibias filled with 1% strontium-containing nanostructured hydroxyapatite microspheres (SrHA), stoichiometric hydroxyapatite without strontium microspheres (HA), or blood clots. Santa Ines sheep were subjected to three perforations on the medial side of the left tibia. The biomaterials were characterized by X-ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) before implantation and by X-Ray Microfluorescence (µFRX) and Scanning Electron Microscopy (SEM) after sheep tibias implantation. Surgical defects were filled with blood clots (control), SrHA (Group 1) or HA (Group 2). After 30 days, 5-µm bone blocks were obtained for histological evaluation, and the blocks obtained from 1 animal were embedded in methylmethacrylate for undecalcified sections. Mononuclear inflammatory infiltrate remained mild in all experimental groups. Giant cells were observed surrounding biomaterials particles of both groups and areas of bone formation were detected in close contact with biomaterials. All groups showed newly formed bone from the periphery to the center of the defects, which the control, HA and SrHA presented 36.4% (± 21.8), 31.2% (± 14.7) and 26.2% (± 12.9) of newly formed bone density, respectively, not presenting statistical differences. In addition, the connective tissue density did not show any significant between groups. The SrHA showing a higher volume density of biomaterial (51.2 ± 14.1) present in the defect compared to HA (32.6 ± 8.5) after 30 days (p = 0.03). Microspheres containing 1% SrHA or HA can be considered biocompatible, have osteoconductive properties and may be useful biomaterials for clinical applications.

Histomorphometric evaluation of strontium-containing nanostructured hydroxyapatite as bone substitute in sheep

Abstract The aim of this study is to evaluate the biocompatibility and osteoconductivity in surgical defects of sheep tibias filled with 1% strontium-containing nanostructured hydroxyapatite microspheres (SrHA), stoichiometric hydroxyapatite without strontium microspheres (HA), or blood clots. Santa Ines sheep were subjected to three perforations on the medial side of the left tibia. The biomaterials were characterized by X-ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) before implantation and by X-Ray Microfluorescence (µFRX) and Scanning Electron Microscopy (SEM) after sheep tibias implantation. Surgical defects were filled with blood clots (control), SrHA (Group 1) or HA (Group 2). After 30 days, 5-µm bone blocks were obtained for histological evaluation, and the blocks obtained from 1 animal were embedded in methylmethacrylate for undecalcified sections. Mononuclear inflammatory infiltrate remained mild in all experimental groups. Giant cells were observed surrounding biomaterials particles of both groups and areas of bone formation were detected in close contact with biomaterials. All groups showed newly formed bone from the periphery to the center of the defects, which the control, HA and SrHA presented 36.4% (± 21.8), 31.2% (± 14.7) and 26.2% (± 12.9) of newly formed bone density, respectively, not presenting statistical differences. In addition, the connective tissue density did not show any significant between groups. The SrHA showing a higher volume density of biomaterial (51.2 ± 14.1) present in the defect compared to HA (32.6 ± 8.5) after 30 days (p = 0.03). Microspheres containing 1% SrHA or HA can be considered biocompatible, have osteoconductive properties and may be useful biomaterials for clinical applications.

Radiolabelled nanohydroxyapatite with 99mTc: perspectives to nanoradiopharmaceuticals construction.

The use of nanoparticles is under intense investigation. The possible advantages proposed by these systems are very impressive and the results may be quite schemer. In this scenario, the association of nanoparticles with radioactive materials (radionuclide) may be the most important step since the discovery of radioactive for nuclear medicine and radiopharmacy, especially for cancer targeting and therapy. In this study, we developed radiolabelled nanoparticles of hydroxyapatite with technetium 99m for bone cancer imaging. The results demonstrated that it is possible to label nanoparticles of hydroxyapatite, and due to its physicochemical properties is possible to develop nano-radiopharmaceutical for bone imaging.

Avaliação do reparo ósseo no levantamento do seio maxilar de coelhos após implantação de esferas de hidroxiapatita carbonatada nanoestruturada contendo 5% de estrôncio / Evaluation of bone repair after maxillary sinus grafting with 5% strontium, nanostructured, carbonated hydroxyapatite microspheres in a rabbit model

A hidroxiapatita (HA) tem sido amplamente utilizada como um importante substituto ósseo. Quando em dimensão nanométrica, assemelha-se em tamanho e morfologia à apatita biológica, podendo ser considerada um biomaterial promissor para aplicação clínica. O estrôncio contribui por atuar na redução da reabsorção óssea e indução na atividade osteoblástica, enquanto os carbonatos favorecem a bioabsorção. Objetivos: caracterizar físico-quimicamente e analisar histologicamente, e de forma comparativa, a hidroxiapatita carbonatada contendo 5% de estrôncio com a hidroxiapatita estequiométrica. Material e métodos: foram utilizados 12 coelhos brancos Nova Zelândia, divididos em: hidroxiapatita carbonatada nanoestruturada contendo 5% de estrôncio (nSrcHA-experimental) e hidroxiapatita carbonatada nanoestruturada (ncHA-controle). Após a confecção dos sítios cirúrgicos, foram implantadas nas cavidades dos seios maxilares microesferas de ncSrHA e ncHA, nos lados esquerdo e direito, respectivamente. Os animais foram eutanasiados para análise histológica após quatro e 12 semanas. Resultados: após quatro semanas, o grupo ncHA apresentou osso neoformado e pavimentação osteoblástica próximo da parede do defeito. No grupo nSrcHA, o biomaterial apresentou-se de forma difusa com uma maior deposição de matriz osteogênica em torno do biomaterial, tecido ósseo neoformado próximo das paredes e no interior dos defeitos. No período de 12 semanas o grupo ncHA exibiu biomaterial no interior do defeito e osso neoformado, enquanto no grupo nSrcHA observou-se uma intensa formação óssea no interior do defeito com presença de osteócitos. Conclusão: ambos os materiais foram biocompatíveis e osteocondutores.

Hydroxyapatite (HA) has been widely used as an important bone substitute. Its nanometer scale is similar in size and morphology of biological apatite, which can be considered a promising biomaterial for clinical application. Strontium contributes to reduce bone resorption and induces osteoblast activity, whereas the carbonates favor bio-absorption. Objectives: to perform physico-chemical and histological characterization of nanostructured carbonated hydroxyapatite containing 5% strontium and the stoichiometric hydroxyapatite. Material and methods: twelve white New Zealand rabbits were used in this study and divided into nanostructured carbonated hydroxyapatite containing 5% strontium (ncSrHA-experimental) and nanostructured carbonated hydroxyapatite (ncHA-control). Two surgical defects were created in the maxillary sinus cavities and received microspheres of ncSrHA and ncHA in the left and right sides, respectively. After the experimental periods of 4 and 12 weeks, the animals were euthanized for histological analysis. Results: after four weeks, the ncHA group showed new bone formation and osteoblastic layer near the defect wall. For ncSrHA, a diffuse, increased osteogenic matrix deposition was seen around the biomaterial, with newly formed bone near the walls and inside the defects. At 12 weeks, the ncHA group exhibited biomaterial inside the defect and new bone formation, while in the ncSrHA group an intense bone formation within the defect with presence of osteocytes was observed. Conclusion: both materials are biocompatible and osteoconductive.

Characterization of antibiotic-loaded alginate-OSA starch microbeads produced by ionotropic pregelation.

The aim of this study was to characterize the penicillin-loaded microbeads composed of alginate and octenyl succinic anhydride (OSA) starch prepared by ionotropic pregelation with calcium chloride and to evaluate their in vitro drug delivery profile. The beads were characterized by size, scanning electron microscopy (SEM), zeta potential, swelling behavior, and degree of erosion. Also, the possible interaction between penicillin and biopolymers was investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), and Fourier transform infrared (FTIR) analysis. The SEM micrograph results indicated a homogeneous drug distribution in the matrix. Also, based on thermal analyses (TGA/DSC), interactions were detected between microbead components. Although FTIR spectra of penicillin-loaded microbeads did not reveal the formation of new chemical entities, they confirmed the chemical drug stability. XRD patterns showed that the incorporated crystalline structure of penicillin did not significantly alter the primarily amorphous polymeric network. In addition, the results confirmed a prolonged penicillin delivery system profile. These results imply that alginate and OSA starch beads can be used as a suitable controlled-release carrier for penicillin.

Avaliação histológica da biocompatibilidade e biodegradação de carbonatoapatitas nanoestruturadas / Histological evaluation of biocompatibility and biodegradation of nanostructured carbonateapatites

Os fosfatos de cálcio, como a hidroxiapatita, constituem um dos materiais mais utilizados para terapias ósseas devido à sua biocompatibilidade e atividade osseocondutora, contudo, sua utilização pelo Sistema Único de Saúde foi descontinuado em função de sua baixa bioabsorção.A carbonatoapatita foi desenvolvida com o objetivo de melhorar as propriedades de dissolução da hidroxiapatita em fluidos corporais, além de mimetizar o osso natural graças à composição nanoestruturada de suas partículas menores que 100 nm. O objetivo deste estudo foi avaliar a biocompatibilidade e biodegradação da carbonatoapatita sintetizada a 5°C, 37°C e 90°C não sinterizada, em comparação à hidroxiapatita estequiométrica sintetizada a 90°C e sinterizada. Foram utilizados 60 camundongos Balb-C, ambos os gêneros, distribuídos aleatoriamente em quatro grupos, de acordo com os materiais estudados, e subdivididos em três subgrupos seguindo os períodos experimentais. Após os procedimentos de anestesia, tricotomia e antissepsia, uma incisão de 10 mm foi realizada na região dorsal dos animais para implantação subcutânea de esferas do biomaterial, seguido de sutura. Os animais foram eutanasiados após uma, três e nove semanas para remoção das amostras e tecidos circunjacentes. As amostras foram processadas histologicamente e incluídas em parafina, e cortes com 5 μm de espessura foram obtidos e corados com hematoxilina e eosina. Os resultados histológicos demonstraram que os grupos de carbonatoapatita testados apresentaram biodegradação nos períodos avaliados, além de diminuição da reação inflamatória e neoformação de vasos sanguíneos circundando as esferas. Concluiu-se que, independente da temperatura de síntese, a carbonatoapatita apresentou-se biocompatível e biodegradável nos períodos avaliados...

Calcium phosphates, such as hydroxyapatite, constitute one of the most used materials for bone therapies due to its biocompatibility and osteoconductive activity, however, its use by the National Health System was discontinued due to its low bioabsorption rate. The carbonate apatite was developed with the objective of improving the dissolution properties of hydroxyapatite in body fl uids and mimic natural bone through their nanostructured particles smaller than 100 nm. The aim of this study was to evaluate the biocompatibility and biodegradation of carbonate apatite synthesized at 5°C, 37°C, and 90°C and not sintered, compared to stoichiometric hydroxyapatite synthesized at 90ºC. Sixty mice Balb-C (both genders) were randomly distributed into four groups according to the materials studied and subdivided into three subgroups following the experimental periods. After anesthesia and trychotomy procedures, a ten-millimeter incision was made in the dorsal region for subcutaneous implantation of biomaterial spheres. The animals were killed after one, three, and nine weeks after surgery. Samples containing biomaterials and surrounding tissues were removed, histologically processed, included in 5μm thick paraffin, and stained with hematoxylin and eosin method. The histological results showed that the carbonate apatite groups tested presented biodegradation in the evaluated periods, plus a decrease in inflammation and neovascularization surrounding the spheres. It is concluded that regardless of synthesis temperature, the carbonate apatite presented biocompatible and demonstrated biodegradation in the evaluated periods...