Comparative In Vivo Study of Biocompatibility of Apatites Incorporated with 1% Zinc or Lead Ions versus Stoichiometric Hydroxyapatite

2014 ◽  
Vol 19 ◽  
pp. 109-120 ◽  
Author(s):  
Bruno Giorno ◽  
Igor Iuco Castro-Silva ◽  
Alexandre Malta Rossi ◽  
José Mauro Granjeiro
Keyword(s):  
Inflammatory Response ◽  
Bone Repair ◽  
Divalent Cations ◽  
Subcutaneous Tissue ◽  
Microscopic Analysis ◽  
Lead Toxicity ◽  
Positive Control ◽  
Physico Chemical ◽  
Histological Processing

Hydroxyapatite is the main ceramic material that has being used in bone repair, although its physico-chemical and in vivo behavior should be better understood. A method to improve the biocompatibility of HA is the substitution of calcium with divalent cations which enhance mechanic resistance and can modulate inflammatory response against implanted material. In this study we analyzed the biocompatibility of HA doped with one per cent of Zn2+ or Pb2+. The first one has being described as an inflammation modulator and the second would be a model for chronic toxicity assay. Biocompatibility of the both materials was studied in vivo following the ISO 10993-6 standard. HA cylinders (ZnHA, PbHA and stoichiometric HA as positive control) were implanted into subcutaneous tissue of 45 Balb-c mice and after 1, 3 and 9 weeks the animals were euthanized (5 for each experimental condition). Necropsies of the skin containing reactional tissue were removed, fixed in 10% formaldehyde and followed the histological processing for paraffin embedding and staining with Hematoxylin-Eosine and Picrosirius red. Microscopic analysis showed for all groups moderate inflammatory response, decreasing throughout the experimental periods, with ZnHA group showing more intense response. Similar presence of macrophages, fibrosis and angiogenesis were observed among the groups. Thereby, we can conclude that ZnHA and PbHA are biocompatible and not bioresorbable, being the ZnHA potentially indicated as bone graft. Detailed studies are required to better understand the role of PbHA as chronic model for lead toxicity.

scholarly journals Physico-chemical and Histomorphometric Evaluation of Zinc-containing Hydroxyapatite in Rabbits Calvaria

2016 ◽  
Vol 27 (6) ◽  
pp. 717-726 ◽  
Author(s):  
Alinne Azevedo Pereira da Silva Suruagy ◽  
Adriana Terezinha Neves Novellino Alves ◽  
Suelen Cristina Sartoretto ◽  
José de Albuquerque Calasans-Maia ◽  
José Mauro Granjeiro ◽  
...  
Keyword(s):  
Bone Repair ◽  
Chemical Properties ◽  
Wilcoxon Test ◽  
In Vivo Studies ◽  
Control Group ◽  
Porous Hydroxyapatite ◽  
Physico Chemical ◽  
Hydroxyapatite Scaffold ◽  
Xrd Patterns

Abstract The aim of this study was to characterize the physico-chemical properties and bone repair after implantation of zinc-containing nanostructured porous hydroxyapatite scaffold (nZnHA) in rabbits' calvaria. nZnHA powder containing 2% wt/wt zinc and stoichiometric nanostructured porous hydroxyapatite (nHA - control group) were shaped into disc (8 mm) and calcined at 550 °C. Two surgical defects were created in the calvaria of six rabbits (nZnHA and nHA). After 12 weeks, the animals were euthanized and the grafted area was removed, fixed in 10% formalin with 0.1 M phosphate buffered saline and embedded in paraffin (n=10) for histomorphometric evaluation. In addition, one sample from each group (n=2) was embedded in methylmethacrylate for the SEM and EDS analyses. The thermal treatment transformed the nZnHA disc into a biphasic implant composed of Zn-containing HA and Zn-containing β-tricalcium phosphate (ZnHA/βZnTCP). The XRD patterns for the nHA disc were highly crystalline compared to the ZnHA disc. Histological analysis revealed that both materials were biologically compatible and promoted osteoconduction. X-ray fluorescence and MEV-EDS of nZnHA confirmed zinc in the samples. Histomorphometric evaluation revealed the presence of new bone formation in both frameworks but without statistically significant differences (p>0.05), based on the Wilcoxon test. The current study confirmed that both biomaterials improve bone repair, are biocompatible and osteoconductive, and that zinc (2wt%) did not increase the bone repair. Additional in vivo studies are required to investigate the effect of doping hydroxyapatite with a higher Zn concentration.

scholarly journals In vitro response of macrophages to ceramic scaffolds used for bone regeneration

2016 ◽  
Vol 13 (120) ◽  
pp. 20160346 ◽  
Author(s):  
Pamela L. Graney ◽  
Seyed-Iman Roohani-Esfahani ◽  
Hala Zreiqat ◽  
Kara L. Spiller
Keyword(s):  
Gene Expression ◽  
Inflammatory Response ◽  
Bone Regeneration ◽  
Bone Repair ◽  
Principal Component ◽  
Human Monocyte ◽  
Macrophage Phenotype ◽  
In Vitro Response

Macrophages, the primary cells of the inflammatory response, are major regulators of healing, and mediate both bone fracture healing and the inflammatory response to implanted biomaterials. However, their phenotypic contributions to biomaterial-mediated bone repair are incompletely understood. Therefore, we used gene expression and protein secretion analysis to investigate the interactions in vitro between primary human monocyte-derived macrophages and ceramic scaffolds that have been shown to have varying degrees of success in promoting bone regeneration in vivo . Specifically, baghdadite (Ca 3 ZrSi 2 O 9 ) and strontium–hardystonite–gahnite (Sr–Ca 2 ZnSi 2 O 7 –ZnAl 2 O 4 ) scaffolds were chosen as two materials that enhanced bone regeneration in vivo in large defects under load compared with clinically used tricalcium phosphate–hydroxyapatite (TCP–HA). Principal component analysis revealed that the scaffolds differentially regulated macrophage phenotype. Temporal changes in gene expression included shifts in markers of pro-inflammatory M1, anti-inflammatory M2a and pro-remodelling M2c macrophage phenotypes. Of note, TCP–HA scaffolds promoted upregulation of many M1-related genes and downregulation of many M2a- and M2c-related genes. Effects of the scaffolds on macrophages were attributed primarily to direct cell–scaffold interactions because of only minor changes observed in transwell culture. Ultimately, elucidating macrophage–biomaterial interactions will facilitate the design of immunomodulatory biomaterials for bone repair.

scholarly journals Host Chemokine and Cytokine Response in the Endocervix within the First Developmental Cycle of Chlamydia muridarum

2009 ◽  
Vol 78 (1) ◽  
pp. 536-544 ◽  
Author(s):  
Roger G. Rank ◽  
H. Marie Lacy ◽  
Anna Goodwin ◽  
James Sikes ◽  
Judy Whittimore ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Host Response ◽  
Microscopic Analysis ◽  
Developmental Cycle ◽  
Time Interval ◽  
Expression Array ◽  
Electron Microscopic ◽  
Chlamydia Muridarum ◽  
Stage Of Development

ABSTRACT The initial host response in a primary chlamydial infection is the onset of acute inflammation. However, we still know very little about the early temporal events in the induction of the acute inflammatory response and how these events relate to the initial chlamydial developmental cycle in an actual genital infection. Because it was critical to initiate a synchronous infection in the endocervix in the first 24 h to evaluate the sequential expression of the host response, we developed the surgical methodology of depositing Chlamydia muridarum directly on the endocervix. Cervical tissue was collected at 3, 12, and 24 h after inoculation and the expression array of chemokines, cytokines, and receptors was assessed to characterize the response during the initial developmental cycle. Polymorphonuclear leukocyte (PMN) infiltration was first observed at 12 h after inoculation, and a few PMNs could be seen in the epithelium at 24 h. Electron microscopic analysis at 24 h showed that virtually all inclusions were at the same stage of development, indicating a synchronous infection. Several chemokine and cytokine genes were expressed as early as 3 h after infection, but by 12 h, 41 genes were expressed. Thus, activation of the host response occurs both with the introduction of elementary bodies into the host and early replication of reticulate bodies. No significant response was observed when UV-inactivated organisms were inoculated into the cervix at any time interval. This model provides an ideal opportunity to investigate the mechanisms by which the early inflammatory response is induced in vivo.

scholarly journals Comparison between a piezoelectric device and rotary instruments in implant site preparation: an in vivo morphological, histological analysis using pigs

2015 ◽  
Vol 63 (1) ◽  
pp. 47-54
Author(s):  
Gilson Sakita ◽  
Sergio Allegrini Junior ◽  
Marcos Barbosa Salles ◽  
Marcos Pearce Cirilo Batista ◽  
Luciana Yazawa Pistarini ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Bone Repair ◽  
Surface Preparation ◽  
Piezoelectric Device ◽  
Rotary Instruments ◽  
Carbon Coated ◽  
Histological Processing ◽  
The Right ◽  
Drill System

OBJECTIVE: To carry out a histological comparison, at different postoperative periods, of bone tissue repair after implant site preparations on the tibia of pigs using both a piezoelectric device and rotary instruments. METHODS: Surgical procedures were performed on the tibia of four pigs. Five perforations were made in the left tibia using star shaped piezosurgery tips (Piezosonic Driller(r)) and five perforations in the right tibia using carbon coated rotary drills (DSP Biomedical(r)). The pigs were then sacrificed at 2, 7, 14, and 28 days. The tibiae were removed and the tissues were prepared for histological processing and analysis under a light microscope. RESULTS: The histological analyses showed similar results at 2 days and both groups presented inflammatory infiltrate. At 7 days, the drill system produces a regular surface preparation and the process of bone repair was greater when compared with the piezoelectric device. At 14 days the presence of new bone formation was more intense with the drill system. However, at 28 days both systems showed similar results, with the presence of an organized, newly formed bone tissue. CONCLUSION: It was possible to conclude that both implant site preparations, using the piezoelectric device and rotatory instruments, resulted in similar bone neoformation at 28 days.

Effects of 2-Hydroxypropil-Β-Cyclodextrin-Lidocaine on Tumor Growth and Inflammatory Response

2020 ◽  
Vol 17 (7) ◽  
pp. 588-598
Author(s):  
Luiz Eduardo Nunes Ferreira ◽  
Henrique Ballassini Abdalla ◽  
Jéssica Pereira da Costa ◽  
Juliana Souza de Freitas Domingues ◽  
Jonny Burga-Sánchez ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Positive Control ◽  
Control Group ◽  
Prostaglandin E ◽  
Antitumor Effects ◽  
Proliferation And Apoptosis ◽  
Plantar Region ◽  
Walker 256

Background: Antiproliferative and cytotoxic effects of lidocaine have been reported in tumor cells. However, the use of these drugs is restricted due to their short action with rapid dispersion from the injected site. The complexation of local anesthetics in 2-hydroxypropyl-β-cyclodextrin (HP-β- CD) is able to improve pharmacological features. Objective: This study evaluated the antitumor effects of lidocaine and the complex HP-β-CD-lidocaine (HP-β-CD-lido). Methods: In vitro, human adenocarcinoma (HeLa) and keratinocytes (HaCaT) were exposed to lidocaine formulations and cell viability, proliferation and apoptosis induction were measured. In vivo, Walker 256 carcinoma cells were subcutaneously injected into the plantar region of the rat right hind paw. The animals were treated with a local application of 5% lidocaine or 5% HP-β-CD-lido. Doxorubicin (3 mg/Kg/day, intraperitoneal) was used as a positive control. Edema sizes were measured daily and the release of cytokines (TNF-α, IL-1α and CXCL-1) and prostaglandin E2 was evaluated. Histological analysis was also performed. Results: HaCaT IG50 values were 846 μM and 2253 μM for lido and HP-β-CD-lido, respectively. In HeLa cells, the IG50 was 1765 μM for lido and 2044 μM for HP-β-CD-lido. Lidocaine formulations significantly reduced the paw edema on day 6 after Walker 256 cells inoculation. However, there were no differences in the release of inflammatory mediators in comparison to the control group. Conclusion: Lidocaine formulations were able to reduce the edema in vivo, without affecting the tumor- induced inflammatory response. The antiproliferative effects of lidocaine formulations may have contributed to tumor reduction.

Investigation of a Novel Cross-Linked Hyaluronan Hydrogel for Use as a Soft-Tissue Filler

2005 ◽  
Vol 22 (2) ◽  
pp. 105-108 ◽  
Author(s):  
James Chan ◽  
Aniq B. Darr ◽  
Daniel Alam ◽  
Anthony Calabro
Keyword(s):  
Soft Tissue ◽  
Inflammatory Response ◽  
Subcutaneous Tissue ◽  
Normal Component ◽  
Soft Tissue Augmentation ◽  
Cross Linking ◽  
Full Spectrum ◽  
Tissue Augmentation ◽  
In Vivo Analysis

Objective: To investigate an innovative tyramine-based hyaluronan (TB-HA) biomaterial for soft-tissue augmentation. Specifically, to test: (1) the ability of the TB-HA biomaterial to be injected subcutaneously; and (2) to test the in vivo response of the TB-HA biomaterial in an immunocompetent animal model. Introduction: Hyaluronan (HA) is a normal component of most tissues and, as such, is nonimmunogenic, nontoxic, and noninflammatory. Cross-linked hydrogels are formed from HA by substitution (approximately 5%) with tyramine followed by enzymatic cross-linking with peroxidase in the presence of very dilute hydrogen peroxide. From a single formulation of tyramine-substituted HA (TS-HA), a full spectrum of biomaterial properties can be produced by varying the HA concentration before cross-linking. The properties of these biomaterials ranged from a soft, optically clear hydrogel (6.25 mg/mL), suitable for soft-tissue augmentation as an injectable material, to a paste-like material (12.5–25.0 mg/mL). Materials and Methods: The hydrogel was evaluated in vivo as an injectable material (6.25 mg/mL). The material was injected into the subcutaneous tissue of an adult Sprague-Dawley rat, harvested at 8 weeks, and evaluated grossly and histologically. The specimens were paraffin embedded, sectioned on a microtome, and stained with hematoxylin and eosin. Results: In vivo analysis of the TB-HA hydrogels at 8 weeks revealed that they were resistant to degradation. Histological analysis revealed no evidence of rejection or tissue inflammatory response. Conclusions: Novel enzymatic cross-linking of HA enables the development of a versatile new biomaterial that can be used for soft-tissue augmentation. Preliminary in vivo analysis in an immunocompetent rat model revealed that the hydrogel material resisted degradation and did not elicit a host inflammatory response.

scholarly journals Calcium Phosphate Cement Plus 10% Wollastonite Whiskers: An In Vivo Study

2020 ◽  
Vol 47 ◽  
pp. 117-126
Author(s):  
Ana Claudia de Souza ◽  
Craig McNulty ◽  
José Ângelo Camilli ◽  
Celso Aparecido Bertran ◽  
Mariana Motisuke
Keyword(s):  
Sodium Phosphate ◽  
Bone Repair ◽  
Parietal Bone ◽  
New Bone Formation ◽  
Viable Option ◽  
Natural Bone ◽  
Different Types ◽  
Histological Processing ◽  
Made In

Biomaterials can be used in several areas of regenerative bioengineering, and is a viable option in the repair of bone injuries. A number of different types of biomaterials have been studied in relation to bone repair. Ceramics such as α-TCP have low fracture toughness compared to natural bone, so reinforcements such as wollastonite whiskers are developed so that they can be used in places with greater overload. This study aimed to evaluate the biocompatibility and bone neoformation of α-TCP plus 10% wollastonite whiskers, in vivo. To obtain the cement, α-TCP powders with or without 10% wollastonite whiskers were added to an aqueous solution containing 2.5% by weight of Na2HPO4 (anhydrous bibasic sodium phosphate). The biomaterial then became a paste, which was molded into the critical 5 mm defect made in the parietal bone of Wistar rats. Ten rats were divided into two groups. The animals from each group were euthanized within 30 days. Calvaries were removed and subjected to histological processing with Eosin and Hematoxylin. The implementation of the whisker biomaterial revealed the formation of intensely vascularized connective tissue in the implemented region; however, animals with the biomaterial α-TCP showed the formation of this tissue around the implemented region. On the other hand, intense bone resorption was observed only in the animals with Wollastonite Whiskers, but new bone formation in both groups. The biomaterial evaluated was shown to be non-cytotoxic, resorbable, and capable of inducing bone neoformation; however, more studies should be carried out to assess the application of this biomaterial in bone injuries.

In Vivo Evaluation of Zinc-Containing Nanostructured Carbonated Hydroxyapatite

2016 ◽  
Vol 696 ◽  
pp. 223-229 ◽  
Author(s):  
Simone Ribeiro ◽  
Suelen Cristina Sartoretto ◽  
Rodrigo Resende ◽  
Marcelo Uzeda ◽  
Adriana Terezinha Alves ◽  
...  
Keyword(s):  
Sham Group ◽  
Subcutaneous Tissue ◽  
Descriptive Analysis ◽  
Microscopic Analysis ◽  
Experimental Period ◽  
Negative Control ◽  
X Ray Diffraction ◽  
Carbonated Hydroxyapatite ◽  
Low Solubility

The hydroxyapatite (HA) is a biocompatible and bioactive biomaterial used as bone substitute, however, the high crystallinity of HA and consequently its low solubility may be a limitation for its clinical use. In order to improve the biosorption of HA, the partial substitutions in the chemical structure and doping with small amounts of impurities have been study. The objective of this study was to evaluate the biocompatibility of 3% Zinc-containing nanostructured carbonated hydroxyapatite (ZncHA) compared with the carbonated hydroxyapatite (cHA), both synthesized at 37°C and non-sintered, using as control the stoichiometric HA microspheres in subcutaneous of mice. The X-ray Diffraction (XRD) and Vibrational Spectroscopy in Infra Red Fourier Transform (FTIR) were used to characterize the biomaterials. In vivo test was performed in BALB/c mice by implanting of HA, cHA and ZncHA spheres in the subcutaneous tissue for 1, and 9 weeks (n=5). The negative control consisted in incision without material implantation (Sham group). The samples were histological processed to descriptive analysis of biological effect. The microscopic analysis showed a similar granulation reaction between groups at the first experimental period. In 9 weeks there was a time dependent biosorption of cHA compared with other groups. In conclusion, the biomaterials tested were biocompatible and cHA group showed a significant biosorption in comparison with HA and ZncHA groups. The doping of zinc did not influence the biocompatibility of biomaterial, however, change the biosorption response

Inhibitory effects of epimedium herb water extract on the inflammatory response in vitro and in vivo

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
YC Oh ◽  
YH Jeong ◽  
WK Cho ◽  
SJ Lee ◽  
JY Ma
Keyword(s):  
Inflammatory Response ◽  
Water Extract ◽  
Inhibitory Effects
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