Optimizing Manufacturing and Osseointegration of Ti6Al4V Implants through Precision Casting and Calcium and Phosphorus Ion Implantation? In Vivo Results of a Large-Scale Animal Trial

Background: Uncemented implants are still associated with several major challenges, especially with regard to their manufacturing and their osseointegration. In this study, a novel manufacturing technique—an optimized form of precision casting—and a novel surface modification to promote osseointegration—calcium and phosphorus ion implantation into the implant surface—were tested in vivo. Methods: Cylindrical Ti6Al4V implants were inserted bilaterally into the tibia of 110 rats. We compared two generations of cast Ti6Al4V implants (CAST 1st GEN, n = 22, and CAST 2nd GEN, n = 22) as well as cast 2nd GEN Ti6Al4V implants with calcium (CAST + CA, n = 22) and phosphorus (CAST + P, n = 22) ion implantation to standard machined Ti6Al4V implants (control, n = 22). After 4 and 12 weeks, maximal pull-out force and bone-to-implant contact rate (BIC) were measured and compared between all five groups. Results: There was no significant difference between all five groups after 4 weeks or 12 weeks with regard to pull-out force (p > 0.05, Kruskal Wallis test). Histomorphometric analysis showed no significant difference of BIC after 4 weeks (p > 0.05, Kruskal–Wallis test), whereas there was a trend towards a higher BIC in the CAST + P group (54.8% ± 15.2%), especially compared to the control group (38.6% ± 12.8%) after 12 weeks (p = 0.053, Kruskal–Wallis test). Conclusion: In this study, we found no indication of inferiority of Ti6Al4V implants cast with the optimized centrifugal precision casting technique of the second generation compared to standard Ti6Al4V implants. As the employed manufacturing process holds considerable economic potential, mainly due to a significantly decreased material demand per implant by casting near net-shape instead of milling away most of the starting ingot, its application in manufacturing uncemented implants seems promising. However, no significant advantages of calcium or phosphorus ion implantation could be observed in this study. Due to the promising results of ion implantation in previous in vitro and in vivo studies, further in vivo studies with different ion implantation conditions should be considered.

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Alternativas farmacéuticas: ¿pueden ser intercambiables?

Latin american journal of clinical sciences and medical technology ◽

10.34141/ljcs4648190 ◽

2020 ◽

Vol 2 (2) ◽

pp. 38-42

Author(s):

Miriam del Carmen Carrasco-Portugal ◽

Francisco Javier Flores-Murrieta

Keyword(s):

Generic Substitution ◽

In Vivo Studies ◽

Regulatory Agencies ◽

European Medicines Agency ◽

Reference Formulation ◽

Active Moiety ◽

Significant Difference ◽

Pharmaceutical Form ◽

Extent Of Absorption

Pharmaceutical alternatives are products with the same active moiety, but different salt, ester or pharmaceutical form. Regulatory agencies have different criteria for this kind of drug. The European Medicines Agency (EMA) accepts the generic substitution using these alternatives, whereas the Food and Drug Administration (FDA) only authorizes generic substitution of pharmaceutical equivalents. The objective of this paper is to describe some relevant aspects that should be considered before deciding on making a generic substitution with pharmaceutical alternatives. It is important to note that a pharmaceutical alternative must show no significant difference in the rate and extent of absorption (bioequivalence) in a well-conducted in vivo study when compared with the reference formulation. Current Mexican regulations state that generic substitution is possible using pharmaceutical alternatives when bioequivalence is demonstrated in in vivo studies conducted under the NOM-177-SSA1-2013 criteria. In conclusion, generic substitution with pharmaceutical alternatives is possible if these products demonstrate in vivo bioequivalence when compared with the reference product.

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Effect of Different Titanium Dental Implant Surfaces on Human Adipose Mesenchymal Stem Cell Behavior. An In Vitro Comparative Study

Applied Sciences ◽

10.3390/app11146353 ◽

2021 ◽

Vol 11 (14) ◽

pp. 6353

Author(s):

Vittoria D’Esposito ◽

Josè Camilla Sammartino ◽

Pietro Formisano ◽

Alessia Parascandolo ◽

Domenico Liguoro ◽

...

Keyword(s):

Cell Viability ◽

Dental Implant ◽

In Vivo Studies ◽

Implant Surface ◽

Cytokines And Chemokines ◽

Titanium Dental Implant ◽

Adhesive Ability ◽

Stimulating Factor

Background: The aim of this research was to evaluate the effects of three different titanium (Ti) implant surfaces on the viability and secretory functions of mesenchymal stem cells isolated from a Bichat fat pad (BFP-MSCs). Methods: Four different Ti disks were used as substrate: (I) D1: smooth Ti, as control; (II) D2: chemically etched, resembling the Kontact S surface; (III) D3: sandblasted, resembling the Kontact surface; (IV) D4: blasted/etched, resembling the Kontact N surface. BFP-MSCs were plated on Ti disks for 72 h. Cell viability, adhesion on disks and release of a panel of cytokines, chemokines and growth factor were evaluated. Results: BFP-MSCs plated in wells with Ti surface showed a viability rate (~90%) and proliferative rate comparable to cells plated without disks and to cells plated on D1 disks. D2 and D4 showed the highest adhesive ability. All the Ti surfaces did not interfere with the release of cytokines, chemokines and growth factors by BFP-MSCs. However, BFP-MSCs cultured on D4 surface released a significantly higher amount of Granulocyte Colony-Stimulating Factor (G-CSF) compared either to cells plated without disks and to cells plated on D1 and D2. Conclusions: The implant surfaces examined do not impair the BFP-MSCs cell viability and preserve their secretion of cytokines and chemokines. Further in vitro and in vivo studies are necessary to define the implant surface parameters able to assure the chemokines’ optimal release for a real improvement of dental implant osseointegration.

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Human Oligodendrocytes and Myelin In Vitro to Evaluate Developmental Neurotoxicity

International Journal of Molecular Sciences ◽

10.3390/ijms22157929 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7929

Author(s):

Megan Chesnut ◽

Thomas Hartung ◽

Helena Hogberg ◽

David Pamies

Keyword(s):

Large Scale ◽

In Vitro Models ◽

Environmental Chemicals ◽

Developmental Neurotoxicity ◽

In Vivo Studies ◽

Regulatory Guidelines ◽

In Vitro Systems ◽

Human Oligodendrocytes

Neurodevelopment is uniquely sensitive to toxic insults and there are concerns that environmental chemicals are contributing to widespread subclinical developmental neurotoxicity (DNT). Increased DNT evaluation is needed due to the lack of such information for most chemicals in common use, but in vivo studies recommended in regulatory guidelines are not practical for the large-scale screening of potential DNT chemicals. It is widely acknowledged that developmental neurotoxicity is a consequence of disruptions to basic processes in neurodevelopment and that testing strategies using human cell-based in vitro systems that mimic these processes could aid in prioritizing chemicals with DNT potential. Myelination is a fundamental process in neurodevelopment that should be included in a DNT testing strategy, but there are very few in vitro models of myelination. Thus, there is a need to establish an in vitro myelination assay for DNT. Here, we summarize the routes of myelin toxicity and the known models to study this particular endpoint.

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Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽

10.3390/pharmaceutics13030386 ◽

2021 ◽

Vol 13 (3) ◽

pp. 386

Author(s):

Tung-Hu Tsai ◽

Yu-Jen Chen ◽

Li-Ying Wang ◽

Chen-Hsi Hsieh

Keyword(s):

Stereotactic Body Radiation Therapy ◽

In Vivo Studies ◽

Control Group ◽

High Dose ◽

Dependent Manner ◽

Hep G2 ◽

Time Curve ◽

Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

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Assessment of the Tissue Response to Modification of the Surface of Dental Implants with Carboxyethylphosphonic Acid and Basic Fibroblastic Growth Factor Immobilization (Fgf-2): An Experimental Study on Minipigs

Biology ◽

10.3390/biology10050358 ◽

2021 ◽

Vol 10 (5) ◽

pp. 358

Author(s):

Javier Aragoneses ◽

Ana Suárez ◽

Nansi López-Valverde ◽

Francisco Martínez-Martínez ◽

Juan Manuel Aragoneses

Keyword(s):

Surface Treatment ◽

Test Group ◽

Mean Value ◽

Control Group ◽

P Value ◽

Implant Surface ◽

Bone Contact ◽

Bone Implant ◽

Significant Difference ◽

The Mean

The aim of this study was to evaluate the effect of implant surface treatment with carboxyethylphosphonic acid and fibroblast growth factor 2 on the bone–implant interface during the osseointegration period in vivo using an animal model. The present research was carried out in six minipigs, in whose left tibia implants were inserted as follows: eight implants with a standard surface treatment, for the control group, and eight implants with a surface treatment of carboxyethylphosphonic acid and immobilization of FGF-2, for the test group. At 4 weeks after the insertion of the implants, the animals were sacrificed for the histomorphometric analysis of the samples. The means of the results for the implant–bone contact variable (BIC) were 46.39 ± 17.49% for the test group and 34.00 ± 9.92% for the control group; the difference was not statistically significant. For the corrected implant–bone contact variable (BICc), the mean value of the test group was 60.48 ± 18.11%, and that for the control group, 43.08 ± 10.77%; the difference was statistically significant (p-value = 0.035). The new bone formation (BV/TV) showed average results of 27.28 ± 3.88% for the test group and 26.63 ± 7.90% for the control group, meaning that the differences were not statistically significant (p-value = 0.839). Regarding the bone density at the interthread level (BAI/TA), the mean value of the test group was 32.27 ± 6.70%, and that of the control group was 32.91 ± 7.76%, with a p-value of 0.863, while for the peri-implant density (BAP/TA), the mean value of the test group was 44.96 ± 7.55%, and that for the control group was 44.80 ± 8.68%, without a significant difference between the groups. The current research only found a significant difference for the bone–implant contact at the cortical level; therefore, it could be considered that FGF-2 acts on the mineralization of bone tissue. The application of carboxyethylphosphonic acid on the surface of implants can be considered a promising alternative as a biomimetic coating for the immobilization of FGF-2. Despite no differences in the new bone formation around the implants or in the interthread or peri-implant bone density being detected, the biofunctionalization of the implant surface with FGF-2 accelerates the mineralization of the bone–implant interface at the cortical level, thereby reducing the osseointegration period.

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An in Vivo Comparison of Antimicrobial Efficacy of Sodium Hypochlorite and Biopure MTAD™ against Enterococcus Faecalis in Primary Teeth: A qPCR Study

Journal of Clinical Pediatric Dentistry ◽

10.17796/jcpd.39.1.c4q2155r16817219 ◽

2014 ◽

Vol 39 (1) ◽

pp. 30-34 ◽

Cited By ~ 3

Author(s):

SG Tulsani ◽

N Chikkanarasaiah ◽

S Bethur

Keyword(s):

Root Canal ◽

Primary Teeth ◽

Antimicrobial Efficacy ◽

Permanent Teeth ◽

Control Group ◽

Statistical Significant Difference ◽

Anterior Teeth ◽

Significant Difference ◽

Root Canal Irrigant

Objectives: Biopure MTAD™, a new root canal irrigant has shown promising results against the most common resistant microorganism, E. faecalis, in permanent teeth. However, there is lack of studies comparing its antimicrobial effectiveness with NaOCl in primary teeth. The purpose of this study was to compare the in vivo antimicrobial efficacy of NaOCl 2.5% and Biopure MTAD™ against E. faecalis in primary teeth. Study design: Forty non vital single rooted primary maxillary anterior teeth of children aged 4-8 years, were irrigated either with NaOCl 2.5% (n=15), Biopure MTAD™ (n=15) and 0.9% Saline (n=10, control group). Paper point samples were collected at baseline (S1) and after chemomechanical preparation (S2) during the pulpectomy procedure. The presence of E. faecalis in S1 & S2 was evaluated using Real time Polymerase Chain Reaction. Results: Statistical significant difference was found in the antimicrobial efficacy of NaOCl 2.5 % and BioPure MTAD™ when compared to saline (p>0.05). However, no statistical significant difference was found between the efficacies of both the irrigants. Conclusions: NaOCl 2.5% and BioPure MTAD™, both irrigants are equally efficient against E. faecalis in necrotic primary anterior teeth. MTAD is a promising irrigant, however clinical studies are required to establish it as ideal root canal irrigant in clinical practice.

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Evaluation of Annona muricata (Graviola) leaves activity against experimental trichinellosis: in vitro and in vivo studies

Journal of Helminthology ◽

10.1017/s0022149x21000481 ◽

2021 ◽

Vol 95 ◽

Author(s):

E.S. El-Wakil ◽

H.F. Abdelmaksoud ◽

T.S. AbouShousha ◽

M.M.I. Ghallab

Keyword(s):

Culture Media ◽

Trichinella Spiralis ◽

Drug Effects ◽

In Vivo Studies ◽

Control Group ◽

Annona Muricata ◽

Group I ◽

Small Intestinal

Abstract Our work aimed to evaluate the possible effect of Annona muricata (Graviola) leaf extract on Trichinella spiralis in in vitro and in vivo studies. Trichinella spiralis worms were isolated from infected mice and transferred to three culture media – group I (with no drugs), group II (contained Graviola) and group III (contained albendazole) – then they were examined using the electron microscope. In the in vivo study, mice were divided into five groups: GI (infected untreated), GII (prophylactically treated with Graviola for seven days before infection), GIII (infected and treated with Graviola), GIV (infected and treated with albendazole) and GV (infected and treated with a combination of Graviola plus albendazole in half doses). Drug effects were assessed by adults and larvae load beside the histopathological small intestinal and muscular changes. A significant reduction of adult and larval counts occurred in treated groups in comparison to the control group. Histopathologically, marked improvement in the small intestinal and muscular changes was observed in treated groups. Also, massive destruction of the cultured adults’ cuticle was detected in both drugs. This study revealed that Graviola leaves have potential activity against trichinellosis, especially in combination with albendazole, and could serve as an adjuvant to anti-trichinellosis drug therapy.

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Capacity of Human Nisin- and Pediocin-Producing Lactic Acid Bacteria To Reduce Intestinal Colonization by Vancomycin-Resistant Enterococci

Applied and Environmental Microbiology ◽

10.1128/aem.02150-07 ◽

2008 ◽

Vol 74 (7) ◽

pp. 1997-2003 ◽

Cited By ~ 85

Author(s):

Mathieu Millette ◽

Gilbert Cornut ◽

Claude Dupont ◽

François Shareck ◽

Denis Archambault ◽

...

Keyword(s):

Lactic Acid ◽

Lactic Acid Bacteria ◽

In Vivo Study ◽

Control Group ◽

Intestinal Colonization ◽

Strong Activity ◽

Vancomycin Resistant Enterococci ◽

Significant Difference ◽

Vancomycin Resistant

ABSTRACT This study demonstrated the capacity of bacteriocin-producing lactic acid bacteria (LAB) to reduce intestinal colonization by vancomycin-resistant enterococci (VRE) in a mouse model. Lactococcus lactis MM19 and Pediococcus acidilactici MM33 are bacteriocin producers isolated from human feces. The bacteriocin secreted by P. acidilactici is identical to pediocin PA-1/AcH, while PCR analysis demonstrated that L. lactis harbors the nisin Z gene. LAB were acid and bile tolerant when assayed under simulated gastrointestinal conditions. A well diffusion assay using supernatants from LAB demonstrated strong activity against a clinical isolate of VRE. A first in vivo study was done using C57BL/6 mice that received daily intragastric doses of L. lactis MM19, P. acidilactici MM33, P. acidilactici MM33A (a pediocin mutant that had lost its ability to produce pediocin), or phosphate-buffered saline (PBS) for 18 days. This study showed that L. lactis and P. acidilactici MM33A increased the concentrations of total LAB and anaerobes while P. acidilactici MM33 decreased the Enterobacteriaceae populations. A second in vivo study was done using VRE-colonized mice that received the same inocula as those in the previous study for 16 days. In L. lactis-fed mice, fecal VRE levels 1.73 and 2.50 log10 CFU/g lower than those in the PBS group were observed at 1 and 3 days postinfection. In the P. acidilactici MM33-fed mice, no reduction was observed at 1 day postinfection but a reduction of 1.85 log10 CFU/g was measured at 3 days postinfection. Levels of VRE in both groups of mice treated with bacteriocin-producing LAB were undetectable at 6 days postinfection. No significant difference in mice fed the pediocin-negative strain compared to the control group was observed. This is the first demonstration that human L. lactis and P. acidilactici nisin- and pediocin-producing strains can reduce VRE intestinal colonization.

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PENGARUH EKSTRAK DAGING LIDAH BUAYA (Aloe Vera) TERHADAP PENYEMBUHAN ULSERASI MUKOSA MULUT PADA MALE WISTAR RATS

ODONTO Dental Journal ◽

10.30659/odj.1.1.25-28 ◽

2015 ◽

Vol 1 (1) ◽

pp. 25

Author(s):

Laila Fitrotuz Zahroh ◽

Rahmawati Sri Praptiningsih ◽

Moh. Baehaqi

Keyword(s):

Oral Mucosa ◽

Wistar Rats ◽

Healing Process ◽

Research Result ◽

Aloe Vera ◽

Control Group ◽

Control Group Design ◽

Significant Difference ◽

Male Wistar Rats

Background: Oral mucosa ulceration which often occurs usually in the form of white-yellowish spot with concave surface, reddish edge and pain. Based on previous research, Aloe vera process anti-inflammation substance that could help quickening ulceration healing process. This research aims to know the effect of Aloe vera flesh extract on Male wistar rats oral mucosa ulceration in-vivo. Method: this research was quasi experimental research with the post-test only control group design using Male wistar rats as the testing animal. In the research, there were three treatment groups: The first groups which was given aquadest treatment, second groups with Aloe vera flesh extract, and third groups which was given chlorhexidine gluconate 0,2% treatment. The data collecting was based on histopathology observation concerning the increase of fibroblast quantity. Result: The research result based on comparison test among the three groups with One Way Anova showed that on Day 3th, the average quantity of fibroblast didn't have significant difference between the treatment group and control group positive that was p>0,05, meanwhile on Day 7th every group showed significant difference p<0,05. Conclusion: It concluded that Aloe vera flesh extract has influence on the healing of Male wistar rats oral mucosa ulceration as shown by fibroblast increasing quantity.

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Comparison of Biocompatibility of Experimental Tricalcium Phosphate Cement versus Biodentin and Mineral Trioxide Aggregate used for Furcation Perforation Repair (in vivo study)

The Open Dentistry Journal ◽

10.2174/1874210602115010532 ◽

2021 ◽

Vol 15 (1) ◽

pp. 532-538

Author(s):

Mostafa M. El-Bialy ◽

Magdy M. Ali ◽

Engy M. Kataia ◽

Reham S. El Nemr ◽

Reham Hassan

Keyword(s):

Tricalcium Phosphate ◽

Mineral Trioxide Aggregate ◽

Positive Control ◽

Control Group ◽

Tooth Survival ◽

Significant Difference ◽

Operative Evaluation ◽

Root Canal System ◽

Bone Deposition

Background: The interaction between the root canal system and the oral cavity caused by iatrogenic perforations significantly affects the treatment outcome and tooth survival. Objectives: This study was directed to compare the biocompatibility of an experimental tricalcium phosphate cement versus biodentine and mineral Trioxide aggregate used for furcation perforation repair in dogs. Methods: Perforations were done in 60 teeth (premolars and molars) of six adult dogs. Animals were divided randomly into 3 equal groups of 2 animals each according to the post-operative evaluation period of 1 week, 1 month, and 3-months. Each group was further subdivided into 4 subgroups according to either being repaired with the experimental tricalcium phosphate cement (n=6), or Biodentine (n=6), Mineral Trioxide Aggregate (MTA) (n=6), and positive control(n=2). After evaluation periods, tissue blocks were harvested and histologically examined. Results: No statistically significant difference was found regarding bone deposition scores and inflammatory reaction in the three groups after 1 week, 1 month, or 3 months. All three groups showed a statistically significant difference between all three time periods. Regardless of the repair material used, inflammation scores at 1-week showed the highest scores, decreasing over time except for the control group. Conclusion: The experimental material could be considered as a successful treatment option for repairing furcation perforation.

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