Comparing the Healing Abilities of Fluorapatite and Hydroxyapatite Ceramics in Regenerating Bone Tissue: An In Vivo Study.

Some reports in the literature show the advantages of fluoride-containing apatite ceramics over hydroxyapatite (HAP), at least in some aspects. While HAP has been used extensively in the treatment of bone defects, fluoridated apatite has hardly been tested in vivo. In order to verify the biological properties of fluoride-doped apatite and to assess its therapeutic potential, we synthesized fluorapatite (FAP) and applied it as a filling in bone defects of experimental animals (rabbits). The treatment effects were evaluated on extracted bones after 3 and 6 months from implantation using peripheral quantitative computed tomography (pQCT), dual-energy X-ray absorptiometry (DXA), radiography (X-ray) and histological staining. The study proved the integration between FAP and the bone tissue, thus indicating its stimulating effect on new bone formation and mineralization. The results achieved after 3 months of treatment were difficult to interpret unequivocally and suggested the transient delay in FAP integration of bone in comparison with HAP. The reasons for this phenomenon are unclear. Most likely, these differences between FAP and HAP resulted mainly from the different porosities, densities and ionic reactivity of the ceramics, which in our opinion affected their solubility, integration and degree of bone tissue resorption. However, it was shown that 6 months after implantation, similar level of bone defect regeneration was achieved for both FAP and HAP. In this article, we present our hypothesis concerning the basis of this phenomenon.

Smoking as an Additional Risk Factor in Arthroscopic Rotator Cuff Repair among Type 2 Diabetics.

BACKGROUND: Rotator cuff tear is a common condition that affects majority of people at some point during lifetime. The purpose of this study was to investigate if smoking minimum 1 pack year before arthroscopic rotator cuff repair is an additional risk factor for lesser outcomes among patients suffering simultaneously of diabetes type 2. MATERIAL AND METHODS: 40 patients Aged 41-74 operated on between 2017-2020 at St. Lukes Hospital by the same team, were dived into 2 groups. 26 of them suffered Diabetes Mellitus t. 2 prior to surgery and 14 apart from DM t.2 declared additionaly current smoking for at least 1 pack year before the repair. The patients were then assessed pre-op and at 3 and 6 months post-op using QuickDASH score and VR-12 questionnaire. The patients were also investigated for early complications rate within 90 days post-op as well as for secondary hospitalization within 30 days post- op. RESULTS: Using standard statistical procedures, the study revealed significantly worse repair outcomes in the smokers group confirming the hypothesis. None of the patients regardless of smoking status and comorbidities suffered any complication or secondary hospitalization during first 3 months post-op . CONCLUSION: Smoking at least 1 pack year prior to arthroscopic rotator cuff repair is an additional factor for lesser outcomes.

Solid-State NMR and Raman Spectroscopic Investigation of Fluoride-Substituted Apatites Obtained in Various Thermal Conditions.

Fluoride-substituted apatites were synthesized by the standard sol-gel method and then calcined at three different temperatures: 800 °C, 1000 °C, and 1200 °C. Using a similar method, hydroxyapatite was synthesized and used as a reference material. The obtained powders were characterized by physicochemical methods: powder X-ray diffractometry, Raman spectroscopy, transmission electron microscopy, and solid-state nuclear magnetic resonance. All these methods allowed to identify additional α-TCP phase (tricalcium phosphate) in the HAP samples heated at 1000 °C and 1200 °C while fluoridated apatites turned out to be thermally stable. Moreover, Raman spectroscopy and NMR allowed to establish that the powders substituted with fluoride ions are not pure fluorapatite and contain OH- groups in the crystal structure. All the obtained materials had crystals with a shape similar to that of biological apatite.

Highly Porous Fluorapatite/ß-1,3-Glucan Composite for Bone Tissue Regeneration: Characterization and In-Vitro Assessment of Biomedical Potential.

A novel fluorapatite/glucan composite ("FAP/glucan") was developed for the treatment of bone defects. Due to the presence of polysaccharide polymer (ß-1,3-glucan), the composite is highly flexible and thus very convenient for surgery. Its physicochemical and microstructural properties were evaluated using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), mercury intrusion, mechanical testing and compared with the reference material, which was a hydroxyapatite/glucan composite ("HAP/glucan") with hydroxyapatite granules (HAP) instead of FAP. It was found that FAP/glucan has a higher density and lower porosity than the reference material. The correlation between the Young's modulus and the compressive strength between the materials is different in a dry and wet state. Bioactivity assessment showed a lower ability to form apatite and lower uptake of apatite-forming ions from the simulated body fluid by FAP/glucan material in comparison to the reference material. Moreover, FAP/glucan was determined to be of optimal fluoride release capacity for osteoblasts growth requirements. The results of cell culture experiments showed that fluoride-containing biomaterial was non-toxic, enhanced the synthesis of osteocalcin and stimulated the adhesion of osteogenic cells.

The Strategies to Support the COVID-19 Vaccination with Evidence-Based Communication and Tackling Misinformation.

COVID-19 vaccinations are about to begin in various countries or are already ongoing. This is an unprecedented operation that is also met with a loud response from anti-vaccine communities-currently using all available channels to manipulate public opinion. At the same time, the strategy to educate on vaccinations, explain their mechanism of action, and build trust in science is subdued in different world parts. Such actions should go much beyond campaigns promoting the COVID-19 vaccines solely on the information provided by the health institutions and national authorities. In this paper, actions provided by independent expert groups needed to counteract the anti-vaccine propaganda and provide scientific-based information to the general public are offered. These actions encompass organizing groups continuously communicating science on COVID-19 vaccines to the general public; tracking and tackling emerging and circulating fake news; and equipping celebrities and politicians with scientific information to ensure the quality of messages they communicate, as well as public letters, and statements of support for vaccination by healthcare workers, recognized scientists, VIPs, and scientific societies; and no tolerance to false and manipulated claims on vaccination spread via traditional and social media as well as by health professionals, scientists, and academics. These activities should be promptly implemented worldwide, regardless of the current status and availability of the COVID-19 vaccine in a particular region. If we are about to control the pandemic for the sake of public benefit, it is high time to collectively speak out as academic and medical societies with support from decision-makers. Otherwise, the battle will be lost to those who stand against scientific evidence while offering no feasible solution to the problem.

Fluorapatite ceramics for bone tissue regeneration: Synthesis, characterization and assessment of biomedical potential.

Calcium phosphates, due to their similarity to the inorganic fraction of mineralized tissues, are of great importance in treatment of bone defects. In order to improve the biological activity of hydroxyapatite (HAP), its fluoride-substituted modification (FAP) was synthesized using the sol-gel method and calcined at three different temperatures in the range of 800-1200 °C. Physicochemical and biological properties were evaluated to indicate which material would support bone regeneration the best. X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive X-ray spectrometry (EDS), and Fourier transform infrared spectroscopy (FTIR) revealed that fluoride ions were incorporated into the apatite lattice structure. In studies it was found that fluorapatite sintered at the highest temperature had the lowest porosity, no internal pores and the highest density. In vitro ion reactivity assessments showed that during the 28-day immersion of the samples in the simulated body fluid, the uptake of calcium and phosphorus ions was inversely correlated to the calcination temperature. All tested materials were non-toxic since the cytotoxicity MTT assay demonstrated that the viability of preosteoblast cells incubated with sample extracts was high. Fluorapatite sintered at 800 °C was determined to be of optimal porosity and fluoride release capacity and then used in cell proliferation studies. The results showed that it significantly shortened the doubling time and thus enhanced the proliferation of osteogenic cells, as compared to the fluoride solutions and control group. Therefore, this material is proposed for the use in orthopedic applications and bone tissue engineering.

Behavior of new hydroxyapatite/glucan composite in human serum.

Biomaterials for bone tissue regeneration, including polymer-based composites, are typically evaluated in vitro prior to the clinical trials. However, such composites tested in vivo may behave different due to the specific body conditions. For example, some composites implanted into the tissue acidified due to transient postoperative inflammation may unexpectedly swell which delays the wound healing. Such massive swelling in acidic medium was previously observed for new elastic hydroxyapatite (HAp)/ß-glucan biomaterial. However, in further clinical cases concerning the composite implantation in patients without significant inflammation indicators, no side effects were observed. Therefore, it was reasonable to test the effect of human serum of neutral pH (typical for noninflamed tissues) on the composite parameters, in particular volume changes. Thus, this article shows the characterization of physicochemical parameters of the composite after incubation (5 days) in human serum of neutral pH by means of weight and volume measurement, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, microcomputed tomography, mercury intrusion, and biochemical techniques. Results showed that human serum collected from healthy people caused no uncontrolled changes in weight and volume, porosity and mechanical properties of the composite. Therefore, this suggests the lack of volume change-related side effects of HAp/glucan composite in bone defects treatment if postoperative inflammation is prevented. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2653-2664, 2018.

New approach in evaluation of ceramic-polymer composite bioactivity and biocompatibility.

Regeneration of bone defects was promoted by a novel ß-glucan/carbonate hydroxyapatite composite and characterized by Raman spectroscopy, microCT and electron microscopy. The elastic biomaterial with an apatite-forming ability was developed for bone tissue engineering and implanted into the critical-size defects of rabbits' tibiae. The bone repair process was analyzed on non-decalcified bone/implant sections during a 6-month regeneration period. Using spectroscopic methods, we were able to determine the presence of amides, lipids and assign the areas of newly formed bone tissue. Raman spectroscopy was also used to assess the chemical changes in the composite before and after the implantation process. SEM analyses showed the mineralization degree in the defect area and that the gap size decreased significantly. Microscopic images revealed that the implant debris were interconnected to the poorly mineralized inner side of a new bone tissue. Our study demonstrated that the composite may serve as a biocompatible background for collagen ingrowth and exhibits the advantages of applying Raman spectroscopy, SEM and microCT in studying these samples.

Unexpected reaction of new HAp/glucan composite to environmental acidification: Defect or advantage?

Natural polymer-based composites become very popular in design of biomaterials for bone tissue regeneration. Their rheological and mechanical properties are typically evaluated in vitro according to standard methods. However, in vivo such composites may behave completely different due to specific body conditions (e.g., inflammation-assisted acidification of tissue liquids). Such surprising phenomenon was observed for hydroxyapatite/ß-1, 3-glucan composite during alveolus extraction socket augmentation in people. Implanted composite showed unexpected massive swelling, caused stitches loosening and wound reopening 5 days after implantation. Acidic pH was selected as a potential factor affecting this phenomenon, as all implantations are accompanied by transient local inflammation and acidification. Composite parameters were therefore studied after 5 days of soaking in acidic medium by weight and volume measurement, SEM, XRD, FTIR, microCT, and mercury intrusion techniques. Results showed significant volume increase, pore size remodelling and ceramic phase rearrangement in the composite, accompanied by change of mechanical properties. Simple quantitative correction of amount of implanted composite was sufficient to control in vivo appearance of side effects, confirming that pH-related volume increase of HAp/glucan composite is not a disqualifying factor. This strongly suggests the necessity of very detailed and individually designed tests concerning all new polymer-based composite biomaterials before clinical trials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1178-1190, 2017.

Structural transformation of synthetic hydroxyapatite under simulated in vivo conditions studied with ATR-FTIR spectroscopic imaging.

Hydroxyapatite and carbonate-substituted hydroxyapatite are widely used in bone tissue engineering and regenerative medicine. Both apatite materials were embedded into recently developed ceramic/polymer composites, subjected to Simulated Body Fluid (SBF) for 30days and characterized using ATR-FTIR spectroscopic imaging to assess their behaviour and structures. The specific aim was to detect the transition phases between both types of hydroxyapatite during the test and to analyze the surface modification caused by SBF. ATR-FTIR spectroscopic imaging was successfully applied to characterise changes in the hydroxyapatite lattice due to the elastic properties of the scaffolds. It was observed that SBF treatment caused a replacement of phosphates in the lattice of non-substituted hydroxyapatite by carbonate ions. A detailed study excluded the formation of pure A type carbonate apatite. In turn, CO32- content in synthetic carbonate-substituted hydroxyapatite decreased. The usefulness of ATR-FTIR spectroscopic imaging studies in the evaluation of elastic and porous ß-glucan hydroxyapatite composites has been demonstrated.

The comparison study of bioactivity between composites containing synthetic non-substituted and carbonate-substituted hydroxyapatite.

Apatite forming ability of hydroxyapatite (HAP) and carbonate hydroxyapatite (CHAP) containing composites was compared. Two composite materials, intended for filling bone defects, were made of polysaccharide polymer and one of two types of hydroxyapatite. The bioactivity of the composites was evaluated in vitro by soaking in a simulated body fluid (SBF), and the formation of the apatite layer was determined by scanning electron microscopy with energy-dispersive spectrometer and Raman spectroscopy. The results showed that both the composites induced the formation of apatite layer on their surface after soaking in SBF. In addition, the sample weight changes and the ion concentration of the SBF were scrutinized. The results showed the weight increase for both materials after SBF treatment, higher weight gain and higher uptake of calcium ions by HAP containing scaffolds. SBF solution analysis indicated loss of calcium and phosphorus ions during experiment. All these results indicate apatite forming ability of both biomaterials and suggest comparable bioactive properties of composite containing pure hydroxyapatite and carbonate-substituted one.

The biocompatibility of carbon hydroxyapatite/ß-glucan composite for bone tissue engineering studied with Raman and FTIR spectroscopic imaging.

The spectroscopic approaches of FTIR imaging and Raman mapping were applied to the characterisation of a new carbon hydroxyapatite/ß-glucan composite developed for bone tissue engineering. The composite is an artificial bone material with an apatite-forming ability for the bone repair process. Rabbit bone samples were tested with an implanted bioactive material for a period of several months. Using spectroscopic and chemometric methods, we were able to determine the presence of amides and phosphates and the distribution of lipid-rich domains in the bone tissue, providing an assessment of the composite's bioactivity. Samples were also imaged in transmission using an infrared microscope combined with a focal plane array detector. CaF2 lenses were also used on the infrared microscope to improve spectral quality by reducing scattering artefacts, improving chemometric analysis. The presence of collagen and lipids at the bone/composite interface confirmed biocompatibility and demonstrate the suitability of FTIR microscopic imaging with lenses in studying these samples. It confirmed that the composite is a very good background for collagen growth and increases collagen maturity with the time of the bone growth process. The results indicate the bioactive and biocompatible properties of this composite and demonstrate how Raman and FTIR spectroscopic imaging have been used as an effective tool for tissue characterisation.

Effect of a carbonated HAP/ß-glucan composite bone substitute on healing of drilled bone voids in the proximal tibial metaphysis of rabbits.

A novel elastic hydroxyapatite-based composite of high surgical handiness has been developed. Its potential application in orthopedics as a filler of bone defects has been studied. The biomaterial was composed of carbonated hydroxyapatite (CHAP) granules and polysaccharide polymer (ß-1,3-glucan). Cylinders of 4mm in diameter and 6mm in length were implanted into bone cavities created in the proximal metaphysis of tibiae of 24 New Zealand white rabbits. 18 sham-operated animals were used as controls. After 1, 3 or 6 months, the rabbits were euthanized, the bones were harvested and subjected to analysis. Radiological images and histological sections revealed integration of implants with bone tissue with no signs of graft rejection. Peripheral quantitative computed tomography (pQCT) indicated the stimulating effect of the biomaterial on bone formation and mineralization. Densitometry (DXA) analysis suggested that biomineralization of bones was preceded by bioresorption and gradual disappearance of porous ceramic granules. The findings suggest that the CHAP-glucan composite material enables regeneration of bone tissue and could serve as a bone defect filler.