Analysis of the impact of different schemes of preparation to trabeculectomy on the healing markers on the Tenon fibroblasts cultures.

The aim of the study was to assess the influence of different regimes of patient's preparation before trabeculectomy on the markers of healing process in Tenon's fibroblast cultures.The studied group consisted of 66 patients with open angle glaucoma undergoing primary trabeculectomy. The patients were divided into 5 groups with different regimes of preparation before the surgery based on application or withdrawal of topical antiglaucoma medications and steroids (G1-patients using antiglaucoma drops until the day of the surgery; G2-patients using antiglaucoma drops until the day of the surgery and additionally dexamethasone for 4 weeks before surgery; G3-patients who stopped using antiglaucoma drops 4 weeks before the surgery and introduced dexamethasone for 4 weeks before surgery; G4-patients who stopped using antiglaucoma drops 4 weeks before the surgery; G5-control group, patients with newly diagnosed glaucoma in whom trabeculectomy was the first treatment option without medical treatment). During trabeculectomy the samples of Tenon's capsule were obtained. Tenon fibroblasts were isolated directly from the explants to test their proliferation ability and the level of released healing markers. Following factors typical of healing process were evaluated using commercially available ELISA kits: IL 1-ß, IL-6, IL-8, VEGF-A, TGF-ß1 and MMP-9. Concentrations of IL-1ß, IL-6 and TGF-ß1 were significantly higher in the group obtaining antiglaucoma drops. Additionally, in this group the fibroblasts revealed the highest proliferation potential, indicating the active healing process. The levels of IL-8, VEGF-A and MMP-9 were similar between the groups. Our study shows that for the best conjunctival anti-inflammatory control, the most influential factor is the withdrawal of antiglaucoma medications.

Effectiveness of the production of tissue-engineered living bone graft: a comparative study using perfusion and rotating bioreactor systems.

Bioreactor systems are very precious tools to generate living bone grafts in vitro. The aim of this study was to compare the effectiveness of rotating and perfusion bioreactor in the production of a living bone construct. Human bone marrow-derived mesenchymal stem cells (BMDSCs) were seeded on the surfaces of hydroxyapatite-based scaffolds and cultured for 21 days in three different conditions: (1) static 3D culture, (2) 3D culture in a perfusion bioreactor, and (3) dynamic 3D culture in a rotating bioreactor. Quantitative evaluation of cell number showed that cultivation in the perfusion bioreactor significantly reduced cell proliferation compared to the rotating bioreactor and static culture. Osteogenic differentiation test demonstrated that BMDSCs cultured in the rotating bioreactor produced significantly greater amount of osteopontin compared to the cells cultured in the perfusion bioreactor. Moreover, Raman spectroscopy showed that cultivation of BMDSCs in the rotating bioreactor enhanced extracellular matrix (ECM) mineralization that was characterized by B-type carbonated substitution of hydroxyapatite (associated with PO43- groups) and higher mineral-to-matrix ratio compared to the ECM of cells cultured in the perfusion system. Thus, it was concluded that the rotating bioreactor was much more effective than the perfusion one in the generation of bone tissue construct in vitro.

Analysis of In Vitro Leukocyte Responses to Biomaterials in the Presence of Antimicrobial Porcine Neutrophil Extract (AMPNE).

Implant insertion can evoke excessive inflammation which disrupts the healing process and potentially leads to complications such as implant rejection. Neutrophils and macrophages play a vital role in the early inflammatory phase of tissue repair, necessitating the study of cellular responses in host-implant interactions. In order to deepen the knowledge about these interactions, the response of neutrophils and macrophages to contact with selected biomaterials was examined in vitro on the basis of secretory response as well as reactive oxygen species/reactive nitrogen species (ROS/RNS) generation. Porcine neutrophils exposed to hydroxyapatite (HA) released more enzymes and generated higher levels of ROS/RNS compared to the control group. The addition of AMPNE diminished these responses. Although the results from porcine cells can provide valuable preliminary data, further validation using human cells or clinical studies would be necessary to fully extrapolate the findings to human medicine. Our study revealed that human neutrophils after contact of with HA increased the production of nitric oxide (NO) (10.00 ± 0.08 vs. control group 3.0 ± 0.11 µM, p < 0.05), while HAP or FAP did not elicit a significant response. Human macrophages cultured with HA produced more superoxide and NO, while HAP or FAP had a minimal effect, and curdlan reduced ROS/RNS generation. The addition of AMPNE to cultures with all biomaterials, except curdlan, reduced neutrophil activity, regardless of the peptides' origin. These results highlight the potential of antimicrobial peptides in modulating excessive biomaterial/host cell reactions involving neutrophils and macrophages, enhancing our understanding of immune reactions, and suggesting that AMPNE could regulate leukocyte response during implantation.

Optimization of the Composition of Mesoporous Polymer-Ceramic Nanocomposite Granules for Bone Regeneration.

Difficult-to-treat bone damage resulting from metabolic bone diseases, mechanical injuries, or tumor resection requires support in the form of biomaterials. The aim of this research was to optimize the concentration of individual components of polymer-ceramic nanocomposite granules (nanofilled polymer composites) for application in orthopedics and maxillofacial surgery to fill small bone defects and stimulate the regeneration process. Two types of granules were made using nanohydroxyapatite (nanoHA) and chitosan-based matrix (agarose/chitosan or curdlan/chitosan), which served as binder for ceramic nanopowder. Different concentrations of the components (nanoHA and curdlan), foaming agent (sodium bicarbonate-NaHCO3), and chitosan solvent (acetic acid-CH3COOH) were tested during the production process. Agarose and chitosan concentrations were fixed to be 5% w/v and 2% w/v, respectively, based on our previous research. Subsequently, the produced granules were subjected to cytotoxicity testing (indirect and direct contact methods), microhardness testing (Young's modulus evaluation), and microstructure analysis (porosity, specific surface area, and surface roughness) in order to identify the biomaterial with the most favorable properties. The results demonstrated only slight differences among the resultant granules with respect to their microstructural, mechanical, and biological properties. All variants of the biomaterials were non-toxic to a mouse preosteoblast cell line (MC3T3-E1), supported cell growth on their surface, had high porosity (46-51%), and showed relatively high specific surface area (25-33 m2/g) and Young's modulus values (2-10 GPa). Apart from biomaterials containing 8% w/v curdlan, all samples were predominantly characterized by mesoporosity. Nevertheless, materials with the greatest biomedical potential were obtained using 5% w/v agarose, 2% w/v chitosan, and 50% or 70% w/v nanoHA when the chitosan solvent/foaming agent ratio was equal to 2:2. In the case of the granules containing curdlan/chitosan matrix, the most optimal composition was as follows: 2% w/v chitosan, 4% w/v curdlan, and 30% w/v nanoHA. The obtained test results indicate that both manufactured types of granules are promising implantable biomaterials for filling small bone defects that can be used in maxillofacial surgery.

In Vitro Screening Studies on Eight Commercial Essential Oils-Derived Compounds to Identify Promising Natural Agents for the Prevention of Osteoporosis.

Over the years, essential oils (EOs) and their compounds have gained growing interest due to their anti-inflammatory, antimicrobial, antioxidant, and immunomodulatory properties. The aim of this study was to evaluate the effect of eight commercially available EO-derived compounds ((R)-(+)-limonene, (S)-(-)-limonene, sabinene, carvacrol, thymol, alpha-pinene (α-pinene), beta-pinene (ß-pinene), and cinnamaldehyde) on the bone formation process in vitro to select the most promising natural agents that could potentially be used in the prevention or treatment of osteoporosis. Within this study, evaluation of cytotoxicity, cell proliferation, and osteogenic differentiation was performed with the use of mouse primary calvarial preosteoblasts (MC3T3-E1). Moreover, extracellular matrix (ECM) mineralization was determined using MC3T3-E1 cells and dog adipose tissue-derived mesenchymal stem cells (ADSCs). The two highest non-toxic concentrations of each of the compounds were selected and used for testing other activities. The conducted study showed that cinnamaldehyde, thymol, and (R)-(+)-limonene significantly stimulated cell proliferation. In the case of cinnamaldehyde, the doubling time (DT) for MC3T3-E1 cells was significantly shortened to approx. 27 h compared to the control cells (DT = 38 h). In turn, cinnamaldehyde, carvacrol, (R)-(+)-limonene, (S)-(-)-limonene, sabinene, and α-pinene exhibited positive effects on either the synthesis of bone ECM or/and mineral deposition in ECM of the cells. Based on the conducted research, it can be assumed that cinnamaldehyde and (R)-(+)-limonene are the most promising among all tested EO-derived compounds and can be selected for further detailed research in order to confirm their biomedical potential in the chemoprevention or treatment of osteoporosis since they not only accelerated the proliferation of preosteoblasts, but also significantly enhanced osteocalcin (OC) synthesis by preosteoblasts (the OC level was approx. 1100-1200 ng/mg compared to approx. 650 ng/mg in control cells) and ECM calcification of both preosteoblasts and mesenchymal stem cells. Importantly, cinnamaldehyde treatment led to a three-fold increase in the mineral deposition in ADSCs, whereas (R)-(+)-limonene caused a two-fold increase in the ECM mineralization of both MC3T3-E1 cells and ADSCs.

The Comparison between the Composition of 100% Autologous Serum and 100% Platelet-Rich Plasma Eye Drops and Their Impact on the Treatment Effectiveness of Dry Eye Disease in Primary Sjogren Syndrome.

PURPOSE: The aim of the study was to compare the difference in composition between 100% autologous serum (AS) and 100% platelet-rich plasma (PRP) eye drops and assess their impact on the clinical outcomes after the treatment of severe dry eye (DE) in primary Sjogren Syndrome patients (pSS). MATERIALS AND METHODS: This is an interventional, non-randomized, comparative, three-month study. 22 patients with severe DE in pSS were treated with 100% AS (22 eyes) and 100% PRP (22 eyes) eye drops 5 times per day in monotherapy mode. The quantifications of growth factors (GFs) such as fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), nerve growth factor (NGF), transforming growth factor (TGF-b), insulin-like growth factor (IGF), fibronectin, and substance p in hemoderivates were done. The main outcome measures were: Ocular Surface Disease Index (OSDI), Best Corrected Visual Acuity (BCVA), the Schirmer test, tear break-up time (TBUT), corneal and conjunctival staining according to the Oxford scale, conjunctival hyperaemia, and Meibomian gland parameters. The results were compared at baseline, 1 month, and 3 months following the treatment. The clinical results were correlated with the concentration of GFs in the biological tear substitutes. RESULTS: Significant differences were observed in the concentration of FGF (4.42 ± 0.86 vs. 15.96 ± 7.63, p < 0.0001), EGF (4.98 ± 0.97 vs. 39.06 ± 20.18, p < 0.0001), fibronectin (929.6 ± 111.5 vs. 823.64 ± 98.49, p = 0.0005), VEGF (175.45 ± 65.93 vs. 717.35 ± 488.15, p < 0.0001), PDGF AB (619.6 ± 117.30 vs. 349.66 ± 79.82, p < 0.0001), NGF (85.22 ± 23.49 vs. 8.29 ± 9.06, p < 0.0001), PDGF (935.38 ± 434.26 vs. 126.66 ± 54.41, p < 0.0001), substance p (112.58 ± 27.28 vs. 127.51 ± 26.56, p = 0.0125) in PRP compared to AS. The level of TGF-ß was undoubtedly higher in AS than in PRP (1031.37 ± 330.23 vs. 726.03 ± 298.95, p = 0.0004). No significant differences between AS and PRP were observed in the concentration of IGF. Therapy with blood products relieved the signs and symptoms in pSS DE patients. There was a statistically significant improvement in BCVA, the Schirmer test, TBUT, Meibomian gland parameters, and the reduction of the OSDI scores, Oxford staining, and conjunctiva hyperaemia in each of the groups. However, the clinical changes were more significant in the PRP group. There were numerous correlations between the level of GFs and the mean change in clinical outcomes. No adverse events were reported. CONCLUSIONS: Despite the fact that blood derivatives differ in composition, they seem to be effective and safe in the treatment of severe DE in pSS patients. The signs and symptoms of DE were reduced in both groups, but only the mean change in OSDI was statistically significant. A greater reduction in OSDI scores was observed in the PRP group. The obtained results and the composition of haemoderivates may indicate the superiority of PRP in relieving the symptoms of DE in pSS patients compared to AS.

Wound Dressing Modifications for Accelerated Healing of Infected Wounds.

Infections that occur during wound healing involve the most frequent complications in the field of wound care which not only inhibit the whole process but also lead to non-healing wound formation. The diversity of the skin microbiota and the wound microenvironment can favor the occurrence of skin infections, contributing to an increased level of morbidity and even mortality. As a consequence, immediate effective treatment is required to prevent such pathological conditions. Antimicrobial agents loaded into wound dressings have turned out to be a great option to reduce wound colonization and improve the healing process. In this review paper, the influence of bacterial infections on the wound-healing phases and promising modifications of dressing materials for accelerated healing of infected wounds are discussed. The review paper mainly focuses on the novel findings on the use of antibiotics, nanoparticles, cationic organic agents, and plant-derived natural compounds (essential oils and their components, polyphenols, and curcumin) to develop antimicrobial wound dressings. The review article was prepared on the basis of scientific contributions retrieved from the PubMed database (supported with Google Scholar searching) over the last 5 years.

The Impact of Hydroxyapatite Sintering Temperature on Its Microstructural, Mechanical, and Biological Properties.

Hydroxyapatite (HA), the principal mineral of bone tissue, can be fabricated as an artificial calcium phosphate (CaP) ceramic and potentially used as bioceramic material for bone defect treatment. Nevertheless, the production method (including the applied sintering temperature) of synthetic hydroxyapatite directly affects its basic properties, such as its microstructure, mechanical parameters, bioabsorbability, and osteoconductivity, and in turn influences its biomedical potential as an implantable biomaterial. The wide application of HA in regenerative medicine makes it necessary to explain the validity of the selection of the sintering temperature. The main emphasis of this article is on the description and summarization of the key features of HA depending on the applied sintering temperature during the synthesis process. The review is mainly focused on the dependence between the HA sintering temperature and its microstructural features, mechanical properties, biodegradability/bioabsorbability, bioactivity, and biocompatibility.

Hydroxyapatite or Fluorapatite-Which Bioceramic Is Better as a Base for the Production of Bone Scaffold?-A Comprehensive Comparative Study.

Hydroxyapatite (HAP) is the most common calcium phosphate ceramic that is used in biomedical applications, e.g., as an inorganic component of bone scaffolds. Nevertheless, fluorapatite (FAP) has gained great attention in the area of bone tissue engineering in recent times. The aim of this study was a comprehensive comparative evaluation of the biomedical potential of fabricated HAP- and FAP-based bone scaffolds, to assess which bioceramic is better for regenerative medicine applications. It was demonstrated that both biomaterials had a macroporous microstructure, with interconnected porosity, and were prone to slow and gradual degradation in a physiological environment and in acidified conditions mimicking the osteoclast-mediated bone resorption process. Surprisingly, FAP-based biomaterial revealed a significantly higher degree of biodegradation than biomaterial containing HAP, which indicated its higher bioabsorbability. Importantly, the biomaterials showed a similar level of biocompatibility and osteoconductivity regardless of the bioceramic type. Both scaffolds had the ability to induce apatite formation on their surfaces, proving their bioactive property, that is crucial for good implant osseointegration. In turn, performed biological experiments showed that tested bone scaffolds were non-toxic and their surfaces promoted cell proliferation and osteogenic differentiation. Moreover, the biomaterials did not exert a stimulatory effect on immune cells, since they did not generate excessive amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS), indicating a low risk of inflammatory response after implantation. In conclusion, based on the obtained results, both FAP- and HAP-based scaffolds have an appropriate microstructure and high biocompatibility, being promising biomaterials for bone regeneration applications. However, FAP-based biomaterial has higher bioabsorbability than the HAP-based scaffold, which is a very important property from the clinical point of view, because it enables a progressive replacement of the bone scaffold with newly formed bone tissue.

Application of Vibrational Spectroscopic Techniques in the Study of the Natural Polysaccharides and Their Cross-Linking Process.

Polysaccharides are one of the most abundant natural polymers and their molecular structure influences many crucial characteristics-inter alia hydrophobicity, mechanical, and physicochemical properties. Vibrational spectroscopic techniques, such as infrared (IR) and Raman spectroscopies are excellent tools to study their arrangement during polymerization and cross-linking processes. This review paper summarizes the application of the above-mentioned analytical methods to track the structure of natural polysaccharides, such as cellulose, hemicellulose, glucan, starch, chitosan, dextran, and their derivatives, which affects their industrial and medical use.

Medical Use of Polycatecholamines + Oxidoreductases-Modified Curdlan Hydrogels-Perspectives.

Curdlan (ß-1,3-glucan), as a biodegradable polymer, is still an underestimated but potentially attractive matrix for the production of dressing materials. However, due to its lack of susceptibility to functionalization, its use is limited. The proposed curdlan modification, using a functional polycatecholamine layer, enables the immobilization of selected oxidoreductases (laccase and peroxidase) on curdlan hydrogel. The following significant changes of biological and mechanical properties of polycatecholamines + oxidoreductases-modified matrices were observed: reduced response of human monocytes in contact with the hydrogels, modulated reaction of human blood, in terms of hemolysis and clot formation, and changed mechanical properties. The lack of toxicity towards human fibroblasts and the suppression of cytokines released by human monocytes in comparison to pristine curdlan hydrogel, seems to make the application of such modifications attractive for biomedical purposes. The obtained results could also be useful for construction of a wide range of biomaterials based on other polymer hydrogels.

Osteoclast-mediated acidic hydrolysis of thermally gelled curdlan component of the bone scaffolds: Is it possible?

Many biomaterials for bone regeneration have recently been produced using thermally gelled curdlan (1,3-ß-d-glucan) as a binder for bioceramics. As the human organism does not produce enzymes having the ability to degrade curdlan, it is not clear what is the fate of curdlan gel after its implantation in the bone. To clarify this point, in this research osteoclasts were cultured on the curdlan gel to show its degradation by acidic hydrolysis. The studies clearly demonstrated microstructural (AFM and SEM imaging) and chemical changes (Raman spectroscopy) on the curdlan surface caused by osteoclast culture. Moreover, degradation test in a cell-free system using HCl solution (pH = 4.5), mimicking environment in the resorption lacuna, showed great weight loss of the sample, release of glucose, and chemical changes typical of curdlan degradation. Thus, the presented research for the first time provides a strong evidence of osteoclast-mediated acidic hydrolysis of thermally obtained curdlan gel.

Biocompatible curdlan-based biomaterials loaded with gentamicin and Zn-doped nano-hydroxyapatite as promising dressing materials for the treatment of infected wounds and prevention of surgical site infections.

A topical application of antibiotic-loaded wound dressings is recommended only for chronically infected wounds with poor vascularization. Thus, more often dressing materials loaded with antibacterial metal ions are produced. In turn, gentamicin sponges are commonly used to prevent surgical site infections. The aim of this study was to produce curdlan-based biomaterials enriched with gentamicin and zinc (Zn)-doped nano-hydroxyapatite to prevent wound and surgical site infections. Developed biomaterials were subjected to basic microstructural characterization, cytotoxicity test against human skin fibroblasts (BJ cell line), and comprehensive microbiological experiments using Staphylococcus aureus and Pseudomonas aeruginosa strains. To evaluate the in vivo healing capacity of the developed biomaterials, severely infected chronic wound in a veterinary patient was treated with the use of gentamicin-loaded dressing. Fabricated biomaterials were characterized by a highly porous microstructure with high plasma absorption capacity (approx. 7 mL/g for Zn-loaded biomaterial and 13 mL/g for gentamicin-enriched dressing) and optimal water vapor transmission rate (approx. 1700 g/m2/day). Due to the presence of bioceramics, material containing Zn showed slightly higher compressive strength (0.37 MPa) and Young's modulus (3.33 MPa) values compared to gentamicin-loaded biomaterial (0.12 MPa and 1.29 MPa, respectively). Gentamicin-enriched biomaterial showed burst release of the drug within the first 5 h, while, the zinc-loaded biomaterial exhibited a constant gradual release of the zinc ions. Conducted assays showed that developed biomaterials were non-toxic against human skin fibroblasts (cell viability in the range of 71-95 %) and revealed strong bactericidal activity (99.9 % reduction in the number of viable bacterial CFUs in direct contact test) against S. aureus. In the case of P. aeruginosa, only gentamicin-loaded biomaterial exhibited bactericidal effect. Additionally, biomaterials had the ability to uptake, lock in, and kill bacteria within their gel structure, enabling the cleansing of the wound bed at every dressing change. Finally, the treatment of severely infected wound in veterinary patient confirmed the effectiveness of gentamicin-loaded biomaterial. Biomaterial enriched with gentamicin possesses great potential to be used as a dressing material or sponge for the treatment of chronically infected wounds and surgical site infections. In turn, the zinc-loaded biomaterial may be used as a wound dressing to reduce and prevent microbial contamination.

Noncytotoxic zinc-doped nanohydroxyapatite-based bone scaffolds with strong bactericidal, bacteriostatic, and antibiofilm activity.

Development of bone scaffolds that are nontoxic to eukaryotic cells, while revealing bactericidal activity still remains a huge challenge for the scientific community. It should be noted that only bacteriostatic (the ability of the biomaterial to inhibit the growth of bacteria) and bactericidal (the ability to kill >99.9 % bacteria) activities have clinical importance. Unfortunately, many material scientists are confused with the microbiological definition of antibacterial action and consider biomaterials causing reduction in colony-forming units (CFUs) by 50-80 % as promising antibacterial implants. The aim of this study was to synthesize three variants of Zn-doped hydroxyapatite (HA) nanopowder, which were characterized by different content of Zn2+ and served as a powder phase for the production of novel macroporous chitosan/agarose/nanoHA biomaterials with high antibacterial activity. Within this study, it was proven that the scaffold with a low zinc content (doping level 0.03 mol for 1 mol of HA; 0.2 wt%) revealed the gradual and slow release of the Zn2+ ions, preventing against accumulation of high and toxic concentration of therapeutic agents and providing prolonged antibacterial activity. Moreover, developed biomaterial was nontoxic to human osteoblasts and showed anti-biofilm properties, bactericidal activity (> 99.9 % of bacteria killed) against Staphylococcus epidermidis and Escherichia coli, significant antibacterial activity against Staphylococcus aureus (98.5 % of bacteria killed), and also bacteriostatic activity against Pseudomonas aeruginosa. Thus, the developed Zn-doped HA-based bone scaffold has excellent antibacterial properties without toxicity against eukaryotic cells, being a promising biomaterial for biomedical applications to repair bone defects and prevent post-surgery infections.

Surface Chemical and Morphological Analysis of Chitosan/1,3-ß-d-Glucan Polysaccharide Films Cross-Linked at 90 °C.

The cross-linking temperature of polymers may affect the surface characteristics and molecular arrangement, which are responsible for their mechanical and physico-chemical properties. The aim of this research was to determine and explain in detail the mechanism of unit interlinkage of two-component chitosan/1,3-ß-d-glucan matrices gelled at 90 °C. This required identifying functional groups interacting with each other and assessing surface topography providing material chemical composition. For this purpose, various spectroscopic and microscopic approaches, such as attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM), were applied. The results indicate the involvement mainly of the C-C and C-H groups and C=O⋯HN moieties in the process of biomaterial polymerization. Strong chemical interactions and ionocovalent bonds between the N-glucosamine moieties of chitosan and 1,3-ß-d-glucan units were demonstrated, which was also reflected in the uniform surface of the sample without segregation. These unique properties, hybrid character and proper cell response may imply the potential application of studied biomaterial as biocompatible scaffolds used in regenerative medicine, especially in bone restoration and/or wound healing.

Mesh Ti6Al4V Material Manufactured by Selective Laser Melting (SLM) as a Promising Intervertebral Fusion Cage.

Intervertebral cages made of Ti6Al4V alloy show excellent osteoconductivity, but also higher stiffness, compared to commonly used polyether-ether-ketone (PEEK) materials, that may lead to a stress-shielding effect and implant subsidence. In this study, a metallic intervertebral fusion cage, with improved mechanical behavior, was manufactured by the introduction of a three-dimensional (3D) mesh structure to Ti6Al4V material, using an additive manufacturing method. Then, the mechanical and biological properties of the following were compared: (1) PEEK, with a solid structure, (2) 3D-printed Ti6Al4V, with a solid structure, and (3) 3D-printed Ti6Al4V, with a mesh structure. A load-induced subsidence test demonstrated that the 3D-printed mesh Ti6Al4V cage had significantly lower tendency (by 15%) to subside compared to the PEEK implant. Biological assessment of the samples proved that all tested materials were biocompatible. However, both titanium samples (solid and mesh) were characterized by significantly higher bioactivity, osteoconductivity, and mineralization ability, compared to PEEK. Moreover, osteoblasts revealed stronger adhesion to the surface of the Ti6Al4V samples compared to PEEK material. Thus, it was clearly shown that the 3D-printed mesh Ti6Al4V cage possesses all the features for optimal spinal implant, since it carries low risk of implant subsidence and provides good osseointegration at the bone-implant interface.

Burn Wound Healing: Clinical Complications, Medical Care, Treatment, and Dressing Types: The Current State of Knowledge for Clinical Practice.

According to the World Health Organization (WHO), it is estimated that each year approximately 11 million people suffer from burn wounds, 180,000 of whom die because of such injuries. Regardless of the factors causing burns, these are complicated wounds that are difficult to heal and are associated with high mortality rates. Medical care of a burn patient requires a lot of commitment, experience, and multidirectional management, including surgical activities and widely understood pharmacological approaches. This paper aims to comprehensively review the current literature concerning burn wounds, including classification of burns, complications, medical care, and pharmacological treatment. We also overviewed the dressings (with an emphasis on the newest innovations in this field) that are currently used in medical practice to heal wounds.

Multifunctional Silver(I) Complexes with Metronidazole Drug Reveal Antimicrobial Properties and Antitumor Activity against Human Hepatoma and Colorectal Adenocarcinoma Cells.

Silver salts and azole derivatives are well known for their antimicrobial properties. Recent evidence has demonstrated also their cytotoxic and genotoxic potential toward both normal and cancer cells. Still, little is known about the action of complexes of azoles with silver(I) salts. Thus, the goal of the study was to compare the chemical, cytotoxic and antimicrobial properties of metronidazole complexes with silver(I) nitrate and silver(I) sulfate to metronidazole and pure silver(I) salts. We synthetized a novel complex, [Ag(MTZ)2]2SO4, and confirmed its chemical structure and properties using 1H and 13C NMR spectroscopy and X-Ray, IR and elemental analysis. To establish the stability of complexes [Ag(MTZ)2NO3] and [Ag(MTZ)2]2SO4, they were exposed to daylight and UV-A rays and were visually assessed. Their cytotoxicity toward human cancer cells (HepG2, Caco-2) and mice normal fibroblasts (Balb/c 3T3 clone A31) was determined by MTT, NRU, TPC and LDH assays. The micro-dilution broth method was used to evaluate their antimicrobial properties against Gram-positive and Gram-negative bacteria. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy. The photo-stability of the complexes was higher than silver(I) salts. In human cancer cells, [Ag(MTZ)2]2SO4 was more cytotoxic than Ag2SO4 and, in turn, AgNO3 was more cytotoxic than [Ag(MTZ)2NO3]. For Balb/c 3T3 cells, Ag2SO4 was more cytotoxic than [Ag(MTZ)2]2SO4, while the cytotoxicity of AgNO3 and [Ag(MTZ)2NO3] was similar. Metronidazole in the tested concentration range was non-cytotoxic for both normal and cancer cells. The complexes showed increased bioactivity against aerobic and facultative anaerobic bacteria when compared to metronidazole. For the majority of the tested bacterial strains, the silver(I) salts and complexes showed a higher antibacterial activity than MTZ; however, some bacterial strains presented the reverse effect. Our results showed that silver(I) complexes present higher photo-stability, cytotoxicity and antimicrobial activity in comparison to MTZ and, to a certain extent, to silver(I) salts.

Bioengineered Living Bone Grafts-A Concise Review on Bioreactors and Production Techniques In Vitro.

It has been observed that bone fractures carry a risk of high mortality and morbidity. The deployment of a proper bone healing method is essential to achieve the desired success. Over the years, bone tissue engineering (BTE) has appeared to be a very promising approach aimed at restoring bone defects. The main role of the BTE is to apply new, efficient, and functional bone regeneration therapy via a combination of bone scaffolds with cells and/or healing promotive factors (e.g., growth factors and bioactive agents). The modern approach involves also the production of living bone grafts in vitro by long-term culture of cell-seeded biomaterials, often with the use of bioreactors. This review presents the most recent findings concerning biomaterials, cells, and techniques used for the production of living bone grafts under in vitro conditions. Particular attention has been given to features of known bioreactor systems currently used in BTE: perfusion bioreactors, rotating bioreactors, and spinner flask bioreactors. Although bioreactor systems are still characterized by some limitations, they are excellent platforms to form bioengineered living bone grafts in vitro for bone fracture regeneration. Moreover, the review article also describes the types of biomaterials and sources of cells that can be used in BTE as well as the role of three-dimensional bioprinting and pulsed electromagnetic fields in both bone healing and BTE.

Microwave-Assisted Synthesis of Modified Glycidyl Methacrylate-Ethyl Methacrylate Oligomers, Their Physico-Chemical and Biological Characteristics.

In this study, well-known oligomers containing ethyl methacrylate (EMA) and glycidyl methacrylate (GMA) components for the synthesis of the oligomeric network [P(EMA)-co-(GMA)] were used. In order to change the hydrophobic character of the [P(EMA)-co-(GMA)] to a more hydrophilic one, the oligomeric chain was functionalized with ethanolamine, xylitol (Xyl), and L-ornithine. The oligomeric materials were characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy, scanning electron microscopy, and differential thermogravimetric analysis. In the final stage, thanks to the large amount of -OH groups, it was possible to obtain a three-dimensional hydrogel (HG) network. The HGs were used as a matrix for the immobilization of methylene blue, which was chosen as a model compound of active substances, the release of which from the matrix was examined using spectrophotometric detection. The cytotoxic test was performed using fluid extracts of the HGs and human skin fibroblasts. The cell culture experiment showed that only [P(EMA)-co-(GMA)] and [P(EMA)-co-(GMA)]-Xyl have the potential to be used in biomedical applications. The studies revealed that the obtained HGs were porous and non-cytotoxic, which gives them the opportunity to possess great potential for use as an oligomeric network for drug reservoirs in in vitro application.