Hyaluronic Acid/Ellagic Acid as Materials for Potential Medical Application.

The aim of this work was to develop and characterize a thin films composed of hyaluronic acid/ellagic acid for potential medical application. Its principal novelty, distinct from the prior literature in terms of hyaluronic acid films supplemented with phenolic acids, resides in the predominant incorporation of ellagic acid-a distinguished compound-as the primary constituent of the films. Herein, ellagic acid was dissolved in two different solvents, i.e., acetic acid (AcOH) or sodium hydroxide (NaOH), and the surface properties of the resultant films were assessed using atomic force microscopy and contact angle measurements. Additionally, various physicochemical parameters were evaluated including moisture content, antioxidant activity, and release of ellagic acid in phosphate buffered saline. Furthermore, the evaluation of films' biocompatibility was conducted using human epidermal keratinocytes, dermal fibroblasts, and human amelanotic melanoma cells (A375 and G361), and the antimicrobial activity was elucidated accordingly against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 15442. Our results showed that the films exhibited prominent antibacterial properties particularly against Staphylococcus aureus, with the 80HA/20EA/AcOH film indicating the strong biocidal activity against this strain leading to a significant reduction in viable cells. Comparatively, the 50HA/50EA/AcOH film also displayed biocidal activity against Staphylococcus aureus. This experimental approach could be a promising technique for future applications in regenerative dermatology or novel strategies in terms of bioengineering.

Biodegradability Study of Modified Chitosan Films with Cinnamic Acid and Ellagic Acid in Soil.

Currently, natural polymer materials with bactericidal properties are extremely popular. Unfortunately, although the biopolymer material itself is biodegradable, its enrichment with bactericidal compounds may affect the efficiency of biodegradation by natural soil microflora. Therefore, the primary objective of this study was to evaluate the utility of fungi belonging to the genus Trichoderma in facilitating the degradation of chitosan film modified with cinnamic acid and ellagic acid in the soil environment. Only two strains (T.07 and T.14) used chitosan films as a source of carbon and nitrogen. However, their respiratory activity decreased with the addition of tested phenolic acids, especially cinnamic acid. Addition of Trichoderma isolates to the soil increased oxygen consumption during the biodegradation process compared with native microorganisms, especially after application of the T.07 and T.14 consortium. Isolates T.07 and T.14 showed high lipolytic (55.78 U/h and 62.21 U/h) and chitinase (43.03 U/h and 41.27 U/h) activities. Chitinase activity after incorporation of the materials into the soil was higher for samples enriched with T.07, T.14 and the consortium. The isolates were classified as Trichoderma sp. and Trichoderma koningii. Considering the outcomes derived from our findings, it is our contention that the application of Trichoderma isolates holds promise for expediting the degradation process of chitosan materials containing bactericidal compounds.

PVA-Based Films with Strontium Titanate Nanoparticles Dedicated to Wound Dressing Application.

Bioactive materials may be applied in tissue regeneration, and an example of such materials are wound dressings, which are used to accelerate skin healing, especially after trauma. Here, we proposed a novel dressing enriched by a bioactive component. The aim of our study was to prepare and characterize poly(vinyl alcohol) films modified with strontium titanate nanoparticles. The physicochemical properties of films were studied, such as surface free energy and surface roughness, as well as the mechanical properties of materials. Moreover, different biological studies were carried out, like in vitro hemo- and cyto-compatibility, biocidal activity, and anti-biofilm formation. Also, the degradation of the materials' utilization possibilities and enzymatic activity in compost were checked. The decrease of surface free energy, increase of roughness, and improvement of mechanical strength were found after the addition of nanoparticles. All developed films were cyto-compatible, and did not induce a hemolytic effect on the human erythrocytes. The PVA films containing the highest concentration of STO (20%) reduced the proliferation of Eschericha coli, Pseudomonas aeruginosa, and Staphylococcus aureus significantly. Also, all films were characterized by surface anti-biofilm activity, as they significantly lowered the bacterial biofilm abundance and its dehydrogenase activity. The films were degraded by the compost microorganism. However, PVA with the addition of 20%STO was more difficult to degrade. Based on our results, for wound dressing application, we suggest using bioactive films based on PVA + 20%STO, as they were characterized by high antibacterial properties, favorable physicochemical characteristics, and good biocompatibility with human cells.

Hyaluronic acid/tannic acid films for wound healing application.

In this study, thin films based on hyaluronic acid (HA) with tannic acid (TA) were investigated in three different weight ratios (80HA/20TA, 50HA/50TA, 20HA/80TA) for their application as materials for wound healing. Surface free energy, as well as their roughness, mechanical properties, water vapor permeability rate, and antioxidant activity were determined. Moreover, their compatibility with blood and osteoblast cells was investigated. The irritation effect caused by hyaluronic acid/tannic acid films was also considered with the use of are constructed human epidermis model. The irritation effect for hyaluronic acid/tannic acid films by the in vitro method was also studied. The low surface free energy, surface roughness, and antioxidant activity presented by the obtained films were examined. All the tested compositions of hyaluronic acid/tannic acid films were hemocompatible, but only films based on 50HA/50TA were fully cytocompatible. Regarding the potential implantation, all the films except 80HA/20TA showed appropriate mechanical properties. The specimens did not exert the irritation effect during the studies involving reconstructed human epidermis.

Cold plasma treatment of tannic acid as a green technology for the fabrication of advanced cross-linkers for bioactive collagen/gelatin hydrogels.

Tannic acid (TA) is a natural compound studied as the cross-linker for biopolymers due to its ability to form hydrogen bonds. There are different methods to improve its reactivity and effectiveness to be used as a modifier for biopolymeric materials. This work employed plasma to modify tannic acid TA, which was then used as a cross-linker for fabricating collagen/gelatin scaffolds. Plasma treatment did not cause any significant changes in the structure of TA, and the resulting oxidized TA showed a higher antioxidant activity than that without treatment. Adding TA to collagen/gelatin scaffolds improved their mechanical properties and stability. Moreover, the obtained plasma-treated TA-containing scaffolds showed antibacterial properties and were non-hemolytic, with improved cytocompatibility towards human dermal fibroblasts. These results suggest the suitability of plasma treatment as a green technology for the modification of TA towards the development of advanced TA-crosslinked hydrogels for various biomedical applications.

Evaluating Gelatin-Based Films with Graphene Nanoparticles for Wound Healing Applications.

In this study, gelatin-based films containing graphene nanoparticles were obtained. Nanoparticles were taken from four chosen commercial graphene nanoplatelets with different surface areas, such as 150 m2/g, 300 m2/g, 500 m2/g, and 750 m2/g, obtained in different conditions. Their morphology was observed using SEM with STEM mode; porosity, Raman spectra and elemental analysis were checked; and biological properties, such as hemolysis and cytotoxicity, were evaluated. Then, the selected biocompatible nanoparticles were used as the gelatin film modification with 10% concentration. As a result of solvent evaporation, homogeneous thin films were obtained. The surface's properties, mechanical strength, antioxidant activity, and water vapor permeation rate were examined to select the appropriate film for biomedical applications. We found that the addition of graphene nanoplatelets had a significant effect on the properties of materials, improving surface roughness, surface free energy, antioxidant activity, tensile strength, and Young's modulus. For the most favorable candidate for wound dressing applications, we chose a gelatin film containing nanoparticles with a surface area of 500 m2/g.

Gelatin and gelatin/starch-based films modified with sorbitol for wound healing.

Gelatin-based films modified with sorbitol were produced from gelatin solution or gelatin/starch blends using a simple and low-cost solvent casting method, and subsequently, their physicochemical, mechanical, and biocompatibility properties were characterized. This work focused on developing and optimizing a biopolymeric blend to improve the pure biopolymers' properties for potential biomedical applications such as wound dressing. The films were characterized in terms of morphology and transparency, mechanical, moisture and swelling properties, thermal stability, and degradation potential. Moreover, hemocompatibility, as well as cytocompatibility of prepared films, were examined. The addition of sorbitol contributed to improving mechanical properties, swelling reduction, and increasing biostability over time. The cytocompatibility of obtained films was confirmed in vitro with two different human cell lines, fibroblastic and osteoblastic, and a more favorable cellular response was received for fibroblasts. Further, in hemocompatibility studies, it was found that all films may be classified as non-hemolytic as they did not have a negative effect on the human erythrocytes. The obtained results indicate the great potential of the gelatin/starch blends modified with sorbitol as regenerative biomaterials intended for wound healing applications.

Application Potential of Trichoderma in the Degradation of Phenolic Acid-Modified Chitosan.

The aim of the study was to determine the potential use of fungi of the genus Trichoderma for the degradation of phenolic acid-modified chitosan in compost. At the same time, the enzymatic activity in the compost was checked after the application of a preparation containing a suspension of the fungi Trichoderma (spores concentration 105/mL). The Trichoderma strains were characterized by high lipase and aminopeptidase activity, chitinase, and ß-1,3-glucanases. T. atroviride TN1 and T. citrinoviride TN3 metabolized the modified chitosan films best. Biodegradation of modified chitosan films by native microorganisms in the compost was significantly less effective than after the application of a formulation composed of Trichoderma TN1 and TN3. Bioaugmentation with a Trichoderma preparation had a significant effect on the activity of all enzymes in the compost. The highest oxygen consumption in the presence of chitosan with tannic acid film was found after the application of the consortium of these strains (861 mg O2/kg after 21 days of incubation). Similarly, chitosan with gallic acid and chitosan with ferulic acid were found after the application of the consortium of these strains (849 mgO2/kg and 725 mg O2/kg after 21 days of incubation). The use of the Trichoderma consortium significantly increased the chitinase activity. The application of Trichoderma also offers many possibilities in sustainable agriculture. Trichoderma can not only degrade chitosan films, but also protect plants against fungal pathogens by synthesizing chitinases and ß-1,3 glucanases with antifungal properties.

Engineering Antioxidant Surfaces for Titanium-Based Metallic Biomaterials.

Prolonged inflammation induced by orthopedic metallic implants can critically affect the success rates, which can even lead to aseptic loosening and consequent implant failure. In the case of adverse clinical conditions involving osteoporosis, orthopedic trauma and implant corrosion-wear in peri-implant region, the reactive oxygen species (ROS) activity is enhanced which leads to increased oxidative stress. Metallic implant materials (such as titanium and its alloys) can induce increased amount of ROS, thereby critically influencing the healing process. This will consequently affect the bone remodeling process and increase healing time. The current review explores the ROS generation aspects associated with Ti-based metallic biomaterials and the various surface modification strategies developed specifically to improve antioxidant aspects of Ti surfaces. The initial part of this review explores the ROS generation associated with Ti implant materials and the associated ROS metabolism resulting in the formation of superoxide anion, hydroxyl radical and hydrogen peroxide radicals. This is followed by a comprehensive overview of various organic and inorganic coatings/materials for effective antioxidant surfaces and outlook in this research direction. Overall, this review highlights the critical need to consider the aspects of ROS generation as well as oxidative stress while designing an implant material and its effective surface engineering.

The characterization of collagen-based scaffolds modified with phenolic acids for tissue engineering application.

The aim of the experiment was to study the morphology of collagen-based scaffolds modified by caffeic acid, ferulic acid, and gallic acid, their swelling, and degradation rate, as well as the biological properties of scaffolds, such as antioxidant activity, hemo- and cytocompatibility, histological observation, and antibacterial properties. Scaffolds based on collagen with phenolic acid showed higher swelling rate and enzymatic stability compared to scaffolds based on pure collagen, and the radical scavenging activity was in the range 85-91%. All scaffolds were non-hemolytic and compatible with surrounding tissues. Collagen modified by ferulic acid showed potentially negative effects on hFOB cells as a significantly increased LDH release was found, but all of the studied materials had antimicrobial activity against Staphylococcus aureus and Escherichia coli. It may be assumed that phenolic acids, such as caffeic, ferulic, and gallic acid, are modifiers and provide novel biological properties of collagen-based scaffolds. This paper provides the summarization and comparison of the biological properties of scaffolds based on collagen modified with three different phenolic acids.

Chitosan-Based Membranes as Gentamicin Carriers for Biomedical Applications-Influence of Chitosan Molecular Weight.

Over the past decade, much attention has been paid to chitosan as a potential drug carrier because of its non-toxicity, biocompatibility, biodegradability and antibacterial properties. The effect of various chitosan characteristics on its ability to carry different antibiotics is discussed in the literature. In this work, we evaluated the influence of the different molecular weights of this polymer on its potential as an antibacterial membrane after adding gentamicin (1% w/w). Three types of chitosan membranes without and with antibiotic were prepared using a solvent casting process. Their microstructures were analyzed with a 4K digital microscope, and their chemical bonds were studied using FTIR spectroscopy. Furthermore, cytocompatibility on human osteoblasts and fibroblasts as well as antibacterial activity against Staphylococcus aureus (S. aureus.) and Escherichia coli (E. coli) were assessed. We observed that the membrane prepared from medium-molecular-weight chitosan exhibited the highest contact angle (≈85°) and roughness (10.96 ± 0.21 µm) values, and its antibacterial activity was unfavorable. The maximum tensile strength and Young's modulus of membranes improved and elongation decreased with an increase in the molecular weight of chitosan. Membranes prepared with high-molecular-weight chitosan possessed the best antibacterial activity, but mainly against S. aureus. For E. coli, is not advisable to add gentamicin to the chitosan membrane, or it is suggested to deplete its content. None of the fabricated membranes exhibited a full cytotoxic effect on osteoblastic and fibroblast cells. Based on our results, the most favorable membrane as a gentamicin carrier was obtained from high-molecular-weight chitosan.

The Application of Phenolic Acids in The Obtainment of Packaging Materials Based on Polymers-A Review.

This article provides a summarization of present knowledge on the fabrication and characterization of polymeric food packaging materials that can be an alternative to synthetic ones. The review aimed to explore different studies related to the use of phenolic acids as cross-linkers, as well as bioactive additives, to the polymer-based materials upon their application as packaging. This article further discusses additives such as benzoic acid derivatives (sinapic acid, gallic acid, and ellagic acid) and cinnamic acid derivatives (p-coumaric acid, caffeic acid, and ferulic acid). These phenolic acids are mainly used as antibacterial, antifungal, and antioxidant agents. However, their presence also improves the physicochemical properties of materials based on polymers. Future perspectives in polymer food packaging are discussed.

3D-Structured and Blood-Contact-Safe Graphene Materials.

Graphene is a promising material that may be potentially used in biomedical applications, mainly for drug delivery applications. In our study, we propose an inexpensive 3D graphene preparation method by wet chemical exfoliation. The morphology of the graphene was studied by SEM and HRTEM. Moreover, the volumetric elemental composition (C, N, and H) of the materials was analyzed, and Raman spectra of prepared graphene samples were obtained. X-ray photoelectron spectroscopy, relevant isotherms, and specific surface area were measured. Survey spectra and micropore volume calculations were made. In addition, the antioxidant activity and hemolysis rate in contact with blood were determined. Activity against free radicals of graphene samples before and after thermal modification was tested using the DPPH method. The RSA of the material increased after graphene modification, which suggests that antioxidant properties were improved. All tested graphene samples caused hemolysis in the range of 0.28-0.64%. The results showed that all tested 3D graphene samples might be classified as nonhemolytic.

Chitosan/Phenolic Compounds Scaffolds for Connective Tissue Regeneration.

Chitosan-based scaffolds modified by gallic acid, ferulic acid, and tannic acid were fabricated. The aim of the experiment was to compare the compatibility of scaffolds based on chitosan with gallic acid, ferulic acid, or tannic acid using the in vivo method. For this purpose, materials were implanted into rabbits in the middle of the latissimus dorsi muscle length. A scaffold based on unmodified chitosan was implanted by the same method as a control. Moreover, the Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) spectra and scanning electron microscope (SEM) observations were made to study the interactions between chitosan and phenolic acids. Additionally, antioxidant properties and blood compatibility were investigated. The results showed that all studied materials were safe and non-toxic. However, chitosan scaffolds modified by gallic acid and tannic acid were resorbed faster and, as a result, tissues were organized faster than those modified by ferulic acid or unmodified.

Scaffolds Loaded with Dialdehyde Chitosan and Collagen-Their Physico-Chemical Properties and Biological Assessment.

In this work, dialdehyde chitosan (DAC) and collagen (Coll) scaffolds have been prepared and their physico-chemical properties have been evaluated. Their structural properties were studied by Fourier Transform Infrared Spectroscopy with Attenuated Internal Reflection (FTIR-ATR) accompanied by evaluation of thermal stability, porosity, density, moisture content and microstructure by Scanning Electron Microscopy-SEM. Additionally, cutaneous assessment using human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF) and melanoma cells (A375 and G-361) was performed. Based on thermal studies, two regions in DTG curves could be distinguished in each type of scaffold, what can be assigned to the elimination of water and the polymeric structure degradation of the materials components. The type of scaffold had no major effect on the porosity of the materials, but the water content of the materials decreased with increasing dialdehyde chitosan content in subjected matrices. Briefly, a drop in proliferation was noticed for scaffolds containing 20DAC/80Coll compared to matrices with collagen alone. Furthermore, increased content of DAC (50DAC/50Coll) either significantly induced the proliferation rate or maintains its ratio compared to the control matrix. This delivery is a promising technique for additional explorations targeting therapies in regenerative dermatology. The using of dialdehyde chitosan as one of the main scaffolds components is the novelty in terms of bioengineering.

Assessment of Melatonin-Cultured Collagen/Chitosan Scaffolds Cross-Linked by a Glyoxal Solution as Biomaterials for Wound Healing.

Chitosan (CTS) and collagen (Coll) are natural biomaterials that have been extensively used in tissue engineering or wound healing applications, either separately or as composite materials. Most methods to fabricate CTS/Coll matrices employ chemical crosslinking to obtain solid and stable scaffolds with the necessary porosity and mechanical properties to facilitate regeneration. In this study, we comparatively assessed the physicochemical properties of 3D scaffolds loaded with a cross-linker, glyoxal. Using a scanning electron microscope, we evaluated the microstructure of resultant matrices and their mechanistic testing by the determination of the compressive modulus (Emod), the maximum force (Fmax), thermogravimetric analysis (TG), Fourier Transform Infrared Spectroscopy-Attenuated Total Reflectance (FTIR-ATR), and proliferation rate in vitro using human epidermal keratinocytes and dermal fibroblasts cultured in presence of melatonin solution (10-5 M). We observed that enhanced content of collagen (50CTS/50Coll or 20CTS/80Coll compared to 80CTS/20Coll) significantly elevated the physicochemical capacities of resultant materials. Besides, presence of 5% glyoxal increased porosity, Emod and Fmax, compared to scaffolds without glyoxal. Finally, keratinocytes and dermal fibroblasts cultured on subjected matrices in presence of melatonin revealed a prominently enhanced growth rate. This indicates that the combination of glyoxal and melatonin make it imperative to consider these materials as a promising approach for targeting skin tissue engineering or regenerative dermatology.

Characterization of Collagen/Beta Glucan Hydrogels Crosslinked with Tannic Acid.

Hydrogels based on collagen/ß-glucan crosslinked with tannic acid were obtained by neutralization using dialysis. The presence of tannic acid allowed obtaining stable hydrogel materials with better mechanical properties. Tannic acid was released from matrices gradually and not rapidly. The antioxidant properties of the obtained hydrogels increased over the course of their incubation in culture media and were dependent on the concentration of tannic acid in the matrices. The obtained materials influenced dehydrogenase activity and the ATP level of pathogens. Additionally, the materials' extracts improved the HaCaT cells' viability. Therefore, the obtained hydrogels seem to be promising biocompatible materials which display antimicrobial properties.

Chitosan-based films enriched by caffeic acid with poly(ethylene glycol) - A physicochemical and antibacterial properties evaluation.

In this work, chitosan/caffeic acid mixtures in the weight ratios of 80/20 and 50/50 were used to obtain thin films enriched with poly(ethylene glycol). It was hypothesized that the presence of caffeic acid indicates the antibacterial properties of the materials (i) and that poly(ethylene glycol) acts as a films modifier (ii). The results showed that by poly(ethylene glycol) addition, the surface free energy as well as mechanical and thermal properties were improved. Moreover, water vapor permeability was observed. All the tested materials showed antioxidant properties in the range of approximately 90%. They also showed antibacterial effectiveness against both Gram-positive and Gram-negative bacteria. The most appropriate material for the application as packaging was composed of chitosan and caffeic acid mixed in a 50/50 weight ratio with 20% PEG addition.

The Study of Physicochemical Properties and Blood Compatibility of Sodium Alginate-Based Materials via Tannic Acid Addition.

In this study, sodium alginate-based thin films were modified by the addition of tannic acid. Materials were obtained by solvent evaporation. They were characterized by the observation of its morphology and its surface by scanning electron microscope and atomic force microscope. The thermal properties were studied by differential scanning calorimetry. The concentration of tannic acid released from the material was determined by the Folin-Ciocalteu method. The material safety for biomedical application was determined by the hemolysis rate study in contact with sheep blood as well as platelet adhesion to the material surface. Based on the obtained results, we assume that proposed films based on sodium alginate/tannic acid are safe and may potentially find application in medicine.

The Characterization of Scaffolds Based on Dialdehyde Chitosan/Hyaluronic Acid.

In this work, two-component dialdehyde chitosan/hyaluronic acid scaffolds were developed and characterized. Dialdehyde chitosan was obtained by one-step synthesis with chitosan and sodium periodate. Three-dimensional scaffolds were prepared by the lyophilization method. Fourier transform infrared spectroscopy (FTIR) was used to observe the chemical structure of scaffolds and scanning electron microscopy (SEM) imaging was done to assess the microstructure of resultant materials. Thermal analysis, mechanical properties measurements, density, porosity and water content measurements were used to characterize physicochemical properties of dialdehyde chitosan/hyaluronic acid 3D materials. Additionally, human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF) and human melanoma cells (A375 and G-361) were used to evaluate cell viability in the presence of subjected scaffolds. It was found that scaffolds were characterized by a porous structure with interconnected pores. The scaffold composition has an influence on physicochemical properties, such as mechanical strength, thermal resistance, porosity and water content. There were no significant differences between cell viability proliferation of all scaffolds, and this observation was visible for all subjected cell lines.