Alginate is a natural polymer of marine origin and, due to its exceptional properties, has great importance as an essential component for the preparation of hydrogels and scaffolds for biomedical ...applications. The design of biologically interactive hydrogels and scaffolds with advanced, expected and required properties are one of the key issues for successful outcomes in the healing of injured tissues. This review paper presents the multifunctional biomedical applications of alginate-based hydrogels and scaffolds in selected areas, highlighting the key effect of alginate and its influence on the essential properties of the selected biomedical applications. The first part covers scientific achievements for alginate in dermal tissue regeneration, drug delivery systems, cancer treatment, and antimicrobials. The second part is dedicated to our scientific results obtained for the research opus of hydrogel materials for scaffolds based on alginate in synergy with different materials (polymers and bioactive agents). Alginate has proved to be an exceptional polymer for combining with other naturally occurring and synthetic polymers, as well as loading bioactive therapeutic agents to achieve dermal, controlled drug delivery, cancer treatment, and antimicrobial purposes. Our research was based on combinations of alginate with gelatin, 2-hydroxyethyl methacrylate, apatite, graphene oxide and iron(III) oxide, as well as curcumin and resveratrol as bioactive agents. Important features of the prepared scaffolds, such as morphology, porosity, absorption capacity, hydrophilicity, mechanical properties, in vitro degradation, and in vitro and in vivo biocompatibility, have shown favorable properties for the aforementioned applications, and alginate has been an important link in achieving these properties. Alginate, as a component of these systems, proved to be an indispensable factor and played an excellent "role" in the optimal adjustment of the tested properties. This study provides valuable data and information for researchers and demonstrates the importance of the role of alginate as a biomaterial in the design of hydrogels and scaffolds that are powerful medical "tools" for biomedical applications.
Antibacterial hydrogels, as an advanced approach, can create optimal conditions for wound healing, even in the fight against stubborn and difficult‐to‐treat wound infections. Interestingly, pH is an ...often neglected clinical parameter, although it has a significant impact on the wound healing process. At different stages of wound healing, the pH in the wound bed changes from slightly alkaline to neutral to acidic. To develop novel pH‐sensitive antibacterial hydrogel dressings, Zn2+‐loaded poly(2‐hydroxyethyl acrylate/itaconic acid) hydrogels are synthesized. The hydrogels exhibit pH‐sensitive swelling in the physiologically relevant pH range, with a pronounced swelling ability at neutral pH. The controlled release of Zn2+ occurs in a buffer of pH 7.40 at 37 °C. The liquid transport mechanism and release kinetics are evaluated using the specific kinetic models of Ritger‐Peppas and Peppas‐Sahlin. The effect of Zn2+ on structural, thermal, swelling, cytocompatibility, and antibacterial properties is evaluated by Fourier transform infrared spectroscopy, differential scanning calorimetry, swelling studies, MTT, and antibacterial tests. The hydrogels show excellent antibacterial activity against Escherichia coli. The research opens new perspectives for efficient wound healing management, and the extension of the study will be orchestrated by optimising the hydrogel composition to achieve improved performance.
The application of stimuli‐sensitive antibacterial hydrogel dressings represents an innovative approach to addressing global healthcare problems caused by ineffective wound treatments, especially when antibiotic resistance is rapidly increasing. This manuscript describes the synthesis and characterization of Zn2+‐loaded hydrogels based on 2‐hydroxyethyl acrylate and itaconic acid as novel pH‐sensitive antibacterial hydrogel dressings.
Since the management of infections becomes prior global healthcare issue, the “post antibiotic era” requires innovative and interdisciplinary approach. As an alternative to widespread and, nowdays ...mostly uneffective, antibiotic treatment of infections, the series of hydrogels were developed and further investigated as novel antibacterial biomaterials. The hydrogels based on 2-hydroxyethyl acrylate and itaconic acid were synthesized and used for silver(I) ions incorporation. The structural, thermal and swelling characteristics were examined by Fourier transform infrared spectroscopy, differential scanning calorimetry, and swelling study conducted in wide range of pHs at 37 °C. Results confirmed the expected structure, while the glass transition temperatures (
T
g
) of the hydrogels were detected in range of 10–37 °C. The
in vitro
release study revealed suitability of these pH sensitive hydrogels as the systems for topical delivery of silver(I) ions. Performed MTT test and Comet assay proved biocompatibility of the hydrogels, as well as the absence of acute genotoxic effect on human fibroblast cells (MRC-5). The hydrogels exhibited satisfying antibacterial activity against methicillin sensitive
Staphylococcus aureus
(MSSA) and methicillin resistant
Staphylococcus aureus
(MRSA), indicating the capacity to treat the life-threatening infections.
Hydrogel scaffolding biomaterials are one of the most attractive polymeric biomaterials for regenerative engineering and can be engineered into tissue mimetic scaffolds to support cell growth due to ...their similarity to the native extracellular matrix. The novel, versatile hydrogel scaffolds based on alginate, gelatin, 2-hydroxyethyl methacrylate, and inorganic agent hydroxyapatite were prepared by modified cryogelation. The chemical composition, morphology, porosity, mechanical properties, effects on cell viability, in vitro degradation, in vitro and in vivo biocompatibility were tested to correlate the material's composition with the corresponding properties. Scaffolds showed an interconnected porous microstructure, satisfactory mechanical strength, favorable hydrophilicity, degradation, and suitable in vitro and in vivo biocompatible behavior. Materials showed good biocompatibility with healthy human fibroblast in cell culture, as well as in vivo with zebrafish assay, suggesting newly synthesized hydrogel scaffolds as a potential new generation of hydrogel scaffolding biomaterials with tunable properties for versatile biomedical applications and tissue regeneration.
Scaffold hydrogel biomaterials designed to have advantageous biofunctional properties, which can be applied for controlled bioactive agent release, represent an important concept in biomedical tissue ...engineering. Our goal was to create scaffolding materials that mimic living tissue for biomedical utilization. In this study, two novel series of interpenetrating hydrogel networks (IPNs) based on 2-hydroxyethyl methacrylate/gelatin and 2-hydroxyethyl methacrylate/alginate were crosslinked using N-ethyl-N′-(3-dimethyl aminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Characterization included examining the effects of crosslinker type and concentration on structure, morphological and mechanical properties, in vitro swelling, hydrophilicity as well as on the in vitro cell viability (fibroblast cells) and in vivo (Caenorhabditis elegans) interactions of novel biomaterials. The engineered IPN hydrogel scaffolds show an interconnected pore morphology and porosity range of 62.36 to 85.20%, favorable in vitro swelling capacity, full hydrophilicity, and Young’s modulus values in the range of 1.40 to 7.50 MPa. In vitro assay on healthy human fibroblast (MRC5 cells) by MTT test and in vivo (Caenorhabditis elegans) survival assays show the advantageous biocompatible properties of novel IPN hydrogel scaffolds. Furthermore, in vitro controlled release study of the therapeutic agent resveratrol showed that these novel scaffolding systems are suitable controlled release platforms. The results revealed that the use of EDC and the combination of EDC/NHS crosslinkers can be applied to prepare and tune the properties of the IPN 2-hydroxyethyl methacrylate/alginate and 2-hydroxyethyl methacrylate/gelatin hydrogel scaffolds series, which have shown great potential for biomedical engineering applications.
The idea of this study was to create a new scaffolding system based on 2-hydroxyethyl methacrylate, gelatin, and alginate that contains titanium(IV) oxide nanoparticles as a platform for the ...controlled release of the bioactive agent curcumin. The innovative strategy to develop hybrid scaffolds was the modified porogenation method. The effect of the scaffold composition on the chemical, morphology, porosity, mechanical, hydrophilicity, swelling, degradation, biocompatibility, loading, and release features of hybrid scaffolds was evaluated. A porous structure with interconnected pores in the range of 52.33–65.76%, favorable swelling capacity, fully hydrophilic surfaces, degradability to 45% for 6 months, curcumin loading efficiency above 96%, and favorable controlled release profiles were obtained. By applying four kinetic models of release, valuable parameters were obtained for the curcumin/PHEMA/gelatin/alginate/TiO2 release platform. Cytotoxicity test results depend on the composition of the scaffolds and showed satisfactory cell growth with visible cell accumulation on the hybrid surfaces. The constructed hybrid scaffolds have suitable high-performance properties, suggesting potential for further in vivo and clinical studies.
The strategy of combining polymers of natural and synthetic origin with inorganic components to use their unique synergistic effect for the development of the novel, sophisticated, and efficient 3D ...polymeric biomaterials, whose structure and properties mimic the extracellular matrix and simultaneously represent the suitable hydrogel platform for controlled drug release, is presented. The novel versatile 2‐hydroxyethyl methacrylate/gelatin/alginate/iron(III) oxide based hydrogels are prepared by a simple but effective method‐modified porogenation. Chemical composition, morphology, swelling capacity, porosity, mechanical properties, effects on cell viability, and in vitro degradation are tested to correlate the material's composition with the corresponding properties. The hydrogels show an interconnected porous microstructure, satisfactory mechanical strength, pH‐sensitivity, and favorable curcumin release performances. The materials show good compatibility with healthy human fibroblast in cell culture judged by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, suggesting newly synthesized hydrogels as potentially a new generation of 3D biomaterials with tunable properties for versatile biomedical and pharmaceutical applications.
A series of novel, favorable porosity and degradability hydrogels are obtained in four steps, combining natural polymeric components, gelatin and alginate, and synthetic monomeric component 2‐hydroxyethyl methacrylate with iron(III) oxide (PHEMA/G/A/Fe), by modified porogenation followed by freeze‐drying treatment. Properties of novel hydrogels can be tuned by varying gelatin/alginate ratio.
Our goal was to create bioimitated scaffolding materials for biomedical purposes. The guiding idea was that we used an interpenetrating structural hierarchy of natural extracellular matrix as a ...“pattern” to design hydrogel scaffolds that show favorable properties for tissue regeneration. Polymeric hydrogel scaffolds are made in a simple, environmentally friendly way without additional functionalization. Gelatin and 2-hydroxyethyl methacrylate were selected to prepare interpenetrating polymeric networks and linear alginate chains were added as an interpenetrant to study their influence on the scaffold’s functionalities. Cryogelation and porogenation methods were used to obtain the designed scaffolding biomaterials. The scaffold’s structural, morphological, and mechanical properties, in vitro degradation, and cell viability properties were assessed to study the effects of the preparation method and alginate loading. Apatite as an inorganic agent was incorporated into cryogelated scaffolds to perform an extensive biological assay. Cryogelated scaffolds possess superior functionalities essential for tissue regeneration: fully hydrophilicity, degradability and mechanical features (2.08–9.75 MPa), and an optimal LDH activity. Furthermore, cryogelated scaffolds loaded with apatite showed good cell adhesion capacity, biocompatibility, and non-toxic behavior. All scaffolds performed equally in terms of metabolic activity and osteoconductivity. Cryogelated scaffolds with/without HAp could represent a new advance to promote osteoconductivity and enhance hard tissue repair. The obtained series of scaffolding biomaterials described here can provide a wide range of potential applications in the area of biomedical engineering.
The design and evaluation of novel 2-hydroxyethyl methacrylate/gelatin/alginate/graphene oxide hydrogels as innovative scaffolding biomaterials, which concurrently are the suitable drug delivery ...carrier, was proposed. The hydrogels were prepared by the adapted porogen leaching method; this is also the first time this method has been used to incorporate nanocolloidal graphene oxide through the hydrogel and simultaneously form porous structures. The effects of a material's composition on its chemical, morphological, mechanical, and swelling properties, as well as on cell viability and in vitro degradation, were assessed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), measurements of Young's modulus, gravimetric method and MTT test, respectively. The engineered hydrogels show good swelling capacity, fully hydrophilic surfaces, tunable porosity (from 56 to 76%) and mechanical properties (from 1.69 to 4.78 MPa), curcumin entrapment efficiency above 99% and excellent curcumin release performances. In vitro cytotoxicity on healthy human fibroblast (MRC5 cells) by MTT test reveal that the materials are nontoxic and biocompatible, proposing novel hydrogels for in vivo clinical evaluation to optimize tissue regeneration treatments by coupling the hydrogels with cells and different active agents to create material/biofactor hybrids with new levels of biofunctionality.
Gelatin hydrogels have great potential in regenerative medicine but their weak mechanical properties are a major drawback for the load-bearing applications, such as scaffolds for tissue engineering. ...To overcome this deficiency, novel biodegradable hydrogels with improved mechanical properties were prepared by combining gelatine with 2-hydroxyethyl methacrylate (HEMA), using a double network synthetic procedure. The first, superporous and mechanically strong network, was obtained by free radical polymerization of HEMA at cryogenic temperature, in the presence of gelatin. Degradable poly (β-amino ester) (PBAE) macromers of different chemical composition or molecular weight were used as crosslinkers to introduce hydrolytically labile bonds in PHEMA. The second gelatin network was formed by crosslinking gelatin with glutaraldehyde. For comparison, a set of biodegradable PHEMA networks was obtained by polymerization of HEMA at cryogenic temperature. All samples were characterized revealing that mechanical strength, swelling behavior and degradation rate as well as high biocompatibility of new IPNs are in accordance with values required for scaffolds in tissue engineering applications and that tuning of these properties is accomplished by simply using different PBAE macromers.
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•Synthesis and characterization of novel biodegradable poly(2-hydroxyethyl metacrylate)/gelatine based IPN scaffolds.•Tunable IPN scaffold properties with different PBAE crosslinkers for HEMA networks.•The advantages of gelatine containing IPNs, due to the combination of natural and synthetic hydrogel.•High viability with MRC5 cells validated for all novel IPNs.
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