Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO2 Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform.

This study proposes synthesis and evaluation of gelatin-/alginate-based hydrogel scaffolds reinforced with titanium dioxide (TiO2) nanoparticles which, through their combination with allantoin, quercetin, and caffeic acid, provide multi-target therapy directed on all phases of the wound healing process. These scaffolds provide the simultaneous release of bioactive agents and concurrently support cell/tissue repair through the replicated structure of a native extracellular matrix. The hydrogel scaffolds were synthesized via a crosslinking reaction using EDC as a crosslinker for gelatin. Synthesized hydrogel scaffolds and the effect of TiO2 on their properties were characterized by structural, mechanical, morphological, and swelling properties, and the porosity, wettability, adhesion to skin tissue, and simultaneous release features. The biocompatibility of the scaffolds was tested in vitro on fibroblasts (MRC5 cells) and in vivo (Caenorhabditis elegans) in a survival probe. The scaffolds revealed porous interconnected morphology, porosity of 88.33 to 96.76%, elastic modulus of 1.53 to 4.29 MPa, full hydrophilicity, favorable skin adhesivity, and biocompatibility. The simultaneous release was investigated in vitro indicating dependence on the scaffold's composition and type of bioactive agents. The novel scaffolds designed as multi-target therapy have significant promise for improved wound healing in a beneficial and non-invasive manner.

2-Hydroxyethyl Methacrylate/Gelatin/Alginate Scaffolds Reinforced with Nano TiO2 as a Promising Curcumin Release Platform.

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.

Alginate-Based Hydrogels and Scaffolds for Biomedical Applications.

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.

Manuka Honey/2-Hydroxyethyl Methacrylate/Gelatin Hybrid Hydrogel Scaffolds for Potential Tissue Regeneration.

Scaffolding biomaterials are gaining great importance due to their beneficial properties for medical purposes. Targeted biomaterial engineering strategies through the synergy of different material types can be applied to design hybrid scaffolding biomaterials with advantageous properties for biomedical applications. In our research, a novel combination of the bioactive agent Manuka honey (MHo) with 2-hydroxyethyl methacrylate/gelatin (HG) hydrogel scaffolds was created as an efficient bioactive platform for biomedical applications. The effects of Manuka honey content on structural characteristics, porosity, swelling performance, in vitro degradation, and in vitro biocompatibility (fibroblast and keratinocyte cell lines) of hybrid hydrogel scaffolds were studied using Fourier transform infrared spectroscopy, the gravimetric method, and in vitro MTT biocompatibility assays. The engineered hybrid hydrogel scaffolds show advantageous properties, including porosity in the range of 71.25% to 90.09%, specific pH- and temperature-dependent swelling performance, and convenient absorption capacity. In vitro degradation studies showed scaffold degradability ranging from 6.27% to 27.18% for four weeks. In vitro biocompatibility assays on healthy human fibroblast (MRC5 cells) and keratinocyte (HaCaT cells) cell lines by MTT tests showed that cell viability depends on the Manuka honey content loaded in the HG hydrogel scaffolds. A sample containing the highest Manuka honey content (30%) exhibited the best biocompatible properties. The obtained results reveal that the synergy of the bioactive agent, Manuka honey, with 2-hydroxyethyl methacrylate/gelatin as hybrid hydrogel scaffolds has potential for biomedical purposes. By tuning the Manuka honey content in HG hydrogel scaffolds advantageous properties of hybrid scaffolds can be achieved for biomedical applications.

In Vitro and In Vivo Biocompatible and Controlled Resveratrol Release Performances of HEMA/Alginate and HEMA/Gelatin IPN Hydrogel Scaffolds.

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.

Bioactive Interpenetrating Hydrogel Networks Based on 2-Hydroxyethyl Methacrylate and Gelatin Intertwined with Alginate and Dopped with Apatite as Scaffolding Biomaterials.

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.

Removal of Nickel Ions from Aqueous Solutions by 2-Hydroxyethyl Acrylate/Itaconic Acid Hydrogels Optimized with Response Surface Methodology.

The adsorption of Ni2+ ions from water solutions by using hydrogels based on 2-hydroxyethyl acrylate (HEA) and itaconic acid (IA) was studied. Hydrogel synthesis was optimized with response surface methodology (RSM). The hydrogel with the best adsorption capacity towards Ni2+ ions was chosen for further experiments. The hydrogel was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis before and after the adsorption of Ni2+ ions. Batch equilibrium experiments were conducted to investigate the influence of solution pH, hydrogel weight, ionic strength, adsorption time, temperature and initial concentration of nickel ions on the adsorption. Time-dependent adsorption fitted the best to the pseudo-second-order kinetic model. A thermodynamic study revealed that the adsorption was an exothermic and non-spontaneous process. Five isotherm models were studied, and the best fit was obtained with the Redlich-Peterson model. Consecutive adsorption/desorption studies indicated that the HEA/IA hydrogel can be efficiently used as a sorbent for the removal of Ni2+ ions from the water solution. This study develops a potential adsorbent for the effective removal of trace nickel ions.

Novel Hydrogel Scaffolds Based on Alginate, Gelatin, 2-Hydroxyethyl Methacrylate, and Hydroxyapatite.

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.

Biodegradable Hydrogel Scaffolds Based on 2-Hydroxyethyl Methacrylate, Gelatin, Poly(ß-amino esters), and Hydroxyapatite.

New composite 3D scaffolds were developed as a combination of synthetic polymer, poly(2-hydroxyethyl methacrylate) (PHEMA), and a natural polymer, gelatin, with a ceramic component, nanohydroxyapatite (ID nHAp) dopped with metal ions. The combination of a synthetic polymer, to be able to tune the structure and the physicochemical and mechanical properties, and a natural polymer, to ensure the specific biological functions of the scaffold, with inorganic filler was applied. The goal was to make a new material with superior properties for applications in the biomedical field which mimics as closely as possible the native bone extracellular matrix (ECM). Biodegradable PHEMA hydrogel was obtained by crosslinking HEMA by poly(ß-amino esters) (PBAE). The scaffold's physicochemical and mechanical properties, in vitro degradation, and biological activity were assessed so to study the effects of the incorporation of nHAp in the (PHEMA/PBAE/gelatin) hydrogel, as well as the effect of the different pore-forming methods. Cryogels had higher elasticity, swelling, porosity, and percent of mass loss during degradation than the samples obtained by porogenation. The composite scaffolds had a higher mechanical strength, 10.14 MPa for the porogenated samples and 5.87 MPa for the cryogels, but a slightly lower degree of swelling, percent of mass loss, and porosity than the hybrid ones. All the scaffolds were nontoxic and had a high cell adhesion rate, which was 15-20% higher in the composite samples. Cell metabolic activity after 2 and 7 days of culture was higher in the composites, although not statistically different. After 28 days, cell metabolic activity was similar in all scaffolds and the TCP control. No effect of integrating nHAp into the scaffolds on osteogenic cell differentiation could be observed. Synergetic effects occurred which influenced the mechanical behavior, structure, physicochemical properties, and interactions with biological species.

Degradable 2-Hydroxyethyl Methacrylate/Gelatin/Alginate Hydrogels Infused by Nanocolloidal Graphene Oxide as Promising Drug Delivery and Scaffolding Biomaterials.

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.