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.

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.

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.

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.

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(β-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.