In recent years, interest in nanotechnology has increased exponentially due to enhanced progress and technological innovation. In tissue engineering, the development of metallic nanoparticles has been amplified, especially due to their antibacterial properties. Another important characteristic of metal NPs is that they enable high control over the features of the developed scaffolds (optimizing their mechanical strength and offering the controlled release of bioactive agents). Currently, the main concern related to the method of synthesis of metal oxide NPs is the environmental impact. The physical and chemical synthesis uses toxic agents that could generate hazards or exert carcinogenicity/environmental toxicity. Therefore, a greener, cleaner, and more reliable approach is needed. Green synthetic has come as a solution to counter the aforementioned limitations. Nowadays, green synthesis is preferred because it leads to the prevention/minimization of waste, the reduction of derivatives/pollution, and the use of non-toxic (safer) solvents. This method not only uses biomass sources as reducing agents for metal salts. The biomolecules also cover the synthesized NPs or act as in situ capping and reducing agents. Further, their involvement in the formation process reduces toxicity, prevents nanoparticle agglomeration, and improves the antimicrobial activity of the nanomaterial, leading to a possible synergistic effect. This study aims to provide a comprehensive review of the green synthesis of metal and metal oxide nanoparticles, from the synthesis routes, selected solvents, and parameters to their latest application in the biomedical field.

In recent years, biomaterials development and characterization for new applications in regenerative medicine or controlled release represent one of the biggest challenges. Tissue engineering is one of the most intensively studied domain where hydrogels are considered optimum applications in the biomedical field. The delicate nature of hydrogels and their low mechanical strength limit their exploitation in tissue engineering. Hence, developing new, stronger, and more stable hydrogels with increased biocompatibility, is essential. However, both natural and synthetic polymers possess many limitations. Hydrogels based on natural polymers offer particularly high biocompatibility and biodegradability, low immunogenicity, excellent cytocompatibility, variable, and controllable solubility. At the same time, they have poor mechanical properties, high production costs, and low reproducibility. Synthetic polymers come to their aid through superior mechanical strength, high reproducibility, reduced costs, and the ability to regulate their composition to improve processes such as hydrolysis or biodegradation over variable periods. The development of hydrogels based on mixtures of synthetic and natural polymers can lead to the optimization of their properties to obtain ideal scaffolds. Also, incorporating different nanoparticles can improve the hydrogel’s stability and obtain several biological effects. In this regard, essential oils and drug molecules facilitate the desired biological effect or even produce a synergistic effect. This study’s main purpose is to establish the main properties needed to develop sustainable polymeric scaffolds. These scaffolds can be applied in tissue engineering to improve the tissue regeneration process without producing other side effects to the environment.

Magnesium oxide nanoparticles, or MgO NPs, have garnered a lot of attention because of their exceptional stability, biocompatibility, and antibacterial properties. However, many of the green production methods used today have limited mechanistic knowledge and low reproducibility. In order to get over these challenges, we created a standardized and environmentally friendly process for producing MgO NPs using orange peel extract, a naturally occurring biowaste source rich in phytochemicals that acts as a stabilizing and reducing agent. Active precursor alteration during synthesis was clearly shown by X-ray diffraction (XRD) and thermal analysis (TGA-FTIR), while imaging techniques showed extremely crystalline cubic-phase MgO nanoparticles that were about 9 nm in size. The NPs displayed an irregular shape between 10 and 40 nm and a positive surface charge of +11.74 mV. Terpenoids, polymethoxyflavones, fatty acids, and sugars all work in collaboration with direct nucleation, regulate particle growth, and stabilize the nanoparticles, according to GC-MS analysis. The MgO NPs showed remarkable cytocompatibility in biology, preserving >80% viability in fibroblast and osteoblast cell lines while causing distinct metabolic regulation in osteoblasts without changing the shape of the cells. Consistent moderate activity against a variety of pathogens was confirmed by antimicrobial and antibiofilm assays, with special effectiveness against Gram-positive bacteria and Pseudomonas aeruginosa biofilms. This study shows that these MgO NPs have good biocompatibility and antimicrobial qualities, indicating the need for more research for possible biomedical applications. It also clarifies the molecular role of phytochemicals in nanoparticle formation and provides a repeatable green synthesis pathway.

The production of green nanomaterials has drawn considerable interest lately in the fields of tissue engineering and biomedicine. Thus, the environmentally friendly synthesis of ZnO and CuO nanoparticles (NPs) utilizing orange peel extract as a natural capping and reducing agent is the main focus of this study. Our comprehensive approach allows for a direct and systematic comparison of physicochemical attributes, biocompatibility, and antimicrobial activity under identical experimental circumstances, in contrast to other research that looked at individual nanoparticles under different conditions. The produced nanoparticles were characterized by techniques such as FTIR, XRD, SEM, TGA, and zeta potential assessment. MG-63 osteoblast-like cells, primary human dermal fibroblast BJ cells, and murine fibroblast L929 cells were used to evaluate biocompatibility using the MTT assay. The results showed dose-dependent cytotoxicity, especially above 25 µg/mL. Furthermore, both qualitative (growth inhibition zone diameter) and quantitative (minimum inhibitory concentration, MIC) techniques were used to assess the antimicrobial efficacy against Candida albicans and Gram-positive and Gram-negative bacteria. According to the obtained results, ZnO NPs showed broad-spectrum efficacy, whereas CuO NPs showed excellent antibacterial activity against Gram-positive bacteria (e.g., S. aureus, MIC = 0.313 μg/μL). The study highlights the potential of green-synthesized nanoparticles for utilization in biomedical applications, and it stresses the need for additional mechanistic research, including ROS measurement, to completely understand how they work.