Oxidative stress modulating nanomaterials and their biochemical roles in nanomedicine.

Many pathological conditions are predominantly associated with oxidative stress, arising from reactive oxygen species (ROS); therefore, the modulation of redox activities has been a key strategy to restore normal tissue functions. Current approaches involve establishing a favorable cellular redox environment through the administration of therapeutic drugs and redox-active nanomaterials (RANs). In particular, RANs not only provide a stable and reliable means of therapeutic delivery but also possess the capacity to finely tune various interconnected components, including radicals, enzymes, proteins, transcription factors, and metabolites. Here, we discuss the roles that engineered RANs play in a spectrum of pathological conditions, such as cancer, neurodegenerative diseases, infections, and inflammation. We visualize the dual functions of RANs as both generator and scavenger of ROS, emphasizing their profound impact on diverse cellular functions. The focus of this review is solely on inorganic redox-active nanomaterials (inorganic RANs). Additionally, we deliberate on the challenges associated with current RANs-based approaches and propose potential research directions for their future clinical translation.

The biological and therapeutic assessment of a P(3HB-co-4HB)-bioactive glass-graphene composite biomaterial for tissue regeneration.

An ideal wound dressing should create a healing environment that relieves pain, protects against infections, maintains moisture, removes debris, and speeds up wound closure and repair. However, conventional options like gauze often fall short in fulfilling these requirements, especially for chronic or nonhealing wounds. Hence there is a critical need for inventive formulations that offer efficient, cost-effective, and eco-friendly alternatives. This study focuses on assessing the innovative formulation based on a microbial-derived copolymer known as poly(3-hydroxybutyrate-co-4-hydroxybutyrate), P(3HB-co-4HB) bioactive glass and graphene particles, and exploring their biological response in vitro and in vivo-to find the best combination that promotes cell adhesion and enhances wound healing. The formulation optimized at concentration of bioactive glass (1 w/w%) and graphene (0.01 w/w%) showed accelerated degradation and enhanced blood vessel formation. Meanwhile biocompatibility was evaluated using murine osteoblasts, human dermal fibroblasts, and standard cell culture assays, demonstrating no adverse effects after 7 days of culture and well-regulated inflammatory kinetics. Whole thickness skin defect using mice indicated the feasibility of the biocomposites for a faster wound closure and reduced inflammation. Overall, this biocomposite appears promising as an ideal wound dressing material and positively influencing wound healing rates.

Lithium-loaded GelMA-Phosphate glass fibre constructs: Implications for astrocyte response.

Combinations of different biomaterials with their own advantages as well as functionalization with other components have long been implemented in tissue engineering to improve the performance of the overall material. Biomaterials, particularly hydrogel platforms, have shown great potential for delivering compounds such as drugs, growth factors, and neurotrophic factors, as well as cells, in neural tissue engineering applications. In central the nervous system, astrocyte reactivity and glial scar formation are significant and complex challenges to tackle for neural and functional recovery. GelMA hydrogel-based tissue constructs have been developed in this study and combined with two different formulations of phosphate glass fibers (PGFs) (with Fe3+ or Ti2+ oxide) to impose physical and mechanical cues for modulating astrocyte cell behavior. This study was also aimed at investigating the effects of lithium-loaded GelMA-PGFs hydrogels in alleviating astrocyte reactivity and glial scar formation offering novel perspectives for neural tissue engineering applications. The rationale behind introducing lithium is driven by its long-proven therapeutic benefits in mental disorders, and neuroprotective and pronounced anti-inflammatory properties. The optimal concentrations of lithium and LPS were determined in vitro on primary rat astrocytes. Furthermore, qPCR was conducted for gene expression analysis of GFAP and IL-6 markers on primary astrocytes cultured 3D into GelMA and GelMA-PGFs hydrogels with and without lithium and in vitro stimulated with LPS for astrocyte reactivity. The results suggest that the combination of bioactive phosphate-based glass fibers and lithium loading into GelMA structures may impact GFAP expression and early IL-6 expression. Furthermore, GelMA-PGFs (Fe) constructs have shown improved performance in modulating glial scarring over GFAP regulation.

The Development and Characterisation of a P(3HB-co-4HB)-Bioactive Glass-Graphene Hydrogel as a Potential Formulation for Biomedical and Therapeutical Translation.

The clinical management of wounds is known to be a significant challenge: not only does the dressing need to ensure and provide the appropriate barrier and healing characteristics, but consideration of patient compliance concerning comfort, functionality, and practicality also needs to be included. The poly(3-hydroxybutyrate-co-4-hydroxubutyrate) (P(3HB-co-4HB)) copolymer, isolated from Cupriavidus malaysiensis USM1020 (C. malaysiensis USM1020), was produced in the presence of excess carbon sources (1,4-butanediol and 1,6-hexanediol) using either a shake flask cultivation process or a bioreactor fermentation system. P(3HB-co-4HB) is widely known to be biodegradable and highly biocompatible and contains a tuneable 4HB monomer molar fraction, which is known to affect the final physicochemical properties of the intracellular copolymer. In this paper, we describe not only the fabrication of the polymeric gel but also its optimised profiling using a range of physical and mechanical techniques, i.e., SEM, FTIR, DMA, DSC, and WCA. The further enhancement of the gel through additional functionalisation with sol-gel-derived bioactive glass and liquid-exfoliated graphene was also investigated. The biocompatibility and biological characterisation of the substrates was assessed using murine osteoblasts (MC3T3), human primary dermal fibroblasts (HDFs), human fibroblast (BJ) cells, and standard cell culture assays (i.e., metabolic activity, LDH release, and live/dead staining). In short, P(3HB-co-4HB) was successfully isolated from the bacteria, with the defined physico-chemical profiles dependent on the culture substrate and culturing platform used. The additional enhancement of the copolymer with bioactive glass and/or graphene was also demonstrated by varying the combination loading of the materials, i.e., graphene resulted in an increase in tensile strength (~11 MPa) and the wettability increased following the incorporation of bioactive glass and 0.01 wt% graphene (WCA ~46.3°). No detrimental effects in terms of biocompatibility were noticed during the 7 days of culture in the primary and established cell lines. This study demonstrates the importance of optimising each of the individual components within the biocomposite and their relationship concerning the fine-tuning of the material's properties, thus targeting and impacting the endpoint application.

X-Ray Visible Protein Scaffolds by Bulk Iodination.

Protein-based biomaterial use is expanding within medicine, together with the demand to visualize their placement and behavior in vivo. However, current medical imaging techniques struggle to differentiate between protein-based implants and surrounding tissue. Here a fast, simple, and translational solution for tracking transplanted protein-based scaffolds is presented using X-ray CT-facilitating long-term, non-invasive, and high-resolution imaging. X-ray visible scaffolds are engineered by selectively iodinating tyrosine residues under mild conditions using readily available reagents. To illustrate translatability, a clinically approved hernia repair mesh (based on decellularized porcine dermis) is labeled, preserving morphological and mechanical properties. In a mouse model of mesh implantation, implants retain marked X-ray contrast up to 3 months, together with an unchanged degradation rate and inflammatory response. The technique's compatibility is demonstrated with a range of therapeutically relevant protein formats including bovine, porcine, and jellyfish collagen, as well as silk sutures, enabling a wide range of surgical and regenerative medicine uses. This solution tackles the challenge of visualizing implanted protein-based biomaterials, which conventional imaging methods fail to differentiate from endogenous tissue. This will address previously unanswered questions regarding the accuracy of implantation, degradation rate, migration, and structural integrity, thereby accelerating optimization and safe translation of therapeutic biomaterials.