Borrowing From Nature: Biopolymers and Biocomposites as Smart Wound Care Materials

Wound repair is a complex and tightly regulated physiological process, involving the activation of various cell types throughout each subsequent step (homeostasis, inflammation, proliferation, and tissue remodeling). Any impairment within the correct sequence of the healing events could lead to chronic wounds, with potential effects on the patience quality of life, and consequent fallouts on the wound care management. Nature itself can be of inspiration for the development of fully biodegradable materials, presenting enhanced bioactive potentialities, and sustainability. Naturally-derived biopolymers are nowadays considered smart materials. They provide a versatile and tunable platform to design the appropriate extracellular matrix able to support tissue regeneration, while contrasting the onset of adverse events. In the past decades, fabrication of bioactive materials based on natural polymers, either of protein derivation or polysaccharide-based, has been extensively exploited to tackle wound-healing related problematics. However, in today's World the exclusive use of such materials is becoming an urgent challenge, to meet the demand of environmentally sustainable technologies to support our future needs, including applications in the fields of healthcare and wound management. In the following, we will briefly introduce the main physico-chemical and biological properties of some protein-based biopolymers and some naturally-derived polysaccharides. Moreover, we will present some of the recent technological processing and green fabrication approaches of novel composite materials based on these biopolymers, with particular attention on their applications in the skin tissue repair field. Lastly, we will highlight promising future perspectives for the development of a new generation of environmentally-friendly, naturally-derived, smart wound dressings

Keratin–cinnamon essential oil biocomposite fibrous patches for skin burn care

Keratin based electrospun fibres containing cinnamon essential oil are highly antioxidant and antibacterial, and promote reduced tissue inflammation after skin burns

Mycelium-based biomaterials as smart devices for skin wound healing

Introduction: Recently, mycelia of Ganoderma lucidum and Pleurotus ostreatus, edible fungi, have been characterized in vitro as self-growing biomaterials for tissue engineering since they are constituted of interconnected fibrous networks resembling the dermal collagen structure.Aim: This work aims to investigate the biopharmaceutical properties of G. lucidum and P. ostreatus mycelia to prove their safety and effectiveness in tissue engineering as dermal substitutes.Methods: The mycelial materials were characterized using a multidisciplinary approach, including physicochemical properties (morphology, thermal behavior, surface charge, and isoelectric point). Moreover, preclinical properties such as gene expression and in vitro wound healing assay have been evaluated using fibroblasts. Finally, these naturally-grown substrates were applied in vivo using a murine burn/excisional wound model.Conclusions: Both G. lucidum and P. ostreatus mycelia are biocompatible and able to safely and effectively enhance tissue repair in vivo in our preclinical model

Light-Based Anti-Biofilm and Antibacterial Strategies

Biofilm formation and antimicrobial resistance pose significant challenges not only in clinical settings (i.e., implant-associated infections, endocarditis, and urinary tract infections) but also in industrial settings and in the environment, where the spreading of antibiotic-resistant bacteria is on the rise. Indeed, developing effective strategies to prevent biofilm formation and treat infections will be one of the major global challenges in the next few years. As traditional pharmacological treatments are becoming inadequate to curb this problem, a constant commitment to the exploration of novel therapeutic strategies is necessary. Light-triggered therapies have emerged as promising alternatives to traditional approaches due to their non-invasive nature, precise spatial and temporal control, and potential multifunctional properties. Here, we provide a comprehensive overview of the different biofilm formation stages and the molecular mechanism of biofilm disruption, with a major focus on the quorum sensing machinery. Moreover, we highlight the principal guidelines for the development of light-responsive materials and photosensitive compounds. The synergistic effects of combining light-triggered therapies with conventional treatments are also discussed. Through elegant molecular and material design solutions, remarkable results have been achieved in the fight against biofilm formation and antibacterial resistance. However, further research and development in this field are essential to optimize therapeutic strategies and translate them into clinical and industrial applications, ultimately addressing the global challenges posed by biofilm and antimicrobial resistance

Peptide-Functionalized Nanoparticles for the Targeted Delivery of Cytotoxins to MMP-14-Expressing Cancer Cells

As 90% of cancer-patient deaths are due to metastasis, novel therapeutics that selectively target and kill metastatic cells are desperately needed. Matrix metalloproteinase-14 (MMP-14), which plays a critical role in digesting the basement membrane and in inducing cancer cell migration, has been found to be expressed at the cell surface of circulating and metastasized tumor cells in various human cancers. We have recently shown that the IVS4 peptide, which mimics the minimal binding motif of the hemopexin-like (PEX) domain of MMP-14, interrupts MMP-14 dimerization and decreases MMP-14-mediated cell invasion. In this study, cancer-homing nanocarriers were assembled by linking IVS4 to polysaccharide-based nanoparticles (NPs), followed by the encapsulation of a pharmaceutical agent. IVS4-NPs efficiently prevented MMP-14-mediated cell migration and conferred an uptake advantage compared to the control peptide in an MMP-14-dependent manner. While the IVS4-NPs alone were not cytotoxic, drug-encapsulated NPs were shown to effectively target MMP-14-expressing cancer cells. This novel nanotherapeutic is capable of inhibiting MMP-14-mediated functions and efficiently killing MMP-14-expressing cancer cells, without affecting the viability of non-cancer cells

Peptide-Functionalized Nanoparticles for the Targeted Delivery of Cytotoxins to MMP-14-Expressing Cancer Cells

As 90% of cancer-patient deaths are due to metastasis, novel therapeutics that selectively target and kill metastatic cells are desperately needed. Matrix metalloproteinase-14 (MMP-14), which plays a critical role in digesting the basement membrane and in inducing cancer cell migration, has been found to be expressed at the cell surface of circulating and metastasized tumor cells in various human cancers. We have recently shown that the IVS4 peptide, which mimics the minimal binding motif of the hemopexin-like (PEX) domain of MMP-14, interrupts MMP-14 dimerization and decreases MMP-14-mediated cell invasion. In this study, cancer-homing nanocarriers were assembled by linking IVS4 to polysaccharide-based nanoparticles (NPs), followed by the encapsulation of a pharmaceutical agent. IVS4-NPs efficiently prevented MMP-14-mediated cell migration and conferred an uptake advantage compared to the control peptide in an MMP-14-dependent manner. While the IVS4-NPs alone were not cytotoxic, drug-encapsulated NPs were shown to effectively target MMP-14-expressing cancer cells. This novel nanotherapeutic is capable of inhibiting MMP-14-mediated functions and efficiently killing MMP-14-expressing cancer cells, without affecting the viability of non-cancer cells

3D-Printed, Pocket-Size Diffusion Cells for Skin Permeation Investigation

Here we present a novel, compact 3D-printed diffusion cell as an in vitro tool for skin permeation investigation. As proof-of-concept, a diffusion cell for studying the permeation of a model molecule (FITC-dextran, 4 kDa) through explanted mice skin is fabricated and characterized. Good viability of the tissue up to 24 h incubation in the cell is demonstrated via MTT assays. The real-time diffusion of the molecule by means of fluorescence microscopy allowed the determination of its diffusivity through the skin (~2·10−10 m2/s). Our results open the door for the real-time, high-throughput and cost-effective investigation of skin in any labs

Magnetoelectric Nanoparticles: Evaluating Stimulation Feasibility of the Possible Next Generation Approach for Deep Brain Stimulation

The purpose of this study is to quantify the distributions of the electric field induced by CoFe2O4 core - BaTiO3 shell magneto-electric nanoparticles (MENPs) when localized in deep brain structures. These fields can be used for deep brain stimulation (DBS), and their effect is compared to the fields induced by conventional DBS electrodes in monopolar and bipolar configuration. A computational approach based on finite element method was applied, along with the use of a highly detailed anatomical model of the brain structures. Different MENPs configurations were investigated and compared to conventional DBS electrode configuration. The activation of nervous fibers was quantified by calculating the Activation Function (AF) defined as the second derivative of the electric potential along the fiber. Electric field amplitudes obtained by MENPs were much lower than the ones obtained by the monopolar and bipolar electrode configurations. The AF values showed that MENPs were able to obtain very localized activation patterns along the fibers. In addition to the minimal invasiveness and proven biocompatibility of the MENPs, the results show that the proposed approach represents an important step towards a selective and minimally invasive strategy for DBS. All these findings are essential in identifying the unique characteristics that MENPs could provide for nervous system stimulation, and how the use of MENPs could improve the development of a new generation of DBS techniques

Hydroxycinnamic Acids and Derivatives Formulations for Skin Damages and Disorders: A Review

Alterations of skin homeostasis are widely diffused in our everyday life both due to accidental injuries, such as wounds and burns, and physiological conditions, such as late-stage diabetes, dermatitis, or psoriasis. These events are locally characterized by an intense inflammatory response, a high generation of harmful free radicals, or an impairment in the immune response regulation, which can profoundly change the skin tissue’ repair process, vulnerability, and functionality. Moreover, diabetes diffusion, antibiotic resistance, and abuse of aggressive soaps and disinfectants following the COVID-19 emergency could be causes for the future spreading of skin disorders. In the last years, hydroxycinnamic acids and derivatives have been investigated and applied in several research fields for their anti-oxidant, anti-inflammatory, and anti-bacterial activities. First, in this study, we give an overview of these natural molecules’ current source and applications. Afterwards, we review their potential role as valid alternatives to the current therapies, supporting the management and rebalancing of skin disorders and diseases at different levels. Also, we will introduce the recent advances in the design of biomaterials loaded with these phenolic compounds, specifically suitable for skin disorders treatments. Lastly, we will suggest future perspectives for introducing hydroxycinnamic acids and derivatives in treating skin disorders

Advanced mycelium materials as potential self-growing biomedical scaffolds

Abstract Mycelia, the vegetative part of fungi, are emerging as the avant-garde generation of natural, sustainable, and biodegradable materials for a wide range of applications. They are constituted of a self-growing and interconnected fibrous network of elongated cells, and their chemical and physical properties can be adjusted depending on the conditions of growth and the substrate they are fed upon. So far, only extracts and derivatives from mycelia have been evaluated and tested for biomedical applications. In this study, the entire fibrous structures of mycelia of the edible fungi Pleurotus ostreatus and Ganoderma lucidum are presented as self-growing bio-composites that mimic the extracellular matrix of human body tissues, ideal as tissue engineering bio-scaffolds. To this purpose, the two mycelial strains are inactivated by autoclaving after growth, and their morphology, cell wall chemical composition, and hydrodynamical and mechanical features are studied. Finally, their biocompatibility and direct interaction with primary human dermal fibroblasts are investigated. The findings demonstrate the potentiality of mycelia as all-natural and low-cost bio-scaffolds, alternative to the tissue engineering systems currently in place