Wound healing is a naturally occurring process that can be aided by a wound dressing properly designed to assure an efficient healing process. An infection caused by several microorganisms could interfere with this process, delaying or even impairing wound healing. Hyaluronic acid (HA), a main constituent of the extracellular matrix (ECM) of a vertebrate’s connective tissue, represents a promising biomaterial for wound dressing thanks to its intrinsic biocompatibility, hydrophilicity and bacteriostatic properties. In this review, different and recent types of HA-based wound dressings endowed with intrinsic antimicrobial properties or co-adjuvated by antimicrobial natural or synthetic agents are highlighted.

Nanoparticle systems are functional carriers that can be used in the cancer therapy field for the delivery of a variety of hydrophobic and/or hydrophilic drugs. Recently, the advent of microfluidic platforms represents an advanced approach to the development of new nanoparticle-based drug delivery systems. Particularly, microfluidics can simplify the design of new nanoparticle-based systems with tunable physicochemical properties such as size, size distribution and morphology, ensuring high batch-to-batch reproducibility and consequently, an enhanced therapeutic effect in vitro and in vivo. In this perspective, we present accurate state-of-the-art microfluidic platforms focusing on the fabrication of polymer-based, lipid-based, lipid/polymer-based, inorganic-based and metal-based nanoparticles for biomedical applications.

Pharmacological therapies in lung diseases are nowadays useful in reducing the symptomatology of lung injury. However, they have not yet been translated to effective treatment options able to restore the lung tissue damage. Cell-therapy based on Mesenchymal Stem Cells (MSCs) is an attractive, as well as new therapeutic approach, although some limitations can be ascribed for therapeutic use, such as tumorigenicity and immune rejection. However, MSCs have the capacity to secrete multiple paracrine factors, namely secretome, capable of regulating endothelial and epithelial permeability, decrease inflammation, enhancing tissue repair, and inhibiting bacterial growth. Furthermore, Hyaluronic acid (HA) has been demonstrated to have particularly efficacy in promoting the differentiation of MSCs in Alveolar type II (ATII) cells. In this frame, the combination of HA and secretome to achieve the lung tissue regeneration has been investigated for the first time in this work. Overall results showed how the combination of HA (low and medium molecular weight HA) plus secretome could enhance MSCs differentiation in ATII cells (SPC marker expression of about 5 ng/mL) compared to the only HA or secretome solutions alone (SPC about 3 ng/mL, respectively). Likewise, cell viability and cell rate of migration were reported to be improved for HA and secretome blends, indicating an interesting potentiality of such systems for lung tissue repair. Moreover, an anti-inflammatory profile has been revealed when dealing with HA and secretome mixtures. Therefore, these promising results can allow important advance in the accomplishment of the future therapeutic approach in respiratory diseases, up to date still missing.

Mesenchymal stem cells (MCSs) secretome provide MSC-like therapeutic effects in preclinical models of lung injury, circumventing safety concerns with the use of live cells. Secretome consists of Extracellular Vesicles (EVs), including populations of nano- to micro-sized particles (exosomes and microvesicles) delimited by a phospholipidic bilayer. However, its poor stability and bioavailability severely limit its application. The role of Hyaluronic acid (HA) as potential carrier in biomedical applications has been widely demonstrated. Here, we investigated the interplay between HA and MSCs- secretome blends and their ability to exert a bioactive effect on pulmonary differentiation in a 3D microenvironment mimicking lung niche. To this aim, the physical-chemical properties of HA/Secre blends have been characterized at low, medium and high HA Molecular Weights (MWs), by means of SEM/TEM, DLS, confocal microscopy and FTIR. Collectively physical-chemical properties highlight the interplay between the HA and the EVs. In 3D matrices, HA/Secre blends showed to promote differentiation in pulmonary lineage , improved as the MW of the HA in the blends decreased. Finally, HA/Secre blends' ability to cross an artificial mucus has been demonstrated. Overall, this work provides new insights for the development of future devices for the therapy of respiratory diseases that are still unmet.

Bacterial infections are a major complication in chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS), where mucus accumulation and pH fluctuations further hinder treatment. Nanostructured systems such as carbon dots (CDs) are increasingly investigated as antimicrobial agents due to their scalability, low cost, and biocompatibility, compared to conventional antibiotics. Here, CDs were synthesized by a one-step microwave-assisted method at three reaction temperatures (130 °C, 170 °C, and 185 °C, named LT-CDs, MT-CDs, HT-CDs, respectively) to explore the effect of carbonization on their structure and function. TEM, Raman, and FTIR analyses were employed to investigate the size and distribution of carbon groups. UV–vis confirmed distinct pH-dependent spectral responses, and mucoadhesion studies revealed stronger and more stable interactions for MT-CDs. Biological assays demonstrated high biocompatibility across all samples on lung fibroblasts, while antimicrobial tests highlighted a selective effect against Staphylococcus aureus, due to ROS generation. Overall, MT-CDs represented the best compromise in terms of size, functionalization, biocompatibility, mucoadhesion, and antimicrobial activity, emerging as promising nanoplatforms for respiratory infection management in COPD and ARDS.