Investigation on Electrospun and Solvent-Casted PCL-PLGA Blends Scaffolds Embedded with Induced Pluripotent Stem Cells for Tissue Engineering.

The design, production, and characterisation of tissue-engineered scaffolds made of polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL) and their blends obtained through electrospinning (ES) or solvent casting/particulate leaching (SC) manufacturing techniques are presented here. The polymer blend composition was chosen to always obtain a prevalence of one of the two polymers, in order to investigate the contribution of the less concentrated polymer on the scaffolds' properties. Physical-chemical characterization of ES scaffolds demonstrated that tailoring of fibre diameter and Young modulus (YM) was possible by controlling PCL concentration in PLGA-based blends, increasing the fibre diameter from 0.6 to 1.0 µm and reducing the YM from about 22 to 9 MPa. SC scaffolds showed a "bubble-like" topography, caused by the porogen spherical particles, which is responsible for decreasing the contact angles from about 110° in ES scaffolds to about 74° in SC specimens. Nevertheless, due to phase separation within the blend, solvent-casted samples displayed less reproducible properties. Furthermore, ES samples were characterised by 10-fold higher water uptake than SC scaffolds. The scaffolds suitability as iPSCs culturing support was evaluated using XTT assay, and pluripotency and integrin gene expression were investigated using RT-PCR and RT-qPCR. Thanks to their higher wettability and appropriate YM, SC scaffolds seemed to be superior in ensuring high cell viability over 5 days, whereas the ability to maintain iPSCs pluripotency status was found to be similar for ES and SC scaffolds.

Effects of Comano Spring Water-derived Bacterial Lysates on Skin Regeneration: An Ex-vivo Study.

BACKGROUND/AIM: A native non-pathogenic bacterial microflora was identified in Comano (TN, Italy) spring water. The aim of this study was to investigate the regenerative effects of some of the bacterial lysates extracted from this water in a human ex-vivo skin experimental wound model. MATERIALS AND METHODS: Bacterial lysates were extracted from four new isolates: lysate 1 (L1) - closest relative Rudaea cellulosilytica, phylum Proteobacteria; lysate 2 (L2) - closest relative Mesorhizobium erdmanii, phylum Proteobacteria; lysate 3 (L3) - closest relative Herbiconiux ginseng, phylum Actinobacteria; lysate 4 (L4) - closest relative Fictibacillus phosphorivorans, phylum Firmicutes. Their regenerative effects were investigated in a human ex-vivo skin experimental wound healing model at 3 (T1), 5 (T2), and 10 days (T3). RESULTS: The samples cultured with the L2 lysate displayed both an earlier and complete restoration of all the skin layers and their features were the closest to the normal skin. The regenerated epidermis demonstrated a complete maturation as the normal epidermis. The papillary dermis appeared mature, and the reticular dermis displayed both collagen and elastic fibres regularly parallel to the skin surface. An anti-inflammatory effect was displayed by the L1 lysate, but this action did not constitute a regenerative effect, suggesting that pathways for inflammation and regeneration might be different. CONCLUSION: The therapeutic power of spring waters is not exclusively related to their mineral composition, but it may also be attributable to their native non-pathogenic bacterial microflora.

Electrospun Fibers Loaded with Pirfenidone: An Innovative Approach for Scar Modulation in Complex Wounds.

Hypertrophic scars (HTSs) are pathological structures resulting from chronic inflammation during the wound healing process, particularly in complex injuries like burns. The aim of this work is to propose Biofiber PF (biodegradable fiber loaded with Pirfenidone 1.5 w/w), an electrospun advanced dressing, as a solution for HTSs treatment in complex wounds. Biofiber has a 3-day antifibrotic action to modulate the fibrotic process and enhance physiological healing. Its electrospun structure consists of regular well-interconnected Poly-L-lactide-co-poly-ε-caprolactone (PLA-PCL) fibers (size 2.83 ± 0.46 µm) loaded with Pirfenidone (PF, 1.5% w/w), an antifibrotic agent. The textured matrix promotes the exudate balance through mild hydrophobic wettability behavior (109.3 ± 2.3°), and an appropriate equilibrium between the absorbency % (610.2 ± 171.54%) and the moisture vapor transmission rate (0.027 ± 0.036 g/min). Through its finer mechanical properties, Biofiber PF is conformable to the wound area, promoting movement and tissue oxygenation. These features also enhance the excellent elongation (>500%) and tenacity, both in dry and wet conditions. The ancillary antifibrotic action of PF on hypertrophic scar fibroblast (HSF) for 3 days downregulates the cell proliferation over time and modulates the gene expression of transforming growth factor ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) at 48-72 h. After 6 days of treatment, a decrement of α-SMA protein levels was detected, proving the potential of biofiber as a valid therapeutic treatment for HTSs in an established wound healing process.

Graphene Nanoplatelets-Based Textured Polymeric Fibrous Fabrics for the Next-Generation Devices.

Graphene is a 2D crystal composed of carbon atoms in a hexagonal arrangement. From their isolation, graphene nanoplatelets (nCD) have revolutionized material science due to their unique properties, and, nowadays, there are countless applications, including drug delivery, biosensors, energy storage, and tissue engineering. Within this work, nCD were combined with PLA, a widely used and clinically relevant thermoplastic polymer, to produce advanced composite texturized electrospun fabric for the next-generation devices. The electrospinning manufacturing process was set-up by virtue of a proper characterization of the composite raw material and its solution. From the morphological point of view, the nCD addition permitted the reduction of the fiber diameter while the texture allowed more aligned fibers. After that, mechanical features of fabrics were tested at RT and upon heating (40 °C, 69 °C), showing the reinforcement action of nCD mainly in the texturized mats at 40 °C. Finally, mats' degradation in simulated physiological fluid was minimal up to 30 d, even if composite mats revealed excellent fluid-handling capability. Moreover, no toxic impurities and degradation products were pointed out during the incubation. This work gains insight on the effects of the combination of composite carbon-based material and texturized fibers to reach highly performing fabrics.

Tobramycin Nanoantibiotics and Their Advantages: A Minireview.

Nowadays, antimicrobial resistance (AMR) represents a challenge for antibiotic therapy, mostly involving Gram-negative bacteria. Among the strategies activated to overcome AMR, the repurposing of already available antimicrobial molecules by encapsulating them in drug delivery systems, such as nanoparticles (NPs) and also engineered NPs, seems to be promising. Tobramycin is a powerful and effective aminoglycoside, approved for complicated infections and reinfections and indicated mainly against Gram-negative bacteria, such as Pseudomonas aeruginosa, Escherichia coli, Proteus, Klebsiella, Enterobacter, Serratia, Providencia, and Citrobacter species. However, the drug presents several side effects, mostly due to dose frequency, and for this reason, it is a good candidate for nanomedicine formulation. This review paper is focused on what has been conducted in the last 20 years for the development of Tobramycin nanosized delivery systems (nanoantibiotics), with critical discussion and comparison. Tobramycin was selected as the antimicrobial drug because it is a wide-spectrum antibiotic that is effective against both Gram-positive and Gram-negative aerobic bacteria, and it is characterized by a fast bactericidal effect, even against multidrug-resistant microorganisms (MDR).

Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration.

Skin wound healing shows an extraordinary cellular function mechanism, unique in nature and involving the interaction of several cells, growth factors and cytokines. Physiological wound healing restores tissue integrity, but in many cases the process is limited to wound repair. Ongoing studies aim to obtain more effective wound therapies with the intention of reducing inpatient costs, providing long-term relief and effective scar healing. The main goal of this comprehensive review is to focus on the progress in wound medication and how it has evolved over the years. The main complications related to the healing process and the clinical management of chronic wounds are described in the review. Moreover, advanced treatment strategies for skin regeneration and experimental techniques for cellular engineering and skin tissue engineering are addressed. Emerging skin regeneration techniques involving scaffolds activated with growth factors, bioactive molecules and genetically modified cells are exploited to overcome wound healing technology limitations and to implement personalized therapy design.