Correction to "Design of Cinnamaldehyde- and Gentamicin-Loaded Double-Layer Corneal Nanofiber Patches with Antibiofilm and Antimicrobial Effects".

[This corrects the article DOI: 10.1021/acsomega.3c00914.].

Whey protein-loaded 3D-printed poly (lactic) acid scaffolds for wound dressing applications.

Chronic skin wounds pose a global clinical challenge, necessitating effective treatment strategies. This study explores the potential of 3D printed Poly Lactic Acid (PLA) scaffolds, enhanced with Whey Protein Concentrate (WPC) at varying concentrations (25, 35, and 50% wt), for wound healing applications. PLA's biocompatibility, biodegradability, and thermal stability make it an ideal material for medical applications. The addition of WPC aims to mimic the skin's extracellular matrix and enhance the bioactivity of the PLA scaffolds. Fourier Transform Infrared Spectroscopy results confirmed the successful loading of WPC into the 3D printed PLA-based scaffolds. Scanning Electron Microscopy (SEM) images revealed no significant differences in pore size between PLA/WPC scaffolds and pure PLA scaffolds. Mechanical strength tests showed similar tensile strength between pure PLA and PLA with 50% WPC scaffolds. However, scaffolds with lower WPC concentrations displayed reduced tensile strength. Notably, all PLA/WPC scaffolds exhibited increased strain at break compared to pure PLA. Swelling capacity was highest in PLA with 25% WPC, approximately 130% higher than pure PLA. Scaffolds with higher WPC concentrations also showed increased swelling and degradation rates. Drug release was found to be prolonged with increasing WPC concentration. After seven days of incubation, cell viability significantly increased in PLA with 50% WPC scaffolds compared to pure PLA scaffolds. This innovative approach could pave the way for personalized wound care strategies, offering tailored treatments and targeted drug delivery. However, further studies are needed to optimize the properties of these scaffolds and validate their effectiveness in clinical settings.

Combination techniques towards novel drug delivery systems manufacturing: 3D PCL scaffolds enriched with tetracycline-loaded PVP nanoparticles.

Drug delivery systems based on synthetic and natural polymers offer a new approach with a capacity to control the release of bio-active agents within time. In this work, we present different designs of Polycaprolactone (PCL) 3D scaffolds containing Polyvinylpyrrolidone (PVP) nanoparticles that can store a hydrophilic drug. The drug delivery system, combined of PCL and PVP polymers fabricated by additive manufacturing, aims for a solution for longer and more stabled drug delivery carrier. The drug, planned to be released to the targeted area, is sprayed with the electrospray method inside PVP nanoparticles on the different layers of the fabricated PCL scaffolds 3D printing. This makes obtaining a layered and porous scaffold and drug-loaded nanoparticles within this structure easier. Obtained PCL scaffolds containing Tetracyclines (Tet) loaded PVP nanoparticles showed that drug encapsulation into the interlayer extended the release time and exhibited a controlled release profile for days. Moreover, produced scaffolds have good biocompatibility and no harmful effects. The combination of 3D scaffolds and drug-loaded nanoparticles aims to develop new functional scaffolds by targeting more efficient and longer-lasting drug delivery.

Design of Cinnamaldehyde- and Gentamicin-Loaded Double-Layer Corneal Nanofiber Patches with Antibiofilm and Antimicrobial Effects.

In this study, two-layer poly(vinyl alcohol)/gelatin (PVA/GEL) nanofiber patches containing cinnamaldehyde (CA) in the first layer and gentamicin (GEN) in the second layer were produced by the electrospinning method. The morphology, chemical structures, and thermal temperatures of the produced pure (PVA/GEL), CA-loaded (PVA/GEL/CA), GEN-loaded (PVA/GEL/GEN), and combined drug-loaded (PVA/GEL/CA/GEN) nanofiber patches were determined by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and differential scanning calorimetry, respectively. Their mechanical properties, swelling and degradation behavior, and drug release kinetics were investigated. SEM images showed that both drug-free and drug-loaded nanofiber patches possess smooth and monodisperse structures, and nanofiber size increase occurred as the amount of drug increased. The tensile test results showed that the mechanical strength decreased as the drug was loaded. According to the drug release results, CA release ended at the 96th hour, while GEN release continued until the 264th hour. The antibacterial and antibiofilm activities of PVA/GEL, PVA/GEL/CA, PVA/GEL/GEN, and PVA/GEL/CA/GEN nanofiber patches against Pseudomonas aeruginosa and Staphylococcus aureus were evaluated. Results showed that PVA/GEL/GEN and PVA/GEL/CA/GEN nanofiber patches have excellent antibacterial and antibiofilm activities. Moreover, all materials were biocompatible, with no cytotoxic effects in the mammalian cell model for 8 days. PVA/GEL/GEN nanofiber patches were the most promising material for a high cell survival ratio, which was confirmed by SEM images. This research aims to develop an alternative method to stop and treat the rapid progression of bacterial keratitis.

Investigation of the antitumor effect on breast cancer cells of the electrospun amygdalin-loaded poly(l-lactic acid)/poly(ethylene glycol) nanofibers.

In this study, PLA/PEG nanofibers (NFs) loaded with amygdalin (AMG) and bitter almond kernels extract were produced by electrospinning to prevent local breast cancer recurrence, and the effect of produced NFs on the MCF-7 cell line was investigated in vitro. The electrospun NFs were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis (DSC) and tensile strength and physical analyzes were performed. Loading of AMG to nanofibers increased fiber diameters from 827.93 ± 174.507 nm to 1855.32 ± 291.057 µm. When drug release results were analyzed, the NFs showed a controlled release profile extending up to 10 h. The encapsulation efficiency of AMG-loaded NFs was calculated at 100 ± 0,01 %, 94 ± 0,02 %, and 88 ± 0,02 %. When in vitro cytotoxicity results were analyzed, showed that all NFs are effective in inducing cytotoxicity against MCF-7 breast cancer cells. Importantly, 20 mg AMG-loaded NFs displayed effectively higher cytotoxic effects against breast cancer cells relative to the other NFs. Considering all the results, AMG-loaded NFs can give sustained release of drugs at the local sites. Therefore, AMG-loaded nanofibers can reduce the risk of local recurrence of cancer after surgery and can be directly implanted into solid tumor cells for treatment.

Production of 3D Printed Bi-Layer and Tri-Layer Sandwich Scaffolds with Polycaprolactone and Poly (vinyl alcohol)-Metformin towards Diabetic Wound Healing.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by impaired insulin secretion, sensitivity, and hyperglycemia. Diabetic wounds are one of the significant complications of T2DM owing to its difficulty in normal healing, resulting in chronic wounds. In the present work, PCL/PVA, PCL/PVA/PCL, and metformin-loaded, PCL/PVA-Met and PCL/PVA-Met/PCL hybrid scaffolds with different designs were fabricated using 3D printing. The porosity and morphological analysis of 3D-printed scaffolds were performed using scanning electron microscopy (SEM). The scaffolds' average pore sizes were between 63.6 ± 4.0 and 112.9 ± 3.0 µm. Molecular and chemical interactions between polymers and the drug were investigated with Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Mechanical, thermal, and degradation analysis of the scaffolds were undertaken to investigate the physico-chemical characteristics of the scaffolds. Owing to the structure, PCL/PVA/PCL sandwich scaffolds had lower degradation rates than the bi-layer scaffolds. The drug release of the metformin-loaded scaffolds was evaluated with UV spectrometry, and the biocompatibility of the scaffolds on fibroblast cells was determined by cell culture analysis. The drug release in the PCL/PVA-Met scaffold was sustained till six days, whereas in the PCL/PVA-Met/PCL, it continued for 31 days. In the study of drug release kinetics, PCL/PVA-Met and PCL/PVA-Met/PCL scaffolds showed the highest correlation coefficients (R2) values for the first-order release model at 0.8735 and 0.889, respectively. Since the layered structures in the literature are mainly obtained with the electrospun fiber structures, these biocompatible sandwich scaffolds, produced for the first time with 3D-printing technology, may offer an alternative to existing drug delivery systems and may be a promising candidate for enhancing diabetic wound healing.

Metformin-Loaded Polymer-Based Microbubbles/Nanoparticles Generated for the Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is increasingly common all over the world with a high risk of progressive hyperglycemia and high microvascular and macrovascular complications. The currently used drugs in the treatment of T2DM have insufficient glucose control and can carry detrimental side effects. Several drug delivery systems have been investigated to decrease the side effects and frequency of dosage, and also to increase the effect of oral antidiabetic drugs. In recent years, the use of microbubbles in biomedical applications has greatly increased, and research into microactive carrier bubbles continues to generate more and more clinical interest. In this study, various monodisperse polymer nanoparticles at different concentrations were produced by bursting microbubbles generated using a T-junction microfluidic device. Morphological analysis by scanning electron microscopy, molecular interactions between the components by FTIR, drug release by UV spectroscopy, and physical analysis such as surface tension and viscosity measurement were carried out for the particles generated and solutions used. The microbubbles and nanoparticles had a smooth outer surface. When the microbubbles/nanoparticles were compared, it was observed that they were optimized with 0.3 wt % poly(vinyl alcohol) (PVA) solution, 40 kPa pressure, and a 110 µL/min flow rate, thus the diameters of the bubbles and particles were 100 ± 10 µm and 70 ± 5 nm, respectively. Metformin was successfully loaded into the nanoparticles in these optimized concentrations and characteristics, and no drug crystals and clusters were seen on the surface. Metformin was released in a controlled manner at pH 1.2 for 60 min and at pH 7.4 for 240 min. The process and structures generated offer great potential for the treatment of T2DM.

Resveratrol-Loaded Levan Nanoparticles Produced by Electrohydrodynamic Atomization Technique.

Considering the significant advances in nanostructured systems in various biomedical applications and the escalating need for levan-based nanoparticles as delivery systems, this study aimed to fabricate levan nanoparticles by the electrohydrodynamic atomization (EHDA) technique. The hydrolyzed derivative of levan polysaccharide from Halomonas smyrnensis halophilic bacteria, hydrolyzed Halomonas levan (hHL), was used. Nanoparticles were obtained by optimizing the EHDA parameters and then they were characterized in terms of morphology, molecular interactions, drug release and cell culture studies. The optimized hHL and resveratrol (RS)-loaded hHL nanoparticles were monodisperse and had smooth surfaces. The particle diameter size of hHL nanoparticles was 82.06 ± 15.33 nm. Additionally, release of RS from the fabricated hHL nanoparticles at different pH conditions were found to follow the first-order release model and hHL with higher RS loading showed a more gradual release. In vitro biocompatibility assay with human dermal fibroblast cell lines was performed and cell behavior on coated surfaces was observed. Nanoparticles were found to be safe for healthy cells. Consequently, the fabricated hHL-based nanoparticle system may have potential use in drug delivery systems for wound healing and tissue engineering applications and surfaces could be coated with these electrosprayed particles to improve cellular interaction.

Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study.

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug.

3D Propolis-Sodium Alginate Scaffolds: Influence on Structural Parameters, Release Mechanisms, Cell Cytotoxicity and Antibacterial Activity.

In this study, the main aim was to fabricate propolis (Ps)-containing wound dressing patches using 3D printing technology. Different combinations and structures of propolis (Ps)-incorporated sodium alginate (SA) scaffolds were developed. The morphological studies showed that the porosity of developed scaffolds was optimized when 20% (v/v) of Ps was added to the solution. The pore sizes decreased by increasing Ps concentration up to a certain level due to its adhesive properties. The mechanical, swelling-degradation (weight loss) behaviors, and Ps release kinetics were highlighted for the scaffold stability. An antimicrobial assay was employed to test and screen antimicrobial behavior of Ps against Escherichia coli and Staphylococcus aureus strains. The results show that the Ps-added scaffolds have an excellent antibacterial activity because of Ps compounds. An in vitro cytotoxicity test was also applied on the scaffold by using the extract method on the human dermal fibroblasts (HFFF2) cell line. The 3D-printed SA-Ps scaffolds are very useful structures for wound dressing applications.

A novel treatment strategy for preterm birth: Intra-vaginal progesterone-loaded fibrous patches.

Progesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for intra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth.

Development of Satureja cuneifolia-loaded sodium alginate/polyethylene glycol scaffolds produced by 3D-printing technology as a diabetic wound dressing material.

Acute wounds are a common health problem, with millions of people affected and decreased granulation tissue formation and vascularization, it is also a big challenge for wound care researchers to promote acute wound healing around the globe. This study aims to produce and characterize Satureja cuneifolia plant extract (SC)-blended with sodium alginate (SA) /polyethylene glycol (PEG) scaffolds for the potential treatment of diabetic ulcer. SA/PEG scaffolds were prepared by adding different concentrations (1, 3, and 5 wt%) of PEG to 9 wt% SA. The morphological and chemical composition of the resulting 3D printed composite scaffolds was determined using scanning electron microscopy (SEM) and Fourier transforms infrared spectroscopy (FTIR), respectively. Mechanical and thermal properties, swelling, and degradation behaviours were also investigated. The release kinetics of SC were performed. The antimicrobial analysis was evaluated against Escherichia coli and Staphylococcus aureus strains. 3D printed scaffolds have shown an excellent antibacterial effect, especially against gram-positive bacteria due to the antibacterial SC extract they contain. Furthermore, the cell viability of fibroblast (L929) cells on/within scaffolds were determined by the colourimetric MTT assay. The SA/PEG/SC scaffolds show a great promising potential candidate for diabetic wound healing and against bacterial infections.

Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study.

In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.