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

FEN-C-YLP-130319-0065 BAPKO Project. UID/CTM/50025/2019In 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.publishersversionpublishe

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

Fabrication, characterization and fibroblast proliferative activity of electrospun Achillea lycaonica-loaded nanofibrous mats

The use of natural compounds such as biocompatible and non-toxic plant extracts, without undesired side effects, in tissue engineering applications, is highly preferred compared to chemical drugs. In this study, the characterization and performance of electrospun Achillea lycaonica-loaded (0.125, 0.250 and 0.500, wt%) poly (lactic acid) (PLA) (8%, w/v) nanofibrous mats for skin tissue engineering were investigated. SEM, FTIR, DSC, and tensile strength test of the electrospun nanofibers have been investigated. Drug releasing test and cell culture study were also carried out. Achillea lycaonica-loaded nanofibrous mats in 0.250 (wt%) and 0.500 (wt%) demonstrated excellent cell compatibility and increased the viability of NIH/3T3 (mouse embryo fibroblast) cells within 72 h. According to the results, Achillea lycaonica-loaded PLA nanofibers have proper tensile strength and controlled release. The working temperature range enlarged for the composites having higher plant extract content. Consequently, Achillea lycaonica-loaded nanofibrous mats have a great potential in skin tissue engineering applications

Levodopa-Loaded 3D-Printed Poly (Lactic) Acid/Chitosan Neural Tissue Scaffold as a Promising Drug Delivery System for the Treatment of Parkinson’s Disease

Parkinson’s disease, the second most common neurodegenerative disease in the world, develops due to decreased dopamine levels in the basal ganglia. Levodopa, a dopamine precursor used in the treatment of Parkinson’s disease, can be used as a drug delivery system. This study presents an approach to the use of 3D-printed levodopa-loaded neural tissue scaffolds produced with polylactic acid (PLA) and chitosan (CS) for the treatment of Parkinson’s disease. Surface morphology and pore sizes were examined by scanning electron microscopy (SEM). Average pore sizes of 100–200 µm were found to be ideal for tissue engineering scaffolds, allowing cell penetration but not drastically altering the mechanical properties. It was observed that the swelling and weight loss behaviors of the scaffolds increased after the addition of CS to the PLA. Levodopa was released from the 3D-printed scaffolds in a controlled manner for 14 days, according to a Fickian diffusion mechanism. Mesenchymal stem cells (hAD-MSCs) derived from human adipose tissue were used in MTT analysis, fluorescence microscopy and SEM studies and confirmed adequate biocompatibility. Overall, the obtained results show that PLA/CS 3D-printed scaffolds have an alternative use for the levodopa delivery system for Parkinson’s disease in neural tissue engineering applications

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-gamma (PPAR-gamma) 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-gamma 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

A Novel Strategy as a Potential Rapid Therapy Modality in the Treatment of Corneal Ulcers: Fluconazole/Vancomycin Dual Drug‐Loaded Nanofibrous Patches

Abstract Corneal ulcer, which is brought on by a breach in the epithelial barrier, is a dangerous infection of the avascular corneal stroma. New treatment strategies are needed, suppressing the aggressive nature of the disease and including a combination of different drugs. In this study, vancomycin (VAN) and fluconazole (FLU) dual‐drug loaded dual‐layered polyvinyl alcohol and gelatin (PVA/GEL) nanofibrous patches are produced by electrospinning. Scanning electron microscopy (SEM) images show smooth surfaces are obtained for both pure and drug‐loaded nanofibrous patches. The tensile test results report that loading the FLU and VAN separately into the PVA/GEL patches decrease both the tensile strength and elongation at break and it is further reduced when combining two drug‐loaded layers in one patch. According to drug release results, the FLU and VAN‐loaded nanofibrous patches show a controlled release profile extending up to 96 h. Moreover, PVA/GEL/FLU, PVA/GEL/VAN, and PVA/GEL/FLU/VAN nanofibrous patches display significant antimicrobial activity against Candida albicans and Staphylococcus aureus. SEM, 4'‐6diamidynofenyloindol (DAPI) staining, and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay show that PVA/FLU and PVA/GEL/FLU/VAN nanofibrous patches have a superior effect on NIH3T3 cell spreading and proliferation. The novelty of this study lays in the development of a potential dual drug rapid treatment for corneal ulcers of aggressive nature

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

© 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.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.Peer reviewe