ABSTRACT
Despite the great progress in developing wound dressings, delayed wound closure still remains a global challenge. Thus, developing novel wound dressings and employing advanced strategies, including tissue engineering, are urgently desired. The carboxylated cellulose was developed through the in situ synthesis method and further reinforced by incorporating pal-KTTKS to stimulate collagen synthesis and improve wound healing. The developed composites supported cell adhesion and proliferation and showed good biocompatibility. To boost wound-healing performance, adipose-derived mesenchymal stem cells (MSC) were seeded on the pal-KTTKS-enriched composites to be implanted in a rat model of burn wound healing. Healthy male rats were randomly divided into four groups and wound-healing performance of Vaseline gauze (control), carboxylated cellulose (CBC), pal-KTTKS-enriched CBC (KTTKS-CBC), and MSCs seeded on the KTTKS-CBC composites (MSC-KTTKS-CBC) were evaluated on days 3, 7, and 14 post-implantation. In each group, the designed therapeutic dressings were renewed every 5 days to increase wound-healing performance. We found that KTTKS-CBC and MSC-KTTKS-CBC composites exhibited significantly better wound healing capability, as evidenced by significantly alleviated inflammation, increased collagen deposition, improved angiogenesis, and considerably accelerated wound closure. Nevertheless, the best wound-healing performance was observed in the MSC-KTTKS-CBC groups among all four groups. This research suggests that the MSC-KTTKS-CBC composite offers a great deal of promise as a wound dressing to enhance wound regeneration and expedite wound closure in the clinic.
Subject(s)
Burns , Cellulose , Disease Models, Animal , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Wound Healing , Animals , Burns/therapy , Wound Healing/drug effects , Male , Rats , Mesenchymal Stem Cell Transplantation/methods , Rats, Sprague-Dawley , Bandages , Collagen/metabolism , Humans , Skin/pathology , Skin/injuries , Skin/drug effects , Cell Proliferation/drug effects , Cells, CulturedABSTRACT
The effect of tissue engineering strategies in combination with Lactobacillus plantarum and platelet-rich growth factor (PRGF) with the aim of creating an appropriate wound dressing can be useful in wound healing and infection prevention in patients suffering from acute and chronic skin damages. Therefore, in this study, a new approach was employed to create a bioactive multilayer electrospun scaffold composed of polyurethane (PU), PRGF, and gelatin fibers, then human adipose-derived mesenchymal stem cells (hAMSCs), fibroblast cells (HU-02) and L. plantarum were cultured on the scaffold. The physicochemical properties, biocompatibility, and antibacterial activity of the scaffold were evaluated. In addition, the expression of the migration and proliferation genes of fibroblast cells were investigated by real-time PCR (polymerase chain reaction). Mitochondrial activity assays revealed that PRFG and L. plantarum had a significant positive effect on the viability of target co-cultured cells.Fluorescent and SEM (scanning electron microscopy) images presented the cells and bacterial proliferation and adhesion in hydrophilic scaffolds within 21 days. The sustained release of PRGF from scaffolds with a zero-order pattern was confirmed. RT-PCR analysis revealed that PRGF elevated the expression of VEGF genes up to fourfold, but L. plantarum had a better effect on DDR2 gene expression compared to the TCPS group. Antibacterial tests showed that L. plantarum has a bacterial load reduction of more than 70% in CFU/mL. The present scaffold is an appropriate model for cell attachment, migration, proliferation, and infection prevention.
Subject(s)
Lactobacillus plantarum , Polyurethanes , Humans , Polyurethanes/chemistry , Polyurethanes/pharmacology , Gelatin/pharmacology , Wound Healing , Tissue Scaffolds/chemistry , Intercellular Signaling Peptides and Proteins/pharmacology , Anti-Bacterial AgentsABSTRACT
Purpose: A hemocompatible substrate can offer a wonderful facility for nitric oxide (NO) production by vascular endothelial cells in reaction to the inflammation following injuries. NO inhibits platelet aggregation this is especially critical in small-diameter vessels. Methods: The substrate films were made of polyurethane (PU) in a casting process and after plasma treatments, their surface was chemically decorated with polyethylene glycol (PEG) 2000, gelatin, gelatin-aspirin, gelatin-heparin and gelatin-aspirin-heparin. The concentrations of these ingredients were optimized in order to achieve the biocompatible values and the resulting modifications were characterized by water contact angle and Fourier transform infra-red (FTIR) assays. The values of NO production and platelet adhesion were then examined. Results: The water contact angle of the modified surface was reduced to 26±4∘ and the newly developed hydrophilic chemical groups were confirmed by FTIR. The respective concentrations of 0.05 mg/ml and 100 mg/mL were found to be the IC50 values for aspirin and heparin. However, after the surface modification with aspirin, the bioactivity of the substrate increased in compared to the other experimental groups. In addition, there was a synergistic effect between these reagents for NO synthesis. While, heparin inhibited platelet adhesion more than aspirin. Conclusion: Because of the highly hydrophilic nature of heparin, this reagent was hydrolyzed faster than aspirin and therefore its influence on platelet aggregation and cell growth was greater. Taken together, the results give the biocompatible concentrations of both biomolecules that are required for endothelial cell proliferation, NO synthesis and platelet adhesion.
