Despite important advances in regenerative medicine and tissue engineering, still, wound healing remains a challenging clinical problem. Cell therapy has opened a new viewpoint in medicine as well as wound management, although it has some limitations. On the other hand, there are some hopes for the eliminated of cellular therapies limitations by "exosomes." The term "exosome" has been frequently used to describe all vesicles released by different cells into the extracellular environment and can influence tissue responses to injury, infection, immune system, and healing. Exosomes contain cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs that have been found in some body fluids and can be transferred between cells to mediating cell-to-cell communication and interactions. Recently, several studies have demonstrated that exosomes are one of the key secretory products of various cell type especially mesenchymal stem cells (MSCs) to regulate many biological processes such wound healing. Hence, understanding these exosomes effects may help to improve wound management and highlight a new therapeutic model for cell-free therapies with decreased side effects for the wound repair.
Electrospun composite scaffolds show high ability to be used in regenerative medicine and drug delivery, due to the nanofibrous structure and high surface area to volume ratio. In this study, we used nanofibrous scaffolds fabricated by chitosan (CS), poly(vinyl alcohol) (PVA), carbopol, and polycaprolactone using a dual electrospinning technique while curcumin (Cur) incorporated inside of the CS/PVA fibers. Scaffolds were fully characterized via scanning electron microscopy, water contact angle, tensile measurement, hydration, protein adsorption, and wrinkled tests. Furthermore, viability of the buccal fat pad‐derived mesenchymal stem cells (BFP‐MSCs) was also investigated using MTT assay for up to 14 days while cultured on these scaffolds. Cell cycle assay was also performed to more detailed evaluation of the stem cells growth when grown on scaffolds (with and without Cur) compared with the culture plate. Results demonstrated that Cur loaded nanofibrous scaffold had more suitable capability for water absorption and mechanical properties compared with the scaffold without Cur and it could also support the stem cells viability and proliferation. Cur release profile showed a decreasing effect on BFP‐MSCs viability in the initial stage, but it showed a positive effect on stem cell viability in a long‐term manner. In general, the results indicated that this nanofibrous scaffold has great potential as a delivery of the Cur and BFP‐MSCs simultaneously, and so holds the promising potential for use in various regenerative medicine applications.
Electrospinning of composite polymer solutions provides fantastic potential to prepare novel nanofibers for use in a variety of applications. The addition of graphene (G) and graphene oxide (GO) nanosheets to bioactive polymers was found to enhance their conductivity and biocompatibility. Composite conductive nanofibers of polyaniline (PANI) and polyacrylonitrile (PAN) with G and GO nanosheets were prepared by an electrospinning process. The fabricated membranes were investigated by physical and chemical examinations including scanning electron microscopy (SEM), Raman spectroscopy, x-ray diffraction (XRD) and tensile assay. The muscle satellite cells enriched by a pre-plating technique were cultured in the following and their proliferation and differentiation behavior studied by MTT, Real-Time PCR assays and 4', 6-diamidino-2-phenylindole (DAPI) staining. The cultured cells on composite nanofibrous PAN/PANI-CSA/G confirmed a higher proliferation and differentiation value compared to other groups including PAN/PANI-CSA/GO and PAN/PANI-CSA scaffolds. Furthermore, the higher stiffness of the former scaffold showed a lower cell spreading as a function of stem cell activation into more proliferative cells. It is supposed that the enhanced conductivity value in addition to relative higher stiffness of the PAN/PANI-CSA/G composite nanofibers plays a favorable role for proliferation and differentiation of satellite cells.
Among polymers, polyaniline (PANi) has been introduced as a good candidate for muscle regeneration due to high conductivity and also biocompatibility. Herein, for the first time, we report the use of electrospun nanofibrous membrane of PAN-PANi as efficient scaffold for muscle regeneration. The prepared PAN-PANi electrospun nanofibrous membrane was characterized by scanning electron microscopy (SEM), Attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR) and tensile examination. The softer scaffolds of non-composite electrospun nanofibrous PAN govern a higher rate of cell growth in spite of lower differentiation value. On the other hand, PAN-PANi electrospun nanofibrous membrane exposed high cell proliferation and also differentiation value. Thank to the conductive property and higher Young's modulus of composite type due to the employment of PANi, satellite cells were induced into more matured form as analyzed by Real-Time PCR. On the other hand, grafting of composite nanofibrous electrospun scaffold with gelatin increased the surface stiffness directing satellite cells into lower cell proliferation and highest value of differentiation. Our results for first time showed the significant role of combination between conductivity, mechanical property and surface modification of PAN-PANi electrospun nanofibers and provid new insights into most biocompatible scaffolds for muscle tissue engineering. The schematic figure conveys the effective combination of conductive and surface stiffness on muscle tissue engineering.
In the embryonic heart, electrical impulses propagate in a unidirectional manner from the sinus venosus and appear to be involved in cardiogenesis. In this work, aligned and random polyaniline/polyetersulfone (PANI/PES) nanofibrous scaffolds doped by Camphor-10-sulfonic acid (β) (CPSA) were fabricated via electrospinning and used to conduct electrical impulses in a unidirectional and multidirectional fashion, respectively. A bioreactor was subsequently engineered to apply electrical impulses to cells cultured on PANI/PES scaffolds. We established cardiovascular disease-specific induced pluripotent stem cells (CVD-iPSCs) from the fibroblasts of patients undergoing cardiothoracic surgeries. The CVD-iPSCs were seeded onto the scaffolds, cultured in cardiomyocyte-inducing factors, and exposed to electrical impulses for 1 h/day, over a 15-day time period in the bioreactor. The application of the unidirectional electrical stimulation to the cells significantly increased the number of cardiac Troponin T (cTnT+) cells in comparison to multidirectional electrical stimulation using random fibrous scaffolds. This was confirmed by real-time polymerase chain reaction for cardiac-related transcription factors (NKX2.5, GATA4, and NPPA) and a cardiac-specific structural gene (TNNT2). Here we report for the first time that applying electrical pulses in a unidirectional manner mimicking the unidirectional wave of electrical stimulation in the heart, could increase the derivation of cardiomyocytes from CVD-iPSCs.
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