Electrospun 3D Fibrous Scaffolds for Chronic Wound Repair.
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ABSTRACT:
SUBMITTER: Chen H
PROVIDER: S-EPMC5502965 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Controlling the structure and organization of electrospun fibers is desirable for fabricating scaffolds and materials with defined microstructures. However, the effects of microtopography on the deposition and, in turn, the organization of the electrospun fibers are not well understood. In this study, conductive polydimethylsiloxane (PDMS) templates with different micropatterns were fabricated by combining photolithography, silicon wet etching, and PDMS molding techniques. The fiber organization was varied by fine-tuning the microtopography of the electrospinning collector. Fiber conformity and alignment were influenced by the depth and the slope of microtopography features, resulting in scaffolds comprising either an array of microdomains with different porosity and fiber alignment or an array of microwells. Microtopography affected the fiber organization for hundreds of micrometers below the scaffold surface, resulting in scaffolds with distinct surface properties on each side. In addition, the fiber diameter was also affected by the fiber conformity. The effects of the fiber arrangement in the scaffolds on the morphology, migration, and infiltration of cells were examined by in vitro and in vivo experiments. Cell morphology and organization were guided by the fibers in the microdomains, and cell migration was enhanced by the aligned fibers and the three-dimensional scaffold structure. Cell infiltration was correlated with the microdomain porosity. Microscale control of the fiber organization and the porosity at the surface and through the thickness of the fibrous scaffolds, as demonstrated by the results of this study, provides a powerful means of engineering the three-dimensional structure of electrospun fibrous scaffolds for cell and tissue engineering.
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Project description:Grafts based on biodegradable polymer scaffolds are increasingly used in tissue-engineering applications as they facilitate natural tissue regeneration. However, monitoring the position and integrity of these scaffolds over time is challenging due to radiolucency. In this study, we used an electrospinning method to fabricate biodegradable scaffolds based on polycaprolactone (PCL) and iodixanol, a clinical contrast agent. Scaffolds were implanted subcutaneously into C57BL/6 mice and monitored in vivo using longitudinal X-ray imaging and micro-computed tomography (CT). The addition of iodixanol altered the physicochemical properties of the PCL scaffold; notably, as the iodixanol concentration increased, the fiber diameter decreased. Radiopacity was achieved with corresponding signal enhancement as iodine concentration increased while exhibiting a steady time-dependent decrease of 0.96% per day in vivo. The electrospun scaffolds had similar performance with tissue culture-treated polystyrene in supporting the attachment, viability, and proliferation of human mesenchymal stem cells. Furthermore, implanted PCL-I scaffolds had more intense acute inflammatory infiltrate and thicker layers of maturing fibrous tissue. In conclusion, we developed radiopaque, biodegradable, biocompatible scaffolds whose position and integrity can be monitored noninvasively. The successful development of other imaging enhancers may further expand the use of biodegradable scaffolds in tissue engineering applications.
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Project description:The novel controlled and localized delivery of drug molecules to target tissues using an external electric stimulus makes electro-responsive drug delivery systems both feasible and desirable, as well as entailing a reduction in the side effects. Novel micro-scaffold matrices were designed based on poly(lactic acid) (PLA) and graphene oxide (GO) via electrospinning. Quercetin (Q), a natural flavonoid, was loaded into the fiber matrices in order to investigate the potential as a model drug for wound dressing applications. The physico-chemical properties, electrical triggering capacity, antimicrobial assay and biocompatibility were also investigated. The newly fabricated PLA/GO/Q scaffolds showed uniform and smooth surface morphologies, without any beads, and with diameters ranging from 1107 nm (10%PLA/0.1GO/Q) to 1243 nm (10%PLA). The in vitro release tests of Q from the scaffolds showed that Q can be released much faster (up to 8640 times) when an appropriate electric field is applied compared to traditional drug-release approaches. For instance, 10 s of electric stimulation is enough to ensure the full delivery of the loaded Q from the 10%PLA/1%GO/Q microfiber scaffold at both 10 Hz and at 50 Hz. The antimicrobial tests showed the inhibition of bacterial film growth. Certainly, these materials could be loaded with more potent agents for anti-cancer, anti-infection, and anti-osteoporotic therapies. The L929 fibroblast cells cultured on these scaffolds were distributed homogeneously on the scaffolds, and the highest viability value of 82.3% was obtained for the 10%PLA/0.5%GO/Q microfiber scaffold. Moreover, the addition of Q in the PLA/GO matrix stimulated the production of IL-6 at 24 h, which could be linked to an acute inflammatory response in the exposed fibroblast cells, as a potential effect of wound healing. As a general conclusion, these results demonstrate the possibility of developing graphene oxide-based supports for the electrically triggered delivery of biological active agents, with the delivery rate being externally controlled in order to ensure personalized release.
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Project description:Poly(glycerol sebacate) (PGS) is a thermally-crosslinked elastomer suitable for tissue regeneration due to its elasticity, degradability, and pro-regenerative inflammatory response. Pores in PGS scaffolds are typically introduced by porogen leaching, which compromises strength. Methods for producing fibrous PGS scaffolds are very limited. Electrospinning is the most widely used method for laboratory scale production of fibrous scaffolds. Electrospinning PGS by itself is challenging, necessitating a carrier polymer which can affect material properties if not removed. We report a simple electrospinning method to produce distinct PGS fibers while maintaining the desired mechanical and cytocompatibility properties of thermally crosslinked PGS. Fibrous PGS demonstrated 5 times higher tensile strength and increased suture retention compared to porous PGS foams. Additionally, similar modulus and elastic recovery were observed. A final advantage of fibrous PGS sheets is the ability to create multi-laminate constructs due to fiber bonding that occurs during thermal crosslinking. Taken together, these highly elastic fibrous PGS scaffolds will enable new approaches in tissue engineering and regenerative medicine.
| S-EPMC4395539 | biostudies-literature
Project description:Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct three-dimensional (3D), fully cellularized scaffolds for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on gelatin methacryloyl (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings.Statement of significanceIn present study, we generate three-dimensional photocrosslinkable gelatin (GelMA)-based fibrous scaffolds with tunable physical and biological properties by using a combined photocrosslinking/electrospinning approach. The developed GelMA fibrous scaffolds can not only support cell viability and cell adhesion, but also facilitate cell migration and proliferation, accelerating regeneration and formation of cutaneous tissues. In addition, the physical properties of the engineered fibrous GelMA hydrogel including water retention capability, mechanical properties and biodegradability can be tuned to accommodate different patients' needs, making it a promising candidate for skin tissue engineering.
| S-EPMC5296408 | biostudies-literature
Project description:In this work we created electrospun fibrous scaffolds with random and aligned fiber orientations in order to mimic the three-dimensional structure of the natural extracellular matrix (ECM). The rigidity and topography of the ECM environment have been reported to alter cancer cell behavior. However, the complexity of the in vivo system makes it difficult to isolate and study such extracellular topographical cues that trigger cancer cells' response. Breast cancer cells were cultured on these fibrous scaffolds for 3-5 days. The cells showed elongated spindle-like morphology in the aligned fibers, whereas they maintained a mostly flat stellar shape in the random fibers. Gene expression profiling of these cells post seeding showed up-regulation of transforming growth factor β-1 (TGFβ-1) along with other mesenchymal biomarkers, suggesting that these cells undergo epithelial-mesenchymal transitions in response to the polymer scaffold. The results of this study indicate that the topographical cue may play a significant role in tumor progression.
| S-EPMC3269532 | biostudies-literature
Project description:BackgroundMost of the natural extracellular matrix (ECM) is a three-dimensional (3D) network structure of micro/nanofibers for cell adhesion and growth of 3D. Electrospun fibers distinctive mimicked 2D ECM, however, it is impossible to simulate 3D ECM because of longitudinal collapse of continuous micro/nanofibers. Herein, 3D electrospun micro/nano-fibrous sponge was fabricated via electrospinning, homogenization, shaping and thermal crosslinking for 3D tissue regeneration of cells and vascular.ResultsFibrous sponge exhibited high porosity, water absorption and compression resilience and no chemical crosslinked agent was used in preparation process. In vitro studies showed that the 3D short fiber sponge provided an oxygen-rich environment for cell growth, which was conducive to the 3D proliferation and growth of HUVECs, stimulated the expression of VEGF, and well promoted the vascularization of HUVECs. In vivo studies showed that the 3D short fiber sponges had a good 3D adhesion to the chronic wound of diabetes in rats. Furthermore, 3D short fibrous sponges were better than 2D micro/nanofiber membranes in promoting the repair of diabetic full-thickness skin defects including wound healing, hair follicle regeneration, angiogenesis, collagen secretion.ConclusionTherefore, electrospun short fibrous sponges are special candidates for mimicking the 3D ECM and promoting 3D regeneration of tissue.
| S-EPMC8106196 | biostudies-literature
Project description:Delayed diabetic wound healing is an adverse event that frequently leads to limb disability or loss. A novel and promising vehicle for the treatment of diabetic wounds is required for clinical purposes. The biocompatible and resorbable poly (lactic-co-glycolic acid) (PLGA)-based fibrous membranes prepared by electrospinning that provide a sustained discharge of saxagliptin for diabetic wound healing were fabricated. The concentration of released saxagliptin in Dulbecco's phosphate-buffered saline was analyzed for 30 days using high-performance liquid chromatography. The effectiveness of the eluted saxagliptin was identified using an endothelial progenitor cell migration assay in vitro and a diabetic wound healing in vivo. Greater hydrophilicity and water storage were shown in the saxagliptin-incorporated PLGA membranes than in the pristine PLGA membranes (both p < 0.001). For diabetic wound healing, the saxagliptin membranes accelerated the wound closure rate, the dermal thickness, and the heme oxygenase-1 level over the follicle areas compared to those in the pristine PLGA group at two weeks post-treatment. The saxagliptin group also had remarkably higher expressions of insulin-like growth factor I expression and transforming growth factor-β1 than the control group (p = 0.009 and p < 0.001, respectively) in diabetic wounds after treatment. The electrospun PLGA-based saxagliptin membranes exhibited excellent biomechanical and biological features that enhanced diabetic wound closure and increased the antioxidant activity, cellular granulation, and functionality.
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Project description:Peripheral nerve regeneration can be enhanced by the stimulation of formation of bands of Büngner prior to implantation. Aligned electrospun poly(epsilon-caprolactone) (PCL) fibers were fabricated to test their potential to provide contact guidance to human Schwann cells. After 7 days of culture, cell cytoskeleton and nuclei were observed to align and elongate along the fiber axes, emulating the structure of bands of Büngner. Microarray analysis revealed a general down-regulation in expression of neurotrophin and neurotrophic receptors in aligned cells as compared to cells seeded on two-dimensional PCL film. Real-time-PCR analyses confirmed the up-regulation of early myelination marker, myelin-associated glycoprotein (MAG), and the down-regulation of NCAM-1, a marker of immature Schwann cells. Similar gene expression changes were also observed on cells cultured on randomly oriented PCL electrospun fibers. However, up-regulation of the myelin-specific gene, P0, was observed only on aligned electrospun fibers, suggesting the propensity of aligned fibers in promoting Schwann cell maturation.
| S-EPMC2713097 | biostudies-literature
Project description:BackgroundTissue engineering of the annulus fibrosus (AF) shows promise as a treatment for patients with degenerative disc disease (DDD). However, it remains challenging due to the intrinsic heterogeneity of AF tissue. Fabrication of scaffolds recapitulating the specific cellular, componential, and microstructural features of AF, therefore, is critical to successful AF tissue regeneration.MethodsPoly-L-lactic acid (PLLA) fibrous scaffolds with various fiber diameters and orientation were prepared to mimic the microstructural characteristics of AF tissue using electrospinning technique. AF-derived stem cells (AFSCs) were cultured on the PLLA fibrous scaffolds for 7 days.ResultsThe morphology of AFSCs significantly varied when cultured on the scaffolds with various fiber diameters and orientation. AFSCs were nearly round on scaffolds with small fibers. However, they became spindle-shaped on scaffolds with large fibers. Meanwhile, upregulated expression of collagen-I gene happened in cells cultured on scaffolds with large fibers, while enhanced expression of collagen-II and aggrecan genes was seen on scaffolds with small fibers. The production of related proteins also showed similar trends. Further, culturing AFSCs on a heterogeneous scaffold by overlaying membranes with different fiber sizes led to the formation of a hierarchical structure approximating native AF tissue.ConclusionFindings from this study demonstrate that fibrous scaffolds with different fiber sizes effectively promoted the differentiation of AFSCs into specific cells similar to the types of cells at various AF zones. It also provides a valuable reference for regulation of cell differentiation and fabrication of engineered tissues with complex hierarchical structures using the physical cues of scaffolds.The translational potential of this articleEffective AF repair is an essential need for treating degenerative disc disease. Tissue engineering is a promising approach to achieving tissue regeneration and restoring normal functions of tissues. By mimicking the key structural features of native AF tissue, including fiber size and alignment, this study deciphered the effect of scaffold materials on the cell differentiation and extracellular matrix deposition, which provides a solid basis for designing new strategies toward more effective AF repair and regeneration.
| S-EPMC7773966 | biostudies-literature