Hybrid Nanofibrous Composites with Anisotropic Mechanics and Architecture for Tendon/Ligament Repair and Regeneration.

Rupture of tendons and ligaments (T/L) is a major clinical challenge due to T/L possess anisotropic mechanical properties and hierarchical structures. Here, to imitate these characteristics, an approach is presented by fabricating hybrid nanofibrous composites. First, hybrid fiber-reinforced yarns are fabricated via successively electrospinning poly(L-lactide-co-ε-caprolactone) (PLCL) and gelatin (Ge) nanofibers onto polyethylene terephthalate (PET) fibers to improve biodurability and biocompatibility. Then, by comparing different manufacturing methods, the knitted structure succeeds in simulating anisotropic mechanical properties, even being stronger than natural ligaments, and possessing comfort compliance superior to clinically used ligament advanced reinforcement system (LARS) ligament. Moreover, after inoculation with tendon-derived stem cells and transplantation in vivo, hybrid nanofibrous composites are integrated with native tendons to guide surrounding tissue ingrowth due to the highly interconnected and porous structure. The knitted hybrid nanofibrous composites are also ligamentized and remodeled in vivo to promote tendon regeneration. Specifically, after the use of optimized anisotropic hybrid nanofibrous composites to repair tendon, the deposition of tendon-associated extracellular matrix proteins is more significant. Thus, this study indicates a strategy of manufacturing anisotropic hybrid nanofibrous composites with superior mechanical properties and good histocompatibility for clinical reconstruction.

Electrospun fibrous sponge via short fiber for mimicking 3D ECM.

BACKGROUND: Most 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. RESULTS: Fibrous 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. CONCLUSION: Therefore, electrospun short fibrous sponges are special candidates for mimicking the 3D ECM and promoting 3D regeneration of tissue.

Photothermal Welding, Melting, and Patterned Expansion of Nonwoven Mats of Polymer Nanofibers for Biomedical and Printing Applications.

We report a simple method for the photothermal welding of nonwoven mats of electrospun nanofibers by introducing a near-infrared (NIR) dye such as indocyanine green. By leveraging the strong photothermal effect of the dye, the nanofibers can be readily welded at their cross points or even over-welded (i.e., melted and/or fused together) to transform the porous mat into a solid film upon exposure to a NIR laser. While welding at the cross points greatly improves the mechanical strength of a nonwoven mat of nanofibers, melting and fusion of the nanofibers can be employed to fabricate a novel class of photothermal papers for laser writing or printing without chemicals or toner particles. By using a photomask, we can integrate photothermal welding with the gas foaming technique to pattern and then expand nonwoven mats into 3D scaffolds with well-defined structures. This method can be applied to different combinations of polymers and dyes, if they can be co-dissolved in a suitable solvent for electrospinning.

The fabrication of 3D surface scaffold of collagen/poly (L-lactide-co-caprolactone) with dynamic liquid system and its application in urinary incontinence treatment as a tissue engineered sub-urethral sling: In vitro and in vivo study.

AIMS: To fabricate a novel nanoyarn biomaterial via a dynamic liquid electrospinning system, and to simultaneously evaluate whether nanoyarn is capable of being applied as a urinary sling for future clinical transfer. METHODS: Nanoyarn was cultured with adipose-derived stem cells (ADSCs). Cell morphology and function were observed on nanoyarn. Female rats that underwent vagina dilatation (VD) and bilateral ovarian resection (BOR) were used as the urinary incontinence model. After 2 weeks, the cells-sling was fixed to the suburethra. A commercial sling that tension-free vaginal tape-obturator (TVT-O) was used as a control. The urodynamic test for leak point pressure (LPP) and histological tests were used to evaluate the sling's performance in vivo. RESULTS: The nanoyarn possessed beneficial properties and the actin filament from ADSCs, which is very similar to muscle. Rats that underwent VD and BOR maintained a low LPP, whereas the LPP in rats with VD alone recovered to normal levels within 2 weeks. LPP in the nanoyarn group gradually decreased on the three urodynamic tests post-suburethral surgery, however, the cell-laden nanoyarn maintained LPP at normal levels for 8 weeks; the TVT-O group showed a significant increase in LPP at 8 weeks. Cell-laden nanoyarn was infiltrated with more cells, collagen, and vessels than the controls. CONCLUSIONS: The nanoyarn showed sufficient efficacy to maintain LPP in urinary incontinence rat model. In addition, it improved cell infiltration, collagen and muscle development compared to TVT-O. Thus, the combination of ADSCs and a nanoyarn scaffold could be a promising tissue-engineered sling for the treatment of urinary incontinence.

Thiol click modification of cyclic disulfide containing biodegradable polyurethane urea elastomers.

Although the thiol click reaction is an attractive tool for postpolymerization modification of thiolmers, thiol groups are easily oxidized, limiting the potential for covalent immobilization of bioactive molecules. In this study, a series of biodegradable polyurethane elastomers incorporating stable cyclic disulfide groups was developed and characterized. These poly(ester urethane)urea (PEUU-SS) polymers were based on polycaprolactone diol (PCL), oxidized dl-dithiothreitol (O-DTT), lysine diisocyanate (LDI), or butyl diisocyanate (BDI), with chain extension by putrescine. The ratio of O-DTT:PCL was altered to investigate different levels of potential functionalization. PEG acrylate was employed to study the mechanism and availability of both bulk and surface click modification of PEUU-SS polymers. All synthesized PEUU-SS polymers were elastic with breaking strengths of 38-45 MPa, while the PEUU-SS(LDI) polymers were more amorphous, possessing lower moduli and relatively small permanent deformations versus PEUU-SS(BDI) polymers. Variable bulk click modification of PEUU-SS(LDI) polymers was achieved by controlling the amount of reduction reagent, and rapid reaction rates occurred using a one-pot, two-step process. Likewise, surface click reaction could be carried out quickly under mild, aqueous conditions. Furthermore, a maleimide-modified affinity peptide (TPS) was successfully clicked on the surface of an electrospun PEUU-SS(BDI) fibrous sheet, which improved endothelial progenitor cell adhesion versus corresponding unmodified films. The cyclic disulfide containing biodegradable polyurethanes described provide an option for cardiovascular and other soft tissue regenerative medicine applications where a temporary, elastic scaffold with designed biofunctionality from a relatively simple click chemistry approach is desired.

Composite superplastic aerogel scaffolds containing dopamine and bioactive glass-based fibers for skin and bone tissue regeneration.

Multifunctional bioactive biomaterials with integrated bone and soft tissue regenerability hold great promise for the regeneration of trauma-affected skin and bone defects. The aim of this research was to fabricate aerogel scaffolds (GD-BF) by blending the appropriate proportions of short bioactive glass fiber (BGF), gelatin (Gel), and dopamine (DA). Electrospun polyvinyl pyrrolidone (PVP)-BGF fibers were converted into short BGF through calcination and homogenization. Microporous GD-BF scaffolds displayed good elastic deformation recovery and promoted neo-tissue formation. The DA could enable thermal crosslinking and enhance the mechanical properties and structural stability of the GD-BF scaffolds. The BGF-mediated release of therapeutic ions shorten hemostatic time (<30 s) in a rat tail amputation model and a rabbit artery injury model alongside inducing the regeneration of skin appendages (e.g., blood vessels, glands, etc.) in a full-thickness excisional defect model in rats (percentage wound closure: GD-BF2, 98 % vs. control group, 83 %) at day 14 in vitro. Taken together, these aerogel scaffolds may have significant promise for soft and hard tissue repair, which may also be worthy for the other related disciplines.

A novel antibiotic: the antimicrobial effects of CFBSA and its application on electronspun wound dressing.

N-chloro-N-fluorobenzenesulfonylamide (CFBSA), was a novel chlorinating reagent, which exhibits potential antibacterial activities. In this study, CFBSA was confirmed as a wide-broad antimicrobial and bactericidal drug against different gram-negative bacteria, gram-positive bacteria and fungi, while it was found to have low cytotoxicity for eukaryotic cells. In addition, microorganism morphology assay and oxidative stress test was used to determine the antimicrobial mechanisms of CFBSA. According to the results, CFBSA probably had a target on cell membrane and killed microorganism by disrupting its cell membrane. Then, CFBSA was first combined with poly(L-lactide-co-caprolactone) (PLCL)/SF via electrospinning and applied in wound dressings. The characterization of different PLCL/SF of CFBSA-loaded nanofibrous mats was investigated by SEM, water contact angle, Fourier transform infrared spectroscopy, cell compatibility and antimicrobial test. CFBSA-loaded PLCL/SF nanofibrous mats showed excellent antimicrobial activities. In order to balance of the biocompatibility and antibacterial efficiency, SP-2.5 was selected as the ideal loading concentration for further application of CFBSA-loaded PLCL/SF. In conclusion, the electrospun CFBSA-loaded PLCL/SF nanofibrous mat with its broad-spectrum antimicrobial and bactericidal activity and good biocompatibility showed enormous potential for wound dressing.

Fiber configuration determines foreign body response of electrospun scaffolds:in vitroandin vivoassessments.

Biomaterial scaffolds boost tissue repair and regeneration by providing physical support, delivering biological signals and/or cells, and recruiting endogenous cells to facilitate tissue-material integration and remodeling. Foreign body response (FBR), an innate immune response that occurs immediately after biomaterial implantation, is a critical factor in determining the biological outcomes of biomaterial scaffolds. Electrospinning is of great simplicity and cost-effectiveness to produce nanofiber scaffolds with well-defined physicochemical properties and has been used in a variety of regenerative medicine applications in preclinical trials and clinical practice. A deep understanding of causal factors between material properties and FBR of host tissues is beneficial to the optimal design of electrospun scaffolds with favorable immunomodulatory properties. We herein prepared and characterized three electrospun scaffolds with distinct fiber configurations and investigated their effects on FBR in terms of immune cell-material interactions and host responses. Our results show that electrospun yarn scaffold results in greater cellular immune reactions and elevated FBR inin vivoassessments. Although the yarn scaffold showed aligned fiber bundles, it failed to induce cell elongation of macrophages due to its rough surface and porous grooves between yarns. In contrast, the aligned scaffold showed reduced FBR compared to the yarn scaffold, indicating a smooth surface is also a contributor to the immunomodulatory effects of the aligned scaffold. Our study suggests that balanced porousness and smooth surface of aligned fibers or yarns should be the key design parameters of electrospun scaffolds to modulate host responsein vivo.

Development of 3D Printed Biodegradable, Entirely X-ray Visible Stents for Rabbit Carotid Artery Implantation.

Biodegradable stents are considered a promising strategy for the endovascular treatment of cerebrovascular diseases. The visualization of biodegradable stents is of significance during the implantation and long-term follow-up. Endowing biodegradable stents with X-ray radiopacity can overcome the weakness of intrinsic radioparency of polymers. Hence, this work focuses on the development of an entirely X-ray visible biodegradable stent (PCL-KIO3) composed of polycaprolactone (PCL) and potassium iodate via physical blending and 3D printing. The in vitro results show that the introduction of potassium iodate makes the 3D-printed PCL stents visualizable under X-ray. So far, there is inadequate study about polymeric stent visualization in vivo. Therefore, PCL-KIO3 stents are implanted into the rabbit carotid artery to evaluate the biosafety and visibility performance. During stent deployment, the visualization of the PCL-KIO3 stent effectively helps to understand the position and dilation status of stents. At 6-month follow-up, the PCL-KIO3 stent could still be observed under X-ray and maintains excellent vessel patency. To sum up, this study demonstrates that PCL-KIO3 stent may provide a robust strategy for biodegradable stent visualization.

Thoroughly Hydrophilized Electrospun Poly(L-Lactide)/ Poly(ε-Caprolactone) Sponges for Tissue Engineering Application.

Biodegradable electrospun sponges are of interest for various applications including tissue engineering, drug release, dental therapy, plant protection, and plant fertilization. Biodegradable electrospun poly(l-lactide)/poly(ε-caprolactone) (PLLA/PCL) blend fiber-based sponge with hierarchical pore structure is inherently hydrophobic, which is disadvantageous for application in tissue engineering, fertilization, and drug delivery. Contact angles and model studies for staining with a hydrophilic dye for untreated, plasma-treated, and surfactant-treated PLLA/PCL sponges are reported. Thorough hydrophilization of PLLA/PCL sponges is found only with surfactant-treated sponges. The MTT assay on the leachates from the sponges does not indicate any cell incompatibility. Furthermore, the cell proliferation and penetration of the hydrophilized sponges are verified by in vitro cell culture studies using MG63 and human fibroblast cells.

Current Advancements and Strategies of Biomaterials for Tendon Repair: A Review.

Tendon is a bundle of tissue comprising of a large number of collagen fibers that connects muscle to bone. However, overuse or trauma may cause degeneration and rupture of the tendon tissues, which imposes an enormous health burden on patients. In addition to autogenous and allogeneic transplantation, which is commonly used in the clinic, the current research on tendon repair is focused on developing an appropriate scaffold via biomaterials and fabrication technology. The development of a scaffold that matches the structure and mechanics of the natural tendon is the key to the success of the repair, so the synergistic optimization of the scaffold fabrication technology and biomaterials has always been a concern of researchers. A series of strategies include the preparation of scaffolds by electrospinning and 3D printing, as well as the application of injectable hydrogels and microspheres, which can be used individually or in combination with cells, growth factors for tendon repair. This review introduces the tendon tissue structure, the repair process, the application of scaffolds, and the current challenges facing biomaterials, and gives an outlook on future research directions. With biomaterials and technology continuing to be developed, we envision that the scaffolds could have an important impact on the application of tendon repair.

Evaluation of electrospun PCL diol-based elastomer fibers as a beneficial matrix for vascular tissue engineering.

The main reason for the failure of artificial blood vessel transplantation is the lack of mechanically matched materials with excellent blood compatibility. The electrospun biodegradable polyurethane (BPU) fibers with micro to nanoscale topography and high porosity similar to the natural extracellular matrix (ECM) is one of the most suitable options for vascular graft. In our recent study, we prepared a series of PCL-based BPU fibers by combining two-step solution polymerization and electrospinning. SEM, 1H NMR, ATR-FTIR, XRD, TG, water contact angle, and mechanical tests were used to analyze the chemical structure, microstructure, thermal properties, surface wettability, degradation, cytocompatibility, and hemocompatibility in vitro of electrospun fibers. The results show that the synthesized H-PEUU, L-PEUU, H-PEEUU, and L-PEEUU have different crystalline properties, thus exhibiting distinctive thermal, mechanical, and degradation properties. Although the existence of the molecular structure of LDI and PEG600 in fibers can promote cell proliferation and migration unilaterally, the microstructure of the material is also the main factor affecting the biocompatibility of cells. The results suggest that the designed PCL-based degradable polyurethane electrospun fiber is expected to be applied to vascular tissue engineering.

Development of Biodegradable Polymeric Stents for the Treatment of Cardiovascular Diseases.

Cardiovascular disease has become the leading cause of death. A vascular stent is an effective means for the treatment of cardiovascular diseases. In recent years, biodegradable polymeric vascular stents have been widely investigated by researchers because of its degradability and clinical application potential for cardiovascular disease treatment. Compared to non-biodegradable stents, these stents are designed to degrade after vascular healing, leaving regenerated healthy arteries. This article reviews and summarizes the recent advanced methods for fabricating biodegradable polymeric stents, including injection molding, weaving, 3D printing, and laser cutting. Besides, the functional modification of biodegradable polymeric stents is also introduced, including visualization, anti-thrombus, endothelialization, and anti-inflammation. In the end, the challenges and future perspectives of biodegradable polymeric stents were discussed.

Composite Superelastic Aerogel Scaffolds Containing Flexible SiO2 Nanofibers Promote Bone Regeneration.

Repairing irregular-shaped bone defects poses enormous challenges. Scaffolds that can fully fit the defect site and simultaneously induce osteogenesis and angiogenesis hold great promise for bone defect healing. This study aimed to produce superelastic organic/inorganic composite aerogel scaffolds by blending silica nanofibers (SiO2 ) and poly (lactic acid)/gelatin (PLA/gel) nanofibers; the content of SiO2 nanofibers is varied from 0-60 wt% (e.g., PLA/gel, PLA/gel/SiO2 -L, PLA/gel/SiO2 -M, and PLA/gel/SiO2 -H for 0%, 20%, 40%, and 60% of SiO2 nanofibers, respectively) to produce a range of scaffolds. The PLA/gel/SiO2 -M scaffold has excellent elasticity and good mechanical properties. In vitro experiments demonstrate that the silicon ions released from PLA/gel/SiO2 -M scaffolds promote the differentiation of rat bone marrow-derived mesenchymal stem cells into osteoblasts, enhancing alkaline phosphatase activity and bone-related genes expressions. The released silicon ions also promote the proliferation of human umbilical vein endothelial cells and the expression of vascular endothelial growth factors, thereby promoting angiogenesis. The assessment of these scaffolds in a calvarial defect model in rats shows good potential of PLA/gel/SiO2 -M to induce bone regeneration as well as promote osteogenesis and angiogenesis. Overall, these organic/inorganic composite scaffolds have good biological activity, which may have broad applications for tissue engineering.

Prodrug inspired bi-layered electrospun membrane with properties of enhanced tissue integration for guided tissue regeneration.

Guided tissue regeneration (GTR) membranes play a vital role in periodontal surgery. Recently a series of composite electrospun membranes have been fabricated to improve the unexpected biodegradation of collagen-based GTR membranes. However, their tissue integrity needs to be studied in depth. In this study, a bi-layered electrospun membrane (BEM) inspired by "prodrug" was fabricated, which contained a dense-layer (BEM-DL) and a potential loose-layer (BEM-LL). The nanofibers of BEM-DL were composed of poly(l-lactic-co-glycolic acid) and tilapia skin collagen (TSC). Whereas the BEM-LL consisted of two types of nanofibers, one was the same as BEM-DL and the other was made from TSC. The morphology, degradation in vitro, cytocompatibility and biocompatibility in rats were investigated with a poly(lactic-co-glycolic acid) electrospun membrane (PLGA) as the negative control. The pore size of BEM-LL soaked for 7 days became larger than the original sample (164.8 ± 90.9 and 52.5 ± 21.0 µm2 , respectively), which was significantly higher (p < .05) than that of BEM-DL and PLGA. The BEM-LL displayed a larger weight loss rate of 82.3 ± 3.6% than the BEM-DL of 46.0 ± 2.8% at day 7 because of the rapid degradation of TSC fibers. The cytocompatibility test demonstrated that L929 cells were only spread on the surface of the BEM-DL while MC3T3-E1 cells grew into the BEM-LL layer. The subcutaneous implantation test further proved that BEM-DL performed as a cellular barrier, whereas BEM-LL was conducive to cell infiltration as deep as 200 µm with reduced fibrous encapsulation. Herein, the BEM inspired by "prodrug" is a promising GTR membrane with a property of enhanced tissue integration.

Converging 3D Printing and Electrospinning: Effect of Poly(l-lactide)/Gelatin Based Short Nanofibers Aerogels on Tracheal Regeneration.

Recently, various tissue engineering based strategies have been pursued for the regeneration of tracheal tissues. However, previously developed tracheal scaffolds do not accurately mimic the microstructure and mechanical behavior of the native trachea, which restrict their clinical translation. Here, tracheal scaffolds are fabricated by using 3D printing and short nanofibers (SF) dispersion of poly(l-lactide)/gelatin (0.5-1.5 wt%) to afford tracheal constructs. The results display that the scaffolds containing 1.0 wt % of SF exhibit low density, good water absorption capacity, reasonable degradation rate, and stable mechanical properties, which were comparable to the native trachea. Moreover, the designed scaffolds possess good biocompatibility and promote the growth and infiltration of chondrocytes in vitro. The biocompatibility of tracheal scaffolds is further assessed after subcutaneous implantation in mice for up to 4 and 8 weeks. Histological assessment of tracheal constructs explanted at week 4 shows that scaffolds can maintain their structural integrity and support the formation of neo-vessels. Furthermore, cell-scaffold constructs gradually form cartilage-like tissues, which mature with time. Collectively, these engineered tracheal scaffolds not only possess appropriate mechanical properties to afford a stabilized structure but also a biomimetic extracellular matrix-like structure to accomplish tissue regeneration, which may have broad implications for tracheal regeneration.

Vascular Endothelial Growth Factor-Capturing Aligned Electrospun Polycaprolactone/Gelatin Nanofibers Promote Patellar Ligament Regeneration.

Ligament injuries are common in sports and other rigorous activities. It is a great challenge to achieve ligament regeneration after an injury due the avascular structure and low self-renewal capability. Herein, we developed vascular endothelial growth factor (VEGF)-binding aligned electrospun poly(caprolactone)/gelatin (PCL/Gel) scaffolds by incorporating prominin-1-binding peptide (BP) sequence and exploited them for patellar ligament regeneration. The adsorption of BP onto scaffolds was discerned by various techniques, such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and confocal laser scanning microscope. The accumulation of VEGF onto scaffolds correlated with the concentration of the peptide in vitro. BP-anchored PCL/Gel scaffolds (BP@PCL/Gel) promoted the tubular formation of human umbilical vein endothelial cells (HUVECs) and wound healing in vitro. Besides, BP containing scaffolds exhibited higher content of CD31+ cells than that of the control scaffolds at 1 week after implantation in vivo. Moreover, BP containing scaffolds improved biomechanical properties and facilitated the regeneration of matured collagen in patellar ligament 4 weeks after implantation in mice. Overall, this strategy of peptide-mediated orchestration of VEGF provides an enticing platform for the ligament regeneration, which may also have broad implications for tissue repair applications. STATEMENT OF SIGNIFICANCE: Ligament injuries are central to sports and other rigorous activities. Given to the avascular nature and poor self-healing capability of injured ligament tissues, it is a burgeoning challenge to fabricate tissue-engineered scaffolds for ligament reconstruction. Vascular endothelial growth factor (VEGF) is pivotal to the neo-vessel formation. However, the high molecular weight of VEGF as well as its short half-life in vitro and in vivo limits its therapeutic potential. To circumvent these limitations, herein, we functionalized aligned electrospun polycaprolactone/gelatin (PCL/Gel)-based scaffolds with VEGF-binding peptide (BP) and assessed their biocompatibility and performance in vitro and in vivo. BP-modified scaffolds accumulated VEGF, improved tube formation of HUVECs, and induced wound healing in vitro, which may have broad implications for regenerative medicine and tissue engineering.

An injectable double cross-linked hydrogel adhesive inspired by synergistic effects of mussel foot proteins for biomedical application.

Hydrogel adhesives with high tissue adhesion, biodegradability and biocompatibility are benefit for promoting surgical procedures and minimizing the pain and post-surgical complications of patients. In this paper, an injectable mussel inspired double cross-linked hydrogel adhesive composed of thiolated mussel inspired chitosan (CSDS) and tetra-succinimidyl carbonate polyethylene glycol (PEG-4S) was designed and developed. CSDS was synthesized with thiol and catechol groups inspired by the synergistic effect of mussel foot proteins (mfps). The double cross-linked hydrogel was first formed by the addition of sodium periodate (or Fe3+) and then double cross-linked with PEG-4S. The results showed that the mechanical and adhesion properties of the double cross-linked hydrogels were significantly improved by the synergistic effects of the functional groups. And the prepared hydrogels showed good cytocompatibility which evaluated by determining the viability of L929 cells and human umbilical vein endothelial cells (HUVECs). Additionally, the biodegradability and biocompatibility in vivo were further confirmed by subcutaneous implantation in mice model, and the histological analysis results identified that the prepared hydrogels were in vivo biocompatible. This work presents an injectable mussel inspired double cross-linked hydrogels that can use as a potential hydrogel adhesive for biomedical application.

Diethyldithiocarbamate/silk fibroin/polyethylene oxide nanofibrous for cancer therapy: Fabrication, characterization and in vitro evaluation.

Cancer has become a serious disease threatening human health. To tackle this issue, developing the existing potent anticancer drugs is critical to reducing the time and cost associated with creating a new drug from scratch. Diethyldithiocarbamate (DDC) - an anticancer drug- has received considerable attention due to its selectivity and reactivity. In this study, we prepared a nanofibrous matrix from silk fibroin/polyethylene oxide loaded with diethyldithiocarbamate (DDC@SF/PEO) from an aqueous solution via an electrospinning process. Upon DDC incorporation, the nanofiber's diameter has increased from 450 nm (SF/PEO) to 1202 nm (DDC@SF/PEO) confirming the successful incorporation of DDC. Furthermore, the hydrophobicity of DDC@SF/PEO nanofibrous matrix was improved by turning SF structure from random coil (silk I) to ß-sheet (silk II) through ethanol vapor treatment. Biocompatibility of DDC@SF/PEO nanofibrous matrix on human normal cells (Wi-38) showed it was safe and the apoptosis-mediated anticancer activity of DDC was enhanced. Thus, loading DDC on SF/PEO nanofibrous matrix is the key descriptor for enhanced anticancer efficacy of DDC. Considering the all-aqueous and simplistic process, the DDC@SF/PEO nanofibrous matrix could be a promising candidate for cancer treatment applications.

Nanofiber configuration affects biological performance of decellularized meniscus extracellular matrix incorporated electrospun scaffolds.

Electrospinning represents the simplest approach to fabricate nanofiber scaffolds that approximate the heterogeneous fibrous structure of the meniscus. More effort is needed to understand the relationship between scaffold properties and cell responses to determine the appropriate scaffolds supporting meniscus tissue repair and regeneration. In this study, we investigate the influence of nanofiber configuration of electrospun scaffolds on phenotype and matrix production of meniscus cells, as well as on scaffold degradation behaviors and biocompatibility. Twisting electrospun nanofibers into yarns not only recapitulates the major collagen bundles of the meniscus but also increases the pore size and porosity of resultant scaffolds. The yarn scaffold significantly regulated expression levels of meniscus-associated genes and promoted extracellular matrix production compared with conventional electrospun scaffolds with random or aligned nanofiber orientation. Additionally, the yarn scaffold allowed considerable cell infiltration and experienced faster degradation and tissue remodeling upon subcutaneous implantation in a rat model. These results suggest that nanofiber configuration dictates cell interactions, scaffold degradation and integration with host tissue, providing design parameters of porosity and pore size of electrospun scaffolds toward meniscus repair.