Electrospun Fibrous Meshes Research Articles

COX-2 inhibitor delivery system aiming intestinal inflammatory disorders

Selective COX-2 inhibitors such as etoricoxib (ETX) are potentially indicated for the treatment of intestinal inflammatory disorders. However, their systemic administration provokes some off-site secondary effects, decreasing the desirable local effectiveness. To circumvent such limitations, herein an ETX delivery system based on electrospun fibrous meshes (eFMs) was proposed. ETX at different concentrations (1, 2, and 3 mg mL−1) was loaded into eFMs, which not affect the morphology and the mechanical properties of this drug delivery system (DDS). The ETX showed a burst release within the first 12 h, followed by a faster release until 36 h, gradually decreasing over time. Importantly, the ETX studied concentrations were not toxic to human colonic cells (i.e. epithelial and fibroblast). Moreover, the DDS loading the highest concentration of ETX, when tested with stimulated human macrophages, promoted a reduction of PGE2, IL-8 and TNF-α secretion. Therefore, the proposed DDS may constitute a safe and efficient treatment of colorectal diseases promoted by inflammatory disorders associated with COX-2.

From Nature to Technology: Exploring Bioinspired Polymer Actuators via Electrospinning.

Nature has always been a source of inspiration for the development of novel materials and devices. In particular, polymer actuators that mimic the movements and functions of natural organisms have been of great interest due to their potential applications in various fields, such as biomedical engineering, soft robotics, and energy harvesting. During recent years, the development and actuation performance of electrospun fibrous meshes with the advantages of high permeability, surface area, and easy functional modification, has received extensive attention from researchers. This review covers the recent progress in the state-of-the-art electrospun actuators based on commonly used polymers such as stimuli-sensitive hydrogels, shape-memory polymers (SMPs), and electroactive polymers. The design strategies inspired by nature such as hierarchical systems, layered structures, and responsive interfaces to enhance the performance and functionality of these actuators, including the role of biomimicry to create devices that mimic the behavior of natural organisms, are discussed. Finally, the challenges and future directions in the field, with a focus on the development of more efficient and versatile electrospun polymer actuators which can be used in a wide range of applications, are addressed. The insights gained from this review can contribute to the development of advanced and multifunctional actuators with improved performance and expanded application possibilities.

Electrospun fiber-based strategies for controlling early innate immune cell responses: Towards immunomodulatory mesh designs that facilitate robust tissue repair.

Electrospun fibrous meshes are widely used for tissue repair due to their ability to guide a host of cell responses including phenotypic differentiation and tissue maturation. A critical factor determining the eventual biological outcomes of mesh-based regeneration strategies is the early innate immune response following implantation. The natural healing process involves a sequence of tightly regulated, temporally varying and delicately balanced pro-/anti-inflammatory events which together promote mesh integration with host tissue. Matrix designs that do not account for the immune milieu can result in dysregulation, chronic inflammation and fibrous capsule formation, thus obliterating potential therapeutic outcomes. In this review, we provide systematic insights into the effects of specific fiber/mesh properties and mechanical stimulation on the responses of early innate immune modulators viz., neutrophils, monocytes and macrophages. We identify matrix characteristics that promote anti-inflammatory immune phenotypes, and we correlate such responses with pro-regenerative in vivo outcomes. We also discuss recent advances in 3D fabrication technologies, bioactive functionalization approaches and biomimetic/bioinspired immunomodulatory mesh design strategies for tissue repair and wound healing. The mechanobiological insights and immunoregulatory strategies discussed herein can help improve the translational outcomes of fiber-based regeneration. STATEMENT OF SIGNIFICANCE: The crucial role played by immune cells in promoting biomaterial-based tissue regeneration is being increasingly recognized. In this review focusing on the interactions of innate immune cells with electrospun fibrous meshes, we systematically elucidate the effects of the fiber microenvironment and mechanical stimulation on biological responses, and build upon these insights to inform the rational design of immunomodulatory meshes for effective tissue repair. We discuss state-of-the-art fabrication methods and mechanobiological advances that permit the orchestration of temporally controlled phenotypic switches in immune cells during different phases of healing. The design strategies discussed herein can also be leveraged to target several complex autoimmune and inflammatory diseases.

The Influence of Feeder Cell-Derived Extracellular Matrix Density on Thymic Epithelial Cell Culture

The thymus is responsible for the selection and development of T cells, having an essential role in the establishment of adaptive immunity. Thymic epithelial cells (TECs) are key players in T cell development interacting with thymocytes in the thymic 3D environment. Feeder-layer cells have been frequently used as platforms for the successful establishment of TEC cultures. Nevertheless, the role of the feeder cell-derived extracellular matrix (ECM) on TEC cultures was not previously reported. Therefore, this work aimed at assessing the effect of the ECM produced by feeder cells cultured at two different densities on the establishment of TEC culture. Due to the high surface area and porosity, electrospun fibrous meshes were used to support ECM deposition. The feeder cell-derived ECM was efficiently recovered after decellularization, maintaining the composition of major proteins. All the decellularized matrices were permeable and showed an increase in surface mechanical properties after decellularization. TEC cultures confirmed that the ECM density impacts cellular performance, with higher densities showing a decreased cellular activity. Our findings provide evidence that feeder cell-derived ECM is a suitable substrate for TEC culture and can potentially be applied in thymus bioengineering.

Characterization of Electrospun Polysuccinimide-Dopamine Conjugates and Effect on Cell Viability and Uptake.

Biocompatible nanofibrous systems made by electrospinning have been studied widely for pharmaceutical applications since they have a high specific surface and the capability to make the entrapped drug molecule amorphous, which increases bioavailability. By covalently conjugating drugs onto polymers, the degradation of the drug as well as the fast clearance from the circulation can be avoided. Although covalent polymer-drug conjugates have a lot of advantages, there is a lack of research focusing on their nano-formulation by electrospinning. In this study, polysuccinimide (PSI) based electrospun fibrous meshes conjugated with dopamine (DA) are prepared. Fiber diameter, mechanical properties, dissolution kinetics and membrane permeability are thoroughly investigated, as these are crucial for drug delivery and implantation. Dopamine release kinetics prove the prolonged release that influenced the viability and morphology of periodontal ligament stem cells (PDLSCs) and SH-SY5Y cells. The presence of dopamine receptors on both cell types is also demonstrated and the uptake of the conjugates is measured. According to flow cytometry analysis, the conjugates are internalized by both cell types, which is influenced by the chemical structure and physical properties. In conclusion, electrospinning of PSI-DA conjugates alters release kinetics, meanwhile, conjugated dopamine can play a key role in cellular uptake.

Mimicking osteochondral interface using pre-differentiated BMSCs/fibrous mesh complexes to promote tissue regeneration

The heterogeneous nature of osteochondral tissue requires the construction of implant with biomimetic gradients. Electrospun fibrous meshes with different designs provide the feasibility in arranging such a kind of gradient structure via layer-by-layer stacking. In this study, a kind of triphasic implant was constructed by layering pre-differentiated cell sheets, which were hold by electrospun poly(L-lactide)/gelatin (PLLA/Gel) fibrous meshes containing hyaluronic acid and chondroitin sulfate for the cartilage layer or hydroxyapatite for the bone layer. As for the calcified interlayer, the bone marrow mesenchymal stromal cells (BMSCs) seeded on PLLA/Gel fibrous mesh was pre-differentiated with a mixed osteoinductive/chondroinductive (1:1) medium. With this gradient construct being implanted in rabbit knee osteochondral defect, it was found that both the cartilage and subchondral bone were regenerated effectively with reproduced tidal line structure. The importance of implants with biomimetic gradients for osteochondral defect repair was confirmed, and cell sheets on electrospun fibrous meshes were flexible for gradient structure construction via the layer-by-layer stacking technology. Highlights Composite fibrous meshes with tissue-specific components are electrospun. Confluent BMSCs on fibrous meshes are chondrogenically or osteogenically induced. BMSCs hypertrophy is induced with the mixture of chondroinductive and osteoinductive medium. The pre-differentiated cell/mesh complexes are stacked layer-by-layer to form gradient construct. The gradient construct efficiently promotes osteochondral regeneration in rabbit joint.

Metronidazole Delivery Nanosystem Able To Reduce the Pathogenicity of Bacteria in Colorectal Infection.

Metronidazole (MTZ) is a drug potentially used for the treatment of intestinal infections, namely, the ones caused by colorectal surgery. The traditional routes of administration decrease its local effectiveness and present off-site effects. To circumvent such limitations, herein a drug delivery system (DDS) based on MTZ-loaded nanoparticles (NPs) immobilized at the surface of electrospun fibrous meshes is proposed. MTZ at different concentrations (1, 2, 5, and 10 mg mL-1) was loaded into chitosan-sodium tripolyphosphate NPs. The MTZ loaded into NPs at the highest concentration showed a quick release in the first 12 h, followed by a gradual release. This DDS was not toxic to human colonic cells. When tested against different bacterial strains, a significant reduction of Escherichia coli and Staphylococcus aureus was observed, but no effect was found against Enterococcus faecalis. Therefore, this DDS offers high potential to locally prevent the occurrence of infections after colorectal anastomosis.

Characterizing the Effect of Adding Boron Nitride Nanotubes on the Mechanical Properties of Electrospun Polymer Nanocomposite Microfibers Mesh.

Electrospun fibrous meshes have a variety of applications such as filtration, drug delivery, energy storage, and engineered tissues due to their high surface area to mass ratio. Therefore, understanding the mechanical properties of these continuously evolving meshes is critical to expand and improve their performance. In this study, the effect of adding Boron Nitride Nanotube (BNNT) to Polymethylmethacrylate (PMMA) composite meshes on the mechanical properties of the polymer is studied. Electrospinning is used to fabricate microfiber meshes of PMMA and BNNT-PMMA. The fabricated meshes are tested experimentally with a uniaxial tensile tester. In addition, a theoretical model is introduced to investigate the effect of the number of fibers and the diameter of fiber inside the mesh on Young’s Modulus and Tensile Strength of the PMMA mesh. By adding 0.5% BNNT to the PMMA, Young’s Modulus and Tensile Strength of the PMMA mesh improved by 62.4% and 9.3%, respectively. Furthermore, simulated results show enhanced mesh properties when increasing the number of fibers and the single fiber diameter inside the mesh. The findings of this study help in understanding the mechanical properties of the nanocomposite electrospun meshes which expands and improves its utilization in different applications.

Microfluidic-assisted electrospinning, an alternative to coaxial, as a controlled dual drug release system to treat inflammatory arthritic diseases

Inflammatory arthritic diseases are characterized by a persistent inflammation of the synovial tissues where tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) pro-inflammatory cytokines are over-expressed, leading to progressive musculoskeletal disability. Methotrexate (MTX), a disease-modifying-anti-rheumatic drug (DMARD) commonly applied in their treatment, can be used in combination with biological-DMARDs as anti-TNFα antibody to improve the treatments efficacy. However, their systemic administration comes with severe side-effects and limited therapeutic efficacy due to their off-target distribution and short half-life. To overcome such limitations, encapsulation of clinically relevant concentrations of MTX and anti-TNFα antibody into polycaprolactone (PCL) or poly(vinyl-alcohol) (PVA) microfluidic-assisted or coaxial electrospun fibrous meshes is proposed as local controlled dual drug release systems.Release studies show that microfluidic-assisted electrospinning meshes encapsulating both drugs achieved higher concentrations than coaxials. Biological assays using human articular chondrocytes (hACs) and monocytic cells (THP-1 cell line) demonstrate that fibrous meshes encapsulating the drugs are non-toxic. The systems' efficacy is proved by a significant decrease of TNFα and IL-6 concentrations in conditioned medium of lipopolysaccharide (LPS)-stimulated THP-1 cells, especially in the presence of microfluidic-assisted electrospun meshes, when compared with THP-1 conditioned medium (59.5% and 83.9% less, respectively).Therefore, microfluidic-assisted electrospinning fibrous meshes with encapsulating drugs represent an alternative to coaxial, as a local therapy for inflammatory arthritis diseases.

Stimulation of Neurite Outgrowth Using Autologous NGF Bound at the Surface of a Fibrous Substrate.

Peripheral nerve injury still remains a major clinical challenge, since the available solutions lead to dysfunctional nerve regeneration. Even though autologous nerve grafts are the gold standard, tissue engineered nerve guidance grafts are valid alternatives. Nerve growth factor (NGF) is the most potent neurotrophic factor. The development of a nerve guidance graft able to locally potentiate the interaction between injured neurons and autologous NGF would be a safer and more effective alternative to grafts that just release NGF. Herein, a biofunctional electrospun fibrous mesh (eFM) was developed through the selective retrieval of NGF from rat blood plasma. The neurite outgrowth induced by the eFM-NGF systems was assessed by culturing rat pheochromocytoma (PC12) cells for 7 days, without medium supplementation. The biological results showed that this NGF delivery system stimulates neuronal differentiation, enhancing the neurite growth more than the control condition.

Novel Poly(ester urethane urea)/Polydioxanone Blends: Electrospun Fibrous Meshes and Films.

In this work, we report the electrospinning and mechano-morphological characterizations of scaffolds based on blends of a novel poly(ester urethane urea) (PHH) and poly(dioxanone) (PDO). At the optimized electrospinning conditions, PHH, PDO and blend PHH/PDO in Hexafluroisopropanol (HFIP) solution yielded bead-free non-woven random nanofibers with high porosity and diameter in the range of hundreds of nanometers. The structural, morphological, and biomechanical properties were investigated using Differential Scanning Calorimetry, Scanning Electron Microscopy, Atomic Force Microscopy, and tensile tests. The blended scaffold showed an elastic modulus (~5 MPa) with a combination of the ultimate tensile strength (2 ± 0.5 MPa), and maximum elongation (150% ± 44%) in hydrated conditions, which are comparable to the materials currently being used for soft tissue applications such as skin, native arteries, and cardiac muscles applications. This demonstrates the feasibility of an electrospun PHH/PDO blend for cardiac patches or vascular graft applications that mimic the nanoscale structure and mechanical properties of native tissue.

Pluronic F127-Modified Electrospun Fibrous Meshes for Synergistic Combination Chemotherapy of Colon Cancer.

Colon cancer ranks as the third most common malignancy in the world. Combination chemotherapy, resorting to electrospun fibrous technology, has been considered as a promising strategy to exert synergistic effects in colon cancer treatment. Herein, we manufactured various pluronic F127 (PF127)-modified electrospun fibrous meshes with different weight ratios of camptothecin (CPT) and curcumin (CUR). The fluorescence characterization of the obtained PF127-CPT-meshes, PF127-CUR-meshes, and PF127-CPT/CUR-meshes (2:1) showed that CPT and CUR were evenly distributed within individual fibers of these meshes. Drug release experiments revealed that both types of drugs could be released from fibrous meshes simultaneously and sustainably. Importantly, these meshes exhibited strong in vitro anti-colon cancer activities, compared with the control meshes without drugs. Moreover, the combination index values of the PF127-CPT/CUR-meshes (CPT/CUR weight ratio = 5:1, 3:1, or 2:1) were <0.5 after incubation for respective 24 and 36 h, indicating the synergistic anti-colon cancer effects of CPT and CUR in fibrous meshes. Collectively, these results demonstrate that PF127-CPT/CUR-meshes can be developed as an efficient implantable system for effective synergistic treatment of colon cancer.

Myogenic Tissue Regeneration: A New Insight

Till today, the conventional therapeutic techniques are used to cure many muscle tissue related diseases. With the advent of modern science and technology, Tissue Engineering (TE) has evolved as a novel means to repair and regenerate different tissues. Recently graphene and graphene based composites are emerging as better materials compared to the conventional biopolymers to fabricate scaffolds for skeletal muscle TE and other biomedical applications. Addition of graphene oxide (GO) nanoplatelets (GOnPs) in bioactive polymers was found to enhance enhanced conductivity (σ) as well as dielectric permittivity (ε) of the scaffolds, due to the presence of GO surface charge, which enhance biocompatibility of the scaffolds. In the thesis work, for the first time, human Umbilical Cord Blood (UBC) derived mesenchymal stem cells (CB-hMSCs) were reported to directly differentiate to skeletal muscle cells (hSkMCs) on spin coated thin GO sheets, composed of GOnPs, and on electrospun fibrous meshes of GO–polymer (poly-caprolactone, PCL and poly lactic co-glycolic acid, PLGA)) composite meshes. These substrates exhibited excellent myoblast differentiations and promoted self-aligned myotubes formation similar to natural orientation. Scanning and transmission electron microscopy, Raman, infrared (vibration spectroscopic) etc. studies were carried out for the characterizations of GO sheet and the composite scaffolds. Significantly enhanced values of both conductivity and dielectric constant of the GO–Polymer composites attributed to the GO surface charge which provided favorable cues for the formation of superior cellular interaction and formation of multinucleated myotubes on the electrospun meshes. The present results demonstrated that such novel GO based polymer composite substrates might be used as potential candidates for the myoblast differentiation and proliferation of CB-hMSCs for the next generation skeletal muscle tissue repair and regeneration.

Fibronectin-Functionalized Fibrous Meshes as a Substrate to Support Cultures of Thymic Epithelial Cells.

Thymic epithelial cells (TECs) are the main regulators of T lymphocyte development and selection, requiring a three-dimensional (3D) environment to properly perform these biological functions. The aim of this work was to develop a 3D culture substrate that allows the survival and proliferation of TECs. Thus, electrospun fibrous meshes (eFMs) were functionalized with fibronectin, one of the major extracellular matrix (ECM) proteins of the thymus. For that, highly porous eFMs were activated using oxygen plasma treatment followed by amine insertion, which allows the immobilization of fibronectin through EDC/NHS chemistry. The medullary TECs presented increased proliferation, viability, and protein synthesis when cultured on fibronectin-functionalized eFMs (FN-eFMs). These cells showed a spread morphology, with increased migration toward the inner layers of FN-eFMs and the production of thymic ECM proteins, such as collagen type IV and laminin. These results suggest that FN-eFMs are an effective substrate for supporting thymic cell cultures.

In Situ Biological Transmutation of Catalytic Lactic Acid Waste into Calcium Lactate in a Readily Processable Three-Dimensional Fibrillar Structure for Bone Tissue Engineering.

A bioinspired three-dimensional (3D) fibrous structure possesses biomimicry, valuable functionality, and performance to scaffolding in tissue engineering. In particular, an electrospun fibrous mesh has been studied as a scaffold material in various tissue regeneration applications. We produced a low-density 3D polycaprolactone/lactic acid (LA) fibrous mesh (3D-PCLS) via the novel lactic-assisted 3D electrospinning technique exploiting the catalytic properties of LA as we reported previously. In the study, we demonstrated a strategy of recycling the LA component to synthesize the osteoinductive biomolecules in situ, calcium lactate (CaL), thereby forming a 3D bioactive PCL/CaL fibrous scaffold (3D-SCaL) for bone tissue engineering. The fiber morphology of 3D-PCLS and its packing degree could have been tailored by modifying the spinning solution and the collector design. 3D-SCaL demonstrated successful conversion of CaL from LA and exhibited the significantly enhanced biomineralization capacity, cell infiltration and proliferation rate, and osteoblastic differentiation in vitro with two different cell lines, MC3T3-e1 and bone marrow stem cells. In conclusion, 3D-SCaL proves to be a highly practical and accessible strategy using a variety of polymers to produce 3D fibers as a potential candidate for future regenerative medicine and tissue engineering applications.

Osteochondral tissue regenerated via a strategy by stacking pre-differentiated BMSC sheet on fibrous mesh in a gradient

The reconstruction of osteochondral tissue remains a challenging task in clinical therapy because of its heterogeneous structure. The best way to face the challenge is to develop a biomimetic construct to mimic the multilayered gradient from cartilage, to calcified cartilage and subchondral bone. In this study, bone marrow mesenchymal stromal cells (BMSCs) were cultured on electrospun fibrous meshes and cell sheets were incubated. The fibrous meshes were composed of 50% poly(L-lactide) and 50% gelatin, displaying excellent biocompatibility, cell affinity and degradability. Differentiation of BMSC sheets on fibrous meshes was induced chondrogenically or osteogenically. In particular, the BMSC sheets were able to be efficiently induced differentiating towards calcified cartilage by using a 1:1 (v/v) mixed medium of chondrogenic and osteogenic inductive media. Thus, a gradient 3D construct was built by stacking the differently pre-differentiated cell/mesh complexes layer by layer from top to bottom to mimic the cartilage-to-bone transition. With this gradient construct being implanted in the rabbit knee osteochondral defect, it was confirmed that it could promote the tissue regeneration with intact cartilage layer formation in comparison with the multilayered construct without a gradient. The strategy of using properly pre-differentiated BMSC sheet on fibrous mesh to build the osteochondral interface was thus suggested as being feasible and effective in mimicking its hierarchical complexity, and favored the repairing of injured joint cartilage.

Modulation of drug release by decoration with Pluronic F127 to improve anti-colon cancer activity of electrospun fibrous meshes

Applications of fibrous meshes for localized chemotherapy have been limited by the lack of optimal carriers that are capable of releasing sufficient drug locally. To overcome this obstacle, we introduced Pluronic F127 (PF127) to the camptothecin (CPT)-loaded poly(lactic acid/glycolic acid) (PLGA) electrospun fibrous meshes, abbreviated as PPC, for modulation of drug release. These PPC meshes had smooth surface and high drug loading (5.6–6.8%). Addition of PF127 obviously improved the hydrophilicity of the meshes. Interestingly, the CPT release rate of PPC meshes was significantly higher than that of CPT-loaded PLGA (PLGA-CPT) meshes. Most importantly, incorporation of PF127 in the meshes led to significant reduction in the CT-26 viability compared to PLGA-CPT mesh. The improved anticancer effects of PPC meshes were mainly due to the induction of apoptosis in CT-26 cells. These findings suggest that PPC mesh could be a promising implantable system that may enhance the therapeutic efficacy and prevent tumor recurrence after surgical resection.

Fabrication of in vitro 3D mineralized tissue by fusion of composite spheroids incorporating biomineral-coated nanofibers and human adipose-derived stem cells

Development of a bone-like 3D microenvironment with stem cells has always been intriguing in bone tissue engineering. In this study, we fabricated composite spheroids by combining functionalized fibers and human adipose-derived stem cells (hADSCs), which were fused to form a 3D mineralized tissue construct. We prepared fragmented poly (ι-lactic acid) (PLLA) fibers approximately 100 μm long by partial aminolysis of electrospun fibrous mesh. PLLA fibers were then biomineralized with various concentrations of NaHCO3 (0.005, 0.01, and 0.04 M) to form mineralized fragmented fibers (mFF1, mFF2, and mFF3, respectively). SEM analysis showed that the minerals in mFF2 and mFF3 completely covered the fiber surface, and surface chemistry analysis confirmed the presence of hydroxyapatite peaks. Additionally, mFFs formed composite spheroids with hADSCs, demonstrating that the cells were strongly attached to mFFs and homogeneously distributed throughout the spheroid. In vitro culture of spheroids in the media without osteogenic supplements showed significantly enhanced expression of osteogenic genes including Runx2 (20.83 ± 2.83 and 22.36 ± 2.18 fold increase), OPN (14.24 ± 1.71 and 15.076 ± 1.38 fold increase), and OCN (4.36 ± 0.41 and 5.63 ± 0.51 fold increase) in mFF2 and mFF3, respectively, compared to the no mineral fiber group. In addition, mineral contents were significantly increased at day 7. Blocking the biomineral-mediated signaling by PSB 603 significantly down regulated the expression of these genes in mFF3 at day 7. Finally, we fused composite spheroids to form a mineralized 3D tissue construct, which maintained the viability of cells and showed pervasively distributed minerals within the structure. Our composite spheroids could be used as an alternative platform for the development of in vitro bone models, in vivo cell carriers, and as building blocks for bioprinting 3D bone tissue. Statement of SignificanceThis manuscript described our recent work for the preparation of biomimeral-coated fibers that can be assembled with mesenchymal stem cells and provide bone-like environment for directed control over osteogenic differentiation. Biomineral coating onto synthetic, biodegradable single fibers was successfully carried out using multiple steps, combination of template protein coating inspired from mussel adhesion and charge-charge interactions between template proteins and mineral ions. The biomineral-coated single micro-scale fibers (1–2.5 μm in diameter) were then assembled with human adipose tissue derived stem cells (hADSCs). The assembled structure exhibited spheroidal architecture with few hundred micrometers. hADSCs within the spheroids were differentiated into osteogenic lineage in vitro and mineralized in the growth media. These spheroids were fused to form in vitro 3D mineralized tissue with larger size.

A novel biocompatible conducting polyvinyl alcohol (PVA)-polyvinylpyrrolidone (PVP)-hydroxyapatite (HAP) composite scaffolds for probable biological application

We have prepared biocompatible composites of 80wt% polyvinyl alcohol (PVA)-(20wt%) polyvinylpyrrolidone (PVP) blend with different concentrations of bioactive nanohydroxyapatite, Ca10(PO4)6(HO)2 (HAP). The composite films demonstrated maximum effective conductivity (σ∼1.64×10−4S/m) and effective dielectric constant (ε∼290) at percolation threshold concentration (∼10wt% HAP) at room temperature. These values of σ and ε are much higher than those of PVA, PVP or HAP. Our preliminary observation indicated excellent biocompatibility of the electrospun fibrous meshes of two of these composites with different HAP contents (8.5 and 5wt% within percolation threshold concentration) using NIH 3T3 fibroblast cell line. Cells viability on the well characterized composite fibrous scaffolds was determined by MTT [3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay analysis. Enhancement of σ, due to HAP addition, was found to show increased biocompatibility of the fibrous scaffold. Enhanced σ value of the PVA/PVP-HAP composite provided supporting cues for the increased cell viability and biocompatibility of the composite fibrous meshes. Excellent biocompatibility these electrospun composite scaffolds made them to plausible potential candidates for tissue engineering or other biomedical applications.

A Patient-Inspired Ex Vivo Liver Tissue Engineering Approach with Autologous Mesenchymal Stem Cells and Hepatogenic Serum.

Design and development of ex vivo bioengineered liver tissue substitutes intended for subsequent in vivo implantation has been considered therapeutically relevant to treat many liver diseases that require whole-organ replacement on a long-term basis. The present study focus on patient-inspired ex vivo liver tissue engineering strategy to generate hepatocyte-scaffold composite by combining bone marrow mesenchymal stem cells (BMSCs) derived from cardiac failure patients with secondary hyperbilirubinemia as primers of hepatic differentiation and hepatocyte growth factor (HGF)-enriched sera from same individuals as hepatic inducer. A biodegradable and implantable electrospun fibrous mesh of poly-l-lactic acid (PLLA) and gelatin is used as supporting matrix (average fiber diameter = 285 ± 64 nm, porosity = 81 ± 4%, and average pore size = 1.65 ± 0.77 μm). The fibrous mesh supports adhesion, proliferation, and hepatic commitment of patient-derived BMSCs of adequate stemness using HGF-enriched sera generating metabolically competent hepatocyte-like cells, which is comparable to the hepatic induction with defined recombinant growth factor cocktail. The observed results confirm the combinatorial effects of nanofiber topography and biochemical cues in guiding hepatic specification of BMSCs. The fibrous mesh-hepatocyte construct developed in this study using natural growth factors and BMSCs of same individual is promising for future therapeutic applications in treating damaged livers.