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The paper describes the synthesis of hydroxyapatite (HAp) and strontium-substituted hydroxyapatite (SrHAp) from sand lobster shells by a hydrothermal method. The HAp and SrHAp were incorporated into the polyvinyl alcohol (PVA) nanofiber scaffold through the eletrospinning method. The scaffolds were incorporated with 5wt% of hydroxyapatite (HAp), 5wt%, 10wt%, and 15% of SrHAp. The physicochemical, mechanical, and in vitro biological properties of the scaffold were evaluated. The incorporation of HAp or SrHAp was evidenced by the diffraction patterns and the phosphate functional groups related to HAp. The morphological results showed the decrement of fiber diameter in line with the increased SrHAp concentration. A tensile test was conducted to investigate the mechanical properties of the scaffolds, and the results showed that the scaffolds perform poorly at a higher SrHAp concentration because of exceeding agglomeration levels. The PVA/SrHAp15 performed the best antibacterial activity against E. coli and S. aureus with an inhibition zone of (15.2 ± 0.2) and (14.5 ± 0.8), respectively. The apatite formation was more abundant in PVA/SrHAp10 after immersion in a simulated body fluid (SBF). Cell viability results showed that the scaffold enabled the osteoblast cells to grow and proliferate. The biocompatibility of HAp and SrHAp resulted in the enhancement of cell adhesion. Based on all tests, the PVA/SrHAp 10 scaffold shows a strong candidate for further in vivo studies., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Critical-sized segmental long bone defects represent a challenging clinical dilemma in the management of battlefield and trauma-related injuries. The residual bone marrow cavity of damaged long bones contains many bone marrow mesenchymal stem cells (BMSCs), which provide a substantial source of cells for bone repair. Thus, a three-dimensional (3D) vertically aligned nanofiber scaffold (VAS) is developed with long channels and large pore size. The pore of VAS toward the bone marrow cavity after transplantation, enables the scaffolds to recruit BMSCs from the bone marrow cavity to the defect area. In vivo, it is found that VAS can significantly shorten gap distance and promote new bone formation compared to the control and collagen groups after 4 and 8 weeks of implantation. The single-cell sequencing results discovered that the 3D nanotopography of VAS can promote BMSCs differentiation to chondrocytes and osteoblasts, and up-regulate related gene expression, resulting in enhancing the activities of bone regeneration, endochondral ossification, bone trabecula formation, bone mineralization, maturation, and remodeling. The Alcian blue and bone morphogenetic protein 2 (BMP-2) immunohistochemical staining verified significant cartilage formation and bone formation in the VAS group, corresponding to the single-cell sequencing results. The study can inspire the design of next-generation scaffolds for effective long-bone regeneration is expected by the authors., (© 2024 Wiley‐VCH GmbH.)

High strength and ductility are highly desired in fiber-reinforced composites, yet achieving both simultaneously remains elusive. A hierarchical architecture is developed utilizing high aspect ratio chemically transformable thermoplastic nanofibers that form covalent bonding with the matrix to toughen the fiber-matrix interphase. The nanoscale fibers are electrospun on the micrometer-scale reinforcing carbon fiber, creating a physically intertwined, randomly oriented scaffold. Unlike conventional covalent bonding of matrix molecules with reinforcing fibers, here, the nanofiber scaffold is utilized - interacting non-covalently with core fiber but bridging covalently with polymer matrix - to create a high volume fraction of immobilized matrix or interphase around core reinforcing elements. This mechanism enables efficient fiber-matrix stress transfer and enhances composite toughness. Molecular dynamics simulation reveals enhancement of the fiber-matrix adhesion facilitated by nanofiber-aided hierarchical bonding with the matrix. The elastic modulus contours of interphase regions obtained from atomic force microscopy clearly indicate the formation of stiffer interphase. These nanoengineered composites exhibit a ≈60% and ≈100% improved in-plane shear strength and toughness, respectively. This approach opens a new avenue for manufacturing toughened high-performance composites., (© 2023 Oak Ridge National Laboratory, managed by UT-Battelle, LLC. Advanced Science published by Wiley-VCH GmbH.)

Pulp-Dentin regeneration is a key aspect of maintain tooth vitality and enabling good oral-systemic health. This study aimed to investigate a nanofibrous scaffold loaded with a small molecule i.e. Tideglusib to promote odontogenic differentiation. Tideglusib (GSK-3β inhibitor) interaction with GSK-3β was determined using molecular docking and stabilization of β-catenin was examined by confocal microscopy. 3D nanofibrous scaffolds were fabricated through electrospinning and their physicochemical characterizations were performed. Scaffolds were seeded with mesenchymal stem cells or pre-odontoblast cells to determine the cells proliferation and odontogenic differentiation. Our results showed that Tideglusib (TG) binds with GSK-3β at Cys199 residue. Stabilization and nuclear translocation of β-catenin was increased in the odontoblast cells treated with TG. SEM analysis revealed that nanofibers exhibited controlled architectural features that effectively mimicked the natural ECM. UV-Vis spectroscopy demonstrated that TG was incorporated successfully and released in a controlled manner. Both kinds of biomimetic nanofibrous matrices (PCLF-TG100, PCLF-TG1000) significantly stimulated cells proliferation. Furthermore, these scaffolds significantly induced dentinogenic markers (ALP, and DSPP) expression and biomineralization. In contrast to current pulp capping material driving dentin repair, the sophisticated, polymeric scaffold systems with soluble and insoluble spatiotemporal cues described here can direct stem cell differentiation and dentin regeneration. Hence, bioactive small molecule-incorporated nanofibrous scaffold suggests an innovative clinical tool for dentin tissue engineering.

Nanofiber scaffolds have emerged as a revolutionary drug delivery platform for promoting wound healing, due to their unique properties, including high surface area, interconnected porosity, excellent breathability, and moisture absorption, as well as their spatial structure which mimics the extracellular matrix. However, the use of nanofibers to achieve controlled drug loading and release still presents many challenges, with ongoing research still exploring how to load drugs onto nanofiber scaffolds without loss of activity and how to control their release in a specific spatiotemporal manner. This comprehensive study systematically reviews the applications and recent advances related to drug-laden nanofiber scaffolds for skin-wound management. First, we introduce commonly used methods for nanofiber preparation, including electrostatic spinning, sol-gel, molecular self-assembly, thermally induced phase separation, and 3D-printing techniques. Next, we summarize the polymers used in the preparation of nanofibers and drug delivery methods utilizing nanofiber scaffolds. We then review the application of drug-loaded nanofiber scaffolds for wound healing, considering the different stages of wound healing in which the drug acts. Finally, we briefly describe stimulus-responsive drug delivery schemes for nanofiber scaffolds, as well as other exciting drug delivery systems.

Synthetic peptides are promising structural and functional components of bioactive and tissue-engineering scaffolds. Here, we demonstrate the design of self-assembling nanofiber scaffolds based on peptide amphiphile (PA) molecules containing multi-functional histidine residues with trace metal (TM) coordination ability. The self-assembly of PAs and characteristics of PA nanofiber scaffolds along with their interaction with Zn, Cu, and Mn essential microelements were studied. The effects of TM-activated PA scaffolds on mammalian cell behavior, reactive oxygen species (ROS), and glutathione levels were shown. The study reveals the ability of these scaffolds to modulate adhesion, proliferation, and morphological differentiation of neuronal PC-12 cells, suggesting a particular role of Mn(II) in cell-matrix interaction and neuritogenesis. The results provide a proof-of-concept for the development of histidine-functionalized peptide nanofiber scaffolds activated with ROS- and cell-modulating TMs to induce regenerative responses.

Bone fractures are often companied with poor bone healing and high rates of infection. Early recruitment of mesenchymal stem cells (MSCs) is critical for initiating efficient bone repair, and mild thermal stimulation can accelerate the recovery of chronic diseases. Here, a bioinspired, staged photothermal effect-reinforced multifunctional scaffold was fabricated for bone repair. Uniaxially aligned electrospun polycaprolactone nanofibers were doped with black phosphorus nanosheets (BP NSs) to endow the scaffold with excellent near-infrared (NIR) responsive capability. Apt19S was then decorated on the surface of the scaffold to selectively recruit MSCs toward the injured site. Afterward, microparticles of phase change materials loaded with antibacterial drugs were also deposited on the surface of the scaffold, which could undergo a solid-to-liquid phase transition above 39 °C, triggering the release of payload to eliminate bacteria and prevent infection. Under NIR irradiation, photothermal-mediated up-regulation of heat shock proteins and accelerated biodegradation of BP NSs could promote the osteogenic differentiation of MSCs and biomineralization. Overall, this strategy shows the ability of bacteria elimination, MSCs recruitment, and bone regeneration promotion with the assistance of photothermal effect in vitro and in vivo , which emphasizes the design of a bioinspired scaffold and its potential for a mild photothermal effect in bone tissue engineering.

Electrospinning has contributed substantially to the construction of nanofibrous scaffolds for potential tissue engineering and regenerative medicine applications. However, conventional electrospinning only has the ability to generate and collect nanofiber scaffolds with a randomly oriented fibrous pattern, which lack the necessary cell alignment guidance function. In this study, a novel electrospinning fiber-collecting device was designed and developed by setting a series of small pin-ring-structured collectors on a large plain plate. Specifically, we demonstrated that the pin-ring-structured collectors, which were constructed by inserting a metal pin into the center of a metal ring, could collect the as-electrospun nanofibers with radially oriented structures in an innovative manner. We first investigated the suitable polymeric concentration for electrospinning poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and the optimum electrospinning concentration of PHBV was found to be 12% ( w / v ) PHBV dissolved in hexafluoroisopropyl alcohol (HFIP). Then, 12% ( w / v ) PHBV solution was electrospun into radially oriented nanofiber scaffolds using our novel electrospinning strategy, and their various performances were further compared with conventionally randomly oriented nanofiber scaffolds that were also produced from 12% ( w / v ) PHBV solution. The results showed that the radially oriented PHBV nanofiber scaffolds exhibited obviously enhanced mechanical properties and decreased hydrophobicity compared with the randomly oriented PHBV nanofiber scaffold controls. Importantly, the biological properties of radially oriented PHBV nanofiber scaffolds were also demonstrated to be enhanced, compared with randomly oriented PHBV nanofiber scaffolds, by effectively inducing cell alignment and significantly promoting cell proliferation. In sum, the present study indicates that our as-prepared nanofiber scaffolds with a radially oriented pattern are of great interest for advanced applications, such as wound dressings and tissue-engineered scaffolds.

Objective: This project's primary purpose was to create engineered vascular scaffolds using polyurethane, polycaprolactone, and pullulan polymers, along with suitable mechanical-dynamic conditions. Therefore, electrospun scaffolds with optimized intrinsic physiological properties and the ability to support endothelial cells were prepared in vitro, and cell viability was studied in PCL-PU and PCL-PU scaffolds containing Pullulan., The Main Methods: The electrospinning method has been used to prepare PCL-PU and PCL-PU scaffolds containing Pullulan. The scaffold's surface morphology was evaluated using SEM microscopic imaging. The scaffolds' physicochemical properties were prepared using ATR-FTIR, strain stress, and water contact angle tests, and the biocompatibility of PCL-PU and PU-PCL-Pl nanofibers was evaluated using the MTT test., Principal Findings: The test results showed that PCL-PU scaffolds containing Pullulan have more suitable mechanical properties such as stress-strain, water contact angle, swelling rate, biocompatibility, fiber diameter, and pore size compared to PU-PCL. The culture of endothelial cells under static conditions on these scaffolds did not cause cytotoxic effects under static conditions compared to the control group. SEM images confirmed the ability of endothelial cells to attach to the scaffold surface., Summary and Conclusion: The results showed that PCL-PU substrate containing pullulan could stimulate endothelial cells' proliferation under static conditions.

Electrospun fibers, with proven ability to promote tissue regeneration, are widely being explored for rotator cuff repairing. However, without post treatment, the microstructure of the electrospun scaffold is vastly different from that of natural extracellular matrix (ECM). Moreover, during mechanical loading, the nanofibers slip that hampers the proliferation and differentiation of migrating stem cells. Here, electrospun nanofiber scaffolds, with crimped nanofibers and welded joints to biomimic the intricate natural microstructure of tendon-to-bone insertion, were prepared using poly(ester-urethane)urea and gelatin via electrospinning and double crosslinking by a multi-bonding network densification strategy. The crimped nanofiber scaffold (CNS) features bionic tensile stress and induces chondrogenic differentiation, laying credible basis for in vivo experimentation. After repairing a rabbit massive rotator cuff tear using a CNS for 3 months, the continuous translational tendon-to-bone interface was fully regenerated, and fatty infiltration was simultaneously inhibited. Instead of micro-CT, μCT was employed to visualize the integrity and intricateness of the three-dimensional microstructure of the CNS-induced-healed tendon-to-bone interface at an ultra-high resolution of less than 1 μm. This study sheds light on the correlation between nanofiber post treatment and massive rotator cuff repair and provides a general strategy for crimped nanofiber preparation and tendon-to-bone interface imaging characterization., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors.)

The Caco-2 cell monolayer has been extensively used for the high-throughput assessing of nutrient absorption, screening of drug permeability, and studying the intestinal physiological process in vitro . The most used Caco-2 cell model is the Transwell model with polycarbonate microporous membranes. However, Caco-2 cells in the classical Transwell model need 21 days to gain an intact and mature monolayer. Electrospun nanofiber scaffolds mimicking the natural extracellular matrix could improve cell adhesion, proliferation, and expression, whereas there are no reports that intestinal cells were cultured on the electrospun nanofiber scaffolds. Here, electrospun polylactic acid (PLA) nanofiber scaffolds were chosen as the ideal scaffolds for Caco-2 cell monolayers to construct a modified Transwell. Cell morphology and polarity were studied. Monolayer barrier properties were assessed by measuring transepithelial electrical resistance (TEER) and the leakage of phenol red. As found, intact Caco-2 cell monolayers were formed on the PLA nanofiber scaffolds after 4 days of culture. After 4 days, the TEER increased to 422 Ω·cm 2 and the apparent permeability coefficients of phenol red decreased to 1.0 ± 0.1 × 10 -6 cm/s, suggesting that Caco-2 cell monolayers developed a formidable barrier to small molecules on the surface of PLA nanofiber scaffolds. Microvilli and tight junctions were clearly visible after day 3. Besides, Caco-2 cell monolayers on the surface of PLA nanofiber scaffolds presented higher differentiation properties than on the surface of the polycarbonate microporous membrane in traditional Transwell including higher alkaline phosphatase activity and higher P-gp activity. Results of quercetin absorption and probiotics adhesion demonstrated that Caco-2 cell monolayers formed on the surface of PLA nanofiber scaffolds also had better physiological function and prediction function in vitro . Overall, the present study indicated that the Transwell with the structurally and functionally biomimetic electrospun PLA nanofiber scaffold could be potentially developed as a promising in vitro intestinal model.

In tissue engineering, scaffolds should provide the topological and physical cues as native tissues to guide cell adhesion, growth, migration, and differentiation. Fibrous structure is commonly present in human musculoskeletal tissues, including muscles, tendons, ligaments, and cartilage. Biomimetic fibrous scaffolds are thus critical for musculoskeletal tissue engineering. Electrospinning is a versatile technique for fabricating nanofibers from a variety of biomaterials. However, conventional electrospinning can only generate 2D nanofiber mats. Postprocessing methods are often needed to create 3D electrospun nanofiber scaffolds. In this chapter, we present two novel electrospinning-based scaffold fabrication techniques, which can generate 3D nanofiber scaffolds in one-station process: divergence electrospinning and hybrid 3D printing with parallel electrospinning. These techniques can be applied for engineering tissues with aligned fiber structures.

In this study, a system of dexamethasone sodium phosphate (DEXP)-loaded chitosan nanoparticles embedded in poly-ε-caprolacton (PCL) and gelatin electrospun nanofiber scaffold was introduced with potential therapeutic application for treatment of the nervous system. Besides anti-inflammatory properties, DEXP act through its glucocorticoid receptors, which are involved in the inhibition of astrocyte proliferation and microglial activation. Bovine serum albumin (BSA) was used to improve the encapsulation efficiency of DEXP within chitosan nanoparticles and to overcome its initial burst release. BSA incorporation within the chitosan nanoparticles increased the encapsulation efficiency of DEXP from 30% to 77%. The comparison between DEXP release profile from PCL/gelatin scaffold with and without chitosan nanoparticles revealed that the system of DEXP-BSA-loaded chitosan nanoparticles embedded in electrospun PCL nanofiber scaffold provided a more controlled release pattern of the loaded drug. The scaffolds properties in terms of structure, hydrophilicity, cell compatibility, mechanical property, and biodegradability were further investigated, which might show its potential application for the repair of spinal cord injury.

Full-thickness skin defect is one of the main clinical problems, which cannot be repaired spontaneously. The aim of this study was to evaluate the feasibility of combining nanofibers with ADM as a bilayer scaffold for treatment of full-thickness skin wounds in a single-step procedure. The nanofibrous polycaprolactone/fibrinogen scaffolds were fabricated by electrospinning. Subsequently, mesenchymal stem cells were isolated from rat adipose tissues and characterized by flow cytometry. Cell adhesion, proliferation, and the epidermal differentiation potential of adipose-derived stem cells (ADSCs) on nanofibrous scaffolds were investigated by scanning electron microscopy (SEM), alamarBlue, and real-time PCR, respectively. In animal studies, full-thickness excisional wounds were created on the back of rats and treated with following groups: ADM, ADM-ADSCs, nanofiber, nanofiber-ADSCs, bilayer, and bilayer-ADSCs. In all groups, wounds were harvested on days 14 and 21 after treatment to evaluate re-epithelialization, blood vessel density, and collagen content. The results indicated that ADSCs seeded on ADM, nanofiber, and bilayer scaffolds can promote re-epithelialization, angiogenesis, and collagen remodeling in comparison with cell-free scaffolds. In conclusion, nanofiber-ADSCs showed the best results for re-epithelialization (according to histological scoring), average blood vessel density (92.7 ± 6.8), and collagen density (87.4 ± 4.9%) when compared to the control and other experimental groups.

Adult tissue-derived mesenchymal stem cells (MSCs) are known to produce a number of bioactive factors, including neurotrophic growth factors, capable of supporting and improving nerve regeneration. However, with a finite culture expansion capacity, MSCs are inherently limited in their lifespan and use. We examined here the potential utility of an alternative, mesenchymal-like cell source, derived from induced pluripotent stem cells, termed induced mesenchymal progenitor cells (MiMPCs). We found that several genes were upregulated and proteins were produced in MiMPCs that matched those previously reported for MSCs. Like MSCs, the MiMPCs secreted various neurotrophic and neuroprotective factors, including brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), osteopontin, and osteonectin, and promoted neurite outgrowth in chick embryonic dorsal root ganglia (DRG) cultures compared with control cultures. Cotreatment with a pharmacological Trk-receptor inhibitor did not result in significant decrease in MiMPC-induced neurite outgrowth, which was however inhibited upon Jak/STAT3 blockade. These findings suggest that the MiMPC induction of DRG neurite outgrowth is unlikely to be solely dependent on BDNF, but instead Jak/STAT3 activation by IL-6 and/or LIF is likely to be critical neurotrophic signaling pathways of the MiMPC secretome. Taken together, these findings suggest MiMPCs as a renewable, candidate source of therapeutic cells and a potential alternative to MSCs for peripheral nerve repair, in view of their ability to promote nerve growth by producing many of the same growth factors and cytokines as Schwann cells and signaling through critical neurotrophic pathways. Stem Cells Translational Medicine 2018;7:45-58., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Biphasic materials, comprised of an ordered arrangement of two different material phases within a material, have the potential for a wide variety of applications including filtration, protective clothing and tissue engineering. This study reports for the first time, a process for engineering biphasic Janus-type polymeric nanofiber (BJPNF) networks via the centrifugal jet spinning technique. BJPNF alignment and fiber diameter was dependent on fabrication rotational speed as well as solution composition. The biphasic character of these BJPNFs, which was controlled via the rotational speed of fabrication, was confirmed at the individual nanofiber scale using energy dispersive X-ray spectroscopy, and at the bulk, macro-scale using attenuated total reflectance-Fourier transform infrared spectroscopy. Biphasic character was also demonstrated at the functional level via differing affinities on either side of the BJPNF for cell attachment. Our work thus presents a method for fabricating BJPNF scaffold networks where there might be a need for different properties on either side of a material. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2455-2464, 2017., (© 2016 Wiley Periodicals, Inc.)

Considering the important factor of bioactive nanohydoxyapatite (nHA) to enhance osteoconductivity or bone-bonding capacity, nHA was incorporated into an electrospun polycaprolactone (PCL) membrane using electrospinning techniques. The viscosity of the PCL and nHA/PCL with different concentrations of nHA was measured and the morphology of the electrospun membranes was compared using a field emission scanning electron microscopy. The water contact angle of the nanofiber determined the wettability of the membranes of different concentrations. The surface roughness of the electrospun nanofibers fabricated from pure PCL and nHA/PCL was determined and compared using atomic force microscopy. Attenuated total reflectance Fourier transform infrared spectroscopy was used to study the chemical bonding of the composite electrospun nanofibers. Beadless nanofibers were achieved after the incorporation of nHA with a diameter of 200-700 nm. Results showed that the fiber diameter and the surface roughness of electrospun nanofibers were significantly increased after the incorporation of nHA. In contrast, the water contact angle (132° ± 3.5°) was reduced for PCL membrane after addition of 10% (w/w) nHA (112° ± 3.0°). Ultimate tensile strengths of PCL membrane and 10% (w/w) nHA/PCL membrane were 25.02 ± 2.3 and 18.5 ± 4.4 MPa. A model drug tetracycline hydrochloride was successfully loaded in the membrane and the membrane demonstrated good antibacterial effects against the growth of bacteria by showing inhibition zone for E. coli (2.53 ± 0.06 cm) and B. cereus (2.87 ± 0.06 cm).

The capacity of gelatin/chitosan/bioactive glass nanopowders (GEL/CS/BGNPs) scaffolds was investigated for increasing human endometrial stem cells (hEnSCs) differentiation into the endothelial cells in the presence of angiogenic factors. GEL/CS nanofibrous scaffold with different contents of BGNPs were fabricated and assessed. Expression of endothelial markers (CD31, vascular endothelial cadherin (VE-cadherin), and KDR) in differentiated cells was evaluated. Results showed the diameter of nanofiber increases with decreasing the BG content in GEL/CS scaffolds. Moreover, in vitro study indicated that the GEL/CS/BGNPs scaffold with 1.5% BGNPs content provided a suitable three-dimensional structure for endothelial cells differentiation. Thus, the GEL/CS/BGNPs scaffold can be recommended for blood vessels repair.

Periodontitis is a major cause for tooth loss, which affects about 15% of the adult population. Cementum regeneration has been the crux of constructing the periodontal complex. Cementum protein 1 (CEMP1) is a cementum-specific protein that can induce cementogenic differentiation. In this study, poly(ethylene glycol) (PEG)-stabilized amorphous calcium phosphate (ACP) nanoparticles were prepared by wet-chemical method and then loaded with recombinant human CEMP1 (rhCEMP1) for controlled release. An electrospun multiphasic scaffold constituted of poly(ε-caprolactone) (PCL), type I collagen (COL), and rhCEMP1/ACP was fabricated. The effects of rhCEMP1/ACP/PCL/COL scaffold on the attachment proliferation, osteogenic, and cementogenic differentiations of human periodontal ligament cells, (PDLCs) were systematically investigated. A critical size defect rat model was introduced to evaluate the effect of tissue regeneration of the scaffolds in vivo. The results showed that PEG-stabilized ACP nanoparticles formed a core-shell structure with sustained release of rhCEMP1 for up to 4 weeks. rhCEMP1/ACP/PCL/COL scaffold could suppress PDLCs proliferation behavior and upregulate the expression of cementoblastic markers including CEMP1 and cementum attachment protein while downregulating osteoblastic markers including osteocalcin and osteopontin when it was cocultured with PDLCs in vitro for 7 days. Histology analysis of cementum after being implanted with the scaffold in rats for 8 weeks showed that there was cementum-like tissue formation but little bone formation. These results indicated the potential of using electrospun multiphasic scaffolds for controlled release of rhCEMP1 for promoting cementum regeneration in reconstruction of the periodontal complex.

Extracellular matrix (ECM) structure and biochemistry provide cell-instructive cues that promote and regulate tissue growth, function, and repair. From a structural perspective, the ECM is a scaffold that guides the self-assembly of cells into distinct functional tissues. The ECM promotes the interaction between individual cells and between different cell types, and increases the strength and resilience of the tissue in mechanically dynamic environments. From a biochemical perspective, factors regulating cell-ECM adhesion have been described and diverse aspects of cell-ECM interactions in health and disease continue to be clarified. Natural ECMs therefore provide excellent design rules for tissue engineering scaffolds. The design of regenerative three-dimensional (3D) engineered scaffolds is informed by the target ECM structure, chemistry, and mechanics, to encourage cell infiltration and tissue genesis. This can be achieved using nanofibrous scaffolds composed of polymers that simultaneously recapitulate 3D ECM architecture, high-fidelity nanoscale topography, and bio-activity. Their high porosity, structural anisotropy, and bio-activity present unique advantages for engineering 3D anisotropic tissues. Here, we use the heart as a case study and examine the potential of ECM-inspired nanofibrous scaffolds for cardiac tissue engineering. We asked: Do we know enough to build a heart? To answer this question, we tabulated structural and functional properties of myocardial and valvular tissues for use as design criteria, reviewed nanofiber manufacturing platforms and assessed their capabilities to produce scaffolds that meet our design criteria. Our knowledge of the anatomy and physiology of the heart, as well as our ability to create synthetic ECM scaffolds have advanced to the point that valve replacement with nanofibrous scaffolds may be achieved in the short term, while myocardial repair requires further study in vitro and in vivo., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The aim of this study was the ex vivo expansion of Umbilical Cord Blood hematopoietic stem cells on biocompatible nanofiber scaffolds., Materials and Methods: CD133+ hematopoietic stem cells were separated from umbilical cord blood using MidiMacs (positive selection) system by means of monocolonal antibody CD133 (microbeads); subsequently, flowcytometry method was done to assess the purity of separated cells. Isolated cells were cultured on plate (2 Dimensional) and fibronectin conjugated polyethersulfon nanofiber scaffold, simultaneously (3 Dimensional). Colony assay test was performed to show colonization ability of expanded cells., Results: Cell count analysis revealed that expansion of hematopoietic stem cells in 2dimensional (2D) environment was greater than 3dimensional (3D) condition (p= 0.01). Assessment of stem cell- phenotype after expansions was performed by flowcytometric analysis which is showed that the maintenance of CD133 marker in expanded cells in 3 dimensional condition were higher than expanded cells in 2 dimensional condition (p=0.01). Moreover, colony assay test was performed before and after of expansion to show colonization ability of expanded cells both in 3D and 2D culture and results revealed more ability of 3D culture compared with 2D culture (p= 0.03)., Conclusion: The results of current study confirmed that umbilical cord blood CD133+ haematopoietic stem cells are able to expand on fibronectin conjugated polyethersulfon scaffold. These findings indicated that 3D is a proper and valuable cell culture system for hematopoietic stem cells expansion, compared to 2D in invitro situation.

In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold (SAPNS)-containing poly(lactic-co-glycolic acid) (PLGA) conduit (SPC) and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.

Cellular microenvironments are important in coaxing cells to behave collectively as functional, structured tissues. Important cues in this microenvironment are the chemical, mechanical and spatial arrangement of the supporting matrix in the extracellular space. In engineered tissues, synthetic scaffolding provides many of these microenvironmental cues. Key requirements are that synthetic scaffolds should recapitulate the native three-dimensional (3D) hierarchical fibrillar structure, possess biomimetic surface properties and demonstrate mechanical integrity, and in some tissues, anisotropy. Electrospinning is a popular technique used to fabricate anisotropic nanofiber scaffolds. However, it suffers from relatively low production rates and poor control of fiber alignment without substantial modifications to the fiber collector mechanism. Additionally, many biomaterials are not amenable for fabrication via high-voltage electrospinning methods. Hence, we reasoned that we could utilize rotary jet spinning (RJS) to fabricate highly aligned hybrid protein-polymer with tunable chemical and physical properties. In this study, we engineered highly aligned nanofiber constructs with robust fiber alignment from blends of the proteins collagen and gelatin, and the polymer poly-ε-caprolactone via RJS and electrospinning. RJS-spun fibers retain greater protein content on the surface and are also fabricated at a higher production rate compared to those fabricated via electrospinning. We measured increased fiber diameter and viscosity, and decreasing fiber alignment as protein content increased in RJS hybrid fibers. RJS nanofiber constructs also demonstrate highly anisotropic mechanical properties mimicking several biological tissue types. We demonstrate the bio-functionality of RJS scaffold fibers by testing their ability to support cell growth and maturation with a variety of cell types. Our highly anisotropic RJS fibers are therefore able to support cellular alignment, maturation and self-organization. The hybrid nanofiber constructs fabricated by RJS therefore have the potential to be used as scaffold material for a wide variety of biological tissues and organs, as an alternative to electrospinning., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To evaluate the efficacy and safety of a hybrid bioartificial liver (HBAL) system in the treatment of acute liver failure., Methods: Canine models with acute liver failure were introduced with intravenous administration of D-galactosamine. The animals were divided into: the HBAL treatment group (n = 8), in which the canines received a 3-h treatment of HBAL; the bioartificial liver (BAL) treatment group (n = 8), in which the canines received a 3-h treatment of BAL; the non-bioartificial liver (NBAL) treatment group (n = 8), in which the canines received a 3-h treatment of NBAL; the control group (n = 8), in which the canines received no additional treatment. Biochemical parameters and survival time were determined. Levels of xenoantibodies, RNA of porcine endogenous retrovirus (PERV) and reverse transcriptase (RT) activity in the plasma were detected., Results: Biochemical parameters were significantly decreased in all treatment groups. The TBIL level in the HBAL group was lower than that in other groups (2.19 ± 0.55 μmol/L vs 24.2 ± 6.45 μmol/L, 12.47 ± 3.62 μmol/L, 3.77 ± 1.83 μmol/L, P < 0.05). The prothrombin time (PT) in the BAL and HBAL groups was significantly shorter than the NBAL and control groups (18.47 ± 4.41 s, 15.5 ± 1.56 s vs 28.67 ± 5.71 s, 21.71 ± 3.4 s, P < 0.05), and the PT in the HBAL group was shortest of all the groups. The albumin in the BAL and HBAL groups significantly increased and a significantly higher level was observed in the HBAL group compared with the BAL group (27.7 ± 1.7 g/L vs 25.24 ± 1.93 g/L). In the HBAL group, the ammonia levels significantly decreased from 54.37 ± 6.86 to 37.75 ± 6.09 after treatment (P < 0.05); there were significant difference in ammonia levels between other the groups (P < 0.05). The levels of antibodies were similar before and after treatment. The PERV RNA and the RT activity in the canine plasma were all negative., Conclusion: The HBAL showed great efficiency and safety in the treatment of acute liver failure.

RADA16-I peptide hydrogel, a type of nanofiber scaffold derived from self-assembling peptide RADA16-I, has been extensively applied to regenerative medicine and tissue repair in order to develop novel nanomedicine systems. In this study, using RADA16-I peptide hydrogel, a three-dimensional (3D) cell culture model was fabricated for in vitro culture of three ovarian cancer cell lines. Firstly, the peptide nanofiber scaffold was evaluated by transmission electron microscopy and atom force microscopy. Using phase contrast microscopy, the appearance of the representative ovarian cancer cells encapsulated in RADA16-I peptide hydrogel on days 1, 3, and 7 in 24-well Petri dishes was illustrated. The cancer cell-nanofiber scaffold construct was cultured for 5 days, and the ovarian cancer cells had actively proliferative potential. The precultured ovarian cancer cells exhibited nearly similar adhesion properties and invasion potentials in vitro between RADA16-I peptide nanofiber and type I collagen, which suggested that RADA16-I peptide hydrogel had some similar characteristics to type I collagen. The precultured ovarian cancer cells had two-fold to five-fold higher anticancer drug resistance than the conventional two-dimensional Petri dish culture. So the 3D cell model on peptide nanofiber scaffold is an optimal type of cell pattern for anticancer drug screening and tumor biology.