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The dura mater, as the crucial outermost protective layer of the meninges, plays a vital role in safeguarding the underlying brain tissue. Neurosurgeons face significant challenges in dealing with trauma or large defects in the dura mater, as they must address the potential complications, such as wound infections, pseudomeningocele formation, cerebrospinal fluid leakage, and cerebral herniation. Therefore, the development of dural substitutes for repairing or reconstructing the damaged dura mater holds clinical significance. In this review we highlight the progress in the development of dural substitutes, encompassing autologous, allogeneic, and xenogeneic replacements, as well as the polymeric-based dural substitutes fabricated through various scaffolding techniques. In particular, we explore the development of composite materials that exhibit improved physical and biological properties for advanced dural substitutes. Furthermore, we address the challenges and prospects associated with developing clinically relevant alternatives to the dura mater. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) bioprinting is a promising and rapidly evolving technology in the field of additive manufacturing. It enables the fabrication of living cellular constructs with complex architectures that are suitable for various biomedical applications, such as tissue engineering, disease modeling, drug screening, and precision regenerative medicine. The ultimate goal of bioprinting is to produce stable, anatomically-shaped, human-scale functional organs or tissue substitutes that can be implanted. Although various bioprinting techniques have emerged to develop customized tissue-engineering substitutes over the past decade, several challenges remain in fabricating volumetric tissue constructs with complex shapes and sizes and translating the printed products into clinical practice. Thus, it is crucial to develop a successful strategy for translating research outputs into clinical practice to address the current organ and tissue crises and improve patients' quality of life. This review article discusses the challenges of the existing bioprinting processes in preparing clinically relevant tissue substitutes. It further reviews various strategies and technical feasibility to overcome the challenges that limit the fabrication of volumetric biological constructs and their translational implications. Additionally, the article highlights exciting technological advances in the 3D bioprinting of anatomically shaped tissue substitutes and suggests future research and development directions. This review aims to provide readers with insight into the state-of-the-art 3D bioprinting techniques as powerful tools in engineering functional tissues and organs. [ABSTRACT FROM AUTHOR]

On 19 May 2018, more than 12,000 women gathered at Hyehwa subway station in Seoul, South Korea to protest discrimination against Korean women and spy camera involved crimes. This rally was a response to an incident in which a male nude model in a class was secretly photographed by a female model at Hongik University. This study examined how discourses on Twitter regarding the incident led to the demonstration and what was the memory working that shaped significant discourses through critical discourse analysis. First, a discourse that "women have long been victims" emerged through personal remembrances. Second, photographs of the female suspect standing with police officers directed a discourse that "women have been treated unfairly by public authorities" through collective witnessing. Third, many women contextualized the incident as a gendered event by connecting the past feminist movements. Finally, through appropriating past slogans and accumulated hashtags on Twitter, the main slogan of the rally #Equal_punishment_for_equal_crime was established. This study provides an under-researched context of digital mnemonic practices and the logic of connective actions by analyzing feminist movements in South Korea. [ABSTRACT FROM AUTHOR]

Dysfunction in the olfactory system of a person can have adverse effects on their health and quality of life. It can even increase mortality among individuals. Olfactory dysfunction is related to many factors, including post-viral upper respiratory infection, head trauma, and neurodegenerative disorders. Although some clinical therapies such as steroids and olfactory training are already available, their effectiveness is limited and controversial. Recent research in the field of therapeutic nanoparticles and stem cells has shown the regeneration of dysfunctional olfactory systems. Thus, we are motivated to highlight these regenerative approaches. For this, we first introduce the anatomical characteristics of the olfactory pathway, then detail various pathological factors related to olfactory dysfunctions and current treatments, and then finally discuss the recent regenerative endeavors, with particular focus on nanoparticle-based drug delivery systems and stem cells. This review offers insights into the development of future therapeutic approaches to restore and regenerate dysfunctional olfactory systems. [ABSTRACT FROM AUTHOR]

In recent years, freeform three-dimensional (3D) printing has led to significant advances in the fabrication of artificial tissues with vascularized structures. This technique utilizes a supporting matrix that holds the extruded printing ink and ensures shape maintenance of the printed 3D constructs within the prescribed spatial precision. Since the printing nozzle can be translated omnidirectionally within the supporting matrix, freeform 3D printing is potentially applicable for the fabrication of complex 3D objects, incorporating curved, and irregular shaped vascular networks. To optimize freeform 3D printing quality and performance, the rheological properties of the printing ink and supporting matrix, and the material matching between them are of paramount importance. In this review, we shall compare conventional 3D printing and freeform 3D printing technologies for the fabrication of vascular constructs, and critically discuss their working principles and their advantages and disadvantages. We also provide the detailed material information of emerging printing inks and supporting matrices in recent freeform 3D printing studies. The accompanying challenges are further discussed, aiming to guide freeform 3D printing by the effective design and selection of the most appropriate materials/processes for the development of full-scale functional vascularized artificial tissues. [ABSTRACT FROM AUTHOR]

The eggshell membrane (ESM) is an abundant resource with innate complex structure and composition provided by nature. With at least 60 million tonnes of hen eggs produced globally per annum, utilisation of this waste resource is highly attractive in positively impacting sustainability worldwide. Given the morphology and mechanical properties of this membrane, it has great potential as a biomaterials for wound dressing. However, to date, no studies have demonstrated nor reported this application. As such, the objective of this investigation was to identify and optimise a reproducible extraction protocol of the ESM and to assess the physical, chemical, mechanical and biological properties of the substrate with a view to use as a wound dressing. ESM samples were isolated by either manual peeling (ESM-strip) or via extraction using acetic acid [ESM-A0.5] or ethylenediaminetetraacetic acid, EDTA [ESM-E0.9]. Energy dispersive X-ray spectroscopy (EDS) confirmed that there were no traces of calcium residues from the extraction process. Fourier transform infrared (FTIR) spectroscopy revealed that the extraction method (acetic acid and EDTA) did not alter the chemical structures of the ESM and also clarified the composition of the fibrous proteins of the ESM. Scanning electron microscopy (SEM) analyses revealed a three-layer composite structure of the ESM: an inner layer as continuous, dense and non-fibrous (limiting membrane), a middle layer with a network of fibres (inner shell membrane) and the outer layer (outer shell membrane) of larger fibres. Material properties including optical transparency, porosity, fluid absorption/uptake, thermal stability, mechanical profiling of the ESM samples were performed and demonstrated suitable profiles for translational applications. Biological in vitro studies using SV40 immortalised corneal epithelial cells (ihCEC) and corneal mesenchymal stromal cells (C-MSC) demonstrated excellent biocompatibility. Taken together, these results document the development of a novel sustainable biomaterial that may be used for ophthalmic wounds and/or other biomedical therapies. [ABSTRACT FROM AUTHOR]

Current gold standard to treat soft tissue injuries caused by trauma and pathological condition are autografts and off the shelf fillers, but they have inherent weaknesses like donor site morbidity, immuno-compatibility and graft failure. To overcome these limitations, tissue-engineered polymers are seeded with stem cells to improve the potential to restore tissue function. However, their interaction with native tissue is poorly understood so far. To study these interactions and improve outcomes, we have fabricated scaffolds from natural polymers (collagen, fibrin and elastin) by custom-designed processes and their material properties such as surface morphology, swelling, wettability and chemical cross-linking ability were characterised. By using 3D scaffolds, we comprehensive assessed survival, proliferation and phenotype of adipose-derived stem cells in vitro. In vivo, scaffolds were seeded with adipose-derived stem cells and implanted in a rodent model, with X-ray microtomography, histology and immunohistochemistry as read-outs. Collagen-based materials showed higher cell adhesion and proliferation in vitro as well as higher adipogenic properties in vivo. In contrast, fibrin demonstrated poor cellular and adipogenesis properties but higher angiogenesis. Elastin formed the most porous scaffold, with cells displaying a non-aggregated morphology in vitro while in vivo elastin was the most degraded scaffold. These findings of how polymers present in the natural polymers mimicking ECM and seeded with stem cells affect adipogenesis in vitro and in vivo can open avenues to design 3D grafts for soft tissue repair. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), including exosomes, carry the genetic packages of RNA, DNA, and proteins and are heavily involved in cell-cell communications and intracellular signalings. Therefore, EVs are spotlighted as therapeutic mediators for the treatment of injured and dysfunctional tissues as well as biomarkers for the detection of disease status and progress. Several key issues in EVs, including payload content and bioactivity, targeting and bio-imaging ability, and mass-production, need to be improved to enable effective therapeutics and clinical translation. For this, significant efforts have been made recently, including genetic modification, biomolecular and chemical treatment, application of physical/mechanical cues, and 3D cultures. Here we communicate those recent technological advances made mainly in the biogenesis process of EVs or at post-collection stages, which ultimately aimed to improve the therapeutic efficacy in tissue healing and disease curing and the possibility of clinical translation. This communication will help tissue engineers and biomaterial scientists design and produce EVs optimally for tissue regenerative therapeutics. [ABSTRACT FROM AUTHOR]

Using microspherical scaffolds as building blocks to repair bone defects of specific size and shape has been proposed as a tissue engineering strategy. Here, phosphate glass (PG) microcarriers doped with 5 mol % TiO2 and either 0 mol % CoO (CoO 0%) or 2 mol % CoO (CoO 2%) were investigated for their ability to support osteogenic and vascular responses of human mesenchymal stem cells (hMSCs). Together with standard culture techniques, cell-material interactions were studied using a novel perfusion microfluidic bioreactor that enabled cell culture on microspheres, along with automated processing and screening of culture variables. While titanium doping was found to support hMSCs expansion and differentiation, as well as endothelial cell-derived vessel formation, additional doping with cobalt did not improve the functionality of the microspheres. Furthermore, the microfluidic bioreactor enabled screening of culture parameters for cell culture on microspheres that could be potentially translated to a scaled-up system for tissue-engineered bone manufacturing. [ABSTRACT FROM AUTHOR]

Drivers of RNA interference are potent for manipulating gene and protein levels, which enable the restoration of dysregulated mRNA expression that is commonly associated with injuries and diseases. This review summarizes the potential of targeting neuroglial cells, using RNA interference, to treat nerve injuries sustained in the central nervous system. In addition, the various methods of delivering these RNA interference effectors will be discussed. [ABSTRACT FROM AUTHOR]

Cancer stem cells have been shown to be important in tumorigenesis processes, such as tumor growth, metastasis, and recurrence. As such, many three-dimensional models have been developed to establish an ex vivo microenvironment that cancer stem cells experience under in vivo conditions. Cancer stem cells propagating in three-dimensional culture systems show physiologically related signaling pathway profiles, gene expression, cell–matrix and cell–cell interactions, and drug resistance that reflect at least some of the tumor properties seen in vivo. Herein, we discussed the presently available Cancer stem cell three-dimensional culture models that use biomaterials and engineering tools and the biological implications of these models compared to the conventional ones. [ABSTRACT FROM AUTHOR]

Brain diseases including neurodegenerative disorders and tumours are among the most serious health problems, degrading the quality of life and causing massive economic cost. Nanoparticles that load and deliver drugs and genes have been intensively studied for the treatment of brain diseases, and have demonstrated some biological effects in various animal models. Among other efforts taken in the nanoparticle development, targeting of blood brain barrier, specific cell type or local intra-/extra-cellular space is an important strategy to enhance the therapeutic efficacy of the nanoparticle delivery systems. This review underlies the targeting issue in the nanoparticle development for the treatment of brain diseases, taking key exemplar studies carried out in various in vivo models. [ABSTRACT FROM AUTHOR]

For skeletal muscle engineering, scaffolds that can stimulate myogenic differentiation of cells while possessing suitable mechanical properties (e.g. flexibility) are required. In particular, the elastic property of scaffolds is of importance which helps to resist and support the dynamic conditions of muscle tissue environment. Here, we developed highly flexible nanocomposite nanofibrous scaffolds made of polycarbonate diol and isosorbide-based polyurethane and hydrophilic nano-graphene oxide added at concentrations up to 8%. The nano-graphene oxide incorporation increased the hydrophilicity, elasticity, and stress relaxation capacity of the polyurethane-derived nanofibrous scaffolds. When cultured with C2C12 cells, the polyurethane–nano-graphene oxide nanofibers enhanced the initial adhesion and spreading of cells and further the proliferation. Furthermore, the polyurethane–nano-graphene oxide scaffolds significantly up-regulated the myogenic mRNA levels and myosin heavy chain expression. Of note, the cells on the flexible polyurethane–nano-graphene oxide nanofibrous scaffolds could be mechanically stretched to experience dynamic tensional force. Under the dynamic force condition, the cells expressed significantly higher myogenic differentiation markers at both gene and protein levels and exhibited more aligned myotubular formation. The currently developed polyurethane–nano-graphene oxide nanofibrous scaffolds, due to their nanofibrous morphology and high mechanical flexibility, along with the stimulating capacity for myogenic differentiation, are considered to be a potential matrix for future skeletal muscle engineering. [ABSTRACT FROM AUTHOR]

The production of large quantities of functional vascularized bone tissue ex vivo still represent an unmet clinical challenge. Microcarriers offer a potential solution to scalable manufacture of bone tissue due to their high surface area-to-volume ratio and the capacity to be assembled using a modular approach. Microcarriers made of phosphate bioactive glass doped with titanium dioxide have been previously shown to enhance proliferation of osteoblast progenitors and maturation towards functional osteoblasts. Furthemore, doping with cobalt appears to mimic hypoxic conditions that have a key role in promoting angiogenesis. This characteristic could be exploited to meet the clinical requirement of producing vascularized units of bone tissue. In the current study, the human osteosarcoma cell line MG-63 was cultured on phosphate glass microspheres doped with 5% mol titanium dioxide and different concentrations of cobalt oxide (0%, 2% and 5% mol), under static and dynamic conditions (150 and 300 rpm on an orbital shaker). Cell proliferation and the formation of aggregates of cells and microspheres were observed over a period of two weeks in all glass compositions, thus confirming the biocompatibility of the substrate and the suitability of this system for the formation of compact micro-units of tissue. At the concentrations tested, cobalt was not found to be cytotoxic and did not alter cell metabolism. On the other hand, the dynamic environment played a key role, with moderate agitation having a positive effect on cell proliferation while higher agitation resulting in impaired cell growth. Finally, in static culture assays, the capacity of cobalt doping to induce vascular endothelial growth factor (VEGF) upregulation by osteoblastic cells was observed, but was not found to increase linearly with cobalt oxide content. In conclusion, Ti–Co phosphate glasses were found to support osteoblastic cell growth and aggregate formation that is a necessary precursor to tissue formation and the upregaulation of VEGF production can potentially support vascularization. [ABSTRACT FROM AUTHOR]

Angiogenesis is considered an important issue in the development of biomaterials for the successful regeneration of tissues including bone. While growth factors are commonly used with biomaterials to promote angiogenesis, some ions released from biomaterials can also contribute to angiogenic events. Many silica-based biomaterials have been widely used for the repair and regeneration of tissues, mainly hard tissues such as bone and tooth structure. They have shown excellent performance in bone formation by stimulating angiogenesis. The release of silicate and others (Co and Cu ions) has therefore been implicated to play critical roles in the angiogenesis process. In this short review, we highlight the in vitro and in vivo findings of angiogenesis (and the related bone formation) stimulated by the various types of silicon-containing biomaterials where silicate ions released might play essential roles. We discuss further the possible molecular mechanisms underlying in the ion-induced angiogenic events. [ABSTRACT FROM AUTHOR]

Strontium- and calcium-releasing, titanium-stabilised phosphate-based glasses with a controlled degradation rate are currently under development for orthopaedic tissue engineering applications. Ca and/or Sr were incorporated at varying concentrations in quaternary phosphate-based glasses, in order to promote osteoinduction. Ti was incorporated at a fixed concentration in order to prolong degradation. Glasses of the general formula (P2O5)–(Na2O)–(TiO2)–(CaO)–(SrO) were prepared via the melt-quench technique. The materials were characterised by energy-dispersive X-ray spectroscopy, X-ray diffraction, 31P magic angle spinning nuclear magnetic resonance, Fourier transform infrared spectroscopy, differential thermal analysis and density determination. The dissolution rate in distilled water was determined by measuring mass loss, ion release and pH change over a two-week period. In addition, the cytocompatibility and alkaline phosphatase activity of an osteoblast-like cell line cultured on the surface of glass discs was assessed. The glasses were shown to be amorphous and contained Q1, Q2 and Q3 species. Fourier transform infrared spectroscopy revealed small changes in the glass structure as Ca was substituted with Sr and differential thermal analysis confirmed a decrease in crystallisation temperature with increasing Sr content. Degradation and ion release studies also showed that mass loss was positively correlated with Sr content. These results were attributed to the lower electronegativity of Sr in comparison to Ca favouring the formation of phosphate-based mineral phases. All compositions supported cell proliferation and survival and induced at least 2.3-fold alkaline phosphatase activity relative to the control. Glass containing 17.5 mol% Sr had 3.6-fold greater alkaline phosphatase activity than the control. The gradual release of Ca and Sr supported osteoinduction, indicating their potential suitability in orthopaedic tissue engineering applications. [ABSTRACT FROM AUTHOR]

Exploiting hydrogels for the cultivation of stem cells, aiming to provide them with physico-chemical cues suitable for osteogenesis, is a critical demand for bone engineering. Here, we developed hybrid compositions of collagen and silica into hydrogels via a simple sol-gel process. The physico-chemical and mechanical properties, degradation behavior, and bone-bioactivity were characterized in-depth; furthermore, the in vitro mesenchymal stem cell growth and osteogenic differentiation behaviors within the 3D hybrid gel matrices were communicated for the first time. The hydrolyzed and condensed silica phase enabled chemical links with the collagen fibrils to form networked hybrid gels. The hybrid gels showed improved chemical stability and greater resistance to enzymatic degradation. The in vitro apatite-forming ability was enhanced by the hybrid composition. The viscoelastic mechanical properties of the hybrid gels were significantly improved in terms of the deformation resistance to an applied load and the modulus values under a dynamic oscillation. Mesenchymal stem cells adhered well to the hybrid networks and proliferated actively with substantial cytoskeletal extensions within the gel matrices. Of note, the hybrid gels substantially reduced the cell-mediated gel contraction behaviors, possibly due to the stiffer networks and higher resistance to cell-mediated degradation. Furthermore, the osteogenic differentiation of cells, including the expression of bone-associated genes and protein, was significantly upregulated within the hybrid gel matrices. Together with the physico-chemical and mechanical properties, the cellular behaviors observed within 3D gel matrices, being different from the previous approaches reported on 2D substrates, provide new information on the feasibility and usefulness of the silica-collagen system for stem cell culture and tissue engineering of hard tissues. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effects of a composite nanofibrous matrix made of biopolymer blend polycaprolactone-gelatin (BP) and mesoporous bioactive glass nanoparticles (BGNs) on the odontogenic differentiation of human dental pulp cells (HDPCs). BGN-BP nanomatrices, with BGN content of up to 20 wt%, were produced via electrospinning. The differentiation of the HDPCs was evaluated by using an ALP activity assay, calcified nodule formation, and mRNA expression for markers. Integrin and its underlying signal pathways were assessed via reverse transcriptase-polymerase chain reaction and Western blot analysis. Although cell growth and attachment on the BGN-BP nanomatrix was similar to that on BP, ALP activity, mineralized nodule formation, and mRNA, expressions involving ALP, osteocalcin, osteopontin, dentin sialophosphoprotein, and dentin matrix protein-1 were greater on BGN-BP. BGN-BP upregulated the key adhesion receptors (integrin components α1, α2, α5, and β1) and activated integrin downstream pathways, such as phosphorylated-focal adhesion kinase (p-FAK), and p-paxillin. In addition, BGN-BP activated BMP receptors, BMP-2 mRNA, and p-Smad 1/5/8, and such activation was blocked by the BMP antagonist, noggin. Furthermore, BGN-BP induced phosphorylation of extracellular signal-regulated kinase, protein kinase 38, and c-Jun-N-terminal kinase mitogen-activated protein kinases and activated expression of the transcription factors Runx2 and Osterix in HDPCs. Collectively, the results indicated for the first time that a BGN-BP composite nanomatrix promoted odontogenic differentiation of HDPCs through the integrin, BMP, and mitogen-activated protein kinases signaling pathway. Moreover, the nanomatrix is considered to be promising scaffolds for the culture of HDPCs and dental tissue engineering. [ABSTRACT FROM AUTHOR]

Synthetic biopolymers are commonly used for the repair and regeneration of damaged tissues. Specifically targeting bone, the composite approach of utilizing inorganic components is considered promising in terms of improving mechanical and biological properties. We developed gelatin-apatite co-precipitates which mimic the native bone matrix composition within poly(lactide-co-caprolactone) (PLCL). Ionic reaction of calcium and phosphate with gelatin molecules enabled the co-precipitate formation of gelatin-apatite nanocrystals at varying ratios. The gelatin-apatite precipitates formed were carbonated apatite in nature, and were homogeneously distributed within the gelatin matrix. The incorporation of gelatin-apatite significantly improved the mechanical properties, including tensile strength, elastic modulus and elongation at break, and the improvement was more pronounced as the apatite content increased. Of note, the tensile strength increased to as high as 45 MPa (a four-fold increase vs. PLCL), the elastic modulus was increased up to 1500 MPa (a five-fold increase vs. PLCL), and the elongation rate was ∼240% (twice vs. PLCL). These results support the strengthening role of the gelatin-apatite precipitates within PLCL. The gelatin-apatite addition considerably enhanced the water affinity and the acellular mineral-forming ability in vitro in simulated body fluid; moreover, it stimulated cell proliferation and osteogenic differentiation. Taken together, the GAp-PLCL nanocomposite composition is considered to have excellent mechanical and biological properties, which hold great potential for use as bone regenerative matrices. [ABSTRACT FROM PUBLISHER]

The aim of the present study was to fabricate mineralized polycaprolactone nanofibrous scaffold and investigate its ability to elicit odontogenic differentiation of human dental pulp cells, compared to the pure polycaprolactone scaffold. Polycaprolactone nanofibrous scaffold was produced by electrospinning, and the surface was mineralized with apatite. Cellular behaviors on the mineralized polycaprolactone scaffold were assessed in terms of cell adhesion, growth, and odontoblastic differentiation. To evaluate the signal transduction of human dental pulp cells, mRNA expression was analyzed and Western blotting was performed. Mineralized polycaprolactone showed improved cell proliferation, mineralized nodule formation, and expression of odontoblastic marker genes including alkaline phosphatase, osteopontin, osteocalcin, dentin sialophosphoprotein (DSPP), and dentin matrix protein-1, as compared with pure polycaprolactone. Although the cell adhesion on the mineralized polycaprolactone was similar to that of the polycaprolactone, the expression level of proteins including collagen type I and the key adhesion receptor (integrin components α1, α2, and β1) was upregulated in mineralized polycaprolactone compared to polycaprolactone. Especially, cells seeded onto mineralized polycaprolactone scaffolds showed significantly increased levels of phosphorylated focal adhesion kinase, a marker of integrin activation, and downstream pathways, such as phosphor (p)-Akt, p-extracellular signal regulated kinase, p-c Jun N-terminal kinase, nuclear factor-kappa B, c-fos, and c-jun, compared with pure polycaprolactone. The mineralized polycaprolactone scaffold is attractive for dentin tissue engineering by promoting growth and odontogenic differentiation of human dental pulp cells through the integrin-mediated signaling pathway. [ABSTRACT FROM AUTHOR]

Novel microcarriers consisting of calcium phosphate cement and alginate were prepared for use as three-dimensional scaffolds for the culture and expansion of cells that are effective for bone tissue engineering. The calcium phosphate cement-alginate composite microcarriers were produced by an emulsification of the composite aqueous solutions mixed at varying ratios (calcium phosphate cement powder/alginate solution = 0.8–1.2) in an oil bath and the subsequent in situ hardening of the compositions during spherodization. Moreover, a porous structure could be easily created in the solid microcarriers by soaking the produced microcarriers in water and a subsequent freeze-drying process. Bone mineral-like apatite nanocrystallites were shown to rapidly develop on the calcium phosphate cement–alginate microcarriers under moist conditions due to the conversion of the α-tricalcium phosphate phase in the calcium phosphate cement into a carbonate–hydroxyapatite. Osteoblastic cells cultured on the microspherical scaffolds were proven to be viable, with an active proliferative potential during 14 days of culture, and their osteogenic differentiation was confirmed by the determination of alkaline phosphatase activity. The in situ hardening calcium phosphate cement–alginate microcarriers developed herein may be used as potential three-dimensional scaffolds for cell delivery and tissue engineering of bone. [ABSTRACT FROM AUTHOR]

In order to develop novel, effective therapies for central nervous system regeneration, it is essential to better understand the role of neurotrophic factors and to design, accordingly, better artificial scaffolds to support both neurite outgrowth and synapse formation. Both nerve growth factor and brain-derived neurotrophic factor are major factors in neural survival, development, synaptogenesis, and synaptic connectivity of primary cultured neurons. As a prime candidate coating material for such neural cultures, carbon nanotubes offer unique structural, mechanical, and electrical properties. In this study, carbon nanotubes coated glass-coverslips were used as the matrix of a primary neural culture system used to investigate the effects of carbon nanotubes on neurite outgrowth and nerve growth factor/brain-derived neurotrophic factor release and expression. For these purposes, we performed comparative analyses of primary cultured neurons on carbon nanotubes coated, non-coated, and Matrigel-coated coverslips. The morphological findings showed definite carbon nanotubes effects on the neurite outgrowths and synaptogenic figures in both cortical and hippocampal neurons when compared with the non-coated negative control. Although the carbon nanotubes did not change neurotrophin expression levels, it stimulated brain-derived neurotrophic factor release into the media from both types of neurons. Accordingly, we suggest a different mechanism of action between carbon nanotubes and Matrigel in relation to the specific neurotrophic factors. Since carbon nanotubes supply long-term extracellular molecular cues for the survival and neurite outgrowths of cultured neurons, the results from this study will contribute to an understanding of carbon nanotubes biological effects and provide new insight into their role in the secretion of neurotrophic factors. [ABSTRACT FROM PUBLISHER]

An effective tumor-targeted drug delivery system for photodynamic therapy was developed by designing ligand-mediated nanoparticles with stable formulations of a hydrophobic photosensitizer. Novel folic acid (FA)-conjugated amphiphilic block copolymers of polyethylene glycol (PEG) and poly-β-benzyl-L-aspartate (PBLA) with the potential to act as pH-responsive drug release reservoirs were synthesized. The photosensitizer, 2,4-diacetyl deuteroporphyrin IX dimethyl ether (DD-PpIX), was conjugated to the copolymers through pH-sensitive hydrazone linkage. The syntheses and compositions of all copolymers were confirmed by 1H NMR measurement. Photosensitizer-conjugated amphiphilic copolymeric nanoparticles (FA-PEG-P(Asp-Hyd)-DD-PpIX) were prepared by micelle formation in aqueous solution. The particle sizes of the FA-PEG-PBLA and FA-PEG-P(Asp-Hyd)-DD-PpIX nanoparticles were determined by light-scattering measurements. The range was 105–298 nm, depending on copolymer molecular weight and composition. Field emission scanning electron microscopy showed that the FA-PEG-P(Asp-Hyd)-DD-PpIX copolymeric nanoparticles were submicron in size and spherical in shape. The results of in vitro release tests showed that the release profiles of DD-PpIX from the nanoparticles were strongly pH-dependent and influenced by the amount of photosensitizer that was conjugated. In vitro tests using HeLa cells indicated that the FA-PEG-P(Asp-Hyd)-DD-PpIX nanoparticles had low dark-toxicity and showed more than 97% of cellular uptake. Based on our results, the FA-PEG-P(Asp-Hyd)-DD-PpIX nanoparticle system could be a promising approach for developing novel photosensitizer delivery carriers for photodynamic therapy. [ABSTRACT FROM PUBLISHER]

Scalable expansion of cells for regenerative cell therapy or to produce large quantities for high-throughput screening remains a challenge for bioprocess engineers. Laboratory scale cell expansion using t-flasks requires frequent passaging that exposes cells to many poorly defined bioprocess forces that can cause damage or alter their phenotype. Microcarriers offer a potential solution to scalable production, lending themselves to cell culture processes more akin to fermentation, removing the need for frequent passaging throughout the expansion period. One main problem with microcarrier expansion, however, is the difficulty in harvesting cells at the end of the process. Therefore, therapies that rely on cell delivery using biomaterial scaffolds could benefit from a microcarrier expansion system whereby the cells and microcarriers are transplanted together. In the current study, we used bioactive glass microcarriers doped with 5% TiO2 that display a controlled rate of degradation and conducted experiments to assess biocompatibility and growth of primary fibroblast cells as a model for cell therapy products. We found that the microcarriers are highly biocompatible and facilitate cell growth in a gradual controlled manner. Therefore, even without additional biofunctionalization methods, Ti-doped bioactive glass microcarriers offer potential as a cell expansion platform. [ABSTRACT FROM PUBLISHER]

This study assessed gender differences in human papillomavirus (HPV) awareness (including knowledge), health beliefs, and behavioral intentions to prevent infection. The participants comprised 763 and 905 sexually active men and women, respectively. Gender differences were observed in HPV knowledge, health beliefs, and sociodemographics that were significantly correlated with behavioral intentions to prevent infection. There were gender differences in the factors related to behavioral intentions to prevent HPV. In multiple regression analysis, HPV knowledge was not related to behavioral intentions, whereas perceived benefits were related to behavioral intentions consistently among men and women, while the effects of perceived barriers were inconsistent. HPV awareness was very low regardless of gender. While HPV education is urgently required for men, enhancing HPV awareness, reinforcing positive perceptions of HPV prevention, and reducing unhealthy sexual behaviors are necessary for the entire Korean population. [ABSTRACT FROM PUBLISHER]

This study aims to produce a degradable and bone-bioactive membrane for guiding bone regeneration by combining a degradable polymer, poly(lactic acid) (PLA), with a bioactive inorganic zinc-containing bioactive glass (ZnBG). The in vitro osteogenic development of rat bone marrow mesenchymal stem cells (rBMSCs) upon different membrane substrates (pure PLA control, PLA–BG, and PLA–ZnBG) was investigated in terms of bone cell phenotype syntheses and mineralization. Results showed significantly stimulated production of alkaline phosphatase and osteocalcin at days 14 and 21 in the membranes containing BG and ZnBG, with more in the samples containing ZnBG. The addition of ZnBG in PLA allowed the rBMSCs to express a high level of bone sialoprotein as confirmed by immunostaining. Cellular mineralization of the secreted extracellular matrix showed a significantly higher Ca level on the BG- and ZnBG-added membrane than on the PLA, and the more so in the ZnBG-added one. Based on the in vitro assessments using rBMSCs, the ZnBG-added PLA is considered to be of potential use in guiding active bone regeneration within the periodontal pocket. [ABSTRACT FROM AUTHOR]

Nanoparticle-based therapeutics delivery holds great promise for the treatment of intractable diseases. The high loading of drug molecules and their precise delivery to target sites are needed to gain optimal therapeutic functions of the nanoparticle delivery system. In this communication, we highlight, among other properties of nanoparticles (e.g. size, shape, surface chemistry, and degradation), the nanoscale topography, which has recently been shown to be an important parameter, ultimately determining drug loading, cell penetration, and body clearance. This nanotopographical aspect is considered to offer a new effective strategy to the development of nanoparticles for drug and gene delivery with enhanced therapeutic outcome. [ABSTRACT FROM AUTHOR]

Bone/cartilage interfacial tissue engineering needs to satisfy the differential properties and architectures of the osteochondral region. Therefore, biphasic or multiphasic scaffolds that aim to mimic the gradient hierarchy are widely used. Here, we find that two differently structured (topographically) three-dimensional scaffolds, namely, "dense" and "nanofibrous" surfaces, show differential stimulation in osteo- and chondro-responses of cells. While the nanofibrous scaffolds accelerate the osteogenesis of mesenchymal stem cells, the dense scaffolds are better in preserving the phenotypes of chondrocytes. Two types of porous scaffolds, generated by a salt-leaching method combined with a phase-separation process using the poly(lactic acid) composition, had a similar level of porosity (~90%) and pore size (~150 μm). The major difference in the surface nanostructure led to substantial changes in the surface area and water hydrophilicity (nanofibrous ≫ dense); as a result, the nanofibrous scaffolds increased the cell-to-matrix adhesion of mesenchymal stem cells significantly while decreasing the cell-to-cell contracts. Importantly, the chondrocytes, when cultured on nanofibrous scaffolds, were prone to lose their phenotype, including reduced chondrogenic expressions (SOX-9, collagen type II, and Aggrecan) and glycosaminoglycan content, which was ascribed to the enhanced cell–matrix adhesion with reduced cell–cell contacts. On the contrary, the osteogenesis of mesenchymal stem cells was significantly accelerated by the improved cell-to-matrix adhesion, as evidenced in the enhanced osteogenic expressions (RUNX2, bone sialoprotein, and osteopontin) and cellular mineralization. Based on these findings, we consider that the dense scaffold is preferentially used for the chondral-part, whereas the nanofibrous structure is suitable for osteo-part, to provide an optimal biphasic matrix environment for osteochondral tissue engineering. [ABSTRACT FROM AUTHOR]

Angiogenesis is considered an important issue in the development of biomaterials for the successful regeneration of tissues including bone. While growth factors are commonly used with biomaterials to promote angiogenesis, some ions released from biomaterials can also contribute to angiogenic events. Many silica-based biomaterials have been widely used for the repair and regeneration of tissues, mainly hard tissues such as bone and tooth structure. They have shown excellent performance in bone formation by stimulating angiogenesis. The release of silicate and others (Co and Cu ions) has therefore been implicated to play critical roles in the angiogenesis process. In this short review, we highlight the in vitro and in vivo findings of angiogenesis (and the related bone formation) stimulated by the various types of silicon-containing biomaterials where silicate ions released might play essential roles. We discuss further the possible molecular mechanisms underlying in the ion-induced angiogenic events. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries face some clinical obstacles and unsatisfactory functional outcomes. The slow regeneration rate of defected nerve delays functional recovery. To date, various therapeutic agents are used to enhance the survival and regeneration capacity of damaged neurons. Among these, nerve guide conduits held promise for peripheral nerve regeneration, through the physical guidance of the injured nerve across the lesions. Many natural and synthetic polymers are used to produce nerve conduits. Biopolymer-based biomaterials offer important options in control of structure, morphology, and chemistry as reasonable substitutes or mimics of extracellular matrix systems. Silk protein fibroin as a biocompatible natural polymer, possesses biodegradability, tunable mechanical properties, process ability, and suitable for the peripheral nerve conduits. This review highlights recent advances in the use of silk-based conduits for peripheral nerve regeneration. Further, the development of nerve conduits based on other biopolymers, including chitosan, alginate, collagen, and gelatin is discussed and compared. [ABSTRACT FROM PUBLISHER]