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1.
Skin Res Technol ; 30(6): e13764, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38853456

ABSTRACT

Injectable fillers, pivotal in aesthetic medicine, have evolved significantly with recent trends favoring biostimulators like calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) and poly-l-lactic acid (PLLA; Sculptra Aesthetics, Galderma, Dallas, TX). This study aims to compare the particle morphology of these two injectables and examine its potential clinical implications. Utilizing advanced light and scanning electron microscopy techniques, the physical characteristics of CaHA-CMC and PLLA particles were analyzed, including shape, size, circularity, roundness, aspect ratio, and quantity of phagocytosable particles. The findings reveal several morphological contrasts: CaHA-CMC particles exhibited a smooth, homogenous, spherical morphology with diameters predominantly ranging between 20 and 45 µm, while PLLA particles varied considerably in shape and size, appearing as micro flakes ranging from 2 to 150 µm in major axis length. The circularity and roundness of CaHA-CMC particles were significantly higher compared to PLLA, indicating a more uniform shape. Aspect ratio analysis further underscored these differences, with CaHA-CMC particles showing a closer resemblance to circles, unlike the more oblong PLLA particles. Quantification of the phagocytosable content of both injectables revealed a higher percentage of phagocytosable particles in PLLA. These morphological distinctions may influence the tissue response to each treatment. CaHA-CMC's uniform, spherical particles may result in reduced inflammatory cell recruitment, whereas PLLA's heterogeneous particle morphology may evoke a more pronounced inflammatory response.


Subject(s)
Dermal Fillers , Durapatite , Polyesters , Durapatite/chemistry , Polyesters/chemistry , Dermal Fillers/chemistry , Dermal Fillers/administration & dosage , Humans , Cosmetic Techniques , Particle Size , Biocompatible Materials/chemistry , Microscopy, Electron, Scanning
2.
Adv Funct Mater ; 33(1)2023 Jan 03.
Article in English | MEDLINE | ID: mdl-36714167

ABSTRACT

Fast healing of diabetic wounds remains a major clinical challenge. Herein, this work reports a strategy to combine nanofiber aerogels containing precision macrochannels and the LL-37-mimic peptide W379 for rapid diabetic wound healing. Nanofiber aerogels consisting of poly(glycolide-co-lactide) (PGLA 90:10)/gelatin and poly-p-dioxanone (PDO)/gelatin short electrospun fiber segments were prepared by partially anisotropic freeze-drying, crosslinking, and sacrificial templating with three-dimensional (3D)-printed meshes, exhibiting nanofibrous architecture and precision micro-/macrochannels. Like human cathelicidin LL-37, W379 peptide at a concentration of 3 µg/mL enhanced the migration and proliferation of keratinocytes and dermal fibroblasts in a cell scratch assay and a proliferation assay. In vivo studies show that nanofiber aerogels with precision macrochannels can greatly promote cell penetration compared to aerogels without macrochannels. Relative to control and aerogels with and without macrochannels, adding W379 peptides to aerogels with precision macrochannels shows the best efficacy in healing diabetic wounds in mice in terms of cell infiltration, neovascularization, and re-epithelialization. The fast re-epithelization could be due to upregulation of phospho-extracellular signal-regulated kinase (p38 MAPK) after treatment with W379. Together, the approach developed in this work could be promising for the treatment of diabetic wounds and other chronic wounds.

3.
Mol Pharm ; 20(1): 738-749, 2023 01 02.
Article in English | MEDLINE | ID: mdl-36485036

ABSTRACT

Peptide stability to proteases has been a major requirement for developing peptide therapeutics. This study investigates the effects of peptide stability on antimicrobial and antibiofilm activity under various conditions. For this purpose, two human cathelicidin-derived peptides differing in stability to proteases were utilized. While GF-17, a peptide derived from the major antimicrobial region of human LL-37, can be rapidly cleaved by proteases, the engineered peptide 17BIPHE2 is resistant to multiple proteases. In the standard antimicrobial susceptibility, killing kinetics, and membrane permeabilization assays conducted in vitro using planktonic bacteria, these two peptides displayed similar potency. The two peptides were also similarly active against methicillin-resistant Staphylococcus aureus (MRSA) USA300 prior to biofilm formation. However, 17BIPHE2 was superior to GF-17 in disrupting preformed biofilms probably due to both enhanced stability and slightly higher DNA binding capacity. In a wax moth model, 17BIPHE2 better protected insects from MRSA infection-caused death than GF-17, consistent with the slower degradation of 17BIPHE2 than GF-17. Here, peptide antimicrobial activity was found to be critical for in vivo efficacy. When incorporated in the nanofiber/microneedle delivery device, GF-17 and 17BIPHE2 displayed a similar effect in eliminating MRSA in murine chronic wounds, underscoring the advantage of nanofibers in protecting the peptide from degradation. Since nanoformulation can ease the requirement of peptide stability, it opens the door to a direct use of natural peptides or their cocktails for antimicrobial treatment, accelerating the search of effective antibiofilm peptides to treat chronic wounds.


Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Humans , Animals , Mice , Antimicrobial Cationic Peptides/pharmacology , Anti-Infective Agents/pharmacology , Peptide Hydrolases , Biofilms , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests
4.
Mol Pharm ; 19(3): 974-984, 2022 03 07.
Article in English | MEDLINE | ID: mdl-35179903

ABSTRACT

Surgical site infections represent a significant clinical problem. Herein, we report a nanofiber dressing for topical codelivery of immunomodulating compounds including 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and VID400, a CYP24A1 inhibitor in a sustained manner, for inducing the expression of the endogenous cathelicidin antimicrobial peptide (CAMP) gene encoding the hCAP18 protein, which is processed into the LL-37 peptide. Nanofiber wound dressings with coencapsulation of 1,25(OH)2D3 and VID400 were generated by electrospinning. Both 1,25(OH)2D3 and VID400 were coencapsulated into nanofibers with loading efficiencies higher than 90% and exhibited a prolonged release from nanofiber membranes longer than 28 days. Incubation with 1,25(OH)2D3/VID400-coencapsulated poly(ϵ-caprolactone) nanofiber membranes greatly induced the hCAP18/LL-37 gene expression in monocytes, neutrophils, and keratinocytes in vitro. Moreover, the administration of 1,25(OH)2D3/VID400-coencapsulated nanofiber membranes dramatically promoted the hCAP18/LL-37 expression in dermal wounds created in both human CAMP transgenic mice and human skin tissues. The 1,25(OH)2D3- and VID400-coencapsulated nanofiber dressings enhanced innate immunity via the more effective induction of antimicrobial peptide than the free drug alone or 1,25(OH)2D3-loaded nanofibers. Together, 1,25(OH)2D3/VID400-embedded nanofiber dressings presented in this study show potential in preventing surgical site infections.


Subject(s)
Nanofibers , Animals , Antimicrobial Peptides , Bandages , Imidazoles , Mice , Nanofibers/chemistry , Surgical Wound Infection , Vitamin D/analogs & derivatives , Vitamin D3 24-Hydroxylase
5.
Appl Opt ; 61(4): 868-874, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35201054

ABSTRACT

Poly (methyl methacrylate) (PMMA)-doped organic-inorganic composite films are prepared on flexible substrates through a combination of the sol-gel technique and the spin-coating method. Circular and hexagonal microlens arrays (MLAs) are then built into the composite films by using ultraviolet nanoimprint technology. Atomic force microscope and ultraviolet spectrophotometer characterization results of the films show that the films have low surface roughness and good optical transmittance. A scanning electron microscope is used to observe the surface morphology of the MLAs, and the results show that the prepared MLAs are regular and neat. The surface profiles of the MLAs are also measured by using a surface profiler. Optical microscopy results show that the prepared MLAs have good optical imaging properties. Finally, the MLAs are applied on the green organic light-emitting diodes (OLEDs), and the influence of the shape and diameter of the MLAs on the luminance and current efficiency of the OLEDs is discussed. Results indicate that there is a relatively high enhancement of the current efficiency and luminance for the OLEDs with hexagonal MLAs and a single microlens height of 9 µm, where the luminance can reach 10611cd/cm2, and the current efficiency can be enhanced by about 20.1%. Furthermore, there is a higher enhancement of the luminance and current efficiency for the OLEDs with PMMA-doped MLAs than that of the OLEDs with no PMMA-doped MLAs. Based on these results, we believe that the obtained PMMA-doped composite film MLAs on flexible substrates have important applications in the flexible OLEDs displays areas.

6.
Nano Lett ; 21(3): 1508-1516, 2021 02 10.
Article in English | MEDLINE | ID: mdl-33501831

ABSTRACT

Following the COVID-19 outbreak, swabs for biological specimen collection were thrust to the forefront of healthcare materials. Swab sample collection and recovery are vital for reducing false negative diagnostic tests, early detection of pathogens, and harvesting DNA from limited biological samples. In this study, we report a new class of nanofiber swabs tipped with hierarchical 3D nanofiber objects produced by expanding electrospun membranes with a solids-of-revolution-inspired gas foaming technique. Nanofiber swabs significantly improve absorption and release of proteins, cells, bacteria, DNA, and viruses from solutions and surfaces. Implementation of nanofiber swabs in SARS-CoV-2 detection reduces the false negative rates at two viral concentrations and identifies SARS-CoV-2 at a 10× lower viral concentration compared to flocked and cotton swabs. The nanofiber swabs show great promise in improving test sensitivity, potentially leading to timely and accurate diagnosis of many diseases.


Subject(s)
COVID-19 Testing/instrumentation , COVID-19/diagnosis , Nanofibers , SARS-CoV-2 , COVID-19/virology , COVID-19 Testing/methods , COVID-19 Testing/statistics & numerical data , False Negative Reactions , Humans , Materials Testing , Microscopy, Electron, Scanning , Nanofibers/ultrastructure , Nanotechnology , SARS-CoV-2/isolation & purification , Specimen Handling/instrumentation , Specimen Handling/methods , Specimen Handling/statistics & numerical data
7.
Adv Funct Mater ; 30(49)2020 Dec 01.
Article in English | MEDLINE | ID: mdl-34326714

ABSTRACT

The healing of large bone defects represents a clinical challenge, often requiring some form of grafting. Three-dimensional (3D) nanofiber aerogels could be a promising bone graft due to their biomimetic morphology and controlled porous structures and composition. miR-26a has been reported to induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and facilitate bone formation. Introducing miR-26a with a suitable polymeric vector targeting BMSCs could improve and enhance the functions of 3D nanofiber aerogels for bone regeneration. Herein, we first developed the comb-shaped polycation (HA-SS-PGEA) carrying a targeting component, biocleavable groups and short ethanolamine (EA)-decorated poly(glycidyl methacrylate) (PGMA) (abbreviated as PGEA) arms as miR-26a delivery vector. We then assessed the cytotoxicity and transfection efficiency of this polycation and cellular response to miR-26a-incorporated nanoparticles (NPs) in vitro. HA-SS-PGEA exhibited a stronger ability to transport miR-26a and exert its functions than the gold standard polyethyleneimine (PEI) and low-molecular-weight linear PGEA. We finally examined the efficacy of HA-SS-PGEA/miR-26a NPs loaded 3D hybrid nanofiber aerogels showing a positive effect on the cranial bone defect healing. Together, the combination of 3D nanofiber aerogels and functional NPs consisting of a biodegradable and targeting polycation and therapeutic miRNA could be a promising approach for bone regeneration.

8.
Adv Funct Mater ; 30(46)2020 Nov 11.
Article in English | MEDLINE | ID: mdl-33708030

ABSTRACT

Direct injection of cell-laden hydrogels shows high potentials in tissue regeneration for translational therapy. The traditional cell-laden hydrogels are often used as bulk space fillers to tissue defects after injection, likely limiting their structural controllability. On the other hand, patterned cell-laden hydrogel constructs often necessitate invasive surgical procedures. To overcome these problems, herein, we report a unique strategy for encapsulating living human cells in a pore-forming gelatin methacryloyl (GelMA)-based bioink to ultimately produce injectable hierarchically macro-micro-nanoporous cell-laden GelMA hydrogel constructs through three-dimensional (3D) extrusion bioprinting. The hydrogel constructs can be fabricated into various shapes and sizes that are defect-specific. Due to the hierarchically macro-micro-nanoporous structures, the cell-laden hydrogel constructs can readily recover to their original shapes, and sustain high cell viability, proliferation, spreading, and differentiation after compression and injection. Besides, in vivo studies further reveal that the hydrogel constructs can integrate well with the surrounding host tissues. These findings suggest that our unique 3D-bioprinted pore-forming GelMA hydrogel constructs are promising candidates for applications in minimally invasive tissue regeneration and cell therapy.

9.
Small ; 16(19): e1907393, 2020 05.
Article in English | MEDLINE | ID: mdl-32212416

ABSTRACT

Minimally invasive therapies avoiding surgical complexities evoke great interest in developing injectable biomedical devices. Herein, a versatile approach is reported for engineering injectable and biomimetic nanofiber microspheres (NMs) with tunable sizes, predesigned structures, and desired compositions via gas bubble-mediated coaxial electrospraying. The sizes and structures of NMs are controlled by adjusting processing parameters including air flow rate, applied voltage, distance, and spinneret configuration in the coaxial setup. Importantly, unlike the self-assembly method, this technique can be used to fabricate NMs from any material feasible for electrospinning or other nanofiber fabrication techniques. To demonstrate the versatility, open porous NMs are successfully fabricated that consist of various short nanofibers made of poly(ε-caprolactone), poly(lactic-co-glycolic acid), gelatin, methacrylated gelatin, bioglass, and magneto-responsive polymer composites. Open porous NMs support human neural progenitor cell growth in 3D with a larger number and more neurites than nonporous NMs. Additionally, highly open porous NMs show faster cell infiltration and host tissue integration than nonporous NMs after subcutaneous injection to rats. Such a novel class of NMs holds great potential for many biomedical applications such as tissue filling, cell and drug delivery, and minimally invasive tissue regeneration.


Subject(s)
Nanofibers , Animals , Biomimetics , Gelatin , Microspheres , Polyesters , Polymers , Rats , Tissue Engineering , Tissue Scaffolds
10.
Ann Rheum Dis ; 79(5): 646-656, 2020 05.
Article in English | MEDLINE | ID: mdl-32205337

ABSTRACT

OBJECTIVES: Emerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one 'hit' is provided by an adverse gut microbiome that activates innate immunity; the other 'hit' is underlying joint damage. METHODS: Medical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability. RESULTS: Histological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1ß, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations. CONCLUSION: The study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.


Subject(s)
Fecal Microbiota Transplantation/methods , Gastrointestinal Microbiome , Metabolic Syndrome/complications , Osteoarthritis, Knee/therapy , Animals , Biomarkers/analysis , Biopsy, Needle , Disease Models, Animal , Disease Progression , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Menisci, Tibial/pathology , Menisci, Tibial/surgery , Metabolic Syndrome/pathology , Mice, Inbred C57BL , Multivariate Analysis , Osteoarthritis, Knee/pathology , Random Allocation , Reference Values , Regression Analysis , Risk Assessment
11.
Mol Cell ; 48(3): 375-86, 2012 Nov 09.
Article in English | MEDLINE | ID: mdl-23041282

ABSTRACT

Many RNA-binding proteins contain multiple single-strand nucleic acid-binding domains and assemble into large multiprotein messenger ribonucleic acid protein (mRNP) complexes. The mechanisms underlying the self-assembly of these complexes are largely unknown. In eukaryotes, the association of the translation factors polyadenylate-binding protein-1 (PABP) and eIF4G is essential for high-level expression of polyadenylated mRNAs. Here, we report the crystal structure of the ternary complex poly(A)(11)·PABP(1-190)·eIF4G(178-203) at 2.0 Å resolution. Our NMR and crystallographic data show that eIF4G interacts with the RRM2 domain of PABP. Analysis of the interaction by small-angle X-ray scattering, isothermal titration calorimetry, and electromobility shift assays reveals that this interaction is allosterically regulated by poly(A) binding to PABP. Furthermore, we have confirmed the importance of poly(A) for the endogenous PABP and eIF4G interaction in immunoprecipitation experiments using HeLa cell extracts. Our findings reveal interdomain allostery as a mechanism for cooperative assembly of RNP complexes.


Subject(s)
Eukaryotic Initiation Factor-4G/metabolism , Poly A/metabolism , Poly(A)-Binding Protein I/metabolism , RNA, Messenger/metabolism , Amino Acid Sequence , Binding Sites/genetics , Calorimetry , Crystallography, X-Ray , Electrophoretic Mobility Shift Assay , Eukaryotic Initiation Factor-4G/chemistry , Eukaryotic Initiation Factor-4G/genetics , HeLa Cells , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Sequence Data , Multiprotein Complexes/chemistry , Multiprotein Complexes/metabolism , Nucleic Acid Conformation , Poly A/chemistry , Poly A/genetics , Poly(A)-Binding Protein I/chemistry , Poly(A)-Binding Protein I/genetics , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary , RNA, Messenger/chemistry , RNA, Messenger/genetics , Ribonucleoproteins/chemistry , Ribonucleoproteins/metabolism , Scattering, Small Angle , Sequence Homology, Amino Acid , X-Ray Diffraction
12.
Nano Lett ; 19(3): 2059-2065, 2019 03 13.
Article in English | MEDLINE | ID: mdl-30788971

ABSTRACT

Assembling electrospun nanofibers with controlled alignment into three-dimensional (3D), complex, and predesigned shapes has proven to be a difficult task for regenerative medicine. Herein, we report a novel approach inspired by solids of revolution that transforms two-dimensional (2D) nanofiber mats of a controlled thickness into once-inaccessible 3D objects with predesigned shapes. The 3D objects are highly porous, consisting of layers of aligned nanofibers separated by gaps ranging from several micrometers to several millimeters. Upon compression, the objects are able to recover their original shapes. The porous objects can serve as scaffolds, guiding the organization of cells and producing highly ordered 3D tissue constructs. Additionally, subcutaneous implantation in rats demonstrates that the 3D objects enable rapid cell penetration, new blood vessel formation, and collagen matrix deposition. This new class of 3D hierarchical nanofiber architectures offers promising advancements in both in vitro engineering of complex 3D tissue constructs/models or organs and in vivo tissue repair and regeneration.


Subject(s)
Biocompatible Materials/chemistry , Nanofibers/chemistry , Regenerative Medicine , Tissue Engineering , Animals , Biocompatible Materials/chemical synthesis , Cells, Cultured , Collagen/chemistry , Polyesters/chemistry , Porosity , Rats , Tissue Scaffolds
13.
Small ; 15(23): e1805510, 2019 06.
Article in English | MEDLINE | ID: mdl-31033203

ABSTRACT

Over the last decades, the fabrication of 3D tissues has become commonplace in tissue engineering and regenerative medicine. However, conventional 3D biofabrication techniques such as scaffolding, microengineering, and fiber and cell sheet engineering are limited in their capacity to fabricate complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility to fabricate biomimetic, volumetric tissues that are structurally and functionally relevant. It enables precise control of the composition, spatial distribution, and architecture of resulting constructs facilitating the recapitulation of the delicate shapes and structures of targeted organs and tissues. This Review systematically covers the history of bioprinting and the most recent advances in instrumentation and methods. It then focuses on the requirements for bioinks and cells to achieve optimal fabrication of biomimetic constructs. Next, emerging evolutions and future directions of bioprinting are discussed, such as freeform, high-resolution, multimaterial, and 4D bioprinting. Finally, the translational potential of bioprinting and bioprinted tissues of various categories are presented and the Review is concluded by exemplifying commercially available bioprinting platforms.


Subject(s)
Bioprinting/methods , Printing, Three-Dimensional , Regenerative Medicine/trends , Translational Research, Biomedical , Biomimetics/methods , Biomimetics/trends , Humans , Regenerative Medicine/methods , Tissue Engineering/methods , Translational Research, Biomedical/methods , Translational Research, Biomedical/trends
14.
Mol Pharm ; 16(5): 2011-2020, 2019 05 06.
Article in English | MEDLINE | ID: mdl-30916573

ABSTRACT

Biofilms of multidrug-resistant bacteria in chronic wounds pose a great challenge in wound care. Herein, we report the topical delivery of molecularly engineered antimicrobial peptides using electrospun nanofiber dressings as a carrier for the treatment of biofilms of multidrug-resistant bacteria in diabetic wounds. Molecularly engineered human cathelicidin peptide 17BIPHE2 was successfully encapsulated in the core of pluronic F127/17BIPHE2-PCL core-shell nanofibers. The in vitro release profiles of 17BIPHE2 showed an in initial burst followed by a sustained release over 4 weeks. The peptide nanofiber formulations effectively killed methicillin-resistant Staphylococcus aureus (MRSA) USA300. Similarly, the 17BIPHE2 peptide containing nanofibers could also effectively kill other bacteria including Klebsiella pneumoniae (104 to 106 CFU) and Acinetobacter baumannii (104 to 107 CFU) clinical strains in vitro without showing evident cytotoxicity to skin cells and monocytes. Importantly, 17BIPHE2-containing nanofiber dressings without debridement caused five-magnitude decreases of the MRSA USA300 CFU in a biofilm-containing chronic wound model based on type II diabetic mice. In combination with debridement, 17BIPHE2-containing nanofiber dressings could completely eliminate the biofilms, providing one possible solution to chronic wound treatment. Taken together, the biodegradable nanofiber-based wound dressings developed in this study can be utilized to effectively deliver molecularly engineered peptides to treat biofilm-containing chronic wounds.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Bandages , Biofilms/drug effects , Drug Delivery Systems/methods , Nanofibers/administration & dosage , Protein Engineering , Wound Infection/drug therapy , Administration, Cutaneous , Animals , Anti-Bacterial Agents/chemistry , Antimicrobial Cationic Peptides/chemistry , Cell Survival/drug effects , Diabetes Mellitus, Experimental/complications , Disease Models, Animal , Drug Liberation , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Nanofibers/chemistry , Poloxamer/chemistry , Polyesters/chemistry , Skin/drug effects , Skin/microbiology , Wound Infection/pathology , Cathelicidins
15.
Nucleic Acids Res ; 45(17): 10321-10331, 2017 Sep 29.
Article in English | MEDLINE | ID: mdl-28973475

ABSTRACT

Polyadenylate (poly(A)) has the ability to form a parallel duplex with Hoogsteen adenine:adenine base pairs at low pH or in the presence of ammonium ions. In order to evaluate the potential of this structural motif for nucleic acid-based nanodevices, we characterized the effects on duplex stability of substitutions of the ribose sugar with 2'-deoxyribose, 2'-O-methyl-ribose, 2'-deoxy-2'-fluoro-ribose, arabinose and 2'-deoxy-2'-fluoro-arabinose. Deoxyribose substitutions destabilized the poly(A) duplex both at low pH and in the presence of ammonium ions: no duplex formation could be detected with poly(A) DNA oligomers. Other sugar C2' modifications gave a variety of effects. Arabinose and 2'-deoxy-2'-fluoro-arabinose nucleotides strongly destabilized poly(A) duplex formation. In contrast, 2'-O-methyl and 2'-deoxy-2'-fluoro-ribo modifications were stabilizing either at pH 4 or in the presence of ammonium ions. The differential effect suggests they could be used to design molecules selectively responsive to pH or ammonium ions. To understand the destabilization by deoxyribose, we determined the structures of poly(A) duplexes with a single DNA residue by nuclear magnetic resonance spectroscopy and X-ray crystallography. The structures revealed minor structural perturbations suggesting that the combination of sugar pucker propensity, hydrogen bonding, pKa shifts and changes in hydration determine duplex stability.


Subject(s)
Pentoses/chemistry , RNA, Double-Stranded/chemistry , RNA, Messenger/chemistry , Base Pairing , Crystallography, X-Ray , Deoxyribose/chemistry , Hydrogen Bonding , Models, Chemical , Models, Molecular , Molecular Dynamics Simulation , Nuclear Magnetic Resonance, Biomolecular , Nucleic Acid Conformation , Nucleic Acid Denaturation , RNA Stability , Temperature , Water
16.
Nanomedicine ; 22: 102081, 2019 11.
Article in English | MEDLINE | ID: mdl-31400571

ABSTRACT

Biomimetic and injectable nanofiber microspheres (NMs) could be ideal candidate for minimally invasive tissue repair. Herein, we report a facile approach to fabricate peptide-tethered NMs by combining electrospinning, electrospraying, and surface conjugation techniques. The composition and size of NMs can be tuned by varying the processing parameters during the fabrication. Further, bone morphogenic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) mimicking peptides have been successfully tethered onto poly(ε-caprolactone) (PCL):gelatin:(gelatin-methacryloyl) (GelMA)(1:0.5:0.5) NMs through photocrosslinking of the methacrylic group in GelMA and octenyl alanine (OCTAL) in the modified peptides. The BMP-2-OCTAL peptide-tethered NMs significantly promote osteogenic differentiation of bone marrow-derived stem cells (BMSCs). Moreover, human umbilical vein endothelial cells (HUVECs) seeded on VEGF mimicking peptide QK-OCTAL-tethered NMs significantly up-regulated vascular-specific proteins, leading to microvascularization. The strategy developed in this work holds great potential in developing a biomimetic and injectable carrier to efficiently direct cellular response (Osteogenesis and Angiogenesis) for tissue repair.


Subject(s)
Biomimetic Materials/pharmacology , Injections , Mesenchymal Stem Cells/cytology , Microspheres , Nanofibers/chemistry , Peptides/pharmacology , Animals , Bone Morphogenetic Protein 2/pharmacology , Cell Differentiation/drug effects , Cell Differentiation/genetics , Gelatin/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Kinetics , Light , Mesenchymal Stem Cells/drug effects , Microvessels/drug effects , Microvessels/metabolism , Nanofibers/ultrastructure , Neovascularization, Physiologic/drug effects , Osteogenesis/drug effects , Osteogenesis/genetics , Osteopontin/metabolism , Polyesters/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tissue Engineering
17.
Sensors (Basel) ; 20(1)2019 Dec 19.
Article in English | MEDLINE | ID: mdl-31861735

ABSTRACT

Wireless body area networks (WBANs) have attracted great attention from both industry and academia as a promising technology for continuous monitoring of physiological signals of the human body. As the sensors in WBANs are typically battery-driven and inconvenient to recharge, an energy efficient resource allocation scheme is essential to prolong the lifetime of the networks, while guaranteeing the rigid requirements of quality of service (QoS) of the WBANs in nature. As a possible alternative solution to address the energy efficiency problem, energy harvesting (EH) technology with the capability of harvesting energy from ambient sources can potentially reduce the dependence on the battery supply. Consequently, in this paper, we investigate the resource allocation problem for EH-powered WBANs (EH-WBANs). Our goal is to maximize the energy efficiency of the EH-WBANs with the joint consideration of transmission mode, relay selection, allocated time slot, transmission power, and the energy constraint of each sensor. In view of the characteristic of the EH-WBANs, we formulate the energy efficiency problem as a discrete-time and finite-state Markov decision process (DFMDP), in which allocation strategy decisions are made by a hub that does not have complete and global network information. Owing to the complexity of the problem, we propose a modified Q-learning (QL) algorithm to obtain the optimal allocation strategy. The numerical results validate the effectiveness of the proposed scheme as well as the low computation complexity of the proposed modified Q-learning (QL) algorithm.


Subject(s)
Algorithms , Monitoring, Physiologic/methods , Wireless Technology , Electrocardiography , Electromyography , Humans , Markov Chains , Monitoring, Physiologic/instrumentation , Signal-To-Noise Ratio
18.
Acc Chem Res ; 50(8): 1976-1987, 2017 08 15.
Article in English | MEDLINE | ID: mdl-28777535

ABSTRACT

Electrospinning is a simple and versatile technique that relies on the electrostatic repulsion between surface charges to continuously draw nanofibers from a viscoelastic fluid. It has been applied to successfully produce nanofibers, with diameters down to tens of nanometers, from a rich variety of materials, including polymers, ceramics, small molecules, and their combinations. In addition to solid nanofibers with a smooth surface, electrospinning has also been adapted to generate nanofibers with a number of secondary structures, including those characterized by a porous, hollow, or core-sheath structure. The surface and/or interior of such nanofibers can be further functionalized with molecular species or nanoparticles during or after an electrospinning process. In addition, electrospun nanofibers can be assembled into ordered arrays or hierarchical structures by manipulation of their alignment, stacking, and/or folding. All of these attributes make electrospun nanofibers well-suited for a broad spectrum of applications, including those related to air filtration, water purification, heterogeneous catalysis, environmental protection, smart textiles, surface coating, energy harvesting/conversion/storage, encapsulation of bioactive species, drug delivery, tissue engineering, and regenerative medicine. Over the past 15 years, our group has extensively explored the use of electrospun nanofibers for a range of applications. Here we mainly focus on two examples: (i) use of ceramic nanofibers as catalytic supports for noble-metal nanoparticles and (ii) exploration of polymeric nanofibers as scaffolding materials for tissue regeneration. Because of their high porosity, high surface area to volume ratio, well-controlled composition, and good thermal stability, nonwoven membranes made of ceramic nanofibers are terrific supports for catalysts based on noble-metal nanoparticles. We have investigated the use of ceramic nanofibers made of various oxides, including SiO2, TiO2, SnO2, CeO2, and ZrO2, as supports for heterogeneous catalysts based on noble metals such as Au, Pt, Pd, and Rh. On the other hand, the diameter, composition, alignment, porosity, and surface properties of polymeric nanofibers can be engineered in a controllable fashion to mimic the hierarchical architecture of an extracellular matrix and help manipulate cell behaviors for tissue engineering and regenerative medicine. To this end, we can mimic the native structure and morphology of the extracellular matrix in tendon using uniaxially aligned nanofibers; we can use radially aligned nanofibers to direct the migration of cells from the periphery to the center in an effort to speed up wound healing; and we can also use uniaxially aligned nanofibers to guide and expedite the extension of neurites for peripheral nerve repair. Furthermore, we can replicate the anatomic structures at the tendon-to-bone insertion using nanofiber scaffolds with graded mineral coatings. In this Account, we aim to demonstrate the unique capabilities of electrospun nanofibers as porous supports for heterogeneous catalysis and as functional scaffolds for tissue regeneration by concentrating on some of the recent results.


Subject(s)
Electrochemical Techniques/methods , Nanofibers , Drug Delivery Systems , Tissue Engineering
19.
J Aerosol Sci ; 125: 164-181, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30662086

ABSTRACT

Electrospraying (ES) is a robust and versatile technique for the fabrication of micro- and nanoparticulate materials of various compositions, morphologies, shapes, textures and sizes. The physics of ES provides a great degree of flexibility towards the materials design of choice with desired physicochemical and biological properties. Not surprising, this technology has become an important tool for the production of micro- and nanostructured materials, especially in the pharmaceutical and biomedical arena. In this review, a basic introduction to the fundamentals of ES along with a brief description of the experimental parameters that can be manipulated to obtain micro- and nanostructured materials of desired composition, size, and configuration are outlined. A greater focus of this review is to bring to light the broad range of electrosprayed materials and their applications in drug delivery, biomedical imaging, implant coating, tissue engineering, and sensing. Taken together, this review will provide an appreciation of this unique technology, which can be used to fabricate micro- and nanostructured materials with tremendous applications in the pharmaceutical and biomedical fields.

20.
Nanomedicine ; 13(4): 1435-1445, 2017 05.
Article in English | MEDLINE | ID: mdl-28185940

ABSTRACT

Surgical site infections (SSIs) represent the most common nosocomial infection among surgical patients. In order to prevent SSIs in a sustained manner and lessen side effects, we developed a twisting method for generation of nanofiber-based sutures capable of simultaneous delivery of silver and gentamicin. The prepared sutures are composed of core-sheath nanofibers with gentamicin/pluronic F127 in the core and silver/PCL in the sheath produced by co-axial electrospinning. The diameters of obtained sutures range from ~80 µm to ~1.2 mm. The in vitro release profiles of silver and gentamicin exhibit an initial burst followed by a sustained release over 5 weeks. The co-encapsulated sutures were able to kill bacteria much more effectively than gentamicin or silver alone loaded nanofiber sutures, without showing obvious impact on proliferation and migration of dermal fibroblasts and keratinocytes. The gentamicin and silver co-loaded PCL nanofiber sutures may hold great potential for prevention of SSIs.


Subject(s)
Drug Delivery Systems , Gentamicins/chemistry , Nanofibers/chemistry , Silver/chemistry , Sutures , Anti-Bacterial Agents/chemistry , Cell Line , Cross Infection/drug therapy , Drug Liberation , Humans , Microbial Sensitivity Tests , Polyesters/chemistry , Pseudomonas aeruginosa/drug effects , Surgical Wound Infection/drug therapy
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