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... Cell–cell and cell-matrix interactions control cell phenotypes and functions in vivo. Maintaining these interactions in vitro is essential to both produce and retain cultured cell fidelity to normal phenotype and function in the context of drug efficacy and toxicity screening. Two-dimensional (2-D) cultures on culture plastics rarely recapitulate any of these desired conditions. Three dimensional ...
... The combined use of natural ECM components and synthetic materials offers an attractive alternative to fabricate hydrogel-based tissue engineering scaffolds to study cell-matrix interactions in three-dimensions (3D). A facile method was developed to modify gelatin with cysteine via a bifunctional PEG linker, thus introducing free thiol groups to gelatin chains. A covalently crosslinked gelatin hyd ...
Isabelle Leisten; Rafael Kramann; Mónica S. Ventura Ferreira; Manfred Bovi; Sabine Neuss; Patrick Ziegler; Wolfgang Wagner; Ruth Knüchel; Rebekka K. Schneider
... Here, we propose a collagen-based three-dimensional (3D) environment for hematopoietic stem and progenitor cells (HPC) with mesenchymal stem cells (MSC) derived either from bone marrow (BM) or umbilical cord (UC), to recapitulate the main components of the BM niche. Mechanisms described for HPC homeostasis were systematically analyzed in comparison to the conventional liquid HPC culture. The 3D-cu ...
... Realizing the potential of human pluripotent stem cell (hPSC)-based therapy requires the development of defined scalable culture systems with efficient expansion, differentiation and isolation protocols. We report an engineered 3D microfiber system that efficiently supports long-term hPSCs self-renewal under chemically defined conditions. The unique feature of this system lies in the application o ...
... Gold nanoshell-enabled photothermal therapy (NEPTT) utilizes the efficient thermal conversion of near infrared (NIR) light for the ablation of cancer cells. Cancer therapies that combine cell killing with the induction of a strong immune response against the dying tumor cells have been shown to increase therapeutic efficacy in the clearance and regression of cancers. In this study, we assessed the ...
... The first successful reprogramming of differentiated cells to a pluripotent state was done by retroviral introduction of four transcription factors (Oct4, Sox2, Klf4, cMyc) by the group of Yamanaka in 2006. Since then, scientists all over the world have attempted various methods to avoid insertional mutagenesis, a major limitation of the retrovirus-based method, however no technique was found to c ...
... Monocytes/Macrophages have long been recognized as key players in inflammation and wound healing and are often employed in vitro to gain an understanding of the inflammatory response to biomaterials. Previous work has demonstrated a drastic decrease in primary monocyte adherent density on biomaterial surfaces coupled with a change in monocyte behavior over time. However, the mechanism responsible ...
... Platelet-rich plasma (PRP) was prepared from human adult peripheral blood and from human umbilical cord (uc) blood and the properties were compared in a series of in vitro bioassays. Quantification of growth factors in PRP and platelet-poor plasma (PPP) fractions revealed increased levels of mitogenic growth factors PDGF-AB, PDGF-BB, and FGF-2, the angiogenic agent VEGF and the chemokine RANTES in ...
... With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for a small-diameter (<6 mm inner diameter) vascular graft that can provide long-term patency. Tissue engineering provides a very promising solution to this need. Approaches utilizing adult stem cells can address limitations previously realized in the use of ...
bone resorption; breast neoplasms; curcumin; diffusivity; drug carriers; drug therapy; drugs; encapsulation; growth retardation; metastasis; models; myeloma; nanoparticles; neoplasm cells; osteoporosis; particle size; synergism
Abstract:
... Delivery of therapeutic agents to bone is crucial in several diseases such as osteoporosis, Paget’s disease, myeloproliferative diseases, multiple myeloma as well as skeletal metastasizing cancers. Prevention of cancer growth and lowering the cancer induced bone resorption is important in the treatment of bone metastasizing cancers. Keeping in mind the low diffusivity and availability of cell surf ...
alginates; derivatization; drugs; hydrocolloids; hydroxyapatite; islets of Langerhans; nucleic acids; pH; proteins; temperature; value added
Abstract:
... Alginates have become an extremely important family of polysaccharides because of their utility in preparing hydrogels at mild pH and temperature conditions, suitable for sensitive biomolecules like proteins and nucleic acids, and even for living cells such as islets of Langerhans. In addition, the complex monosaccharide sequences of alginates, and our growing ability to create controlled sequence ...
... Rheumatoid arthritis (RA) is a systemic autoimmune disease that is initiated and maintained by various inflammatory/immune cells and their cytokines, leading to cartilage degradation and bone erosion. Despite its potent therapeutic efficacy on RA, the oral administration of methotrexate (MTX) provokes serious adverse systemic complications, thus necessitating the local application of MTX. Here, we ...
... Drug delivery to solid tumours remains a challenge because both tumour physiology and drug solubility are unfavourable. Engineered materials can provide the basis for drug reformulation, incorporating active compounds and modulating their pharmacokinetic and biodistribution behaviour. To this end, we encapsulated docetaxel, a poorly soluble taxane drug, in a self-assembled polymeric nanoparticle m ...
animal models; anti-inflammatory activity; curcumin; cytotoxicity; emulsions; evaporation; gel electrophoresis; heparin; hepatotoxicity; in vivo studies; intravenous injection; lipopolysaccharides; lungs; macrophages; mice; plasmids; solvents; tissues; transfection; tumor necrosis factor-alpha
Abstract:
... In this study, the R7L10 peptide, which is composed of a 7-arginine stretch and a 10-leucine stretch, was evaluated as a carrier for the combined delivery of curcumin and plasmid DNA (pDNA) into the lungs. Curcumin is a natural product with anti-inflammatory and anti-tumor effects. Curcumin-loaded R7L10 (R7L10-curucmin) was prepared by an oil-in-water (O/W) emulsion/solvent evaporation method. In ...
blood vessels; cell movement; cell viability; encapsulation; in vivo studies; mineralization; stem cells; therapeutics
Abstract:
... Improving vascularization of tissue-engineered bone can advance cell performance in vivo and further promote bone regeneration. How to achieve a functional vascular network within the construct is one of the biggest challenges so far. We hypothesized that a mixture of platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) could endue the alginate microspheres with osteogenic and angioge ...
... A hepta-guanidino-β-cyclodextrin (G-CD), its hepta-PEG conjugate (G-CD-PEG), and the corresponding anisamide-terminated PEG conjugate (G-CD-PEG-AA) have been synthesised and compared as delivery vectors for siRNA to prostate cancer cells and tumours in vivo. The G-CD-PEG-AA.siRNA formulations (in which anisamide targets the sigma receptor), but not the non-targeted formulations, induced prostate c ...
... A hybrid biomimetic system comprising high-molecular-weight, linear copolymer of N-(2-hydroxypropyl)methacrylamide (HPMA) grafted with multiple Fab′ fragments of anti-CD20 monoclonal antibody (mAb) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by attachment of Fab′ fragments via thioether bonds. Exposure of human non-Hodgkin’s lymphoma (NHL) Raj ...
acute toxicity; blood-brain barrier; brain; drug delivery systems; endocytosis; intravenous injection; kidneys; liver; low density lipoprotein; nanoparticles; paclitaxel; permeability; physiological transport
Abstract:
... Therapeutic effect of glioma is often limited due to low permeability of delivery systems across the Blood-Brain Barrier (BBB) and poor penetration into the tumor tissue. In order to overcome the two barriers, we proposed Angiopep-conjugated PEG-PCL nanoparticles (ANG-PEG-NP) as a dual targeting drug delivery system for glioma treatment basing on low density lipoprotein receptor related protein (L ...
anti-inflammatory activity; drug delivery systems; drugs; edema; heat; in vitro studies; in vivo studies; irradiation; nanogold; rats; ultrasonics
Abstract:
... A pulsatile ultrasound controlled drug release platform with diclofenac-loaded alginate microcapsules (fabricated with a home-made electrostatic device, 75% embedded rate) was established to evaluate anti-inflammation efficiency. Better anti-inflammation efficiency was found using the ultrasound system and the drug delivery can be adjusted based on the programmed ultrasound cycle. The results of t ...
... Targeted delivery strategies are becoming increasingly important. Herein, a novel hyperbranched amphiphilic poly[(amine-ester)-co-(d,l-lactide)]/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer (HPAE-co-PLA/DPPE) with RGD peptide (cRGDfK) and transferrin (Tf) on the periphery was synthesized and used to prepare paclitaxel-loaded nanoparticles (NPs) for dual-targeting chemotherapy. These ...
... Intravascular catheter-associated infections (CAIs), which are normally induced by microbial adhesion and subsequent biofilm formation, are a major cause of morbidity and mortality. Therefore, strategies to prevent CAIs are in great demand. In this study, a series of diblock copolymers of PEG and cationic polycarbonate with various compositions were synthesized by metal-free organocatalytic ring-o ...
... Gram-negative bacteria (GNB) cause common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance (MDR) and mortality. The emergence and spread of MDR-GNB strains limit therapeutic options and highlight the need to develop new therapeutic strategies. In this study, the peptide (RXR)₄XB- and (KFF)₃K-conjugated peptide nucleic acids (PPNAs) were developed ...
breast neoplasms; doxorubicin; drug therapy; encapsulation; humans; mice; models; neoplasm cells; pH; prognosis
Abstract:
... pH-triggered lipid-membranes designed from biophysical principles are evaluated in the form of targeted liposomal doxorubicin with the aim to ultimately better control the growth of vascularized tumors. We compare the antitumor efficacy of anti-HER2/neu pH-triggered lipid vesicles encapsulating doxorubicin to the anti-HER2/neu form of an FDA approved liposomal doxorubicin of DSPC/cholesterol-based ...
... An immunologically modified nanotube system was developed using an immunoadjuvant, glycated chitosan (GC), as surfactant of single-walled carbon nanotube (SWNTs). This SWNT-GC system not only retained both optical properties of SWNTs and immunological functions of GC, but also could enter cells due to the carrier properties of SWNTs. Cellular SWNTs induced thermal destruction of tumor cells when i ...
... Tumor therapy requires multi-functional treatment strategies with specific targeting of therapeutics to reduce general toxicity and increase efficacy. In this study we fabricated and functionally tested aptamer-conjugated and doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c aptamers provided the ab ...
arginine; atomic force microscopy; biosafety; blood serum; breast neoplasms; cytotoxicity; gene therapy; genes; in vitro studies; light scattering; models; molecular weight; plasmids; transfection
Abstract:
... The quest for highly efficient and safe gene delivery systems has become the key factor for successful application of gene therapy. Peptide dendrimers are currently investigated as excellent candidates for non-viral gene delivery vectors. In this study, we report the synthesis and characterization of arginine functionalized peptide dendrimer-based vectors ranging from 5th generation (G5A) to 6th g ...
... Small interfering RNA (siRNA) represent an interesting class of developmental nucleic acid-based therapeutics. Cationic carriers for deoxyribonucleic acids (DNA) are potential vehicles for siRNA delivery. However, in contrast to supercoiled plasmid DNA, the physical properties of siRNA molecules induces the formation of larger, loosely–packed complexes with most polycationic carriers, and conseque ...
... Hydrogel materials that display inherent activity against bacteria can be used to directly treat accessible wounds to prevent or kill existing infection. Hydrogels composed of self-assembling β-hairpin peptides, having a high content of arginine, were found to be extremely effective at killing both gram-positive and gram-negative bacteria, including multi-drug resistant Pseudomonas aeruginosa. No ...
... Uniform Au NRs-capped magnetic core/mesoporous silica shell nanoellipsoids (Au NRs-MMSNEs) were prepared by coating a uniform layer of Au NRs on the outer surface of a magnetic core/mesoporous silica shell nanostructure, based on a two-step chemical self-assembly process. This multifunctional nanocomposite integrate simultaneous chemotherapy, photo-thermotherapy, in vivo MR-, infrared thermal and ...
... Repair of large calvarial bony defects remains clinically challenging because successful spontaneous calvarial re-ossification rarely occurs. Although bone marrow-derived mesenchymal stem cells (BMSCs) genetically engineered with baculovirus (BV) for transient expression of osteogenic/angiogenic factors hold promise for bone engineering, we hypothesized that calvarial bone healing necessitates pro ...
Hoa H. Truong; Jan de Sonneville; Veerander P.S. Ghotra; Jiangling Xiong; Leo Price; Pancras C.W. Hogendoorn; Herman H. Spaink; Bob van de Water; Erik H.J. Danen
... Cell spheroids (CS) embedded in 3D extracellular matrix (ECM) serve as in vitro mimics for multicellular structures in vivo. Such cultures, started either from spontaneous cell aggregates or single cells dispersed in a gel are time consuming, applicable to restricted cell types only, prone to high variation, and do not allow CS formation with defined spatial distribution required for high-throughp ...
... This study tested the cytotoxicity of a BDNF blended chitosan scaffold with human umbilical cord mesenchymal stem cells (hUC-MSCs), and the in vitro effect of BDNF blended chitosan scaffolds on neural stem cell differentiation with the aim of contributing alternative methods in tissue engineering for the treatment of traumatic brain injury (TBI). The chitosan scaffold based on immobilization of BD ...
... The demand for orthopedic and dental implants will continue to grow, and for these applications, titanium and its alloys have been used extensively. While these implants have achieved high success rates, two major complications may be encountered: the lack of bone tissue integration and implant-centered infection. The surface of the implant, through its interactions with proteins, bacteria and tis ...
... We demonstrate bifunctional combined Au-Fe₂O₃ nanoparticles (NPs) for selectively induction of apoptosis in cancer cells and real-time imaging. The as-prepared Au-Fe₂O₃ NPs combine the merits of both Au and γ-Fe₂O₃ NPs, maintaining excellent fluorescence quenching property and catalytic activity. Conjugated with αⅤβ₃ integrin-targeting peptide (RGD) and fluorescein isothiocyanate (FITC)-labeled ca ...
RNA interference; Western blotting; blood; coatings; confocal microscopy; cytoplasm; cytotoxicity; fatty acids; fatty liver; fluorescence; folic acid; intravenous injection; liver; luciferase; lungs; mice; pancreas; research and development; secretion; small interfering RNA; tissues; uterine cervical neoplasms; zeta potential
Abstract:
... Small interfering RNA (siRNA) is a powerful gene silencing tool and has promising prospects in basic research and the development of therapeutic reagents. However, the lack of an effective and safe tool for siRNA delivery hampers its application. Here, we introduced binary and ternary complexes that effectively mediated siRNA-targeted gene silencing. Both complexes showed excellent siRNA loading e ...
... It is of crucial importance to design reduction-sensitive polysaccharide-based copolymers for intracellular triggered gene and drug delivery. In this work, a simple two-step method involving the reaction of hydroxyl groups of dextran with cystamine was first developed to introduce reduction-sensitive disulfide linked initiation sites of atom transfer radical polymerization (ATRP) onto dextran. Wel ...
... The aim of current study was to evaluate the effect of nano-apatitic particles (nAp) incorporation on the degradation characteristics and biocompatibility of poly(lactide-co-glycolide) (PLGA)-based nanofibrous scaffolds. Composite PLGA/poly(ɛ-caprolactone) (PCL) blended (w/w = 3/1) polymeric electrospun scaffolds with 0–30 wt% of nAp incorporation (n0–n30) were prepared. The obtained scaffolds wer ...
bacteria; biofabrication; biofilm; drugs; phenotype; quorum sensing
Abstract:
... Signaling between cells guides biological phenotype. Communications between individual cells, clusters of cells and populations exist in complex networks that, in sum, guide behavior. There are few experimental approaches that enable high content interrogation of individual and multicellular behaviors at length and time scales commensurate with the signal molecules and cells themselves. Here we pr ...
... Implant infections in orthopaedics, as well as in many other medical fields, are chiefly caused by staphylococci. The ability of growing within a biofilm enhances the chances of staphylococci to protect themselves from host defences, antibiotic therapies, and biocides. Advances in scientific knowledge on structural molecules (exopolysaccharide, proteins, teichoic acids, and the most recently descr ...
basement membrane; chemical composition; chemical structure; esophagus; extracellular matrix; glycosaminoglycans; growth factors; models; muscle development; muscles; rats; skeletal muscle; small intestine; structural proteins; surgery; urinary tract
Abstract:
... Biologic scaffolds prepared from the extracellular matrix (ECM) of decellularized mammalian tissues have been shown to facilitate constructive remodeling in injured tissues such as skeletal muscle, the esophagus, and lower urinary tract, among others. The ECM of every tissue has a unique composition and structure that likely has direct effects on the host response and it is plausible that ECM harv ...
... Acellular biologic scaffolds are commonly used to facilitate the constructive remodeling of three of the four traditional tissue types: connective, epithelial, and muscle tissues. However, the application of extracellular matrix (ECM) scaffolds to neural tissue has been limited, particularly in the central nervous system (CNS) where intrinsic regenerative potential is low. The ability of decellula ...
Johannes Haag; Silvia Baiguera; Philipp Jungebluth; Daniel Barale; Costantino Del Gaudio; Francesca Castiglione; Alessandra Bianco; Camilla E. Comin; Domenico Ribatti; Paolo Macchiarini
... In this study, the obtainment and characterization of decellularized rat tracheal grafts are described. The detergent-enzymatic method, already used to develop bioengineered pig and human trachea scaffolds, has been applied to rat tracheae in order to obtain airway grafts suitable to be used to improve our knowledge on the process of tissue-engineered airway transplantation and regeneration. The r ...
... The presence of reactive primary amines in the backbone structure of chitosan, enables the derivatisation with different functional groups and thereby improving and expanding its properties, such as solubility and mucoadhesiveness, for biomedical applications. Such derivatives can be exploited with good results in a number of biomedical areas, including enhancement of nucleic acid transfection in ...
... Natural joints rely on fluid thin-film lubrication by the hydrated polyelectrolyte layer of cartilage. However, current artificial joints with polyethylene (PE) surfaces have considerably less efficient lubrication and thus much greater wear, leading to osteolysis and aseptic loosening. This is considered a common factor limiting prosthetic longevity in total hip arthroplasty (THA). However, such ...
autocorrelation; cell proliferation; collagen; culture media; extracellular matrix; gels; in vitro studies; neoplasm cells; phenotype; polymerization; reflectance confocal microscopy; temperature
Abstract:
... Fibrillar collagen gels, which are used extensively in vitro to study tumor–microenvironment interactions, are composed of a cell-instructive network of interconnected fibers and pores whose organization is sensitive to polymerization conditions such as bulk concentration, pH, and temperature. Using confocal reflectance microscopy and image autocorrelation analysis to quantitatively assess gel mic ...
cyclosporine; cytosol; drug resistance; endosomes; human serum albumin; intestines; lysosomes; mucus; nanoparticles; polymers; transporters
Abstract:
... An effective intracellular protein delivery system was developed based on linear poly(amidoamine)s (PAAs) that form self-assembled cationic nanocomplexes with oppositely charged proteins. Two differently functionalized PAAs were synthesized by Michael-type polyaddition of 4-amino-1-butanol (ABOL) to cystamine bisacrylamide (CBA) and to bisacryloylpiperazine (BAP), yielding p(CBA-ABOL) and p(BAP-AB ...
... Cytoxicity is an essential concern for polyethyleneimine 25 kDa (PEI 25 kDa), a widely reported, highly effective transfection agent used in gene delivery. In our recent experiments, Small molecular weight cross-linked poly(ethylene imine) by biscarbamate linkage (PEI–Bu) (Mn: 3278, Mw: 4289) can reduce target cell apoptosis induced by polycationic transfection, and has almost the same DNA condens ...
... The successful clinical outcome of the implanted tissue-engineered bone is dependent on the establishment of a functional vascular network. A gene-enhanced tissue engineering represents a promising approach for vascularization. Our previous study indicated that hypoxia-inducible factor-1α (HIF-1α) can up-regulate the expression of vascular endothelial growth factor (VEGF) and stromal-derived facto ...
biomechanics; bone formation; cultured cells; embryonic stem cells; growth factors; harvesting; humans; metabolites; mineral content; mineralization; nutrients
Abstract:
... Decellularized bone has been widely used as a scaffold for bone formation, due to its similarity to the native bone matrix and excellent osteoinductive and biomechanical properties. We have previously shown that human mesenchymal and embryonic stem cells form functional bone matrix on such scaffolds, without the use of growth factors. In this study, we focused on differences in bone matrix that ex ...
... Tissue engineered nerve grafts are considered as a promising alternative to autologous nerve grafts used for peripheral nerve repair. The differences between these two types of nerve grafts are mainly in the regenerative microenvironment established by them. To construct ideal tissue engineered nerve grafts, it is therefore required to develop a better way to introduce biochemical cues into a neur ...