Showing papers in "Macromolecular Bioscience in 2014"

Electrospun Nanofibers as Dressings for Chronic Wound Care: Advances, Challenges, and Future Prospects

Abstract: Chronic non-healing wounds show delayed and incomplete healing processes and in turn expose patients to a high risk of infection. Treatment currently focuses on dressings that prevent microbial infiltration and keep a balanced moisture and gas exchange environment. Antibacterial delivery from dressings has existed for some time, with responsive systems now aiming to trigger release only if infection occurs. Simultaneously, approaches that stimulate cell proliferation in the wound and encourage healing have been developed. Interestingly, few dressings appear capable of simultaneously impairing or treating infection and encouraging cell proliferation/wound healing. Electrospinning is a simple, cost-effective, and reproducible process that can utilize both synthetic and natural polymers to address these specific wound challenges. Electrospun meshes provide high-surface area, micro-porosity, and the ability to load drugs or other biomolecules into the fibers. Electrospun materials have been used as scaffolds for tissue engineering for a number of years, but there is surprisingly little literature on the interactions of fibers with bacteria and co-cultures of cells and bacteria. This Review examines the literature and data available on electrospun wound dressings and the research that is required to develop smart multifunctional wound dressings capable of treating infection and healing chronic wounds.

More than meets the eye in bacterial cellulose: biosynthesis, bioprocessing, and applications in advanced fiber composites.

Abstract: Bacterial cellulose (BC) nanofibers are one of the stiffest organic materials produced by nature. It consists of pure cellulose without the impurities that are commonly found in plant-based cellulose. This review discusses the metabolic pathways of cellulose-producing bacteria and the genetic pathways of Acetobacter xylinum. The fermentative production of BC and the bioprocess parameters for the cultivation of bacteria are also discussed. The influence of the composition of the culture medium, pH, temperature, and oxygen content on the morphology and yield of BC are reviewed. In addition, the progress made to date on the genetic modification of bacteria to increase the yield of BC and the large-scale production of BC using various bioreactors, namely static and agitated cultures, stirred tank, airlift, aerosol, rotary, and membrane reactors, is reviewed. The challenges in commercial scale production of BC are thoroughly discussed and the efficiency of various bioreactors is compared. In terms of the application of BC, particular emphasis is placed on the utilization of BC in advanced fiber composites to manufacture the next generation truly green, sustainable and renewable hierarchical composites.

Polymer Micro‐ and Nanocapsules as Biological Carriers with Multifunctional Properties

Abstract: The design and development of multifunctional polymer capsules with controlled chemical composition and physical properties has been the focus of academic and industrial research in recent years. Especially in the biomedical field, the formulation of novel polymer-based encapsulation systems for the early-stage disease diagnostic and effective delivery of bioactive agents represent one of the most rapidly advancing areas of science. The stimuli-responsive release of cargo molecules from the carrier gains remarkable attention for in vitro and in vivo delivery of contrast agents, genes, and pharmaceutics. In this Review, the current status and the challenges of different polymer-based micro- and nanocapsule formulations are considered, emphasizing on their potential biological application as carriers for specific drug targeting and controlled release upon applying of external stimulus.

Biodegradable, pH-responsive carboxymethyl cellulose/poly(acrylic acid) hydrogels for oral insulin delivery.

Abstract: Biodegradable and pH-responsive carboxymethyl cellulose/poly(acrylic acid) hybrid hydrogels are synthesized. The hydrogels deswell in acidic artificial gastric fluid (AGF) but rapidly swell in neutral artificial intestinal fluid (AIF), rendering selective enzymatic degradation of the gels as well as accelerated drug release from insulin-loaded hydrogels in AIF. Oral administration of insulin-loaded hydrogels to streptozotocin-induced diabetic rats leads to a continuous decline in the fasting blood glucose level within 6 h post-administration, and the relative pharmacological availability increases more than 10 times compared to oral administration of free insulin solution. The relative bioavailability of hydrogel-encapsulated insulin after oral administration to healthy rabbits is 6.6%.

Gold nanoparticle loaded hybrid nanofibers for cardiogenic differentiation of stem cells for infarcted myocardium regeneration.

Abstract: Heart disease is the leading cause of mortality in many industrialized nations and is often related to irregularities in electrical function that can radically damage cardiac functioning. The aim of this study is to develop a novel therapeutic hybrid scaffold that can couple electrical, mechanical, and biological properties, desirable for cardiac tissue regeneration. BSA/PVA scaffolds are fabricated in the ratio 2:1 and gold nanoparticles (AuNPs) embedded scaffolds in the ratios BSA/PVA/Au of 2:1:0.1 (lower concentration) and BSA/PVA/Au of 2:1:0.4 (higher concentration) by electrospinning. The scaffolds are characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle, Fourier transform infrared (FTIR) spectroscopy, and tensile testing to analyze the fiber morphology, AuNP distribution, hydrophilicity, surface functional groups, and mechanical properties of the scaffolds, respectively. Results show that ex vivo pretreatment of MSCs using 5-aza and AuNPs loaded conductive nanofibrous construct could lead to enhanced cardiomyogenic differentiation and result in superior biological and functional effects on infarcted myocardium regeneration.

Bioreducible Polycations in Nucleic Acid Delivery: Past, Present, and Future Trends

Abstract: Polycations that are degradable by reduction of disulfide bonds are developed for applications in delivery of nucleic acids. This Feature Article surveys methods of synthesis of bioreducible polycations and discusses current understanding of the mechanism of action of bioreducible polyplexes. Emphasis is placed on the relationship between the biological redox environment and toxicity, trafficking, transfection activity, and in vivo behavior of bioreducible polycations and polyplexes.

In situ electroactive and antioxidant supramolecular hydrogel based on cyclodextrin/copolymer inclusion for tissue engineering repair.

Abstract: The injectable electroactive and antioxidant hydrogels are prepared from mixing the tetraaniline functional copolymers and α-cyclodextrin (α-CD) aqueous solution UV-vis and CV of the copolymer solution showed good electroactive properties The antioxidant ability of the copolymer is also proved The gelation mechanism and properties of the system are studied by WAXD, DSC, and rheometer The encapsulated cells are highly viable in the hydrogels, suggesting that the hydrogels have excellent cytocompatibility After subcutaneous injection, H&E staining study suggests acceptable biocompatibility of the materials in vivo Moreover, data shows the injectable electroactive material can effectively accelerate the proliferation of encapsulated cells with electrical stimuli, and the mechanism is also elaborated Such an injectable electroactive hydrogel would more closely mimic the native extracellular matrix, thereby combining a biomimetic environment of long-term cell survival and electrical signal to support the generation of functional tissue

Osteogenetic properties of electrospun nanofibrous PCL scaffolds equipped with chitosan-based nanoreservoirs of growth factors.

Abstract: Bioactive implants intended for rapid, robust, and durable bone tissue regeneration are presented. The implants are based on nanofibrous 3D-scaffolds of bioresorbable poly-ϵ-caprolactone mimicking the fibrillar architecture of bone matrix. Layer-by-layer nanoimmobilization of the growth factor BMP-2 in association with chitosan (CHI) or poly-L-lysine over the nanofibers is described. The osteogenetic potential of the scaffolds coated with layers of CHI and BMP-2 is demonstrated in vitro, and in vivo in mouse calvaria, through enhanced osteopontin gene expression and calcium phosphate biomineralization. The therapeutic strategy described here contributes to the field of regenerative medicine, as it proposes a route toward efficient repair of bone defects at reduced risk and cost level.

Tailored Doxorubicin‐Hyaluronan Conjugate as a Potent Anticancer Glyco‐Drug: An Alternative to Prodrug Approach

Abstract: Releasibility of doxorubicin from drug-conjugates is believed to be a prerequisite for its anti-cancer activity. Here, a new glyco-drug approach that circumvents the releasibility restriction is reported, opening a new possibility to design efficient, target specific drug delivery system. It is discovered that stable amide coupling of doxorubicin (DOX) tohyaluronan (HA) shows dose dependent cytotoxicity to CD44 positive human coloncancer cells (HCT116) as compared to human breast cancer cells(MCF-7) and mouse fibroblast cells (NIH-3T3), which express less CD44 receptor. This direct conjugation approach is an easy scalable strategy that could be adopted to design innocuous anti-tumor nanoparticle formulations.

Introducing PeptoPlexes: polylysine-block-polysarcosine based polyplexes for transfection of HEK 293T cells.

Abstract: A series of well-defined polypeptide-polypeptoid block copolymers based on the body's own amino acids sarcosine and lysine are prepared by ring opening polymerization of N-carboxyanhydrides. Block lengths were varied between 200-300 for the shielding polysarcosine block and 20-70 for the complexing polylysine block. Dispersity indexes ranged from 1.05 to 1.18. Polylysine is polymerized with benzyloxycarbonyl as well as trifluoroacetyl protecting groups at the ϵ-amine group and optimized deprotection protocols for both groups are reported. The obtained block ionomers are used to complex pDNA resulting in the formation of polyplexes (PeptoPlexes). The PeptoPlexes can be successfully applied in the transfection of HEK 293T cells and are able to transfect up to 50% of cells in vitro (FACS assay), while causing no detectable toxicity in an Annexin V assay. These findings are a first indication that PeptoPlexes may be a suitable alternative to PEG based non-viral transfection systems.

Reversal of lung cancer multidrug resistance by pH-responsive micelleplexes mediating co-delivery of siRNA and paclitaxel.

Abstract: The recent advances in RNA interference (RNAi) technology provided novel and promising solutions for human cancer treatment. In this study, the application of dual pH-responsive cationic micellar nanoparticles for small interfering RNA (siRNA) and paclitaxel (PTX) co-delivery to overcome cancer multidrug resistance (MDR) is reported. The in vitro siRNA transfection shows that siRNA-luciferase (Luc) loaded micelleplexes efficiently silences Luc expression in various carcinoma cell lines. The Luc knockdown ability of the micelleplexes can be enhanced by choloquine (CQ) co-incubation. However, is abolished by bafilomycin-A1 (Baf-A1) treatment. The micelleplexes are further exploited for co-delivery of siRNA-Bcl-2 and PTX to Bcl-2 overexpressing A549 lung cancer cells (A549-Bcl-2). The experimental results show that the micelleplexes could sensitize A549-Bcl-2 cells to PTX via down-regulation of anti-apoptosis gene of Bcl-2, suggesting that PDMA-b-PDPA micelleplexes are promising nanovectors for siRNA and anti-cancer drug co-delivery to overcome cancer MDR.

Impact of Sterilization on the Enzymatic Degradation and Mechanical Properties of Silk Biomaterials

Abstract: The effect of some sterilization methods (autoclaving and ethanol treatments) on the degradation rate and mechanical properties of two types of porous silk scaffolds (aqueous- and hexafluoroisopropanol-derived) is evaluated. Changes in secondary structure, crystal size, and supramolecular features of silk fibroin, resulting from sterilization, are tracked to elucidate molecular level effects on protease XIV enzymatic degradation and compressive mechanical properties. The structural features and pore sizes of the silk scaffolds remain intact after both sterilization processes. Autoclave sterilization dramatically reduce the degradation rate of the silk scaffolds in response to protease XIV and significantly increase mechanical properties, in contrast to scaffolds sterilized with 70% ethanol. Higher β-sheet content and larger crystal size are observed after autoclaving, unlike in response to 70% ethanol sterilization, based on examination of Fourier transform (FT) IR spectroscopy and wide-angle X-ray scattering (WAXS). In addition, thermal analysis finds supramolecular features within silk fibroin amorphous regions, including the glass transition temperature (Tg ), heat capacity of glass transition (ΔCp-Tg ), and thermal gravimetric degradability. Such supramolecular level changes are related to the shift in enzymatic degradation and mechanical properties due to autoclaving versus treatment with 70% EtOH. The changes in supramolecular organization in amorphous regions can retard enzyme diffusion through the glassy regions of the silk matrix or/and hinder binding of enzymes, while also stiffening these matrices.

Preparation of Biocompatible Aggregation-Induced Emission Homopolymeric Nanoparticles for Cell Imaging

Abstract: A series of new homopolymers with various degrees of polymerization derived from vinyl tetraphenylethene, that is, poly[2-(4-vinylphenyl)ethene-1,1,2-triyl)tribenzene] homopolymers, is synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The homopolymers exhibit a significant aggregation-induced emission (AIE) effect and an ability to assemble themselves into AIE polymer nanoparticles (NPs) during precipitation in a water/tetrahydrofuran (THF) mixture. The NPs also exhibit good dispersibility, stability, and biocompatibility. The AIE polymer NPs are used in imaging studies of HeLa cells.

Dual Delivery of Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Coacervate Displays Strong Angiogenic Effects

Abstract: Controlled delivery of multiple growth factors (GFs) holds great potential for the clinical treatment of ischemic diseases and might be more therapeutically effective to reestablish vasculature than the provision of a single GF. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are two potent angiogenic factors. However, due to rapid degradation and dilution in the body, their clinical potential will rely on an effective mode of delivery. A coacervate, composed of heparin and a biodegradable polycation, which protects GFs from proteolysis and potentiates their bioactivities, is developed. Here, the coacervate incorporates VEGF and HGF and sustains their release for at least three weeks. Their strong angiogenic effects on endothelial cell proliferation and tube formation in vitro are confirmed. Furthermore, it is demonstrated that coacervate-based delivery of these factors has stronger effects than free application of both factors and to coacervate delivery of each GF separately.

New perspectives of HPMA-based copolymers derived by post-polymerization modification.

Abstract: Poly[N-(2-hydroxypropyl) methacrylamide] (HPMA) was one of the first polymers applied as polymer drug conjugate in the clinics. Since then many attempts have been made to expand the functionality of HPMA-based copolymers from advanced synthetic pathways to multiple biomedical applications. This Feature Article highlights multifunctional HPMA based copolymers prepared by controlled radical polymerization and subsequent post-polymerization modification of activated ester precursor polymers via aminolysis. This approach combines precise control of the polymer's microstructure (molecular weight, dispersity, block copolymer formation, end group functionalization) with an easy introduction of various multifunctional groups. The obtained polymers can be used as versatile targeted drug carriers for sophisticated molecular imaging techniques that provide detailed information about structure property relationships both in vitro as well as in vivo. Moreover, recent studies have shown that such multifunctional HPMA copolymers may have high potential as advanced carriers in the field of tumor immunotherapy.

Electrospun Nanofiber Scaffolds and Plasma Polymerization: A Promising Combination Towards Complete, Stable Endothelial Lining for Vascular Grafts

Abstract: In the quest to reduce risk of thrombosis in vascular grafts, it is essential to provide a surface with morphological and mechanical properties close to those of the extracellular matrix beneath the luminal endothelium, and to favor the growth of a confluent, stable monolayer of endothelial cells. This is accomplished here by combining electrospun poly(ethylene terephthalate) (PET) mats with an amine-rich thin plasma-polymerized coating, designated "L-PPE:N." Its deposition does not modify the open, highly porous mats and leads only to small changes in mechanical properties. L-PPE:N significantly improves the adhesion and growth of human umbilical vein endothelial cells (HUVEC) and their resistance to flow-induced shear stress. These properties favor the formation of desired confluent HUVEC monolayers on the topmost surface, unlike conventional vascular grafts (ePTFE or woven PET), where cells migrate inside the material. This combination is therefore highly advantageous for the pre-endothelialization of the luminal side of small-diameter vascular prostheses.

Shape-Memory Effect by Specific Biodegradable Polymer Blending for Biomedical Applications

Abstract: Specific biodegradable polymers having shape-memory properties through "polymer-blend" method are investigated and their shape-switching in body temperature (37 °C) is characterized. Poly(L-lactide-co-caprolactone) (PLCL) and poly(L-lactide-co-glycolide) (PLGA) are dissolved in chloroform and the films of several blending ratios of PLCL/PLGA are prepared by solvent casting. The shape-memory properties of films are also examined using dynamic mechanical analysis (DMA). Among the blending ratios, the PLCL50/PLGA50 film shows good performance of shape-fixity and shape-recovery based on glass transition temperature. It displays that the degree of shape recovery is 100% at 37 °C and the shape recovery proceeds within only 15 s. In vitro biocompatibility studies are shown to have good blood compatibility and cytocompatibility for the PLCL50/PLGA50 films. It is expected that this blended biodegradable polymer can be potentially used as a material for blood-contacting medical devices such as a self-expended vascular polymer stents and vascular closure devices in biomedical applications.

Effect of Cell Density on Mesenchymal Stem Cells Aggregation in RGD‐Alginate 3D Matrices under Osteoinductive Conditions

Abstract: Cellular activities in 3D are differentially affected by several matrix-intrinsic and extrinsic factors. This study highlights the relevance of optimizing initial cell densities when establishing 3D cultures for specific applications. Independently of the entrapping density, MSCs cultured within RGD-alginate hydrogels showed steady-state levels of metabolic activity and were in a nearly non-proliferative state, but recovered "normal" activity levels when retrieved from 3D matrices and re-cultured as monolayers. Importantly, high-densities promoted the establishment of cell-cell contacts with formation of multicellular clusters stabilized by endogenous ECM, and also stimulated MSCs osteogenic differentiation. These MSC-ECM microtissues may be used as building blocks for tissue engineering.

Overcoming Cancer Multidrug Resistance by Codelivery of Doxorubicin and Verapamil with Hydrogel Nanoparticles

Abstract: The efficacy of chemotherapy is often inhibited by multidrug resistance (MDR). A highly engineerable hydrogel nanoparticle (NP) serves as a carrier for the optimal codelivery to tumor cells of the chemodrug, doxorubicin (Dox) and the chemosensitizer, verapamil (Vera), aiming at alleviating tumor MDR. The hydrogel NPs are prepared via the copolymerization of acrylamide and 2-carboxyethyl acrylate. Dox and Vera are post-loaded into the respective NPs, with drug loading around 7.7 wt% and 8.0 wt%, respectively. The codelivery of Dox-NPs and Vera-NPs increases the intracellular accumulation of Dox, and significantly enhances the cell killing ability of Dox with respect to NCI/ADR-RES cells in vitro. These findings suggest that such codelivery nanoplatforms provide a promising route for overcoming tumor MDR.

Protease-sensitive PEG hydrogels regulate vascularization in vitro and in vivo.

Abstract: Forming functional blood vessel networks in engineered or ischemic tissues is a significant scientific and clinical hurdle. Poly(ethylene glycol) (PEG)-based hydrogels are adapted to investigate the role of mechanical properties and proteolytic susceptibility on vascularization. Four arm PEG vinyl sulfone is polymerized by Michael-type addition with cysteine groups on a slowly degraded matrix metalloprotease (MMP) susceptible peptide, GPQG↓IWGQ, or a more rapidly cleaved peptide, VPMS↓MRGG. Co-encapsulation of endothelial cells and supportive fibroblasts within the gels lead to vascular morphogenesis in vitro that is robust to changes in crosslinking peptide identity, but is significantly attenuated by increased crosslinking and MMP inhibition. Perfused vasculature forms from transplanted cells in vivo in all gel types; however, in contrast to the in vitro results, vascularization in vivo is not decreased in the more crosslinked gels. Collectively, these findings demonstrate the utility of this platform to support vascularization both in vitro and in vivo.

Poly(ethylene glycol) Hydrogels with Adaptable Mechanical and Degradation Properties for Use in Biomedical Applications

Abstract: Requirements of hydrogels for drug delivery, wound dressings, and surgical implantation can be extensive, including suitable mechanical properties and tailorable degradation time frames. Herein, an adaptable PEG-based hydrogel, whose mechanical properties and degradation rate can be systematically adjusted to meet these criteria by altering simple variables such as the PEG molecular weight, is described. The performance of these hydrogels in three physical manipulations (pushing, pulling, and folding), representative of manipulations that they may undergo during typical biomedical use, is also assessed. While not all of these formulations can withstand these manipulations, a subset did, and it is intended to further optimize these formulations for specific clinical applications. Additionally, the outcomes of the physical manipulation tests indicate that simply having a high modulus does not correlate with biomedical applicability.

Antitumor efficacy of doxorubicin-loaded laponite/alginate hybrid hydrogels.

Abstract: Degradable hybrid hydrogels with improved stability are prepared by incorporating nanodisks of biocompatible laponite (LP) in alginate (AG) hydrogels using Ca(2+) as a crosslinker. The Dox-loaded hybrid hydrogels give a controlled Dox release at physiological environment in a sustained manner. Under conditions that mimic the tumor environment, both the sustainability in the Dox release (up to 17 d) and the release efficiency from LP/AG-Dox hydrogels are improved. The in situ degradation of these hybrid hydrogels gives rise to nanohybrids that might serve as vehicles for carrying Dox through the cell membrane and diminish the effect of Dox ion-trapping in the acidic extracellular environment of the tumor and/or in the endo-lysosomal cell compartments.

Hydrogen‐Bonded Complexes and Blends of Poly(acrylic acid) and Methylcellulose: Nanoparticles and Mucoadhesive Films for Ocular Delivery of Riboflavin

Abstract: Poly(acrylic acid) (PAA) and methylcellulose (MC) are able to form hydrogen-bonded interpolymer complexes (IPCs) in aqueous solutions. In this study, the complexation between PAA and MC is explored in dilute aqueous solutions under acidic conditions. The formation of stable nanoparticles is established, whose size and colloidal stability are greatly dependent on solution pH and polymers ratio in the mixture. Poly(acrylic acid) and methylcellulose are also used to prepare polymeric films by casting from aqueous solutions. It is established that uniform films can be prepared by casting from polymer mixture solutions at pH 3.4–4.5. At lower pHs (pH < 3.0) the films have inhomogeneous morphology resulting from strong interpolymer complexation and precipitation of polycomplexes, whereas at higher pHs (pH 8.3) the polymers form fully immiscible blends because of the lack of interpolymer hydrogen-bonding. The PAA/MC films cast at pH 4 are shown to be non-irritant to mucosal surfaces. These films provide a platform for ocular formulation of riboflavin, a drug used for corneal cross-linking in the treatment of keratoconus. An in vitro release of riboflavin as well as an in vivo retention of the films on corneal surfaces can be controlled by adjusting PAA/MC ratio in the formulations.

Injectable in situ forming hybrid iron oxide-hyaluronic acid hydrogel for magnetic resonance imaging and drug delivery.

Abstract: The development of multimodal in situ cross-linkable hyaluronic acid nanogels hybridized with iron oxide nanoparticles is reported. Utilizing a chemoselective hydrazone coupling reaction, the nanogels are converted to a macroscopic hybrid hydrogel without any additional reagent. Hydrophobic cargos remain encapsulated in the hydrophobic domains of the hybrid hydrogel without leakage. However, hydrogel degradation with hyaluronidase liberates iron oxide nanoparticles. This allows the utilization of imaging agents as tracers of the hydrogel degradation. UV-vis spectrometry and MRI studies reveal that the degradability of the hydrogels correlates with their structure. The hydrogels presented here are very promising theranostic tools for hyaluronidase-mediated delivery of hydrophobic drugs, as well as imaging of hydrogel degradation and tracking of degradation products in vivo.

Silk-Pectin Hydrogel with Superior Mechanical Properties, Biodegradability, and Biocompatibility

Abstract: A new method is developed to prepare silk hydrogels and silk-pectin hydrogels via dialysis against methanol to obtain hydrogels with high concentrations of silk fibroin. The relationship between the mechanical and biological properties and the structure of the silk-pectin hydrogels is subsequently evaluated. The present results suggest that pectin associates with silk molecules when the silk concentration exceeds 15 wt%, suggesting that a silk concentration of over 15 wt% is critical to construct interacting silk-pectin networks. The silk-pectin hydrogel reported here is composed of a heterogeneous network, which is different from fiber-reinforced, interpenetrated networks and double-network hydrogels, as well as high-stiffness hydrogels (elastic modulus of 4.7 ± 0.9 MPa, elastic stress limit of 3.9 ± 0.1 MPa, and elastic strain limit of 48.4 ± 0.5%) with regard to biocompatibility and biodegradability.

Mussel-inspired cell-adhesion peptide modification for enhanced endothelialization of decellularized blood vessels.

Abstract: Enhanced endothelialization of tissue-engineered blood vessels is essential for vascular regeneration and function of engineered vessels. In this study, mussel-inspired surface chemistry of polydopamine (pDA) coatings are applied to functionalize decellularized vein matrix (DVM) with extracellular matrix-derived cell adhesion peptides (RGD and YIGSR). DVMs engineered with pDA-peptides enhance focal adhesion, metabolic activity, and endothelial differentiation of human endothelial progenitor cells (EPCs) derived from cord blood and embryonic stem cells compared with EPCs on non-coated or pDA-coated DVMs. These results indicate that pDA-peptide functionalization may contribute to enhanced, rapid endothelialization of DVM surfaces by promoting adhesion, proliferation, and differentiation of circulating EPCs. Ultimately, this approach may be useful for improving in vivo patency and function of decellularized matrix-based blood vessels.

Chitosan-coated gold nanorods for cancer therapy combining chemical and photothermal effects.

Abstract: To develop a novel type of nanoparticle for cancer therapy, gold nanorods (GNRs) are coated with chitosan (CS) derivatives to combine chemical and photothermal effects. Thiol-modified chitosan derivatives chemically conjugated to doxorubicin (DOX) are successfully synthesized and their in vitro effect is evaluated. Functional nanocarriers (DOX-CS-GNR) with good biocompatibility and optical properties are prepared by conjugating chitosan derivatives to GNRs. Two types of structures with different molar ratios of chitosan derivatives and GNRs are successfully obtained. In in vitro studies, GNR-loaded nanoparticles show low cytotoxicity and high potential for anti-cancer effects. Under conditions of short exposure time and low light intensity, DOX-CS-GNR nanocarriers with a side-by-side structure exhibit cytoxicity against tumor cells based on a combination of chemical and photothermal therapeutic effects.

Polylysine crosslinked AIE dye based fluorescent organic nanoparticles for biological imaging applications.

Abstract: Fluorescent organic nanoparticles based on aggregation induced emission dyes are fabricated through a ring-opening reaction using polylysine as the linker. The fluorescent organic nanoparticles obtained are characterized by a series of techniques including UV-vis absorption spectroscopy, fluorescence spectroscopy, Fourier Transform infrared spectroscopy, and transmission electron microscopy. A biocompatibility evaluation and the cell uptake behavior of the fluorescent organic nanoparticles are further investigated to evaluate their potential biomedical applications. It is demonstrated that these fluorescent organic nanoparticles can be obtained at room temperature in an air atmosphere without the need for catalyst or initiator. Furthermore, these crosslinked aggregation induced emission dye based fluorescent organic nanoparticles show uniform morphology, strong red fluorescence, high water dispersability, and excellent biocompatibility, making them promising candidates for various biomedical applications.

Boronic acid shell-crosslinked dextran-b-PLA micelles for acid-responsive drug delivery.

Abstract: Herein, 3-carboxy-5-nitrophenylboronic acid (CNPBA) shell-crosslinked micelles based on amphiphilic dextran-block-polylactide (Dex-b-PLA) are prepared and used for efficient intracellular drug deliveries. Due to the reversible pH-dependent binding with diols to form boronate esters, CNPBA modified Dex-b-PLA shows excellent pH-sensitivity. In neutral aqueous conditions, CNPBA-Dex-b-PLA forms shell-crosslinked micelles to enable DOX loading, while in acid conditions, the boronate esters hydrolyze and the micelles de-crosslink to release loaded DOX. In vitro release studies indicate that the release of the DOX cargo is minimized at physiological conditions, while there is a burst release in response to low pHs. The cell viability of CNPBA-Dex-b-PLA investigated by MTT assay was more than 90%, indicating that, as a drug delivery system, CNPBA-Dex-b-PLA has good cytocompatibility. These features suggest that the pH-responsive biodegradable CNPBA-Dex-b-PLA can efficiently load and deliver DOX into tumor cells and enhance the inhibition of cellular proliferation in vitro, providing a favorable platform as a drug delivery system for cancer therapy.

Amphoteric, prevailingly cationic L-arginine polymers of poly(amidoamino acid) structure: synthesis, acid/base properties and preliminary cytocompatibility and cell-permeating characterizations.

Abstract: A linear amphoteric poly(amidoamino acid), L-ARGO7, is prepared by Michael-type polyaddition of L-arginine with N,N'-methylenebisacrylamide. Chain-extension of acrylamide end-capped L-ARGO7 oligomers with piperazine leads to high-molecular-weight copolymers in which L-arginine maintains its absolute configuration. Acid/base properties of L-ARGO7 polymers show isolectric points of ≈ 10 and positive net average charges per repeating unit at pH = 7.4 from 0.25 to 0.40. These arginine-rich synthetic polymers possibly share some of the unique biological properties of polyarginine cell-permeating peptides. In vitro tests with mouse embryo fibroblasts balb/3T3 clone A31 show that L-ARGO7 polymers are endowed with effective cell internalization ability combined with minimal cytotoxicity.