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Showing papers in "Macromolecular Bioscience in 2015"


Journal ArticleDOI
TL;DR: This review has discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration.
Abstract: Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering.

92 citations


Journal ArticleDOI
TL;DR: This mini-review focuses on the recent developments in polypeptoid chemistry, with particular focus on polymers synthesized by the ring-opening polymerization of amino acid N-carboxyanhydrides (NCAs).
Abstract: Polypeptoids have been of great interest in the polymer science community since the early half of the last century; however, they had been basically forgotten materials until the last decades in which they have enjoyed an exciting revival. In this mini-review, we focus on the recent developments in polypeptoid chemistry, with particular focus on polymers synthesized by the ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides (NCAs). Specifically, we will review traditional monomer synthesis (such as Leuchs, Katchalski, and Kricheldorf) and recent advances in polymerization methods to yield both linear, cyclic, and functional polymers, solution and bulk thermal properties, and preliminary results on the use of polypeptoids as biomaterials (i.e immunogenicity, biodistribution, degradability, and drug delivery).

83 citations


Journal ArticleDOI
TL;DR: Interestingly, lamella-like textured surfaces retained the capacity to inhibit S. aureus adhesion both when the surface is coated with human serum proteins and when the material is implanted subcutaneously in a foreign-body associated infection model.
Abstract: Modification of the biomaterial surface topography is a promising strategy to prevent bacterial adhesion and biofilm formation. In this study, we use direct laser interference patterning (DLIP) to modify polystyrene surface topography at sub-micrometer scale. The results revealed that three-dimensional micrometer structures have a profound impact on bacterial adhesion. Thus, line- and pillar-like patterns enhanced S. aureus adhesion, whereas complex lamella microtopography reduced S. aureus adhesion in static and continuous flow culture conditions. Interestingly, lamella-like textured surfaces retained the capacity to inhibit S. aureus adhesion both when the surface is coated with human serum proteins and when the material is implanted subcutaneously in a foreign-body associated infection model.

82 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the amount of intermediate water might play a key role in expressing the blood compatibility of polymeric materials.
Abstract: Six types of poly(2-methoxyethyl acrylate) (PMEA) analogues were synthesized and the water structure in the hydrated polymers was characterized using differential scanning calorimetry (DSC). The hydrated PMEA analogues exhibited the different amounts of intermediate water. Non-thrombogenicity evaluation was performed on PMEA analogues for platelet adhesion and protein adsorption. Platelet adhesion was suppressed on PMEA analogues. In addition, the protein adsorption and deformation were suppressed by increasing the amount of intermediate water. This study demonstrates that the amount of intermediate water might play a key role in expressing the blood compatibility of polymeric materials.

73 citations


Journal ArticleDOI
TL;DR: In this article, doxorubicin and curcumin (Cur; P-gp inhibitor and apoptosis inhibitor) co-encapsulated pegylated polymeric micelles ((DOX+Cur)-PMs) were designed, prepared and characterized to simultaneously deliver chemotherapeutic drug and multidrug resistance (MDR) modulator to tumor sites.
Abstract: P-gp mediated drug efflux has been recognized as a major obstacle limiting the success of cancer chemotherapy. To overcome this issue, doxorubicin (DOX) and curcumin (Cur; P-gp inhibitor and apoptosis inhibitor) co-encapsulated pegylated polymeric micelles ((DOX+Cur)-PMs) were designed, prepared and characterized to simultaneously deliver chemotherapeutic drug and multidrug resistance (MDR) modulator to tumor sites. The (DOX+Cur)-PMs were spherical nano-size particle, with a loading content of 6.83%, and high colloidal stability. Co-delivery micelles exhibited excellent cytotoxicity by reversing MDR, promoting cellular uptake and enhancing cellular apoptosis in MCF7/Adr cells. The tumor growth inhibitory effect of (DOX+Cur)-PMs in 4T1-bearing mice was more effective compared with the combination solution of DOX and Cur and even DOX-PMs. In conclusion, simultaneous delivery of DOX and Cur by (DOX+Cur)-PMs has been demonstrated to be a promising approach for overcoming MDR and improving antitumor efficacy.

67 citations


Journal ArticleDOI
TL;DR: This work uses a triple-flow micro-device to induce hydrogel formation inside droplets before their collection off-chip and produces alginate particles with a unique biconcave shape and dimensions of the mammalian cells.
Abstract: Owing to their biocompatibility and reduced side effects, natural polymers represent an attractive choice for producing drug delivery systems. Despite few successful examples, however, the production of monodisperse biopolymer-based particles is often hindered by high viscosity of polymer fluids. In this work, we present a microfluidic approach for production of alginate-based particles carrying encapsulated antibodies. We use a triple-flow micro-device to induce hydrogel formation inside droplets before their collection off-chip. The fast mixing and gelation process produced alginate particles with a unique biconcave shape and dimensions of the mammalian cells. We show slow and fast dissolution of particles in different buffers and evaluate antibody release over time.

67 citations


Journal ArticleDOI
TL;DR: A special emphasis will be given to the description of novel theranostic nanodevices that combine more than one responsive modality in order to create a local hyperthermia that leads to the polymer phase transition and triggered drug release, cell recognition, and/or appearance of an imaging signal.
Abstract: In the last couple of decades several drug carriers have been tailored on the nanometric scale by taking advantage of new stimuli responsive materials. Thermoresponsive polymers in particular have been extensively employed as stimuli-responsive building blocks that in combination with other environmental-responsive materials allowed the birth of smarter systems that can respond to more than one stimulus. Examples that highlight the different polymers for thermally triggered drug delivery will be described. A special emphasis will be given to the description of novel theranostic nanodevices that combine more than one responsive modality in order to create a local hyperthermia that leads to the polymer phase transition and triggered drug release, cell recognition, and/or appearance of an imaging signal.

64 citations


Journal ArticleDOI
TL;DR: It is considered that the IGF-1-decorated PLGA/HA microcarriers will be of great value in the bone tissue engineering.
Abstract: In this study, insulin-like growth factor 1 (IGF-1) was successfully immobilized on the poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and pure PLGA microcarriers via polydopamine (pDA). The results demonstrated that the pDA layer facilitated simple and highly efficient immobilization of peptides on the microcarriers within 20 min. Mouse adipose-derived stem cells (ADSCs) attachment and proliferation on IGF-1-immobilized microcarriers were much higher than non-immobilized ones. More importantly, the IGF-1-immobilized PLGA/HA microcarriers significantly increased alkaline phosphatase (ALP) activity and expression of osteogenesis-related genes of ADSCs. Therefore, it is considered that the IGF-1-decorated PLGA/HA microcarriers will be of great value in the bone tissue engineering.

62 citations


Journal ArticleDOI
TL;DR: When silk fibroin sponges were sterilized post-casting, autoclaving increased scaffold stiffness, while decreasing scaffold degradation rate in vitro, in contrast, γ irradiation accelerated scaffolding degradation rate.
Abstract: The effects of common sterilization techniques on the physical and biological properties of lyophilized silk fibroin sponges are described. Sterile silk fibroin sponges were cast using a pre-sterilized silk fibroin solution under aseptic conditions or post-sterilized via autoclaving, γ radiation, dry heat, exposure to ethylene oxide, or hydrogen peroxide gas plasma. Low average molecular weight and low concentration silk fibroin solutions could be sterilized via autoclaving or filtration without significant loses of protein. However, autoclaving reduced the molecular weight distribution of the silk fibroin protein solution, and silk fibroin sponges cast from autoclaved silk fibroin were significantly stiffer compared to sponges cast from unsterilized or filtered silk fibroin. When silk fibroin sponges were sterilized post-casting, autoclaving increased scaffold stiffness, while decreasing scaffold degradation rate in vitro. In contrast, γ irradiation accelerated scaffold degradation rate. Exposure to ethylene oxide significantly decreased cell proliferation rate on silk fibroin sponges, which was rescued by leaching ethylene oxide into PBS prior to cell seeding.

61 citations


Journal ArticleDOI
TL;DR: It is outlined that polyP, as a morphogenetically active scaffold, is even suitable for 3D cell printing.
Abstract: The initial mineralization centers during human bone formation onto osteoblasts are composed of CaCO3 . Those bioseeds are enzymatically formed via carbonic anhydrase(s) in close association with the cell surface of the osteoblasts. Subsequently, the bicarbonate/carbonate anions are exchanged non-enzymatically by inorganic phosphate [Pi ]. One source for the supply of Pi is polyphosphate [polyP] which is a physiological polymer, formed in the osteoblasts as well as in the platelets. The energy-rich acid anhydride bonds within the polyP chain are cleaved by phosphatase(s); during this reaction free-energy might be released that could be re-used, as metabolic fuel, for the maintenance of the steady-state concentrations of the substrates/products during mineralization. Finally it is outlined that polyP, as a morphogenetically active scaffold, is even suitable for 3D cell printing.

61 citations


Journal ArticleDOI
TL;DR: Investigations on sequentially prepared PBIs with defined molecular weight Mn and tailored end groups revealed that there is a dependence of antimicrobial activity and selectivity on Mn and nature of the end groups.
Abstract: Amphiphilic polycations are an alternative to biocides but also toxic to mammalian cells. Antimicrobially active hydrophilic polycations based on 1,4-dibromo-2-butene and tetramethyl-1,3-propanediamine named PBI are not hemotoxic for porcine red blood cells with a hemocytotoxicity (HC50) of more than 40,000 μg · mL(-1). They are quickly killing bacterial cells at their MIC (minimal inhibitory concentration). The highest found selectivity HC50 /MIC is more than 20,000 for S. epidermidis. Investigations on sequentially prepared PBIs with defined molecular weight Mn and tailored end groups revealed that there is a dependence of antimicrobial activity and selectivity on Mn and nature of the end groups.

Journal ArticleDOI
TL;DR: Both the fully ELP-based as well as several ELP hybrid materials that have been reported to form nanoparticles will be discussed, followed by a concise description of the promising biomedical applications reported for this class of materials.
Abstract: Elastin-like polypeptides (ELPs) are characterized by a high sequence control, temperature responsiveness and biocompatibility, which make them highly interesting as smart materials for application in nanomedicine. In particular the construction of ELP-based nanoparticles has recently become a focal point of attention in materials research. This review will give an overview of the ELP-based nanoparticles that have been developed until now and their underlying design principles. First a short introduction on ELPs and their stimulus-responsive behavior will be given. This characteristic has been applied for the development of ELP-based block copolymers that can self-assemble into nanoparticles. Both the fully ELP-based as well as several ELP hybrid materials that have been reported to form nanoparticles will be discussed, which is followed by a concise description of the promising biomedical applications reported for this class of materials.

Journal ArticleDOI
TL;DR: The treatment group with combined SDF-1α and BMP-2 hydrogel delivery showed significantly higher bone formation when compared to hydrogels loaded with the same B MP-2 or SDF -1α concentrations alone, suggesting the combined delivery of both biomolecules synergistically improves osteogenesis.
Abstract: In order to achieve bone repair, bone morphogenetic protein-2 (BMP-2) is typically delivered in non-physiological doses and can result in significant adverse side effects. To reduce the amount of BMP-2 necessary for bone formation, we delivered a known chemokine (stromal cell derived factor-1α, SDF-1α) in combination with BMP-2 using proteolytically degradable hydrogels. A critical-sized calvarial defect was used to determine the effect of biomolecule delivery on bone formation in vivo. The treatment group with combined SDF-1α and BMP-2 hydrogel delivery showed significantly higher bone formation when compared to hydrogels loaded with the same BMP-2 or SDF-1α concentrations alone, suggesting the combined delivery of both biomolecules synergistically improves osteogenesis.

Journal ArticleDOI
TL;DR: A layer by layer functionalization of Fe3 O4 nanoparticles by coating biodegradable polyelectrolyte multilayers such as Dextran (DXS) and Poly(l-lysine) (PLL) to demonstrate their therapeutic efficacy against ovarian cancer cell line.
Abstract: The new goal of anticancer agent research is the screening of natural origin drugs with lower systemic adverse effects than synthetic compounds. Here, we focus on curcumin, an important polyphenolic pigment classically used as spice in the Indian cuisine. The molecule has high pleiotropic activities including strong antioxidant and anti-inflammatory properties. However, its clinical potential is limited due its low solubility and bioavailability. We have developed a layer by layer functionalization of Fe3 O4 nanoparticles (nano-Fe3 O4 ) by coating biodegradable polyelectrolyte multilayers such as Dextran (DXS) and Poly(l-lysine) (PLL). Physico-chemical studies were performed to obtain a high upload of curcumin in Fe3 O4 nanoparticles. Nano-Fe3 O4 were then tested against an ovarian cancer cell line, SKOV-3, to demonstrate their therapeutic efficacy.

Journal ArticleDOI
TL;DR: The barriers for gene delivery are discussed, and examples which illustrate defined polymeric vectors, including dendrimers, peptide carriers, and sequence-defined oligoaminoamides are provided.
Abstract: For successful gene therapy, the delivery of the curative genetic information into target cells is the main hurdle and the development of efficient and safe gene delivery carriers the crucial challenge. Polymeric materials have been widely investigated as gene delivery agents, generating first promising results. However, the heterogeneity and polydispersity of polymers and lack of site specific modifications make it difficult to achieve accurate structure-activity relationship studies. Moreover it will hamper manufacturing of highly defined materials which could be used in clinical development. Therefore, polymers with precise chemical structure are required. In this review, we focus on the current design of defined polymeric materials for gene transfer. We first discuss the barriers for gene delivery, and then provide examples which illustrate defined polymeric vectors, including dendrimers, peptide carriers, and sequence-defined oligoaminoamides.

Journal ArticleDOI
TL;DR: Preliminary cell studies focused on characterizing the elastomer-based scaffolds' biocompatibility and the successful 3D incorporation as well as growth of cells in 60 to 150-μm thick elastomers.
Abstract: Here we report on the modular synthesis and characterization of biodegradable, controlled porous, liquid crystal elastomers (LCE) and their use as three-dimensional cell culture scaffolds. The elastomers were prepared by cross-linking of star block-co-polymers with pendant cholesterol units resulting in the formation of smectic-A LCEs as determined by polarized optical microscopy, DSC, and X-ray diffraction. Scanning electron microscopy revealed the porosity of the as-prepared biocompatible LCEs, making them suitable as 3D cell culture scaffolds. Biodegradability studies in physiological buffers at varying pH show that these scaffolds are intact for about 11 weeks after which degradation sets in at an exponential rate. Initial results from cell culture studies indicate that these smectic LCEs are compatible with growth, survival, and expansion of cultured neuroblastomas and myoblasts when grown on the LCEs for extended time periods (about a month). These preliminary cell studies focused on characterizing the elastomer-based scaffolds' biocompatibility and the successful 3D incorporation as well as growth of cells in 60 to 150-μm thick elastomer sheets.

Journal ArticleDOI
TL;DR: All polymer brushes decreased the fouling from blood plasma over 95% and prevented the adhesion of platelets, erythrocytes, and leukocytes as evidenced by SPR and SEM measurements.
Abstract: In the current study, well-defined polymer brushes are shown as an effective surface modification to resist the adhesion of whole blood and its components. Poly[oligo(ethylene glycol)methylether methacrylate] (poly(MeOEGMA)), poly(hydroxyethyl methacrylate) (poly(HEMA)), poly[N-(2-hydroxypropyl) methacrylamide] (poly(HPMA)), and poly(carboxybetaine acrylamide) (poly(CBAA)) brushes were grown by surface initiated atom transfer radical polymerization (SI-ATRP) and subsequently characterized by Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), dynamic contact angle measurements, atomic force microscopy (AFM), and surface plasmon resonance (SPR) spectroscopy. All brushes decreased the fouling from blood plasma over 95% and prevented the adhesion of platelets, erythrocytes, and leukocytes as evidenced by SPR and SEM measurements.

Journal ArticleDOI
TL;DR: Results indicated that the buffering capacity of the polymers primarily impacts endosomal escape and subsequent transfection efficiency, and highlights the significance of cross-linkers in optimizing thebuffering capacity when designing polymers for gene delivery.
Abstract: Endosomal escape is a major bottleneck for efficient non-viral gene delivery. This paper presents the development of two novel non-viral vectors by cross-linking glycerol molecules with low molecular weight polyethylenimine (PEI). The vectors, namely, HG-PEI (45 mol% glycerol content) and LG-PEI (9 mol% glycerol content) have apparently similar DNA binding, DNA unpacking and cellular uptake abilities but differ in buffering capacity. The cellular uptake and subsequent transfection efficiency of LG-PEI is superior to commercially available PEI 25 k. Interestingly, although the cellular uptake of HG-PEI is higher than that of PEI 25 k, the transgene expression by HG-PEI-mediated transfection is very low. Inhibitor and co-localization studies demonstrate the mechanism of endocytosis and formation of endosomes prone to lysosomal lysis of HG-PEI polyplexes as a consequence of its weak buffering capacity. Importantly, when the lysosomal lysis is inhibited, the transgene expression of HG-PEI-mediated transfection increases by 9-fold of its initial capacity which is comparable to the transfection efficiency of PEI 25 k. These results indicated that the buffering capacity of the polymers primarily impacts endosomal escape and subsequent transfection efficiency. Furthermore, this study highlights the significance of cross-linkers in optimizing the buffering capacity when designing polymers for gene delivery.

Journal ArticleDOI
TL;DR: Biodegradable polymer substrates with nanoscale topography for enhancing human NSC (hNSC) differentiation and guided neurite outgrowth and the addition of nerve growth factor enhanced neuronal differentiation of hNSCs, indicating a synergistic effect of biophysical and biochemical cues on NSC differentiation.
Abstract: Biophysical cues provided by nanotopographical surfaces have been used as stimuli to guide neurite extension and regulate neural stem cell (NSC) differentiation. Here, we fabricated biodegradable polymer substrates with nanoscale topography for enhancing human NSC (hNSC) differentiation and guided neurite outgrowth. The substrate was constructed from biodegradable poly(lactic-co-glycolic acid) (PLGA) using solvent-assisted capillary force lithography. We found that precoating with 3,4-dihydroxy-l-phenylalanine (DOPA) facilitated the immobilization of poly-l-lysine and fibronectin on PLGA substrates via bio-inspired catechol chemistry. The DOPA-coated nanopatterned substrates directed cellular alignment along the patterned grooves by contact guidance, leading to enhanced focal adhesion, skeletal protein reorganization, and neuronal differentiation of hNSCs as indicated by highly extended neurites from cell bodies and increased expression of neuronal markers (Tuj1 and MAP2). The addition of nerve growth factor further enhanced neuronal differentiation of hNSCs, indicating a synergistic effect of biophysical and biochemical cues on NSC differentiation. These bio-inspired PLGA nanopatterned substrates could potentially be used as implantable biomaterials for improving the efficacy of hNSCs in treating neurodegenerative diseases.

Journal ArticleDOI
TL;DR: In biotechnology, SAMs and NC hydrogels of functional nanomaterials are of high interest as 2D and 3D cell culture systems, respectively, to mimic natural ECM and to control cell behaviors.
Abstract: In biotechnology, SAMs and NC hydrogels of functional nanomaterials are of high interest as 2D and 3D cell culture systems, respectively, to mimic natural ECM and to control cell behaviors. Advanced biotechnological approaches often use nanoscale topography together with suitable surface functionalization, as a model of ECM, to control cell behaviors and tissue formation. SAMs of NMs are effective ECM models as 2D surfaces due to their larger nanostructured surface areas which provide higher molecular density by functionalization on a planar substrate than molecular SAMs. Additionally, NC hydrogels, produced by cross-linking of organic polymers with NMs, are excellent candidates as 3D cell culture systems owing to their optical, cell-compatibility and the extraordinary mechanical properties.

Journal ArticleDOI
TL;DR: The NIR image-guided chemo-phototherapy of the angiopep-2 modified PLGA/ DTX/ICG nanoparticles (ANG/PLGA/DTX/ ICG NPs) not only highly induced U87MG cell death in vitro, but also efficiently prolonged the life span of the brain orthotopic U87 MG glioma xenograft-bearing mice in vivo.
Abstract: The aim of this study was to develop multifunctional poly lactide-co-glycolide (PLGA) nanoparticles with the ability to simultaneously deliver indocyanine green (ICG) and docetaxel (DTX) to the brain by surface decoration with the brain-targeting peptide angiopep-2 to achieve combined chemo-phototherapy for glioma under near-infrared (NIR) imaging. ICG was selected as a near-infrared imaging and phototherapy agent and DTX was employed as a chemotherapeutic agent. ICG and DTX were simultaneously incorporated into PLGA nanoparticles with higher stability. These nanoparticles were further decorated with angiopep-2 via the outer maleimide group of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleinimide incorporated in the nanoparticles. The NIR image-guided chemo-phototherapy of the angiopep-2 modified PLGA/DTX/ICG nanoparticles (ANG/PLGA/DTX/ICG NPs) not only highly induced U87MG cell death in vitro, but also efficiently prolonged the life span of the brain orthotopic U87MG glioma xenograft-bearing mice in vivo. Thus, this study suggests that ANG/PLGA/DTX/ICG NPs have the potential for combinatorial chemotherapy and phototherapy for glioma.

Journal ArticleDOI
TL;DR: This study investigates the structural features of porcine gastric mucin in aqueous dispersions and its interactions with water-soluble polymers using isothermal titration calorimetry, turbidimetric titration, dynamic light scattering, and transmission electron microscopy.
Abstract: This study investigates the structural features of porcine gastric mucin (PGM) in aqueous dispersions and its interactions with water-soluble polymers (poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), poly(ethylene oxide), and poly(ethylene glycol)) using isothermal titration calorimetry, turbidimetric titration, dynamic light scattering, and transmission electron microscopy. It is established that PAA (450 kDa) and PMAA (100 kDa) exhibit strong specific interactions with PGM causing further aggregation of its particles, while PAA (2 kDa), poly(ethylene oxide) (1 000 kDa), and poly(ethylene glycol) (10 kDa) do not show any detectable effects on mucin. Sonication of mucin dispersions prior to their mixing with PAA (450 kDa) and PMAA (100 kDa) leads to more pronounced intensity of interactions.

Journal ArticleDOI
TL;DR: The preparation of conductive silk foam-based bone tissue scaffolds that enable the electrical stimulation of human mesenchymal stem cells to enhance their differentiation toward osteogenic outcomes are described.
Abstract: Stimuli-responsive materials enabling the behavior of the cells that reside within them to be controlled are vital for the development of instructive tissue scaffolds for tissue engineering. Herein, we describe the preparation of conductive silk foam-based bone tissue scaffolds that enable the electrical stimulation of human mesenchymal stem cells (HMSCs) to enhance their differentiation toward osteogenic outcomes.

Journal ArticleDOI
TL;DR: The results of this work demonstrate that the manipulation and optimization of hydrogel microenvironments, namely permeability and living space, are crucial to direct cell fate and neo-tissue formation.
Abstract: One bottleneck in tissue regeneration with hydrogel scaffolds is the limited understanding of the crucial factors for controlling hydrogel's physical microenvironments to regulate cell fate. Here, the effects of permeability and living space of hydrogels on encapsulated cells' behavior were evaluated, respectively. Three model hydrogel-based constructs are fabricated by using photo-crosslinkable hyaluronic acid as precursor and chondrocytes as model cell type. The better permeable hydrogels facilitate better cell viability and rapid proliferation, which lead to increased production of extracellular matrix (ECM), e.g. collagen, glycosaminoglycan. By prolonged culture, nano-sized hydrogel networks inhibit neo-tissue development, and the presence of macro-porous living spaces significantly enhance ECM deposition via forming larger cell clusters and eventually induce formation of scaffold-free neo-tissue islets. The results of this work demonstrate that the manipulation and optimization of hydrogel microenvironments, namely permeability and living space, are crucial to direct cell fate and neo-tissue formation.

Journal ArticleDOI
TL;DR: Structural and functional characteristics of bio-derived materials are highlighted, which will expedite the design fabrication and synthesis of eco-friendly and recyclable advanced nano-materials and devices.
Abstract: Natural materials have been a fundamental part of human life since the dawn of civilization. However, due to exploitation of natural resources and cost issues, synthetic materials replaced bio-derived materials in the last century. Recent advances in bio- and nano-technologies pave the way for developing eco-friendly materials that could be produced easily from renewable resources at reduced cost and in a broad array of useful applications. This feature article highlights structural and functional characteristics of bio-derived materials, which will expedite the design fabrication and synthesis of eco-friendly and recyclable advanced nano-materials and devices.

Journal ArticleDOI
TL;DR: Protein modifications are detected, which may affect the protein structure, decrease activity and bioavailability, and increase the risk for immune responses.
Abstract: The compatibility of selected cross-linking reactions with lysozyme is investigated. Michael-type additions of nucleophilic amino acids to maleimide, vinyl sulfone and acrylamide groups are detected by gel electrophoresis. The degree of modification depends on the polymer and the pH. Complete modification with more than five PEG chains is observed after incubation with mPEG5k-vinyl sulfone at pH 9, whereas 96% of the protein remains unmodified after incubation with mPEG5k-acrylamide at pH 4. Incubation with mPEG5k-thiol results in thiol-disulfide exchange reactions. Hydrogel preparation is simulated by using polymer mixtures. Protein modifications are detected, which may affect the protein structure, decrease activity and bioavailability, and increase the risk for immune responses.

Journal ArticleDOI
TL;DR: The main issue of the feature is the synthesis and aminolysis of cellulose carbonates with low, intermediate, and high degree of substitution and the evaluation of this chemistry with respect to specific challenges.
Abstract: Cellulose carbonates as a platform compound open new possibilities for the design of advanced materials based on the most important renewable resource cellulose. In the present feature, the chemistry of cellulose carbonates is discussed considering own research results adequately. After a short overview about methods for activation of polysaccharides for a conversion with nucleophilic compounds in particular with amines, details about various methods for the synthesis of polysaccharide carbonates are discussed. The main issue of the feature is the synthesis and aminolysis of cellulose carbonates with low, intermediate, and high degree of substitution and the evaluation of this chemistry with respect to specific challenges. Functional cellulose carbamates, obtained from cellulose phenyl carbonate by aminolysis, show the potential use of this class of celluloses. Immunoassays and zwitterionic polymers are included as representative examples regarding properties and application of the new cellulose-based products.

Journal ArticleDOI
TL;DR: Results showed that although incorporation of 1 wt% sericin promoted survival of the fibroblasts, both Sericin and gelatin acted synergistically to facilitate long-term 3D cell function.
Abstract: A photopolymerizable-tyraminated poly(vinyl alcohol) (PVA-Tyr) system that has the ability to covalently bind proteins in their native state was evaluated as a platform for cell encapsulation. However, a key hurdle to this system is the radicals generated during the cross-linking that can cause oxidative stress to the cells. This research hypothesized that incorporation of anti-oxidative proteins (sericin and gelatin) into PVA-Tyr gels would mitigate any toxicity caused by the radicals. The results showed that although incorporation of 1 wt% sericin promoted survival of the fibroblasts, both sericin and gelatin acted synergistically to facilitate long-term 3D cell function. The encapsulated cells formed clusters with deposition of laminin and collagen, as well as remaining metabolically active after 21 d.

Journal ArticleDOI
TL;DR: Mannosylated micelles showed enhanced cell uptake in DC 2.4 cells and in bone marrow-derived dendritic cells (BMDCs) and therefore appear to be a suitable platform for immune modulation.
Abstract: Core-shell structures based on polypept(o)ides combine stealth-like properties of the corona material polysarcosine with adjustable functionalities of the polypeptidic core. Mannose-bearing block copolypept(o)ides (PSar-block-PGlu(OBn)) have been synthesized using 11-amino-3,6,9-trioxa-undecyl-2,3,4,6-tetra-O-acetyl-O-α-D-mannopyranoside as initiator in the sequential ring-opening polymerization of α-amino acid N-carboxyanhydrides. These amphiphilic block copolypept(o)ides self-assemble into multivalent PeptoMicelles and bind to mannose-binding receptors as expressed by dendritic cells. Mannosylated micelles showed enhanced cell uptake in DC 2.4 cells and in bone marrow-derived dendritic cells (BMDCs) and therefore appear to be a suitable platform for immune modulation.

Journal ArticleDOI
TL;DR: Temperature-triggered formation of nanostructures with distinct biological activity offers opportunities in selective modification of matrices and in drug delivery and the incorporation of CLP domains in these nanostructure may offer opportunities for the selective targeting of collagen-containing matrices.
Abstract: Temperature-triggered formation of nanostructures with distinct biological activity offers opportunities in selective modification of matrices and in drug delivery. Toward these ends, diblock polymers comprising poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA) conjugated to a triple helix-forming collagen-like peptide were produced. Triggered by the collapse of the thermoresponsive domain above its LCST, the conjugate undergoes a reversible transition in aqueous solution to form well-defined nanovesicles with diameters of approximately 100 nm, with a transition temperature of 37 °C. The incorporation of CLP domains in these nanostructures may offer opportunities for the selective targeting of collagen-containing matrices.