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Special Issue "Functional Polymers for Medical Applications"

A special issue of Polymers (ISSN 2073-4360).

Deadline for manuscript submissions: closed (29 February 2016)

Special Issue Editors

Guest Editor
Dr. Jianxun Ding

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, China
Website | E-Mail
Phone: +86 431 8526 2116
Interests: polymer chemistry; controlled polymerization; stimuli-responsive polymers; functional polymers; drug delivery; tissue engineering
Guest Editor
Prof. Dr. Xuesi Chen

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, China
Website | E-Mail
Phone: +86 431 8526 2112
Interests: material science; polymer chemistry; ring-opening polymerization; biodegradable polymers; smart polymers; biomaterials; polymer industrialization
Guest Editor
Prof. Dr. Carsten Werner

Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials & TU Dresden, Center for Regenerative Therapies, Hohe Str. 06, 01069 Dresden, Germany
Website | E-Mail
Interests: biomedical polymers; biointerfacial phenomena; hemocompatible materials; cell-instructive polymer matrices; bio-inspired materials

Special Issue Information

Dear Colleagues,

Functional polymers as biomaterials, obtained by polymerization of functional monomers and by functionalization of synthetic and natural polymers, continue to be a research hotspot. The biomedical polymers exhibit a far-going variability of physical and chemical characteristics, allowing for the adjustment of biocompatibility, bioactivities, stimuli-responsiveness, and biodegradability. The current advancement of medical technology results in new requirements for multifunctional and adaptive polymeric materials, which have to be addressed by appropriate synthesis schemes.
The Special Issue will center on both the preparation and application of various biomedical polymers, and intends to cover the most exciting recent developments in the field. Both original articles and reviews are welcome.

Dr. Jianxun Ding
Prof. Dr. Xuesi Chen
Prof. Dr. Carsten Werner
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Polymers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • functional synthetic polymers
  • functional natural polymers
  • biomaterials
  • drug delivery
  • gene transfection
  • cell-instructive polymer matrices
  • tissue engineering
  • bioseparation
  • biodiagnostics
  • medical devices

Published Papers (37 papers)

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Research

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Open AccessArticle Bactericidal Effect of Lauric Acid-Loaded PCL-PEG-PCL Nano-Sized Micelles on Skin Commensal Propionibacterium acnes
Polymers 2016, 8(9), 321; doi:10.3390/polym8090321
Received: 17 February 2016 / Revised: 14 August 2016 / Accepted: 22 August 2016 / Published: 27 August 2016
PDF Full-text (7184 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Acne is the over growth of the commensal bacteria Propionibacterium acnes (P. acnes) on human skin. Lauric acid (LA) has been investigated as an effective candidate to suppress the activity of P. acnes. Although LA is nearly insoluble in water,
[...] Read more.
Acne is the over growth of the commensal bacteria Propionibacterium acnes (P. acnes) on human skin. Lauric acid (LA) has been investigated as an effective candidate to suppress the activity of P. acnes. Although LA is nearly insoluble in water, dimethyl sulfoxide (DMSO) has been reported to effectively solubilize LA. However, the toxicity of DMSO can limit the use of LA on the skin. In this study, LA-loaded poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) micelles (PCL-PEG-PCL) were developed to improve the bactericidal effect of free LA on P. acnes. The block copolymers mPEG-PCL and PCL-PEG-PCL with different molecular weights were synthesized and characterized using 1H Nuclear Magnetic Resonance spectroscopy (1H NMR), Fourier-transform infrared spectroscopy (FT-IR), Gel Permeation Chromatography (GPC), and Differential Scanning Calorimetry (DSC). In the presence of LA, mPEG-PCL diblock copolymers did not self-assemble into nano-sized micelles. On the contrary, the average particle sizes of the PCL-PEG-PCL micelles ranged from 50–198 nm for blank micelles and 27–89 nm for LA-loaded micelles. The drug loading content increased as the molecular weight of PCL-PEG-PCL polymer increased. Additionally, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of free LA were 20 and 80 μg/mL, respectively. The MICs and MBCs of the micelles decreased to 10 and 40 μg/mL, respectively. This study demonstrated that the LA-loaded micelles are a potential treatment for acne. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle An Osteoconductive Antibiotic Bone Eluting Putty with a Custom Polymer Matrix
Polymers 2016, 8(7), 247; doi:10.3390/polym8070247
Received: 25 March 2016 / Revised: 19 June 2016 / Accepted: 21 June 2016 / Published: 30 June 2016
PDF Full-text (3392 KB) | HTML Full-text | XML Full-text
Abstract
With the rising tide of antibiotic resistant bacteria, extending the longevity of the current antibiotic arsenal is becoming a necessity. Developing local, controlled release antibiotic strategies, particularly for difficult to penetrate tissues such as bone, may prove to be a better alternative. Previous
[...] Read more.
With the rising tide of antibiotic resistant bacteria, extending the longevity of the current antibiotic arsenal is becoming a necessity. Developing local, controlled release antibiotic strategies, particularly for difficult to penetrate tissues such as bone, may prove to be a better alternative. Previous efforts to develop an osteoconductive local antibiotic release device for bone were created as solid molded composites; however, intimate contact with host bone was found to be critical to support host bone regrowth; thus, an osteocondconductive antibiotic releasing bone void filling putty was developed. Furthermore, a controlled releasing polymer matrix was refined using pendant-functionalized diols to provide tailorable pharmacokinetics. In vitro pharmacokinetic and bioactivity profiles were compared for a putty formulation with an analogous composition as its molded counterpart as well as four new pendant-functionalized polymers. A best-fit analysis of polymer composition in either small cylindrical disks or larger spheres revealed that the new pendant-functionalized polymers appear to release vancomycin via both diffusion and erosion regardless of the geometry of the putty. In silico simulations, a valuable technique for diffusion mediated controlled release models, will be used to confirm and optimize this property. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Production and Characterization of a Novel, Electrospun, Tri-Layer Polycaprolactone Membrane for the Segregated Co-Culture of Bone and Soft Tissue
Polymers 2016, 8(6), 221; doi:10.3390/polym8060221
Received: 12 May 2016 / Revised: 31 May 2016 / Accepted: 1 June 2016 / Published: 7 June 2016
PDF Full-text (3711 KB) | HTML Full-text | XML Full-text
Abstract
Composite tissue-engineered constructs combining bone and soft tissue have applications in regenerative medicine, particularly dentistry. This study generated a tri-layer, electrospun, poly-ε-caprolactone membrane, with two microfiber layers separated by a layer of nanofibers, for the spatially segregated culture of mesenchymal progenitor cells (MPCs)
[...] Read more.
Composite tissue-engineered constructs combining bone and soft tissue have applications in regenerative medicine, particularly dentistry. This study generated a tri-layer, electrospun, poly-ε-caprolactone membrane, with two microfiber layers separated by a layer of nanofibers, for the spatially segregated culture of mesenchymal progenitor cells (MPCs) and fibroblasts. The two cell types were seeded on either side, and cell proliferation and spatial organization were investigated over several weeks. Calcium deposition by MPCs was detected using xylenol orange (XO) and the separation between fibroblasts and the calcified matrix was visualized by confocal laser scanning microscopy. SEM confirmed that the scaffold consisted of two layers of micron-diameter fibers with a thin layer of nano-diameter fibers in-between. Complete separation of cell types was maintained and calcified matrix was observed on only one side of the membrane. This novel tri-layer membrane is capable of supporting the formation of a bilayer of calcified and non-calcified connective tissue. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Molecularly Imprinted Polymers for the Identification and Separation of Chiral Drugs and Biomolecules
Polymers 2016, 8(6), 216; doi:10.3390/polym8060216
Received: 31 March 2016 / Revised: 22 April 2016 / Accepted: 24 May 2016 / Published: 3 June 2016
Cited by 1 | PDF Full-text (3051 KB) | HTML Full-text | XML Full-text
Abstract
Molecularly imprinting polymers (MIPs) have been extensively applied in chromatography for the separation of chiral drugs. In this review, we mainly summarize recent developments of various MIPs used as chiral stationary phases (CSPs) in high performance liquid chromatography (HPLC), capillary electrochromatography (CEC), and
[...] Read more.
Molecularly imprinting polymers (MIPs) have been extensively applied in chromatography for the separation of chiral drugs. In this review, we mainly summarize recent developments of various MIPs used as chiral stationary phases (CSPs) in high performance liquid chromatography (HPLC), capillary electrochromatography (CEC), and supercritical fluid chromatography (SFC). Among them, HPLC has the advantages of straightforward operation and high selectivity. However, the low separation efficiency, due to slow interaction kinetics and heavy peak broadening, is the main challenge for the application of MIPs in HPLC. On the other hand, CEC possesses both the high selectivity of HPLC and the high efficiency of capillary electrophoresis. In CEC, electroosmotic flow is formed across the entire column and reduces the heavy peak broadening observed in HPLC mode. SFC can modify the low interaction kinetics in HPLC when supercritical fluids are utilized as mobile phases. If SFC and MIP-based CSPs can be well combined, better separation performance can be achieved. Particles, monoliths and membrane are typical formats of MIPs. Traditional MIP particles produced by bulk polymerization have been replaced by MIP particles by surface imprinting technology, which are highly consistent in size and shape. Monolithic MIPs are prepared by in situ method in a column, greatly shortening the pre-preparation time. Some novel materials, such as magnetic nanoparticles, are integrated into the MIPs to enhance the controllability and efficiency of the polymerization. This review will be helpful to guide the preparation, development, and application of MIPs in chromatographic and electrophoretic enantioseparation. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessFeature PaperArticle Engineering Porous Poly(lactic acid) Scaffolds with High Mechanical Performance via a Solid State Extrusion/Porogen Leaching Approach
Polymers 2016, 8(6), 213; doi:10.3390/polym8060213
Received: 3 March 2016 / Revised: 18 May 2016 / Accepted: 26 May 2016 / Published: 31 May 2016
Cited by 2 | PDF Full-text (4153 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A knotty issue concerning the poor mechanical properties exists in the porogen leaching approach to porous scaffolds, despite its advantage in tuning pore structure. To address this hurdle, solid state extrusion (SSE) combined with porogen leaching was utilized to engineer porous scaffolds of
[...] Read more.
A knotty issue concerning the poor mechanical properties exists in the porogen leaching approach to porous scaffolds, despite its advantage in tuning pore structure. To address this hurdle, solid state extrusion (SSE) combined with porogen leaching was utilized to engineer porous scaffolds of poly(lactic acid) (PLA). Advances introduced by poly(ethylene glycol) (PEG) caused the PLA ductile to be processed and, on the other hand, enabled the formation of interconnected pores. Thus, a well-interconnected porous architecture with high connectivity exceeding 97% and elevated porosity over 60% was obtained in the as-prepared PLA scaffolds with the composition of NaCl higher than 75.00 wt % and PEG beyond 1.25 wt %. More strikingly, the pore walls of macropores encompassed countless micropores and rough surface topography, in favor of transporting nutrients and metabolites as well as cell attachment. The prominent compressive modulus of the PLA scaffolds was in the range of 85.7–207.4 MPa, matching the normal modulus of human trabecular bone (50–250 MPa). By means of alkaline modification to improve hydrophilicity, biocompatible porous PLA scaffolds exhibited good cell attachment. These results suggest that the SSE/porogen leaching approach provides an eligible clue for fabricating porous scaffolds with high mechanical performance for use as artificial extracellular matrices. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Synthesis of New Polyether Ether Ketone Derivatives with Silver Binding Site and Coordination Compounds of Their Monomers with Different Silver Salts
Polymers 2016, 8(6), 208; doi:10.3390/polym8060208
Received: 15 March 2016 / Revised: 13 May 2016 / Accepted: 19 May 2016 / Published: 30 May 2016
PDF Full-text (6657 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Polyether ether ketone (PEEK) is a well-known polymer used for implants and devices, especially spinal ones. To overcome the biomaterial related infection risks, 4-4′-difluorobenzophenone, the famous PEEK monomer, was modified in order to introduce binding sites for silver ions, which are
[...] Read more.
Polyether ether ketone (PEEK) is a well-known polymer used for implants and devices, especially spinal ones. To overcome the biomaterial related infection risks, 4-4′-difluorobenzophenone, the famous PEEK monomer, was modified in order to introduce binding sites for silver ions, which are well known for their antimicrobial activity. The complexation of these new monomers with different silver salts was studied. Crystal structures of different intermediates were obtained with a linear coordination between two pyridine groups and the silver ions in all cases. The mechanical and thermal properties of different new polymers were characterized. The synthesized PEEKN5 polymers showed similar properties than the PEEK ones whereas the PEEKN7 polymers showed similar thermal properties but the mechanical properties are not as good as the ones of PEEK. To improve these properties, these polymers were complexed with silver nitrate in order to “cross-link” with silver ions. The presence of ionic silver in the polymer was then confirmed by thermogravimetric analysis (TGA) and X-ray powder diffraction (XRPD). Finally, a silver-based antimicrobial compound was successfully coated on the surface of PEEKN5. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Repair Effect of Seaweed Polysaccharides with Different Contents of Sulfate Group and Molecular Weights on Damaged HK-2 Cells
Polymers 2016, 8(5), 188; doi:10.3390/polym8050188
Received: 2 April 2016 / Revised: 28 April 2016 / Accepted: 9 May 2016 / Published: 19 May 2016
Cited by 5 | PDF Full-text (7212 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The structure–activity relationships and repair mechanism of six low-molecular-weight seaweed polysaccharides (SPSs) on oxalate-induced damaged human kidney proximal tubular epithelial cells (HK-2) were investigated. These SPSs included Laminaria japonica polysaccharide, degraded Porphyra yezoensis polysaccharide, degraded Gracilaria lemaneiformis polysaccharide, degraded Sargassum fusiforme polysaccharide, Eucheuma
[...] Read more.
The structure–activity relationships and repair mechanism of six low-molecular-weight seaweed polysaccharides (SPSs) on oxalate-induced damaged human kidney proximal tubular epithelial cells (HK-2) were investigated. These SPSs included Laminaria japonica polysaccharide, degraded Porphyra yezoensis polysaccharide, degraded Gracilaria lemaneiformis polysaccharide, degraded Sargassum fusiforme polysaccharide, Eucheuma gelatinae polysaccharide, and degraded Undaria pinnatifida polysaccharide. These SPSs have a narrow difference of molecular weight (from 1968 to 4020 Da) after degradation by controlling H2O2 concentration. The sulfate group (–SO3H) content of the six SPSs was 21.7%, 17.9%, 13.3%, 8.2%, 7.0%, and 5.5%, respectively, and the –COOH contents varied between 1.0% to 1.7%. After degradation, no significant difference was observed in the contents of characteristic –SO3H and –COOH groups of polysaccharides. The repair effect of polysaccharides was determined using cell-viability test by CCK-8 assay and cell-morphology test by hematoxylin-eosin staining. The results revealed that these SPSs within 0.1–100 μg/mL did not express cytotoxicity in HK-2 cells, and each polysaccharide had a repair effect on oxalate-induced damaged HK-2 cells. Simultaneously, the content of polysaccharide –SO3H was positively correlated with repair ability. Furthermore, the low-molecular-weight degraded polysaccharides showed better repair activity on damaged HK-2 cells than their undegraded counterpart. Our results can provide reference for inhibiting the formation of kidney stones and for developing original anti-stone polysaccharide drugs. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Differentiation of Dental Pulp Stem Cells on Gutta-Percha Scaffolds
Polymers 2016, 8(5), 193; doi:10.3390/polym8050193
Received: 8 April 2016 / Revised: 3 May 2016 / Accepted: 4 May 2016 / Published: 13 May 2016
Cited by 2 | PDF Full-text (6133 KB) | HTML Full-text | XML Full-text
Abstract
Advances in treatment of tooth injury have shown that tooth regeneration from the pulp was a viable alternative of root canal therapy. In this study, we demonstrated that Gutta-percha, nanocomposites primarily used for obturation of the canal, are not cytotoxic and can induce
[...] Read more.
Advances in treatment of tooth injury have shown that tooth regeneration from the pulp was a viable alternative of root canal therapy. In this study, we demonstrated that Gutta-percha, nanocomposites primarily used for obturation of the canal, are not cytotoxic and can induce differentiation of dental pulp stem cells (DPSC) in the absence of soluble mediators. Flat scaffolds were obtained by spin coating Si wafers with three Gutta-percha compounds: GuttaCore™, ProTaper™, and Lexicon™. The images of annealed surfaces showed that the nanoparticles were encapsulated, forming surfaces with root mean square (RMS) roughness of 136–211 nm. Then, by culturing DPSC on these substrates we found that after some initial difficulty in adhesion, confluent tissues were formed after 21 days. Imaging of the polyisoprene (PI) surfaces showed that biomineral deposition only occurred when dexamethasone was present in the media. Spectra obtained from the minerals was consistent with that of hydroxyapatite (HA). In contrast, HA deposition was observed on all Gutta-percha scaffolds regardless of the presence or absence of dexamethasone, implying that surface roughness may be an enabling factor in the differentiation process. These results indicate that Gutta-percha nanocomposites may be good candidates for pulp regeneration therapy. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Polyurethane/Polylactide-Blend Films Doped with Zinc Ions for the Growth and Expansion of Human Olfactory Ensheathing Cells (OECs) and Adipose-Derived Mesenchymal Stromal Stem Cells (ASCs) for Regenerative Medicine Applications
Polymers 2016, 8(5), 175; doi:10.3390/polym8050175
Received: 29 February 2016 / Revised: 6 April 2016 / Accepted: 8 April 2016 / Published: 30 April 2016
Cited by 1 | PDF Full-text (10895 KB) | HTML Full-text | XML Full-text
Abstract
Polymeric biomaterials based on polyurethane and polylactide blends are promising candidates for regenerative medicine applications as biocompatible, bioresorbable carriers. In current research we showed that 80/20 polyurethane/polylactide blends (PU/PLDL) with confirmed biological properties in vitro may be further improved by the addition of
[...] Read more.
Polymeric biomaterials based on polyurethane and polylactide blends are promising candidates for regenerative medicine applications as biocompatible, bioresorbable carriers. In current research we showed that 80/20 polyurethane/polylactide blends (PU/PLDL) with confirmed biological properties in vitro may be further improved by the addition of ZnO nanoparticles for the delivery of bioactive zinc oxide for cells. The PU/PLDL blends were doped with different concentrations of ZnO (0.001%, 0.01%, 0.05%) and undertaken for in vitro biological evaluation using human adipose stromal stem cells (ASCs) and olfactory ensheathing cells (OECs). The addition of 0.001% of ZnO to the biomaterials positively influenced the morphology, proliferation, and phenotype of cells cultured on the scaffolds. Moreover, the analysis of oxidative stress markers revealed that 0.001% of ZnO added to the material decreased the stress level in both cell lines. In addition, the levels of neural-specific genes were upregulated in OECs when cultured on sample 0.001 ZnO, while the apoptosis-related genes were downregulated in OECs and ASCs in the same group. Therefore, we showed that PU/PLDL blends doped with 0.001% of ZnO exert beneficial influence on ASCs and OECs in vitro and they may be considered for future applications in the field of regenerative medicine. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Stereocomplex-Reinforced PEGylated Polylactide Micelle for Optimized Drug Delivery
Polymers 2016, 8(4), 165; doi:10.3390/polym8040165
Received: 28 March 2016 / Revised: 19 April 2016 / Accepted: 20 April 2016 / Published: 22 April 2016
Cited by 1 | PDF Full-text (5270 KB) | HTML Full-text | XML Full-text
Abstract
The instability of PEGylated polylactide micelles is a challenge for drug delivery. Stereocomplex interaction between racemic polylactide chains with different configurations provides an effective strategy to enhance the stability of micelles as the nanocarriers of drugs. In this work, a stereocomplex micelle (SCM)
[...] Read more.
The instability of PEGylated polylactide micelles is a challenge for drug delivery. Stereocomplex interaction between racemic polylactide chains with different configurations provides an effective strategy to enhance the stability of micelles as the nanocarriers of drugs. In this work, a stereocomplex micelle (SCM) self-assembled from the amphiphilic triblock copolymers comprising poly(ethylene glycol) (PEG), and dextrorotatory and levorotatory polylactides (PDLA and PLLA) was applied for efficient drug delivery. The spherical SCM showed the smallest scale and the lowest critical micelle concentration (CMC) than the micelles with single components attributed to the stereocomplex interaction between PDLA and PLLA. 10-Hydroxycamptothecin (HCPT) as a model antitumor drug was loaded into micelles. Compared with the loading micelles from individual PDLA and PLLA, the HCPT-loaded SCM exhibited the highest drug loading efficiency (DLE) and the slowest drug release in phosphate-buffered saline (PBS) at pH 7.4, indicating its enhanced stability in circulation. More fascinatingly, the laden SCM was demonstrated to have the highest cellular uptake of HCPT and suppress malignant cells most effectively in comparison to the HCPT-loaded micelles from single copolymer. In summary, the stereocomplex-enhanced PLA–PEG–PLA micelle may be promising for optimized drug delivery in the clinic. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle 2H Solid-State NMR Analysis of the Dynamics and Organization of Water in Hydrated Chitosan
Polymers 2016, 8(4), 149; doi:10.3390/polym8040149
Received: 25 February 2016 / Revised: 7 April 2016 / Accepted: 12 April 2016 / Published: 19 April 2016
Cited by 4 | PDF Full-text (2762 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Understanding water–biopolymer interactions, which strongly affect the function and properties of biopolymer-based tissue engineering and drug delivery materials, remains a challenge. Chitosan, which is an important biopolymer for the construction of artificial tissue grafts and for drug delivery, has attracted extensive attention in
[...] Read more.
Understanding water–biopolymer interactions, which strongly affect the function and properties of biopolymer-based tissue engineering and drug delivery materials, remains a challenge. Chitosan, which is an important biopolymer for the construction of artificial tissue grafts and for drug delivery, has attracted extensive attention in recent decades, where neutralization with an alkali solution can substantially enhance the final properties of chitosan films cast from an acidic solution. In this work, to elucidate the effect of water on the properties of chitosan films, we investigated the dynamics and different states of water in non-neutralized (CTS-A) and neutralized (CTS-N) hydrated chitosan by mobility selective variable-temperature (VT) 2H solid-state NMR spectroscopy. Four distinct types of water exist in all of the samples with regards to dynamic behavior. First, non-freezable, rigid and strongly bound water was found in the crystalline domain at low temperatures. The second component consists of weakly bound water, which is highly mobile and exhibits isotropic motion, even below 260 K. Another type of water undergoes well-defined 180° flips around their bisector axis. Moreover, free water is also present in the films. For the CTS-A sample in particular, another special water species were bounded to acetic acid molecules via strong hydrogen bonding. In the case of CTS-N, the onset of motions of the weakly bound water molecules at 260 K was revealed by 2H-NMR spectroscopy. This water is not crystalline, even below 260 K, which is also the major contribution to the flexibility of chitosan chains and thus toughness of materials. By contrast, such motion was not observed in CTS-A. On the basis of the 2H solid-state NMR results, it is concluded that the unique toughness of CTS-N mainly originates from the weakly bound water as well as the interactions between water and the chitosan chains. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessFeature PaperArticle The in Vitro and in Vivo Degradation of Cross-Linked Poly(trimethylene carbonate)-Based Networks
Polymers 2016, 8(4), 151; doi:10.3390/polym8040151
Received: 18 March 2016 / Revised: 9 April 2016 / Accepted: 14 April 2016 / Published: 19 April 2016
Cited by 1 | PDF Full-text (10111 KB) | HTML Full-text | XML Full-text
Abstract
The degradation of the poly(trimethylene carbonate) (PTMC) and poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-co-CL)) networks cross-linked by 0.01 and 0.02 mol % 2,2′-bis(trimethylene carbonate-5-yl)-butylether (BTB) was carried out in the conditions of hydrolysis and enzymes in vitro and subcutaneous implantation in vivo
[...] Read more.
The degradation of the poly(trimethylene carbonate) (PTMC) and poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-co-CL)) networks cross-linked by 0.01 and 0.02 mol % 2,2′-bis(trimethylene carbonate-5-yl)-butylether (BTB) was carried out in the conditions of hydrolysis and enzymes in vitro and subcutaneous implantation in vivo. The results showed that the cross-linked PTMC networks exhibited much faster degradation in enzymatic conditions in vitro and in vivo versus in a hydrolysis case due to the catalyst effect of enzymes; the weight loss and physical properties of the degraded networks were dependent on the BTB amount. The morphology observation in lipase and in vivo illustrated that enzymes played an important role in the surface erosion of cross-linked PTMC. The hydrolytic degradation rate of the cross-linked P(TMC-co-CL) networks increased with increasing ε-caprolactone (CL) content in composition due to the preferential cleavage of ester bonds. Cross-linking is an effective strategy to lower the degradation rate and enhance the form-stability of PTMC-based materials. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle pH-Triggered Sheddable Shielding System for Polycationic Gene Carriers
Polymers 2016, 8(4), 141; doi:10.3390/polym8040141
Received: 29 February 2016 / Revised: 28 March 2016 / Accepted: 5 April 2016 / Published: 14 April 2016
Cited by 1 | PDF Full-text (3322 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
For improving the therapeutic efficiency of tumors and decreasing undesirable side effects, ternary complexes were developed by coating pH-sensitive PEG-b-PLL-g-succinylsulfathiazole (hereafter abbreviated as PPSD) with DNA/PEI polyplexes via electrostatic interaction. PPSD can efficiently shield the surface charge of DNA/PEI.
[...] Read more.
For improving the therapeutic efficiency of tumors and decreasing undesirable side effects, ternary complexes were developed by coating pH-sensitive PEG-b-PLL-g-succinylsulfathiazole (hereafter abbreviated as PPSD) with DNA/PEI polyplexes via electrostatic interaction. PPSD can efficiently shield the surface charge of DNA/PEI. The gene transfection efficiency of ternary complexes was lower than that of DNA/PEI at pH 7.4; however, it recovered to the same level as that of DNA/PEI at pH 6.0, attributed to the pH-triggered release of DNA/PEI from ternary complexes. Cell uptake results also exhibited the same trend as transfection at different pH values. The suitable ability for pH-triggered shielding/deshielding estimated that PPSD demonstrates potential as a shielding system for use in in vivo gene delivery. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Structural Properties and Antifungal Activity against Candida albicans Biofilm of Different Composite Layers Based on Ag/Zn Doped Hydroxyapatite-Polydimethylsiloxanes
Polymers 2016, 8(4), 131; doi:10.3390/polym8040131
Received: 29 February 2016 / Revised: 25 March 2016 / Accepted: 30 March 2016 / Published: 9 April 2016
Cited by 6 | PDF Full-text (12033 KB) | HTML Full-text | XML Full-text
Abstract
Modern medicine is still struggling to find new and more effective methods for fighting off viruses, bacteria and fungi. Among the most dangerous and at times life-threatening fungi is Candida albicans. Our work is focused on surface and structural characterization of hydroxyapatite,
[...] Read more.
Modern medicine is still struggling to find new and more effective methods for fighting off viruses, bacteria and fungi. Among the most dangerous and at times life-threatening fungi is Candida albicans. Our work is focused on surface and structural characterization of hydroxyapatite, silver doped hydroxyapatite and zinc doped hydroxyapatite deposited on a titanium substrate previously coated with polydimethylsiloxane (HAp-PDMS, Ag:HAp-PDMS, Zn:HAp-PDMS) by different techniques: Scanning Electron Microscopy (SEM), Glow Discharge Optical Emission Spectroscopy (GDOES) and Fourier Transform Infrared Spectroscopy (FTIR). The morphological studies revealed that the use of the PDMS polymer as an interlayer improves the quality of the coatings. The structural characterizations of the thin films revealed the basic constituents of both apatitic and PDMS structure. In addition, the GD depth profiles indicated the formation of a composite material as well as the successful embedding of the HAp, Zn:HAp and Ag:HAp into the polymer. On the other hand, in vitro evaluation of the antifungal properties of Ag:HAp-PDMS and Zn:HAp-PDMS demonstrated the fungicidal effects of Ag:HAp-PDMS and the potential antifungal effect of Zn:HAp-PDMS composite layers against C. albicans biofilm. The results acquired in this research complete previous research on the potential use of new complex materials produced by nanotechnology in biomedicine. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle A Thixotropic Polyglycerol Sebacate-Based Supramolecular Hydrogel as an Injectable Drug Delivery Matrix
Polymers 2016, 8(4), 130; doi:10.3390/polym8040130
Received: 27 February 2016 / Revised: 22 March 2016 / Accepted: 25 March 2016 / Published: 7 April 2016
Cited by 15 | PDF Full-text (7320 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have developed a “self-healing” polyglycerol sebacate—polyethylene glycol methyl ether methacrylate (PGS-PEGMEMA)/α-Cyclodextrin (αCD) hydrogel which could be sheared into a liquid during injection and has the potential to quickly “heal” itself back into gel post-injection. This hydrogel was shown to be biocompatible and
[...] Read more.
We have developed a “self-healing” polyglycerol sebacate—polyethylene glycol methyl ether methacrylate (PGS-PEGMEMA)/α-Cyclodextrin (αCD) hydrogel which could be sheared into a liquid during injection and has the potential to quickly “heal” itself back into gel post-injection. This hydrogel was shown to be biocompatible and biodegradable and therefore appropriate for use in vivo. Furthermore, the storage and loss moduli of the hydrogels could be tuned (by varying the concentration of αCD) between a fraction of a kPa to a few 100 kPa, a range that coincides with the moduli of cells and human soft tissues. This property would allow for this hydrogel to be used in vivo with maximal mechanical compatibility with human soft tissues. In vitro experiments showed that the hydrogel demonstrated a linear mass erosion profile and a biphasic drug (doxorubicin) release profile: Phase I was primarily driven by diffusion and Phase II was driven by hydrogel erosion. The diffusion mechanism was modeled with the First Order equation and the erosion mechanism with the Hopfenberg equation. This established fitting model could be used to predict releases with other drugs and estimate the composition of the hydrogel required to achieve a desired release rate. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Fluorescent BAPAD Dendrimeric Antigens Are Efficiently Internalized by Human Dendritic Cells
Polymers 2016, 8(4), 111; doi:10.3390/polym8040111
Received: 3 March 2016 / Revised: 16 March 2016 / Accepted: 18 March 2016 / Published: 26 March 2016
Cited by 1 | PDF Full-text (5088 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new fluorescent dendrimeric antigen (DeAn) based on a dendron with amoxicilloyl terminal groups was synthesized. The synthesis was carried out using a novel class of all-aliphatic polyamide dendrimer (BisAminoalkylPolyAmide Dendrimers, or BAPAD) involving the direct condensation of 3,3′-diazidopivalic acid as a building
[...] Read more.
A new fluorescent dendrimeric antigen (DeAn) based on a dendron with amoxicilloyl terminal groups was synthesized. The synthesis was carried out using a novel class of all-aliphatic polyamide dendrimer (BisAminoalkylPolyAmide Dendrimers, or BAPAD) involving the direct condensation of 3,3′-diazidopivalic acid as a building block. Iterative azide reduction/amide formation increases the dendrimer generation. The BAPAD dendrimer was designed with a cystamine core. Reduction of the disulfide bond allows the incorporation of BAPAD dendrons into a 1,8-naphthalimide functionalized with a maleimide group. The fluorescence properties of DeAn were studied in PBS and compared with the properties of an equivalent dendron possessing amino-terminal groups. Both molecules shown high fluorescence quantum yields in PBS and could readily be visualized by fluorescence microscopy. DeAn was used as a synthetic antigen in a biomedical assay that tests their potential as an amoxicillin carrier in drug internalization by dendritic cells (DC) from tolerant and allergic patients. Cytometry data suggest that the dendrons are non-toxic and easily internalized by DCs, while confocal microscopy images indicate that the compounds are preferentially accumulated in the cytoplasm. These results indicate that BAPAD dendrons are good candidates for synthetic scaffolds for biomedical applications. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessFeature PaperArticle PEG-Chitosan Hydrogel with Tunable Stiffness for Study of Drug Response of Breast Cancer Cells
Polymers 2016, 8(4), 112; doi:10.3390/polym8040112
Received: 5 March 2016 / Revised: 17 March 2016 / Accepted: 21 March 2016 / Published: 26 March 2016
Cited by 2 | PDF Full-text (4253 KB) | HTML Full-text | XML Full-text
Abstract
Mechanical properties of the extracellular matrix have a profound effect on the behavior of anchorage-dependent cells. However, the mechanisms that define the effects of matrix stiffness on cell behavior remains unclear. Therefore, the development and fabrication of synthetic matrices with well-defined stiffness is
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Mechanical properties of the extracellular matrix have a profound effect on the behavior of anchorage-dependent cells. However, the mechanisms that define the effects of matrix stiffness on cell behavior remains unclear. Therefore, the development and fabrication of synthetic matrices with well-defined stiffness is invaluable for studying the interactions of cells with their biophysical microenvironment in vitro. We demonstrate a methoxypolyethylene glycol (mPEG)-modified chitosan hydrogel network where hydrogel stiffness can be easily modulated under physiological conditions by adjusting the degree of mPEG grafting onto chitosan (PEGylation). We show that the storage modulus of the hydrogel increases as PEGylation decreases and the gels exhibit instant self-recovery after deformation. Breast cancer cells cultured on the stiffest hydrogels adopt a more malignant phenotype with increased resistance to doxorubicin as compared with cells cultured on tissue culture polystyrene or Matrigel. This work demonstrates the utility of mPEG-modified chitosan hydrogel, with tunable mechanical properties, as an improved replacement of conventional culture system for in vitro characterization of breast cancer cell phenotype and evaluation of cancer therapies. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Interpenetration of Natural Polymer Aerogels by Supercritical Drying
Polymers 2016, 8(4), 106; doi:10.3390/polym8040106
Received: 8 January 2016 / Revised: 15 March 2016 / Accepted: 18 March 2016 / Published: 24 March 2016
Cited by 6 | PDF Full-text (1330 KB) | HTML Full-text | XML Full-text
Abstract
Natural polymers, such as alginate and gelatin, can be used to produce scaffolds for tissue engineering applications; but, their mechanical and biochemical performance should be improved. A possible solution to obtain this result, is the generation of multi-component scaffolds, by blending two or
[...] Read more.
Natural polymers, such as alginate and gelatin, can be used to produce scaffolds for tissue engineering applications; but, their mechanical and biochemical performance should be improved. A possible solution to obtain this result, is the generation of multi-component scaffolds, by blending two or more polymers. One way to realize it, is the formation of an interpenetrating polymer network (IPN). In this work, the interpenetration of alginate and gelatin hydrogels has been successfully obtained and preserved by supercritical CO2 (SC-CO2) drying performed at 200 bar and 35 °C, using different blend compositions: from alginate/gelatin = 20:80 v/v to alginate/gelatin = 80:20 v/v. The process allowed modulation of morphology and mechanical properties of these blends. The overall result was made possible by the supercritical drying process that, working at zero surface tension, allows preserving the hydrogels nanostructure in the corresponding aerogels. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessFeature PaperArticle l-Cystine-Crosslinked Polypeptide Nanogel as a Reduction-Responsive Excipient for Prostate Cancer Chemotherapy
Polymers 2016, 8(2), 36; doi:10.3390/polym8020036
Received: 19 December 2015 / Revised: 21 January 2016 / Accepted: 26 January 2016 / Published: 29 January 2016
Cited by 3 | PDF Full-text (1838 KB) | HTML Full-text | XML Full-text
Abstract
Smart polymer nanogel-assisted drug delivery systems have attracted more and more attention in cancer chemotherapy because of their well-defined morphologies and pleiotropic functions in recent years. In this work, an l-cystine-crosslinked reduction-responsive polypeptide nanogel of methoxy poly(ethylene glycol)-poly(l-phenylalanine-co-
[...] Read more.
Smart polymer nanogel-assisted drug delivery systems have attracted more and more attention in cancer chemotherapy because of their well-defined morphologies and pleiotropic functions in recent years. In this work, an l-cystine-crosslinked reduction-responsive polypeptide nanogel of methoxy poly(ethylene glycol)-poly(l-phenylalanine-co-l-cystine) (mPEG-P(LP-co-LC)) was employed as a smart excipient for RM-1 prostate cancer (PCa) chemotherapy. Doxorubicin (DOX), as a regular chemotherapy drug, was embedded in the nanogel. The loading nanogel marked as NG/DOX was shown to exhibit glutathione (GSH)-induced swelling and GSH-accelerated DOX release. Subsequently, NG/DOX showed efficient cellular uptake and proliferation inhibition. Furthermore, NG/DOX presented enhanced antitumor efficacy and security in an RM-1 PCa-grafted mouse model in vivo, indicating its great potential for clinical treatment. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Reversible Self-Assembly of Backbone-Thermoresponsive Long Chain Hyperbranched Poly(N-Isopropyl Acrylamide)
Polymers 2016, 8(2), 33; doi:10.3390/polym8020033
Received: 10 December 2015 / Revised: 18 January 2016 / Accepted: 25 January 2016 / Published: 28 January 2016
Cited by 1 | PDF Full-text (4075 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, we mainly described the reversible self-assembly of a backbone-thermoresponsive, long-chain, hyperbranched poly(N-isopropyl acrylamide) (LCHBPNIPAM) in aqueous solution. Here, we revealed a reversible self-assembly behavior of LCHBPNIPAM aqueous solution derived from temperature. By controlling the temperature of LCHBPNIPAM aqueous
[...] Read more.
In this paper, we mainly described the reversible self-assembly of a backbone-thermoresponsive, long-chain, hyperbranched poly(N-isopropyl acrylamide) (LCHBPNIPAM) in aqueous solution. Here, we revealed a reversible self-assembly behavior of LCHBPNIPAM aqueous solution derived from temperature. By controlling the temperature of LCHBPNIPAM aqueous solution, we tune the morphology of the LCHBPNIPAM self-assemblies. When the solution temperature increased from the room temperature to the lower critical solution temperature of PNIPAM segments, LCHBPNIPAM self-assembled from multi-compartment vesicles into solid micelles. The morphology of LCHBPNIPAM self-assemblies changed from solid micelles to multi-compartment vesicles again when the temperature decreased back to the room temperature. The size presented, at first, an increase, and then a decrease, tendency in the heating-cooling process. The above thermally-triggered self-assembly behavior of LCHBPNIPAM aqueous solution was investigated by dynamic/static light scattering, transmission electron microscopy, atomic force microscopy, fluorescence spectroscopy, 1H nuclear magnetic resonance in D2O, and attenuated total reflectance Fourier transform infrared spectroscopy. These results indicated that LCHBPNIPAM aqueous solution presents a reversible self-assembly process. The controlled release behaviors of doxorubicin from the vesicles and micelles formed by LCHBPNIPAM further proved the feasibility of these self-assemblies as the stimulus-responsive drug delivery system. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Study of Enzymatically Treated Alginate/Chitosan Hydrosols in Sponges Formation Process
Polymers 2016, 8(1), 8; doi:10.3390/polym8010008
Received: 14 August 2015 / Revised: 16 December 2015 / Accepted: 30 December 2015 / Published: 5 January 2016
Cited by 4 | PDF Full-text (2278 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the study was to produce 3D sponges based on enzymatically modified lysozyme selected polysaccharides and assess their physicochemical properties. The alginate/chitosan sponges were formed from polymers hydrosols in different proportions at a final concentration of 1% polysaccharides. Hydrosols were modified
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The aim of the study was to produce 3D sponges based on enzymatically modified lysozyme selected polysaccharides and assess their physicochemical properties. The alginate/chitosan sponges were formed from polymers hydrosols in different proportions at a final concentration of 1% polysaccharides. Hydrosols were modified by lysozyme addition of 1000 U. Hydrosols without or with enzyme were analyzed for their reducing sugar content, rheological properties and ability to scavenge free radicals. Sponges formed from hydrosols were tested for solubility and compressive properties. Only chitosan was hydrolyzed by lysozyme. The morphology of sponges was investigated by scanning electron microscopy (SEM). It was proven that the antioxidant properties of hydrosols are dependent on the concentration of chitosan. It was also shown that the addition of lysozyme negatively affected the free radical scavenging ability of single hydrosols of alginate and chitosan, and their mixtures. The Ostwald de Waele as well as Herschel–Bulkley models of rheological properties fitted the experimental data well (R2 is between 0.947 and 1.000). Increase in textural features values of sponges was observed. Sponges with pure alginate and pure chitosan were almost completely soluble. The enzyme addition significantly changed the characteristics of the cross-section structure of sponges, and made the surface smoother. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Epirubicin-Complexed Polypeptide Micelle Effectively and Safely Treats Hepatocellular Carcinoma
Polymers 2015, 7(11), 2410-2430; doi:10.3390/polym7111521
Received: 17 October 2015 / Revised: 7 November 2015 / Accepted: 19 November 2015 / Published: 24 November 2015
Cited by 8 | PDF Full-text (9168 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Epirubicin (EPI) once acted as a main agent for HCC chemotherapy. However, the dosage-dependent side effects seriously limit its application in clinic. The purpose of this study is to develop an
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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Epirubicin (EPI) once acted as a main agent for HCC chemotherapy. However, the dosage-dependent side effects seriously limit its application in clinic. The purpose of this study is to develop an effective nanocarrier to improve the efficacy and overcome the limitations of EPI. In this regard, the EPI-complexed micelle (i.e., mPEG-b-PGA/EPI) was prepared via the electrostatic interaction between the amino group in EPI and the carboxyl group in PGA segment of methoxy poly(ethylene glycol)-block-poly(l-glutamic acid) (mPEG-b-PGA), and the subsequent hydrophobic interaction among PGA/EPI complexes. The micelle appeared spherical with a diameter at around 90 nm and possessed a pH-sensitive release property of payload. The cytotoxicity and hemolysis assays in vitro, and the maximum tolerated dose tests in vivo confirmed that mPEG-b-PGA was a kind of safe material with excellent biocompatibility, while the drug-loaded micelle could obviously improve the tolerance of EPI. In addition, mPEG-b-PGA/EPI possessed significantly enhanced antitumor efficacy and security toward the H22-xenografted HCC murine model at macroscopic and microscopic levels compared with free EPI. All these results strongly indicate that mPEG-b-PGA/EPI may be a promising nanoplatform for EPI delivery in the chemotherapy of HCC. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Amino Acid-Modified Polyethylenimines with Enhanced Gene Delivery Efficiency and Biocompatibility
Polymers 2015, 7(11), 2316-2331; doi:10.3390/polym7111516
Received: 25 August 2015 / Revised: 2 November 2015 / Accepted: 10 November 2015 / Published: 17 November 2015
Cited by 3 | PDF Full-text (3608 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The development of gene delivery vectors with high efficiency and biocompatibility is one of the key points of gene therapy. A series of polycations were prepared from polyethylenimine (PEI) with several amino acids or their analogs. The target polymers have different charge and
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The development of gene delivery vectors with high efficiency and biocompatibility is one of the key points of gene therapy. A series of polycations were prepared from polyethylenimine (PEI) with several amino acids or their analogs. The target polymers have different charge and hydrophilic/hydrophobic properties, which may affect their performance in the gene transfection process. Gel retardation and DLS assays showed that these polymers may condense DNA into nanoparticles with positive zeta potentials and proper sizes for cellular uptake. Luciferase reporter gene transfection results revealed their higher transfection efficiency than PEI; especially in the presence of serum, in which up to 23 times higher efficiency was achieved by employing glycolic acid-grafted PEI. Moreover, it was found that the degree of substitution on PEI has an apparent influence on the transfection, and the balance between electron-positive/negative groups largely affects the delivery process. The higher serum tolerance was also proven by BSA adsorption, flow cytometry and confocal microscopy assays. Results demonstrate that such type of polycations may serve as promising non-viral gene delivery vectors. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle The Effect of β-Glycerophosphate Crosslinking on Chitosan Cytotoxicity and Properties of Hydrogels for Vaginal Application
Polymers 2015, 7(11), 2223-2244; doi:10.3390/polym7111510
Received: 24 September 2015 / Revised: 21 October 2015 / Accepted: 28 October 2015 / Published: 4 November 2015
Cited by 2 | PDF Full-text (4477 KB) | HTML Full-text | XML Full-text
Abstract
Mucoadhesive gelling systems based on chitosan and chitosan/β-glycerophosphate (β-GP) were developed in order to increase clotrimazole residence time in the vaginal cavity. Ex vivo mucoadhesiveness using porcine vaginal mucosa followed with mechanical, viscoelastic, and swelling properties of prepared hydrogels were evaluated. Drug-free, sterile,
[...] Read more.
Mucoadhesive gelling systems based on chitosan and chitosan/β-glycerophosphate (β-GP) were developed in order to increase clotrimazole residence time in the vaginal cavity. Ex vivo mucoadhesiveness using porcine vaginal mucosa followed with mechanical, viscoelastic, and swelling properties of prepared hydrogels were evaluated. Drug-free, sterile, unmodified, and β-GP crosslinked chitosan were investigated for the in vitro cytotoxicity in CRL 2616 human vaginal mucosa cells using MTT assay, fluorescent microscopy, and flow cytometry analysis. Chitosan/β-GP hydrogels exhibited pseudoplastic and thixotropic properties. Ionic interaction between β-GP and chitosan improved mechanical properties of hydrogels in terms of hardness, cohesiveness, and compressibility. The hydrogels’ ability to interact with porcine vaginal mucosa (measured as force of detachment and work of adhesion) was comparable to those obtained with reference mucoadhesive gel Replens™. Surprisingly, greater mucoadhesive properties were noticed for chitosan/β-GP hydrogels. The cytotoxic effect of unmodified and β-GP crosslinked chitosan was hardly affected by chitosan molecular weight, exhibited mainly through inducing apoptosis, and was found to be significantly lower in the presence of chitosan/β-GP. Furthermore, the higher amount of β-GP was used to crosslink chitosan, the lower cytotoxic effect was observed. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Maleimide-Functionalized PEI600 Grafted Polyurethane: Synthesis, Nano-Complex Formation with DNA and Thiol-Conjugation of the Complexes for Dual DNA Transfection
Polymers 2015, 7(10), 2131-2145; doi:10.3390/polym7101503
Received: 2 August 2015 / Revised: 13 October 2015 / Accepted: 15 October 2015 / Published: 23 October 2015
Cited by 1 | PDF Full-text (3073 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A polyurethane (PU) grafted with small molecular weight polyethylenimine (PEI600) was synthesized. This PU-PEI600 can assemble DNA via electrostatic interactions into nano-sized polymer/DNA complexes. The complexes exhibited great transfection efficiency in delivering DNA along with a reduced cell toxicity comparing to commercial PEI25k
[...] Read more.
A polyurethane (PU) grafted with small molecular weight polyethylenimine (PEI600) was synthesized. This PU-PEI600 can assemble DNA via electrostatic interactions into nano-sized polymer/DNA complexes. The complexes exhibited great transfection efficiency in delivering DNA along with a reduced cell toxicity comparing to commercial PEI25k (Mw ~25,000). In order to establish a system for concurrently delivering two different DNA or RNA molecules for cell reprogramming (e.g., induced pluripotent stem cells) or the necessity of multi-expression (e.g., double knock down), the PU-PEI600 was further functionalized with maleimide molecules. The novel PU-PEI600-maleimide would still effectively interact with assigned DNA and different functions of PU-PEI600-maleimide/DNA complexes were self-conjugated in presence of a dithiol molecule (1,6-hexanedithiol). In this study, two reporter genes (pEGFP-C2 and pLanRFP-N) were used and evidence of green/red fluorescence co-expression in cells was observed. This article brings a new concept and a practical method for a plurality of different DNA molecules that are more efficient to be concurrently delivered and co-expressed. This method is very helpful in studying cellular multi-regulation or in the treatment of disease with multiple gene defects in vivo. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Comparative Efficacies of a 3D-Printed PCL/PLGA/β-TCP Membrane and a Titanium Membrane for Guided Bone Regeneration in Beagle Dogs
Polymers 2015, 7(10), 2061-2077; doi:10.3390/polym7101500
Received: 12 August 2015 / Revised: 30 September 2015 / Accepted: 10 October 2015 / Published: 21 October 2015
Cited by 11 | PDF Full-text (8113 KB) | HTML Full-text | XML Full-text
Abstract
This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes
[...] Read more.
This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes using extrusion-based 3D printing technology; mechanical tensile testing and in vitro cell proliferation testing were performed. Implant surgery and guided bone regeneration were performed randomly in three groups (a no membrane group, a titanium membrane group, and a PCL/PLGA/β-TCP membrane group (n = 8 per group)). Histological and histometric analyses were conducted to evaluate effects on bone regeneration and osseointegration. Using the results of mechanical testing; a PCL/PLGA/β-TCP ratio of 2:6:2 was selected. The new bone areas (%) in buccal defects around implants were highest in the PCL/PLGA/β-TCP group and significantly higher than in the control group (p < 0.05). Bone-to-implant contact ratios (%) were also significantly higher in the PCL/PLGA/β-TCP and titanium groups than in the control group (p < 0.05). When the guided bone regeneration procedure was performed using the PCL/PLGA/β-TCP membrane; new bone formation around the implant and osseointegration were not inferior to those of the non-resorbable pre-formed titanium mesh membrane. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Preparation and Evaluation of Vancomycin-Loaded N-trimethyl Chitosan Nanoparticles
Polymers 2015, 7(9), 1850-1870; doi:10.3390/polym7091488
Received: 14 July 2015 / Revised: 23 August 2015 / Accepted: 6 September 2015 / Published: 22 September 2015
Cited by 9 | PDF Full-text (3487 KB) | HTML Full-text | XML Full-text
Abstract
Chronic intracellular infections caused by drug-resistant pathogens pose a challenge to the treatment of chronic osteomyelitis. Such treatment requires an intracellular delivery system for the sustained release of antibiotics such as vancomycin (VCM), which is an antibiotic of last resort used against many
[...] Read more.
Chronic intracellular infections caused by drug-resistant pathogens pose a challenge to the treatment of chronic osteomyelitis. Such treatment requires an intracellular delivery system for the sustained release of antibiotics such as vancomycin (VCM), which is an antibiotic of last resort used against many clinically resistant bacteria. In this work, we report VCM-loaded N-trimethyl chitosan (TMC) nanoparticles and their potential application for drug delivery. The results showed that the prepared nanoparticles were predominantly spherical in shape with an average particle diameter of 220 nm, a positive zeta potential, and a loading efficiency of 73.65% ± 1.83%. Furthermore, their drug release profile followed the Higuchi model for sustained release, with non-Fickian diffusion. Over a 24-h period, 6.51% ± 0.58% of the drug within the optimized nanoparticles was released. In vitro cytology showed that osteoblasts (OBs) exhibited higher alkaline phosphatase activity (ALP) after exposure to TMC nanoparticle material. Furthermore, TMC nanoparticles increased the uptake of water-soluble quantum dots (QDs) by OBs, and both nanoparticles and VCM/TMC mixtures improved OB proliferative activity. We also investigated the minimum inhibitory concentration (MIC, 60 μg/mL), half maximal inhibitory concentration (IC50, 48.47 μg/mL), diameter of inhibition zone (DIZ, 1.050 cm), and turbidimetric (TB) assay of nanoparticles. All data demonstrated that VCM/TMC nanoparticles had excellent antibacterial activity against the Gram-positive bacterium Staphylococcus aureus. These findings suggest that VCM-loaded TMC nanoparticles have good potential for the sustained delivery of antibiotics to bone infections. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessArticle Conjugation of ß-Adrenergic Antagonist Alprenolol to Implantable Polymer-Aescin Matrices for Local Delivery
Polymers 2015, 7(9), 1820-1836; doi:10.3390/polym7091484
Received: 24 July 2015 / Revised: 8 September 2015 / Accepted: 10 September 2015 / Published: 18 September 2015
Cited by 2 | PDF Full-text (1240 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The sustained release of alprenolol, a ß-adrenergic antagonist, could be beneficial for the treatment of various heart diseases while reducing the side effects resulting from its continuous use. The novel and branched copolymers uniquely composed of biodegradable components (lactide and glycolide) have been
[...] Read more.
The sustained release of alprenolol, a ß-adrenergic antagonist, could be beneficial for the treatment of various heart diseases while reducing the side effects resulting from its continuous use. The novel and branched copolymers uniquely composed of biodegradable components (lactide and glycolide) have been synthesized using natural and therapeutically-efficient ß-aescin-initiator, and consequently characterized to determine their structures and physicochemical properties. The obtained matrices were not cyto- and genotoxic towards bacterial luminescence, protozoan, and Salmonella typhimurium TA1535. The copolymers release the drug in vitro in a sustained manner and without burst release. The value of the drug released was strongly dependent on the copolymer composition and highly correlated with the hydrolytic matrices’ degradation results. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)

Review

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Open AccessReview Polyglycidol, Its Derivatives, and Polyglycidol-Containing Copolymers—Synthesis and Medical Applications
Polymers 2016, 8(6), 227; doi:10.3390/polym8060227
Received: 9 May 2016 / Revised: 30 May 2016 / Accepted: 31 May 2016 / Published: 9 June 2016
Cited by 4 | PDF Full-text (8660 KB) | HTML Full-text | XML Full-text
Abstract
Polyglycidol (or polyglycerol) is a biocompatible polymer with a main chain structure similar to that of poly(ethylene oxide) but with a –CH2OH reactive side group in every structural unit. The hydroxyl groups in polyglycidol not only increase the hydrophilicity of this
[...] Read more.
Polyglycidol (or polyglycerol) is a biocompatible polymer with a main chain structure similar to that of poly(ethylene oxide) but with a –CH2OH reactive side group in every structural unit. The hydroxyl groups in polyglycidol not only increase the hydrophilicity of this polymer but also allow for its modification, leading to polymers with carboxyl, amine, and vinyl groups, as well as to polymers with bonded aliphatic chains, sugar moieties, and covalently immobilized bioactive compounds in particular proteins. The paper describes the current state of knowledge on the synthesis of polyglycidols with various topology (linear, branched, and star-like) and with various molar masses. We provide information on polyglycidol-rich surfaces with protein-repelling properties. We also describe methods for the synthesis of polyglycidol-containing copolymers and the preparation of nano- and microparticles that could be derived from these copolymers. The paper summarizes recent advances in the application of polyglycidol and polyglycidol-containing polymers as drug carriers, reagents for diagnostic systems, and elements of biosensors. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessReview Polymers in Cartilage Defect Repair of the Knee: Current Status and Future Prospects
Polymers 2016, 8(6), 219; doi:10.3390/polym8060219
Received: 18 March 2016 / Revised: 26 May 2016 / Accepted: 31 May 2016 / Published: 4 June 2016
Cited by 1 | PDF Full-text (1458 KB) | HTML Full-text | XML Full-text
Abstract
Cartilage defects in the knee are often seen in young and active patients. There is a need for effective joint preserving treatments in patients suffering from cartilage defects, as untreated defects often lead to osteoarthritis. Within the last two decades, tissue engineering based
[...] Read more.
Cartilage defects in the knee are often seen in young and active patients. There is a need for effective joint preserving treatments in patients suffering from cartilage defects, as untreated defects often lead to osteoarthritis. Within the last two decades, tissue engineering based techniques using a wide variety of polymers, cell sources, and signaling molecules have been evaluated. We start this review with basic background information on cartilage structure, its intrinsic repair, and an overview of the cartilage repair treatments from a historical perspective. Next, we thoroughly discuss polymer construct components and their current use in commercially available constructs. Finally, we provide an in-depth discussion about construct considerations such as degradation rates, cell sources, mechanical properties, joint homeostasis, and non-degradable/hybrid resurfacing techniques. As future prospects in cartilage repair, we foresee developments in three areas: first, further optimization of degradable scaffolds towards more biomimetic grafts and improved joint environment. Second, we predict that patient-specific non-degradable resurfacing implants will become increasingly applied and will provide a feasible treatment for older patients or failed regenerative treatments. Third, we foresee an increase of interest in hybrid construct, which combines degradable with non-degradable materials. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessReview Functionalized Polymers for Enhance Oral Bioavailability of Sensitive Molecules
Polymers 2016, 8(6), 214; doi:10.3390/polym8060214
Received: 16 March 2016 / Revised: 30 April 2016 / Accepted: 11 May 2016 / Published: 2 June 2016
Cited by 3 | PDF Full-text (1381 KB) | HTML Full-text | XML Full-text
Abstract
Currently, many sensitive molecules have been studied for effective oral administration. These substances are biologically active compounds that mainly suffer early degradation in the gastrointestinal tract (GIT) and physicochemical instability, inactivation and poor solubility and permeability. The sensibility of the biomolecules has limited
[...] Read more.
Currently, many sensitive molecules have been studied for effective oral administration. These substances are biologically active compounds that mainly suffer early degradation in the gastrointestinal tract (GIT) and physicochemical instability, inactivation and poor solubility and permeability. The sensibility of the biomolecules has limited their oral administration in the body and today is an important research topic to achieve desired effects in medicine field. Under this perspective, various enhancement approaches have been studied as alternatives to increase their oral bioavailability. Some of these strategies include functionalized polymers to provide specific useful benefits as protection to the intestinal tract by preventing its degradation by stomach enzymes, to increase their absorption, permeability, stability, and to make a proper release in the GIT. Due to specific chemical groups, shapes and sizes, morphologies, mechanical properties, and degradation, recent advances in functionalized polymers have opened the door to great possibilities to improve the physicochemical characteristics of these biopharmaceuticals. Today, many biomolecules are found in basic studies, preclinical steps, and others are late stage clinical development. This review summarizes the contribution of functionalized polymers to enhance oral bioavailability of sensitive molecules and their application status in medicine for different diseases. Future trends of these polymers and their possible uses to achieve different formulation goals for oral delivery are also covered in this manuscript. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessReview Supramolecular Nanostructures Based on Cyclodextrin and Poly(ethylene oxide): Syntheses, Structural Characterizations and Applications for Drug Delivery
Polymers 2016, 8(5), 198; doi:10.3390/polym8050198
Received: 1 March 2016 / Revised: 10 May 2016 / Accepted: 10 May 2016 / Published: 17 May 2016
Cited by 2 | PDF Full-text (3117 KB) | HTML Full-text | XML Full-text
Abstract
Cyclodextrins (CDs) have been extensively studied as drug delivery carriers through host–guest interactions. CD-based poly(pseudo)rotaxanes, which are composed of one or more CD rings threading on the polymer chain with or without bulky groups (or stoppers), have attracted great interest in the development
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Cyclodextrins (CDs) have been extensively studied as drug delivery carriers through host–guest interactions. CD-based poly(pseudo)rotaxanes, which are composed of one or more CD rings threading on the polymer chain with or without bulky groups (or stoppers), have attracted great interest in the development of supramolecular biomaterials. Poly(ethylene oxide) (PEO) is a water-soluble, biocompatible polymer. Depending on the molecular weight, PEO can be used as a plasticizer or as a toughening agent. Moreover, the hydrogels of PEO are also extensively studied because of their outstanding characteristics in biological drug delivery systems. These biomaterials based on CD and PEO for controlled drug delivery have received increasing attention in recent years. In this review, we summarize the recent progress in supramolecular architectures, focusing on poly(pseudo)rotaxanes, vesicles and supramolecular hydrogels based on CDs and PEO for drug delivery. Particular focus will be devoted to the structures and properties of supramolecular copolymers based on these materials as well as their use for the design and synthesis of supramolecular hydrogels. Moreover, the various applications of drug delivery techniques such as drug absorption, controlled release and drug targeting based CD/PEO supramolecular complexes, are also discussed. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessReview Electro-Active Polymers (EAPs): A Promising Route to Design Bio-Organic/Bioinspired Platforms with on Demand Functionalities
Polymers 2016, 8(5), 185; doi:10.3390/polym8050185
Received: 22 March 2016 / Revised: 19 April 2016 / Accepted: 4 May 2016 / Published: 9 May 2016
Cited by 4 | PDF Full-text (3486 KB) | HTML Full-text | XML Full-text
Abstract
Through recent discoveries and new knowledge among correlations between molecular biology and materials science, it is a growing interest to design new biomaterials able to interact—i.e., to influence, to guide or to detect—with cells and their surrounding microenvironments, in order to
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Through recent discoveries and new knowledge among correlations between molecular biology and materials science, it is a growing interest to design new biomaterials able to interact—i.e., to influence, to guide or to detect—with cells and their surrounding microenvironments, in order to better control biological phenomena. In this context, electro-active polymers (EAPs) are showing great promise as biomaterials acting as an interface between electronics and biology. This is ascribable to the highly tunability of chemical/physical properties which confer them different conductive properties for various applicative uses (i.e., molecular targeting, biosensors, biocompatible scaffolds). This review article is divided into three parts: the first one is an overview on EAPs to introduce basic conductivity mechanisms and their classification. The second one is focused on the description of most common processes used to manipulate EAPs in the form of two-dimensional (2D) and three-dimensional (3D) materials. The last part addresses their use in current applications in different biomedical research areas including tissue engineering, biosensors and molecular delivery. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessReview Polymeric Biodegradable Stent Insertion in the Esophagus
Polymers 2016, 8(5), 158; doi:10.3390/polym8050158
Received: 4 March 2016 / Revised: 3 April 2016 / Accepted: 8 April 2016 / Published: 26 April 2016
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Abstract
Esophageal stent insertion has been used as a well-accepted and effective alternative to manage and improve the quality of life for patients diagnosed with esophageal diseases and disorders. Current stents are either permanent or temporary and are fabricated from either metal or plastic.
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Esophageal stent insertion has been used as a well-accepted and effective alternative to manage and improve the quality of life for patients diagnosed with esophageal diseases and disorders. Current stents are either permanent or temporary and are fabricated from either metal or plastic. The partially covered self-expanding metal stent (SEMS) has a firm anchoring effect and prevent stent migration, however, the hyperplastic tissue reaction cause stent restenosis and make it difficult to remove. A fully covered SEMS and self-expanding plastic stent (SEPS) reduced reactive hyperplasia but has a high migration rate. The main advantage that polymeric biodegradable stents (BDSs) have over metal or plastic stents is that removal is not require and reduce the need for repeated stent insertion. But the slightly lower radial force of BDS may be its main shortcoming and a post-implant problem. Thus, strengthening support of BDS is a content of the research in the future. BDSs are often temporarily effective in esophageal stricture to relieve dysphagia. In the future, it can be expect that biodegradable drug-eluting stents (DES) will be available to treat benign esophageal stricture, perforations or leaks with additional use as palliative modalities for treating malignant esophageal stricture, as the bridge to surgery or to maintain luminal patency during neoadjuvant chemoradiation. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessReview Biodegradable Polymer Membranes Applied in Guided Bone/Tissue Regeneration: A Review
Polymers 2016, 8(4), 115; doi:10.3390/polym8040115
Received: 27 February 2016 / Revised: 20 March 2016 / Accepted: 24 March 2016 / Published: 29 March 2016
Cited by 6 | PDF Full-text (1426 KB) | HTML Full-text | XML Full-text
Abstract
Polymer membranes have been widely used in guided tissue regeneration (GTR) and guided bone regeneration (GBR). In this review, various commercially available membranes are described. Much attention is paid to the recent development of biodegradable polymers applied in GTR and GBR, and the
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Polymer membranes have been widely used in guided tissue regeneration (GTR) and guided bone regeneration (GBR). In this review, various commercially available membranes are described. Much attention is paid to the recent development of biodegradable polymers applied in GTR and GBR, and the important issues of biodegradable polymeric membranes, including their classification, latest experimental research and clinical applications, as well as their main challenges are addressed. Herein, natural polymers, synthetic polymers and their blends are all introduced. Pure polymer membranes are biodegradable and biocompatible, but they lack special properties such as antibacterial properties, osteoconductivity, and thus polymer membranes loaded with functional materials such as antibacterial agents and growth factors show many more advantages and have also been introduced in this review. Despite there still being complaints about polymer membranes, such as their low mechanical properties, uncontrollable degradation speed and some other drawbacks, these problems will undoubtedly be conquered and biodegradable polymers will have more applications in GTR and GBR. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessReview Drug Delivery Systems Obtained from Silica Based Organic-Inorganic Hybrids
Polymers 2016, 8(4), 91; doi:10.3390/polym8040091
Received: 22 February 2016 / Revised: 8 March 2016 / Accepted: 10 March 2016 / Published: 24 March 2016
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Abstract
This is a review of hybrid materials based on silica as an inorganic phase used as drug delivery systems (DDS). Silica based DDS have shown effectivity when compared with traditional delivery systems. They present advantages such as: (a) ability to maintain the therapeutic
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This is a review of hybrid materials based on silica as an inorganic phase used as drug delivery systems (DDS). Silica based DDS have shown effectivity when compared with traditional delivery systems. They present advantages such as: (a) ability to maintain the therapeutic range with minor variations; (b) prevention of local and systemic toxic effects; (c) plasma concentrations increase of substances with a short half-life; and (d) reduction of the number of daily doses, which may increase patient adherence to the treatment. These advantages occur due to the physical, chemical and optical properties of these materials. Therefore, we discuss the properties and characteristics of them and we present some applications, using different approaches of DDS to ensure therapeutic effectiveness and side effects reduction such as implantable biomaterial, film-forming materials, stimuli-responsive systems and others. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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Open AccessReview Switchable Materials Containing Polyzwitterion Moieties
Polymers 2015, 7(11), 2344-2370; doi:10.3390/polym7111518
Received: 8 September 2015 / Revised: 2 November 2015 / Accepted: 12 November 2015 / Published: 20 November 2015
Cited by 9 | PDF Full-text (14623 KB) | HTML Full-text | XML Full-text
Abstract
In recent decades, the design and construction of smart materials capable of switching into a polyzwitterionic state by an external trigger have been intensively pursued. Polyzwitterionic states have unique antifouling and surface properties and external triggers, such as pH, light, ions, electric field
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In recent decades, the design and construction of smart materials capable of switching into a polyzwitterionic state by an external trigger have been intensively pursued. Polyzwitterionic states have unique antifouling and surface properties and external triggers, such as pH, light, ions, electric field and CO2, cause significant changes in materials with regard to overall charge, ionic strength and wettability. This survey highlights current progress in the irreversible as well as the reversible switching process involving polyzwitterionic moieties, which can, in turn, be applied to studying the interaction of various interfaces with biological species as protein, DNA, bacteria or platelets and also for advanced use. Full article
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
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