| 1. |
- Atefyekta, Saba, 1987, et al.
(författare)
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Antimicrobial Peptide-Functionalized Mesoporous Hydrogels
- 2021
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Ingår i: ACS Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 7:4, s. 1693-1702
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) are seen as a promising replacement to conventional antibiotics for the prevention of skin wound infections. However, due to the short half-life of AMPs in biological environments, such as blood, their use in clinical applications has been limited. The covalent immobilization of AMPs onto suitable substrates is an effective solution to create contact-killing surfaces with increased long-term stability. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was covalently attached to amphiphilic and ordered mesoporous Pluronic F127 hydrogels made of cross-linked lyotropic liquid crystals through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. The AMP-hydrogels showed high antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, methicillin-resistant S. aureus (MRSA), and multidrug-resistant Escherichia coli for up to 24 h. Furthermore, the AMP-hydrogels did not present any toxicity to human fibroblasts. The AMPs retained their antimicrobial activity up to 48 h in human blood serum, which is a significant increase in stability compared to when used in dissolved state. A pilot in vivo rat model showed 10-100x less viable counts of S. aureus on AMP-hydrogels compared with control hydrogels during the first 3 days of infection. Studies performed on human whole blood showed that blood coagulated more readily in the presence of AMP-hydrogels as compared to hydrogels without AMPs, indicating potential hemostatic activity. Overall, the results suggest that the combination of amphiphilic hydrogels with covalently bonded AMPs has potential to be used as antibacterial wound dressing material to reduce infections and promote hemostatic activity as an alternative to antibiotics or other antimicrobial agents, whose use should be restricted.
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| 2. |
- Blomstrand, Edvin, 1993, et al.
(författare)
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Clinical investigation of use of an antimicrobial peptide hydrogel wound dressing on intact skin
- 2023
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Ingår i: Journal of Wound Care. - 2052-2916 .- 0969-0700. ; 32:6, s. 368-375
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Tidskriftsartikel (refereegranskat)abstract
- A material with the ability to rapidly eradicate bacteria via a contact-killing mechanism has the benefit of a more localised treatment that is easy to implement when needed to prevent or treat a bacterial infection. Here, we present an antimicrobial material based on covalently attached antimicrobial peptides (AMPs) to a soft amphiphilic hydrogel. This results in a material that exhibits an antimicrobial effect based on contact-killing. In this study, the antimicrobial efficacy of the AMP-hydrogel was investigated by observing the changes in total bioburden on the intact skin of healthy human volunteers when the AMP-hydrogel dressing was placed on the forearm for three hours. The AMP-hydrogel significantly reduced the bioburden on the skin from a mean value of 1200CFU/cm2 for the untreated skin to 23CFU/cm2. Biocompatibility evaluations of the AMP-hydrogel showed no sign of cytotoxicity, acute systemic toxicity, irritation or sensitisation, demonstrating the safety of the AMP-hydrogel as a potential wound dressing. Leachability studies confirmed no release of AMPs and that the antimicrobial effect was localised to the surface of the hydrogels, demonstrating a pure contact-killing mode of action.
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| 3. |
- Blomstrand, Edvin, 1993, et al.
(författare)
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Cross-linked lyotropic liquid crystal particles functionalized with antimicrobial peptides
- 2022
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 627
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics for addressing bacterial infections – including life-threatening antibiotic resistant infections. AMPs have a broad spectrum of antimicrobial activity and show a low probability to induce resistance. However, the poor serum stability of AMPs has limited their usage in clinical treatment. To enable improved serum stability while maintaining high antibacterial effect of AMPs, this study describes a material wherein AMPs are covalently bonded to micro-sized particles of cross-linked lyotropic liquid crystals, formed by the self-assembly of the block copolymer Pluronic F-127. The liquid crystal particles were shown to have antibacterial effect corresponding to a 4 log reduction against Staphylococcus aureus. The particles were structurally and chemically analyzed by small angle X-ray scattering, Fourier transform infra-red spectroscopy and Raman spectroscopy, confirming that the liquid crystal structure was maintained within the particles with the AMPs covalently bonded. The bonding to the particles gave the AMPs improved stability in serum, as they retained almost all of the antibacterial potency for 2 days compared to free AMPs, which lost all of its antibacterial potency within a day. Furthermore, insight regarding mode of action was obtained by cryogenic transmission electron microscopy, which showed the antimicrobial particles interacting with the surface of bacteria.
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| 4. |
- He, Wenxiao, 1985, et al.
(författare)
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Mesoscopically Ordered Bone-Mimetic Nanocomposites
- 2015
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Ingår i: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 27:13, s. 2260-2264
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Tidskriftsartikel (refereegranskat)abstract
- A sustainable approach that highly mimics bone-material deposition is reported to produce mechanically stable, degradable composites with nanostructures resembling that of natural bone. Molecular self-assembly combining intermolecular crosslinking leads to resilient matrices possessing long-range ordered aqueous domains, inside which moderately aligned poorly crystalline apatite is converted from the transient amorphous calcium phosphate phase.
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| 5. |
- Kjellin, P., et al.
(författare)
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Investigation of calcium phosphate formation from calcium propionate and triethyl phosphate
- 2016
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Ingår i: Ceramics International. - : Elsevier BV. - 0272-8842. ; 42:12, s. 14061-14065
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic calcium phosphates are used in for example bone cements and implant coatings to increase biocompatibility. The common method to produce tricalcium phosphate (TCP) uses high temperatures, which creates large crystals with low specific surface areas. In order to investigate new methods to produce TCP at lower temperatures, the reaction between calcium propionate and triethyl phosphate conducted at 220 degrees C was studied. The method had a near 100% conversion rate, the main synthesis products were calcium phosphate and ethyl propionate. The formed calcium phosphate polymorph could be controlled depending on the water content of the precursor mixture. Anhydrous conditions created amorphous calcium phosphate. As the concentration of water increased, beta-TCP was formed, followed by calcium deficient hydroxyapatite and monetite. The particle size increased with the water content, from 20 to 40 nm for amorphous calcium phosphate to tenths of micrometers for monetite. The specific surface areas varied between 209 m(2)/g for the amorphous product to 3.6 m(2)/g for the monetite product.
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| 6. |
- Kumar Rajasekharan, Anand, 1990, et al.
(författare)
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Bioinspired Structural Hierarchy within Macroscopic Volumes of Synthetic Composites
- 2018
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Ingår i: Advanced healthcare materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 7:18
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Tidskriftsartikel (refereegranskat)abstract
- A key challenge in developing bioinspired composites is the fabrication of well-defined 3D hierarchical structures ranging from nano to the macroscale. Herein, the development of a synthetic polymer–apatite composite realized by integrating bottom-up self-assembly and additive manufacturing (AM) is described. The resulting composite exhibits a bioinspired hierarchical structure over its 3D macroscopic volume. The composite is assembled in a bottom-up manner, where periodic nanoscale assemblies of organic micellar fibrils and inorganic apatite nanocrystals are organized as bundles of mineralized microstructures. These microstructural bundles are preferentially oriented throughout the macroscopic volume of the material via extrusion based AM. The obtained structural hierarchy is investigated in 3D using electron microscopy and small angle X-ray scattering tensor tomography and correlated to the structural hierarchy and anisotropy observed in biological tissues such as bone and the bone–cartilage interface. This work demonstrates the possibility to form polymer–apatite composites with a well-defined hierarchical structure throughout its macroscopic volume, which is crucial for the development of mechanically optimized materials for applications such as bone and osteochondral implants.
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| 7. |
- Kumar Rajasekharan, Anand, 1990, et al.
(författare)
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Hierarchical and Heterogeneous Bioinspired Composites-Merging Molecular Self-Assembly with Additive Manufacturing
- 2017
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 13:28
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Tidskriftsartikel (refereegranskat)abstract
- Biological composites display exceptional mechanical properties owing to a highly organized, heterogeneous architecture spanning several length scales. It is challenging to translate this ordered and multiscale structural organization in synthetic, bulk composites. Herein, a combination of top-down and bottom-up approach is demonstrated, to form a polymer-ceramic composite by macroscopically aligning the self-assembled nanostructure of polymerizable lyotropic liquid crystals via 3D printing. The polymer matrix is then uniformly reinforced with bone-like apatite via in situ biomimetic mineralization. The combinatorial method enables the formation of macrosized, heterogeneous composites where the nanostructure and chemical composition is locally tuned over microscopic distances. This enables precise control over the mechanics in specific directions and regions, with a unique intrinsic-extrinsic toughening mechanism. As a proof-of-concept, the method is used to form large-scale composites mimicking the local nanostructure, compositional gradients and directional mechanical properties of heterogeneous tissues like the bone-cartilage interface, for mechanically stable osteochondral plugs. This work demonstrates the possibility to create hierarchical and complex structured composites using weak starting components, thus opening new routes for efficient synthesis of high-performance materials ranging from biomaterials to structural nanocomposites.
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| 8. |
- Kumar Rajasekharan, Anand, 1990, et al.
(författare)
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Role of nanoscale confinement on calcium phosphate formation at high supersaturation
- 2015
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7505 .- 1528-7483. ; 15:6, s. 2775-2780
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Tidskriftsartikel (refereegranskat)abstract
- An important factor controlling bone mineralization is spatial restriction within collagen fibrils and matrix vesicles. Such nanoscale confinements in addition to chemical control restrict the growth and final size of calcium phosphate crystals (CaP). To study the role of spatial control on CaP mineralization exclusively, we investigated formation of CaPs under high supersaturations (0.84 M Ca2+ and 2.1 M Ca2+) within ordered aqueous domains (8-27 nm) of polymerized liquid crystals (PLCs). The mineralization of CaPs was achieved by a pressurized gas induced pH rise. CaPs mineralized within varying degrees of confinements showed contrasting results. Confinements 10 nm mediated the formation of CaPs to phase pure calcium apatite (CaAp), while confinements between 11 and 27 nm resulted in a mixture of phases such as CaAp, amorphous calcium phosphates (ACP), and acidic polymorphs such as brushite and monetite. Results indicated that smaller confinements offer a low particle/solution interface effectively forming small nucleation clusters leading to a metastable ACP phase. We suggest that CaP formation from high supersaturations strongly depends on the degree of confinement around the nucleation site to efficiently control the mineral phase purity. Moreover, a possible insight from this study is that synthetic and biological confinements, in addition to spatial restriction, also rely on chemical control to obtain phase pure CaPs such as bone apatite.
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| 9. |
- Kumar Rajasekharan, Anand, 1990, et al.
(författare)
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Tough Ordered Mesoporous Elastomeric Biomaterials Formed at Ambient Conditions
- 2020
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 14:1, s. 241-254
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic dry elastomers are randomly cross-linked polymeric networks with isotropic and unordered higher-level structural features. However, their growing use as soft-tissue biomaterials has demanded the need for an ordered and anisotropic nano-micro (or) mesoarchitecture, which is crucial for imparting specific properties such as hierarchical toughening, anisotropic mechanics, sustained drug delivery, and directed tissue growth. High processing cost, poor control in 3D, and compromised mechanical properties have made it difficult to synthesize tough and dry macroscopic elastomers with well-organized nano-microstructures. Inspired from biological design principles, we report a tough ordered mesoporous elastomer formed via bottom-up lyotropic self-assembly of noncytotoxic, polymerizable amphiphilic triblock copolymers and hydrophobic polymers. The elastomer is cross-linked using covalent cross-links and physical hydrophobic entanglements that are organized in a periodic manner at the nanoscale. This transforms into a well-ordered hexagonal arrangement of nanofibrils that are highly oriented at the micron scale, further organized as 3D macroscale objects. The ordered nano-microstructure and molecular multinetwork endows the elastomer with hierarchical toughening while possessing excellent stiffness and elongation comparable to engineering elastomers like silicone and vulcanized rubber. Processing of the elastomer is performed at ambient conditions using 3D printing and photo-cross-linking, which is fast and energy efficient and enables production of complex 3D objects with tailorable sub-millimeter features such as macroporosity. Furthermore, the periodic and amphiphilic nanostructure permits functionalization of the elastomer with secondary components such as inorganic nanoparticles or drug molecules, enabling complementary mechanical properties such as high stiffness and functional capabilities such as in localized drug delivery applications. © 2019 American Chemical Society.
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| 10. |
- Lotsari, Antiope, 1981, et al.
(författare)
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Transformation of amorphous calcium phosphate to bone-like apatite
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Mineralisation of calcium phosphates in bone has been proposed to proceed via an initial amorphous precursor phase which transforms into nanocrystalline, carbonated hydroxyapatite. While calcium phosphates have been under intense investigation, the exact steps during the crystallisation of spherical amorphous particles to platelet-like bone apatite are unclear. Herein, we demonstrate a detailed transformation mechanism of amorphous calcium phosphate spherical particles to apatite platelet-like crystals, within the confined nanodomains of a bone-inspired nanocomposite. The transformation is initiated under the presence of humidity, where nanocrystalline areas are formed and crystallisation advances via migration of nanometre sized clusters by forming steps at the growth front. We propose that such transformation is a possible crystallisation mechanism and is characteristic of calcium phosphates from a thermodynamic perspective and might be unrelated to the environment. Our observations provide insight into a crucial but unclear stage in bone mineralisation, the origins of the nanostructured, platelet-like bone apatite crystals.
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| 11. |
- Penders, Jelle, 1992, et al.
(författare)
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In Situ Gold Nanoparticle Gradient Formation in a 3D Meso- and Macroporous Polymer Matrix
- 2017
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Ingår i: Macromolecular Rapid Communications. - : Wiley. - 1022-1336 .- 1521-3927. ; 38:16, s. Article no 1700231 -
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Tidskriftsartikel (refereegranskat)abstract
- Herein, the development and characterization of a 3D gradient structure of gold nanoparticles is described. The gradient of gold nanoparticles is made in situ in a macroporous nonionic block copolymer hydrogel matrix, through gold ion diffusion control. The polymer provides a matrix for diffusion of gold ions, acts as a template for controlling nanoparticle growth, and facilitates the in situ reduction of gold ions to gold nanoparticles. A clear gradient in gold nanoparticles is observed across the 3D space of the polymer matrix using scanning electron microscopy, fluorescence microscopy, atomic force microscopy, and thermogravimetric analysis. The particle gradient is further functionalized with both hydrophobic and hydrophilic groups via thiol-gold linkage to demonstrate the ability to form gradients with different chemical functionalities. Using additive manufacturing, the polymer can also be printed as a porous network with possible applications for 3D cell culturing in, e.g., biomaterials research.
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