| 1. |
- Fan, Yanmiao, et al.
(författare)
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Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens
- 2021
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:41, s. 17180-17190
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Tidskriftsartikel (refereegranskat)abstract
- Infections caused by antibiotic-resistant bacteria are globally a major threat, leading to high mortality rates and increased economic burden. Novel treatment strategies are therefore urgently needed by healthcare providers to protect people. Biomaterials that have inherent antibacterial properties and do not require the use of antibiotics present an attractive and feasible avenue to achieve this goal. Herein, we demonstrate the effect of a new class of cationic hydrogels based on amino-functional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs) exhibiting excellent antimicrobial activity toward a wide range of clinical Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. Intriguingly, the hydrogels can induce the expression of the antimicrobial peptides RNase 7 and psoriasin, promoting host-mediated bacterial killing in human keratinocytes (HaCaT). Moreover, treatment with the hydrogels decreased the proinflammatory cytokine IL-1 beta, reactive nitrogen species (NO), and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells, conjunctively resulting in reduced inflammation.
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| 2. |
- Fan, Yanmiao, et al.
(författare)
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Scalable Dendritic Hydrogels Targeting Drug-Resistant Skin Pathogens and the Immunomodulation Activity in Keratinocytes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Microbial infections caused by antibiotic-resistant bacteria are a major threat to humans, associated with a high mortality and for the society increased economic burden. To address this, a series of cationic hydrogels based on amino-functional hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) were formed easily within 1 min through interactions between the amino-terminated HBDLDs and di(N-hydroxysuccinimide ester) functionalized polyethylene glycol (PEG). The hydrogels exhibited excellent inherent antimicrobial activity towards a wide range of Gram-positive and Gram-negative clinical bacteria including drug-resistant strains, isolated from wounds. In vitro cell infection assays showed that the hydrogels were able to significantly reduce cell infections caused by different strains, with the highest killing efficacy of 96% towards S. aureus. The hydrogels also inhibited the initiation of E. coli biofilm formation. Remarkably, the hydrogels induced the expression of the antimicrobial peptides, RNase 7 and psoriasin, in keratinocytes (HaCaT) which suggests that the hydrogels are likely able to promote host-mediated bacterial killing. The expression of pro-inflammatory cytokine IL-1β, reactive nitrogen species (NO) and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells were reduced after the treatment with the hydrogels. The hydrogels degraded within 24 h, showing great promise for treating skin infections and reducing inflammation.
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| 3. |
- Qin, Liguo, et al.
(författare)
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Cellulose nanofibril reinforced functional chitosan biocomposite films
- 2023
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Ingår i: Polymer testing. - : Elsevier BV. - 0142-9418 .- 1873-2348. ; 120, s. 107964-
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Tidskriftsartikel (refereegranskat)abstract
- Recently, chitosan has become attractive due to being biodegradable, biocompatible and renewable. However, the weak mechanical properties of chitosan films limit their large-scale application. In this work, a strategy of blending TEMPO, oxidized CNF (TOCN) and chitosan was developed to fabricate nanocomposite films in order to improve the mechanical properties and maintain biocompatibility. The TOCN/chitosan nanocomposite films exhibited excellent optical transmittance (>85%) and extremely high tensile strength of 235 MPa. The good compatibility of TOCN and chitosan chains, good dispersion of chitosan aggregates and the presence of stiff TOCN crystal domains are the main reasons for getting improved mechanical strength of composite films. The films showed good biocompatible properties based on the cell activity assay results. Furthermore, they were stable in PBS buffer for more than 6 months without significant degradation. The TOCN/chitosan nanocomposite films with these excellent properties could be employed in medical applications.
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| 4. |
- Zhang, Yuning, et al.
(författare)
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Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections
- 2023
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Ingår i: Macromolecular Bioscience. - : John Wiley and Sons Inc. - 1616-5187 .- 1616-5195. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK-060, a human kininogen-derived AMP. Once embedded into the poloxamer gel, DPK-060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time-kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti-infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK-060 at the wound site, all formulations display superior efficacy compared to DPK-060 in solution. © 2023 The Authors.
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| 5. |
- Zhang, Yuning
(författare)
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Novel Therapeutic Platform of Micelles and Nanogels from Dopa-Functionalized Triblock Copolymers
- 2021
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Ingår i: Small. - : Wiley. - 1613-6829 .- 1613-6810. ; 17:17, s. 2007305-
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Tidskriftsartikel (refereegranskat)abstract
- Multi-drug delivery systems constructed from a basic polymeric scaold, and which have the ability to target a variety of biomedical applications, can streamline the development of nanomedicine to provide both environmental and economical relief. Herein, amphiphilic ABA-triblock copolymers are synthesized and assembled sequentially into micelles and nanogels as drug delivery systems following a thorough evaluation on advanced in vitro models to explore their potential for the treatment of cancer and bacterial infections. Short blocks of -methyl--allyloxycarbonyl-,-dioxan--one (MAC) are oli-gomerized from PEGk and thereafter functionalized with dihydroxyphenyla-lanine (dopa)-functional thiols using thiol-ene coupling (TEC) click chemistry. The copolymers self-assemble into well-defined micelles in aqueous solution and are further formulated into nanogels via UV-induced TEC. The resulting spherical micelles and nanogels are stable nanoparticles, with sizes ranging between and nm. The nanogels are found to be non-toxic to a panel of cell lines and mask the toxicity of the potent drugs until their release. The nanogels would be superior to micelles for the elimination of cancer cells supported by both D cell culture and a D spheroid model. The opposite conclusion could be drawn for bacteria inhibition.
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