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Qin, L., Zhang, Y., Fan, Y. & Li, L. (2023). Cellulose nanofibril reinforced functional chitosan biocomposite films. Polymer testing, 120, 107964, Article ID 107964.
Open this publication in new window or tab >>Cellulose nanofibril reinforced functional chitosan biocomposite films
2023 (English)In: Polymer testing, ISSN 0142-9418, E-ISSN 1873-2348, Vol. 120, p. 107964-, article id 107964Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier BV, 2023
Keywords
TEMPO oxidized CNF, Chitosan, Nanocomposites, Biocompatibility, Mechanical properties
National Category
Paper, Pulp and Fiber Technology
Identifiers
urn:nbn:se:kth:diva-328431 (URN)10.1016/j.polymertesting.2023.107964 (DOI)000992869700001 ()2-s2.0-85148330765 (Scopus ID)
Note

QC 20230612

Available from: 2023-06-12 Created: 2023-06-12 Last updated: 2023-06-12Bibliographically approved
Zhang, Y., Håkansson, J., Fan, Y., Andrén, O. C. J., San Jacinto García, J., Qin, L., . . . Malkoch, M. (2023). Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections. Macromolecular Bioscience, 23(4), Article ID 2200433.
Open this publication in new window or tab >>Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections
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2023 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 23, no 4, article id 2200433Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley, 2023
Keywords
antimicrobial peptide delivery, dendritic nanogels, DPK-060, poloxamer gels
National Category
Polymer Technologies
Identifiers
urn:nbn:se:kth:diva-330058 (URN)10.1002/mabi.202200433 (DOI)000919125200001 ()36639138 (PubMedID)2-s2.0-85146683018 (Scopus ID)
Note

QC 20230626

Available from: 2023-06-26 Created: 2023-06-26 Last updated: 2023-06-26Bibliographically approved
Fan, Y., Mohanty, S., Zhang, Y., Lüchow, M., Qin, L., Fortuin, L., . . . Malkoch, M. (2021). Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens. Journal of the American Chemical Society, 143(41), 17180-17190
Open this publication in new window or tab >>Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens
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2021 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 143, no 41, p. 17180-17190Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2021
National Category
Infectious Medicine
Identifiers
urn:nbn:se:kth:diva-305669 (URN)10.1021/jacs.1c07492 (DOI)000710935500033 ()34636555 (PubMedID)2-s2.0-85118244398 (Scopus ID)
Note

QC 20211206

Available from: 2021-12-06 Created: 2021-12-06 Last updated: 2022-06-25Bibliographically approved
Hutchinson, D., Granskog, V., von Kieseritzky, J., Alfort, H., Stenlund, P., Zhang, Y., . . . Malkoch, M. (2021). Highly Customizable Bone Fracture Fixation through the Marriage of Composites and Screws. Advanced Functional Materials, 31(41), Article ID 2105187.
Open this publication in new window or tab >>Highly Customizable Bone Fracture Fixation through the Marriage of Composites and Screws
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2021 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 31, no 41, article id 2105187Article in journal (Refereed) Published
Abstract [en]

Open reduction internal fixation (ORIF) metal plates provide exceptional support for unstable bone fractures; however, they often result in debilitating soft‐tissue adhesions and their rigid shape cannot be easily customized by surgeons. In this work, a surgically feasible ORIF methodology, called AdhFix, is developed by combining screws with polymer/hydroxyapatite composites, which are applied and shaped in situ before being rapidly cured on demand via high‐energy visible‐light‐induced thiol–ene coupling chemistry. The method is developed on porcine metacarpals with transverse and multifragmented fractures, resulting in strong and stable fixations with a bending rigidity of 0.28 (0.03) N m 2 and a maximum load before break of 220 (15) N. Evaluations on human cadaver hands with proximal phalanx fractures show that AdhFix withstands the forces from finger flexing exercises, while short‐ and long‐term in vivo rat femur fracture models show that AdhFix successfully supports bone healing without degradation, adverse effects, or soft‐tissue adhesions. This procedure represents a radical new approach to fracture fixation, which grants surgeons unparalleled customizability and does not result in soft‐tissue adhesions.

Place, publisher, year, edition, pages
Wiley, 2021
Keywords
biomaterials, bone fixation, materials engineering, thiol-ene composites
National Category
Polymer Chemistry Orthopaedics Biomaterials Science
Identifiers
urn:nbn:se:kth:diva-297640 (URN)10.1002/adfm.202105187 (DOI)000663202700001 ()2-s2.0-85108182498 (Scopus ID)
Note

QC 20250331

Available from: 2021-06-21 Created: 2021-06-21 Last updated: 2025-03-31Bibliographically approved
Fan, Y., Lüchow, M., Zhang, Y., Lin, J., Mohanty, S., Brauner, A., . . . Fortuin, L. (2021). Nanogel encapsulated hydrogels as advanced wound dressings for the controlled delivery of antibiotics. Advanced Functional Materials, 31
Open this publication in new window or tab >>Nanogel encapsulated hydrogels as advanced wound dressings for the controlled delivery of antibiotics
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2021 (English)In: Advanced Functional Materials, ISSN 1616-301X, Vol. 31Article in journal (Refereed) Published
Abstract [en]

Biocompatible and degradable dual-delivery gel systems based on hyperbrancheddendritic−linear−dendritic copolymers (HBDLDs) is herein conceptualizedand accomplished via thiol-ene click chemistry. The elasticity of thehydrogels is tunable by varying the lengths of PEG (2, 6, 10 kDa) or the dryweight percentages (20, 30, 40 wt%), and are found to be between 2–14.7 kPa,comparable to human skin. The co-delivery of antibiotics is achieved, wherethe hydrophilic drug novobiocin sodium salt (NB) is entrapped within thehydrophilic hydrogel, while the hydrophobic antibiotic ciprofloxacin (CIP) isencapsulated within the dendritic nanogels (DNGs) with hydrophobic cores(DNGs-CIP). The DNGs-CIP with drug loading capacity of 2.83 wt% are thenphysically entrapped within the hybrid hydrogels through UV curing. Thehybrid hydrogels enabled the quick release of NB and prolonged released ofCIP. In vitro cell infection assays showed that the antibiotic-loaded hybridhydrogels are able to treat bacterial infections with significant bacterialreduction. Hybrid hydrogel band aids are fabricated and exhibited betterantibacterial activity compared with commercial antimicrobial band aids.Remarkably, most hydrogels and hybrid hydrogels showed enhanced humandermal cell proliferation and could be degraded into non-toxic constituents,showing great promise as wound dressing materials.

National Category
Natural Sciences
Research subject
Fibre and Polymer Science; Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-293758 (URN)10.1002/adfm.202006453 (DOI)2-s2.0-85094644501 (Scopus ID)
Note

QC 20210623

Available from: 2021-05-23 Created: 2021-05-23 Last updated: 2022-06-25Bibliographically approved
Zhang, Y. (2021). Novel Therapeutic Platform of Micelles and Nanogels from Dopa-Functionalized Triblock Copolymers. Small, 17(17), 2007305
Open this publication in new window or tab >>Novel Therapeutic Platform of Micelles and Nanogels from Dopa-Functionalized Triblock Copolymers
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2021 (English)In: Small, ISSN 1613-6829, Vol. 17, no 17, p. 2007305-Article in journal (Refereed) Published
Abstract [en]

Multi-drug delivery systems constructed from a basic polymeric scaold, 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 PEGk 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.

Place, publisher, year, edition, pages
Wiley, 2021
National Category
Natural Sciences
Research subject
Fibre and Polymer Science
Identifiers
urn:nbn:se:kth:diva-295580 (URN)10.1002/smll.202007305 (DOI)000632206100001 ()33724720 (PubMedID)2-s2.0-85102510080 (Scopus ID)
Note

QC 20210527

Available from: 2021-05-23 Created: 2021-05-23 Last updated: 2022-06-25Bibliographically approved
Stenström, P., Fan, Y., Zhang, Y., Hutchinson, D., Garcia-Gallego, S. & Malkoch, M. (2021). UV-Cured Antibacterial Hydrogels Based on PEG and Monodisperse Heterofunctional Bis-MPA Dendrimers. Molecules, 26(8), 2364
Open this publication in new window or tab >>UV-Cured Antibacterial Hydrogels Based on PEG and Monodisperse Heterofunctional Bis-MPA Dendrimers
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2021 (English)In: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 26, no 8, p. 2364-Article in journal (Refereed) Published
Abstract [en]

Bacterial infections are one of the major threats to human health due to the raising crisis of antibiotic resistance. Herein, second generation antibacterial heterofunctional dendrimers based on 2,2-bis(methylol)propionic acid were synthesized. The dendrimers possessed six alkenes and 12 ammonium end-groups per molecule and were used to fabricate antibacterial hydrogels together with dithiol-functional polyethylene glycol (mol wt of 2, 6 and 10 kDa) as crosslinkers via thiol-ene chemistry. The network formation can be completed within 10 s upon UV-irradiation as determined by the stabilization of the storage modulus in a rheometer. The hydrogels swelled in aqueous media and could be functionalized with the N-hydroxysuccinimide ester of the dye disperse red 13, which allowed for visually studying the degradation of the hydrogels through the hydrolysis of the ester bonds of the dendritic component. The maximum swelling ratio of the gels was recorded within 4–8 h and the swelling ratios increased with higher molecular weight of the polyethylene glycol crosslinker. The gel formed with 10 kDa polyethylene glycol crosslinker showed the highest swelling ratio of 40 and good mechanical properties, with a storage modulus of 8 kPa. In addition, the hydrogels exhibited good biocompatibility towards both human fibroblasts and mouse monocytes, while showing strong antibacterial activity against both gram-positive and gram-negative bacteria.

Place, publisher, year, edition, pages
MDPI AG, 2021
National Category
Polymer Technologies
Identifiers
urn:nbn:se:kth:diva-294787 (URN)10.3390/molecules26082364 (DOI)000644596400001 ()33921687 (PubMedID)2-s2.0-85105089320 (Scopus ID)
Note

QC 20210607

Available from: 2021-05-18 Created: 2021-05-18 Last updated: 2023-08-28
Zhang, Y., Mesa Antunez, P., Fortuin, L., Andrén, O. C. J. & Malkoch, M. (2020). Degradable High Molecular Weight Monodisperse Dendritic Poly(ethylene glycols). Biomacromolecules, 21(10), 4294-4301
Open this publication in new window or tab >>Degradable High Molecular Weight Monodisperse Dendritic Poly(ethylene glycols)
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2020 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 21, no 10, p. 4294-4301Article in journal (Refereed) Published
Abstract [en]

Poly(ethylene glycols) (PEGs) are extensively explored by the pharma industry as foundations for new therapeutic products. PEGs are typically used for their conjugation to active drugs, peptides, and proteins and the likeliness to increase the half-life and enhance the therapeutic outcome. Considering the necessity of batch-to-batch consistency for clinical products, monodisperse PEGs are highly attractive but are generally limited to 5 kDa as an upper molecular weight (Mw) and with an oligomer purity of 95%. By amalgamating short, monodisperse PEGs with dendritic frameworks based on 2,2-bis(methylol)propionic acid polyesters, we showcase a robust synthetic approach to monodisperse PEGs with Mw ranging from 2 to 65 kDa. The latter is, to our knowledge, the highest Mw structure of its kind ever reported. Importantly, the dendritic multifunctional connector facilitated degradability at pH 7.4 at 37 °C, which is an important feature for the delivery of therapeutic agents.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2020
National Category
Polymer Technologies
Identifiers
urn:nbn:se:kth:diva-288022 (URN)10.1021/acs.biomac.0c01089 (DOI)000580890000032 ()32845125 (PubMedID)2-s2.0-85092803349 (Scopus ID)
Note

QC 20210305

Available from: 2020-12-23 Created: 2020-12-23 Last updated: 2022-06-25Bibliographically approved
Engström, J., Asem, H., Brismar, H., Zhang, Y., Malkoch, M. & Malmström, E. (2020). In situ encapsulation of Nile red or Doxorubicin during RAFT-mediated emulsion polymerization via polymerization-induced self-assembly for biomedical applications. Macromolecular Chemistry and Physics, 221(5), Article ID 1900443.
Open this publication in new window or tab >>In situ encapsulation of Nile red or Doxorubicin during RAFT-mediated emulsion polymerization via polymerization-induced self-assembly for biomedical applications
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2020 (English)In: Macromolecular Chemistry and Physics, ISSN 1022-1352, E-ISSN 1521-3935, Vol. 221, no 5, article id 1900443Article in journal (Refereed) Published
Abstract [en]

Hydrophobic agents, a fluorescent dye (Nile red, NR) or an anticancer drug (doxorubicin, DOX), are encapsulated into poly((N-[3-(dimethylamino) propyl] methacrylamide)-b-poly (methyl methacrylate) (PDMAPMA-b-PMMA) nanoparticles (NPs) via one-pot reversible addition-fragmentation chain-transfer (RAFT)-mediated emulsion polymerization in water. The macroRAFT, PDMAPMA, is chain-extended with the methyl methacrylate (MMA), with the hydrophobic agents soluble in MMA, resulting in loaded NPs, with either NR or DOX via polymerization-induced self-assembly (PISA). The NR-loaded NPs are visualized by structured illumination microscopy (SIM), thus indicating the successful loading of the fluorescent dye into the PMMA core. The DOX-loaded NPs exhibit a sustained release profile over 5 d, showing a small burst effect during the first 2 h, as compared with the free DOX. The DOX-loaded NPs show higher cell toxicity than the free DOX in RAW 264.7 cell line. The results demonstrate the potential of using emulsion polymerization for synthesis of tailored and reproducible NPs encapsulating hydrophobic agents.

Place, publisher, year, edition, pages
Wiley, 2020
National Category
Polymer Technologies Nano Technology
Identifiers
urn:nbn:se:kth:diva-267222 (URN)10.1002/macp.201900443 (DOI)000512141900001 ()2-s2.0-85079443030 (Scopus ID)
Note

QC 20250312

Available from: 2020-02-04 Created: 2020-02-04 Last updated: 2025-03-12Bibliographically approved
Fan, Y., Namata, F., Erlandsson, J., Zhang, Y., Wågberg, L. & Malkoch, M. (2020). Self-Assembled Polyester Dendrimer/Cellulose Nanofibril Hydrogels with Extraordinary Antibacterial Activity. Pharmaceutics, 12(12), Article ID 1139.
Open this publication in new window or tab >>Self-Assembled Polyester Dendrimer/Cellulose Nanofibril Hydrogels with Extraordinary Antibacterial Activity
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2020 (English)In: Pharmaceutics, E-ISSN 1999-4923, Vol. 12, no 12, article id 1139Article in journal (Refereed) Published
Abstract [en]

Cationic dendrimers are intriguing materials that can be used as antibacterial materials; however, they display significant cytotoxicity towards diverse cell lines at high generations or high doses, which limits their applications in biomedical fields. In order to decrease the cytotoxicity, a series of biocompatible hybrid hydrogels based on cationic dendrimers and carboxylated cellulose nanofibrils were easily synthesized by non-covalent self-assembly under physiological conditions without external stimuli. The cationic dendrimers from generation 2 (G2) to generation 4 (G4) based on trimethylolpronane (TMP) and 2,2-bis (methylol)propionic acid (bis-MPA) were synthesized through fluoride promoted esterification chemistry (FPE chemistry). FTIR was used to show the presence of the cationic dendrimers within the hybrid hydrogels, and the distribution of the cationic dendrimers was even verified using elemental analysis of nitrogen content. The hybrid hydrogels formed from G3 and G4 showed 100% killing efficiency towards Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) with bacterial concentrations ranging from 10(5) CFU/mL to 10(7) CFU/mL. Remarkably, the hybrid hydrogels also showed good biocompatibility most probably due to the incorporation of the biocompatible CNFs that slowed down the release of the cationic dendrimers from the hybrid hydrogels, hence showing great promise as an antibacterial material for biomedical applications.

Place, publisher, year, edition, pages
MDPI, 2020
Keywords
cationic dendrimer, antibacterial materials, carboxylated cellulose nanofibrils, hybrid hydrogels
National Category
Physical Chemistry
Identifiers
urn:nbn:se:kth:diva-289013 (URN)10.3390/pharmaceutics12121139 (DOI)000602524100001 ()33255607 (PubMedID)2-s2.0-85096697401 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation
Note

QC 20210125

Available from: 2021-01-25 Created: 2021-01-25 Last updated: 2024-07-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9597-9578

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