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Publications (10 of 39) Show all publications
Nilebäck, L., Widhe, M., Seijsing, J., Bysell, H., Sharma, P. K. & Hedhammar, M. (2019). Bioactive Silk Coatings Reduce the Adhesion of Staphylococcus aureus while Supporting Growth of Osteoblast-like Cells. ACS Applied Materials and Interfaces, 11(28), 24999-25007
Open this publication in new window or tab >>Bioactive Silk Coatings Reduce the Adhesion of Staphylococcus aureus while Supporting Growth of Osteoblast-like Cells
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2019 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 11, no 28, p. 24999-25007Article in journal (Refereed) Published
Abstract [en]

Orthopedic and dental implants are associated with a substantial risk of failure due to biomaterial-associated infections and poor osseointegration. To prevent such outcomes, a coating can be applied on the implant to ideally both reduce the risk of bacterial adhesion and support establishment of osteoblasts. We present a strategy to construct dual-functional silk coatings with such properties. Silk coatings were made from a recombinant partial spider silk protein either alone (silk(wt)) or fused with a cell-binding motif derived from fibronectin (FN-silk). The biofilm-dispersal enzyme Dispersin B (DspB) and two peptidoglycan degrading endolysins, PlySs2 and SAL-1, were produced recombinantly. A sortase recognition tag (SrtTag) was included to allow site-specific conjugation of each enzyme onto silk(wt) and FN-silk coatings using an engineered variant of the transpeptidase Sortase A (SrtA*). To evaluate bacterial adhesion on the samples, Staphylococcus aureus was incubated on the coatings and subsequently subjected to live/dead staining. Fluorescence microscopy revealed a reduced number of bacteria on all silk coatings containing enzymes. Moreover, the bacteria were mobile to a higher degree, indicating a negative influence on the bacterial adhesion. The capability to support mammalian cell interactions was assessed by cultivation of the osteosarcoma cell line U-2 OS on dual-functional surfaces, prepared by conjugating the enzymes onto FN-silk coatings. U-2 OS cells could adhere to silk coatings with enzymes and showed high spreading and viability, demonstrating good cell compatibility.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019
Keywords
recombinant spider silk, multifunctional coating, osseointegration, antibacterial, endolysin, Staphylococcus aureus
National Category
Medical Materials
Identifiers
urn:nbn:se:kth:diva-255753 (URN)10.1021/acsami.9b05531 (DOI)000476684900016 ()31241302 (PubMedID)2-s2.0-85070024701 (Scopus ID)
Note

QC 20190809

Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved
Chouhan, D., Das, P., Thatikonda, N., Nandi, S. K., Hedhammar, M. & Mandal, B. B. (2019). Silkworm Silk Matrices Coated with Functionalized Spider Silk Accelerate Healing of Diabetic Wounds. ACS Biomaterials Science and Engineering, 5(7), 3537-3548
Open this publication in new window or tab >>Silkworm Silk Matrices Coated with Functionalized Spider Silk Accelerate Healing of Diabetic Wounds
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2019 (English)In: ACS Biomaterials Science and Engineering, ISSN 2373-9878, Vol. 5, no 7, p. 3537-3548Article in journal (Refereed) Published
Abstract [en]

Complex cutaneous wounds like diabetic foot ulcers represent a critical clinical challenge and demand a large-scale and low-cost strategy for effective treatment. Herein, we use a rabbit animal model to investigate efficacy of bioactive wound dressings made up of silk biomaterials. Nanofibrous mats of Antheraea assama silkworm silk fibroin (AaSF) are coated with various recombinant spider silk fusion proteins through silk-silk interactions to fabricate multifunctional wound dressings. Two different types of spider silk coatings are used to compare their healing efficiency: FN-4RepCT (contains a cell binding motif derived from fibronectin) and Lac-4RepCT (contains a cationic antimicrobial peptide from lactoferricin). AaSF mats coated with spider silk show accelerated wound healing properties in comparison to the uncoated mats. Among the spider silk coated variants, dual coating of FN-4RepCT and Lac-4RepCT on top of AaSF mat demonstrated better wound healing efficiency, followed by FN-4RepCT and Lac-4RepCT single coated counterparts. The in vivo study also reveals excellent skin regeneration by the functionalized silk dressings in comparison to commercially used Duoderm dressing and untreated wounds. The spider silk coatings demonstrate early granulation tissue development, re-epithelialization, and efficient matrix remodelling of wounds. The results thus validate potential of bioactive silk matrices in faster repair of diabetic wounds.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019
Keywords
silk fibroin, recombinant spider silk, nanofibrous mat, wound healing, diabetic wounds
National Category
Biomaterials Science
Identifiers
urn:nbn:se:kth:diva-255569 (URN)10.1021/acsbiomaterials.9b00514 (DOI)000474812300034 ()
Note

QC 20190802

Available from: 2019-08-02 Created: 2019-08-02 Last updated: 2019-08-02Bibliographically approved
Jiang, W., Askarieh, G., Shkumatov, A., Hedhammar, M. & Knight, S. D. (2019). Structure of the N-terminal domain of Euprosthenops australis dragline silk suggests that conversion of spidroin dope to spider silk involves a conserved asymmetric dimer intermediate. Acta Crystallographica Section D: Structural Biology, 75, 618-627
Open this publication in new window or tab >>Structure of the N-terminal domain of Euprosthenops australis dragline silk suggests that conversion of spidroin dope to spider silk involves a conserved asymmetric dimer intermediate
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2019 (English)In: Acta Crystallographica Section D: Structural Biology, ISSN 2059-7983, Vol. 75, p. 618-627Article in journal (Refereed) Published
Abstract [en]

Spider silk is a biomaterial with exceptional mechanical toughness, and there is great interest in developing biomimetic methods to produce engineered spider silk-based materials. However, the mechanisms that regulate the conversion of spider silk proteins (spidroins) from highly soluble dope into silk are not completely understood. The N-terminal domain (NT) of Euprosthenops australis dragline silk protein undergoes conformational and quaternary-structure changes from a monomer at a pH above 7 to a homodimer at lower pH values. Conversion from the monomer to the dimer requires the protonation of three conserved glutamic acid residues, resulting in a low-pH 'locked' dimer stabilized by symmetric electrostatic interactions at the poles of the dimer. The detailed molecular events during this transition are still unresolved. Here, a 2.1 angstrom resolution crystal structure of an NT T61A mutant in an alternative, asymmetric, dimer form in which the electrostatic interactions at one of the poles are dramatically different from those in symmetrical dimers is presented. A similar asymmetric dimer structure from dragline silk of Nephila clavipes has previously been described. It is suggested that asymmetric dimers represent a conserved intermediate state in spider silk formation, and a revised 'lock-and-trigger' mechanism for spider silk formation is presented.

Place, publisher, year, edition, pages
International Union of Crystallography, 2019
Keywords
spider silk, assembly, pH relay, spidroin, N-terminal domain, Euprosthenops australis
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-255392 (URN)10.1107/S2059798319007253 (DOI)000474450300001 ()31282471 (PubMedID)2-s2.0-85068718706 (Scopus ID)
Note

QC 20190730

Available from: 2019-07-30 Created: 2019-07-30 Last updated: 2019-07-30Bibliographically approved
Thatikonda, N., Nilebäck, L., Kempe, A., Widhe, M. & Hedhammar, M. (2018). Bioactivation of Spider Silk with Basic Fibroblast Growth Factor for in Vitro Cell Culture: A Step toward Creation of Artificial ECM. ACS Biomaterials Science and Engineering, 4(9), 3384-3396
Open this publication in new window or tab >>Bioactivation of Spider Silk with Basic Fibroblast Growth Factor for in Vitro Cell Culture: A Step toward Creation of Artificial ECM
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2018 (English)In: ACS Biomaterials Science and Engineering, ISSN 2373-9878, Vol. 4, no 9, p. 3384-3396Article in journal (Refereed) Published
Abstract [en]

Presentation of immobilized growth factors with retained bioactivity remains a challenge in the field of tissue engineering. In the present study, we propose a strategy to covalently conjugate a pleiotropic growth factor, basic fibroblast growth factor (bFGF) to a partial spider silk protein at gene level. The resulting silk-bFGF fusion protein has the propensity to self-assemble into silk-like fibers, and also surface coatings, as confirmed by quartz crystal microbalance studies. Functionality of the silk-bFGF coating to bind its cognate receptor was confirmed with surface plasmon resonance studies. As a step toward the creation of an artificial ECM, the silk-bFGF protein was mixed with FN-silk, an engineered spider silk protein with enhanced cell adhesive properties. Bioactivity of the thereby obtained combined silk was confirmed by successful culture of primary human endothelial cells on coatings and integrated within fibers, even in culture medium without supplemented growth factors. Together, these findings show that silk materials bioactivated with growth factors can be used for in vitro cell culture studies, and have potential as a tissue engineering scaffold.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
Keywords
artificial ECM, basic fibroblast growth factor, mammalian cell culture, recombinant spider silk
National Category
Biomaterials Science
Identifiers
urn:nbn:se:kth:diva-235446 (URN)10.1021/acsbiomaterials.8b00844 (DOI)000444526900025 ()2-s2.0-85052322322 (Scopus ID)
Note

QC 20180927

Available from: 2018-09-27 Created: 2018-09-27 Last updated: 2018-10-02Bibliographically approved
Gomez-Cid, L., Fuentes, L., Fernandez-Santos, M. E., Suarez-Sancho, S., Plasencia, V., Climent, A. M., . . . Aviles, F. F. (2018). Effect of spider silk matrix on cardiac tissue regeneration of mesenchymal stem cells. European Journal of Clinical Investigation, 48, 150-150
Open this publication in new window or tab >>Effect of spider silk matrix on cardiac tissue regeneration of mesenchymal stem cells
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2018 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, p. 150-150Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2018
National Category
Clinical Medicine
Identifiers
urn:nbn:se:kth:diva-232264 (URN)000434100200324 ()
Note

QC 20180719

Available from: 2018-07-19 Created: 2018-07-19 Last updated: 2018-07-19Bibliographically approved
Petrou, G., Jansson, R., Högqvist, M., Hedhammar, M. & Crouzier, T. (2018). Engineering mucoadhesive silk. Paper presented at 255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA. Abstracts of Papers of the American Chemical Society, 255
Open this publication in new window or tab >>Engineering mucoadhesive silk
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2018 (English)In: Abstracts of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 255Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-240166 (URN)000435537701238 ()
Conference
255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA
Note

OC 20190110

Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-08-20Bibliographically approved
Mittal, N., Lundell, F., Wågberg, L., Hedhammar, M. & Söderberg, D. (2018). Flow-assisted organization of nanostructured bio-based materials. Paper presented at 255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA. Abstract of Papers of the American Chemical Society, 255
Open this publication in new window or tab >>Flow-assisted organization of nanostructured bio-based materials
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2018 (English)In: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 255Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-240164 (URN)000435537702785 ()
Conference
255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA
Note

QC 20190111

Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-01-11Bibliographically approved
Guo, W., Gustafsson, L., Jansson, R., Hedhammar, M. & van der Wijngaart, W. (2018). Formation of a thin-walled Spider Silk Tube on a Micromachined Scaffold. In: Proceeding of 2018 IEEE 31st International Conference on Micro Electro Mechanical Systems (MEMS): . Paper presented at 31st IEEE International Conference on Micro Electro Mechanical Systems, MEMS 2018, Belfast, United Kingdom, 21 January 2018 through 25 January 2018 (pp. 83-85). Institute of Electrical and Electronics Engineers (IEEE), 2018
Open this publication in new window or tab >>Formation of a thin-walled Spider Silk Tube on a Micromachined Scaffold
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2018 (English)In: Proceeding of 2018 IEEE 31st International Conference on Micro Electro Mechanical Systems (MEMS), Institute of Electrical and Electronics Engineers (IEEE), 2018, Vol. 2018, p. 83-85Conference paper, Published paper (Refereed)
Abstract [en]

This paper reports on the first formation of a thin bio-functionalized spider silk tube, supported by an internal micromachined scaffold, in which both the inside and outside of the tube wall are freely accessible. The silk tube could potentially be used as an artificial blood vessel in an in vitro tissue scaffold, where endothelial cells and tissue cells can grow on both sides of the silk tube.

Place, publisher, year, edition, pages
Institute of Electrical and Electronics Engineers (IEEE), 2018
Series
Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS), ISSN 1084-6999
Keywords
spider silk, tissue engineering, artificial blood vessel
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-225863 (URN)10.1109/MEMSYS.2018.8346488 (DOI)000434960900023 ()2-s2.0-85047021023 (Scopus ID)9781538647820 (ISBN)
Conference
31st IEEE International Conference on Micro Electro Mechanical Systems, MEMS 2018, Belfast, United Kingdom, 21 January 2018 through 25 January 2018
Funder
EU, Horizon 2020, 675412Swedish Research Council, 621-2014-6200
Note

QC 20180515

Available from: 2018-04-10 Created: 2018-04-10 Last updated: 2018-12-05Bibliographically approved
Petrou, G., Jansson, R., Hogqvist, M., Erlandsson, J., Wågberg, L., Hedhammar, M. & Crouzier, T. (2018). Genetically Engineered Mucoadhesive Spider Silk. Biomacromolecules, 19(8), 3268-3279
Open this publication in new window or tab >>Genetically Engineered Mucoadhesive Spider Silk
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2018 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, no 8, p. 3268-3279Article in journal (Refereed) Published
Abstract [en]

Mucoadhesion is defined as the adhesion of a material to the mucus gel covering the mucous membranes. The mechanisms controlling mucoadhesion include nonspecific electrostatic interactions and specific interactions between the materials and the mucins, the heavily glycosylated proteins that form the mucus gel. Mucoadhesive materials can be used to develop mucosal wound dressings and noninvasive transmucosal drug delivery systems. Spider silk, which is strong, biocompatible, biodegradable, nontoxic, and lightweight would serve as an excellent base for the development of such materials. Here, we investigated two variants of the partial spider silk protein 4RepCT genetically engineered in order to functionalize them with mucoadhesive properties. The pLys-4RepCT variant was functionalized with six cationically charged lysines, aiming to provide nonspecific adhesion from electrostatic interactions with the anionically charged mucins, while the hGal3-4RepCT variant was genetically fused with the Human Galectin-3 Carbohydrate Recognition Domain which specifically binds the mucin glycans Gal beta 1-3GlcNAc and Gal beta 1-4GlcNAc. First, we demonstrated that coatings, fibers, meshes, and foams can be readily made from both silk variants. Measured by the adsorption of both bovine submaxillary mucin and pig gastric mucin, the newly produced silk materials showed enhanced mucin binding properties compared with materials of wild-type (4RepCT) silk. Moreover, we showed that pLys-4RepCT silk coatings bind mucins through electrostatic interactions, while hGal3-4RepCT silk coatings bind mucins through specific glycan-protein interactions. We envision that the two new mucoadhesive silk variants pLys-4RepCT and hGal3-4RepCT, alone or combined with other biofunctional silk proteins, constitute useful new building blocks for a range of silk protein-based materials for mucosal treatments.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:kth:diva-234195 (URN)10.1021/acs.biomac.8b00578 (DOI)000441852400011 ()29932649 (PubMedID)2-s2.0-85049259614 (Scopus ID)
Note

QC 20180920

Available from: 2018-09-20 Created: 2018-09-20 Last updated: 2019-04-13Bibliographically approved
Nilebäck, L., Arola, S., Kvick, M., Paananen, A., Linder, M. B. & Hedhammar, M. (2018). Interfacial Behavior of Recombinant Spider Silk Protein Parts Reveals Cues on the Silk Assembly Mechanism. Langmuir, 34(39), 11795-11805
Open this publication in new window or tab >>Interfacial Behavior of Recombinant Spider Silk Protein Parts Reveals Cues on the Silk Assembly Mechanism
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2018 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 34, no 39, p. 11795-11805Article in journal (Refereed) Published
Abstract [en]

The mechanism of silk assembly, and thus the cues for the extraordinary properties of silk, can be explored by studying the simplest protein parts needed for the formation of silk-like materials. The recombinant spider silk protein 4RepCT, consisting of four repeats of polyalanine and glycine-rich segments (4Rep) and a globular C-terminal domain (CT), has previously been shown to assemble into silk-like fibers at the liquid-air interface. Herein, we study the interfacial behavior of the two parts of 4RepCT, revealing new details on how each protein part is crucial for the silk assembly. Interfacial rheology and quartz crystal microbalance with dissipation show that 4Rep interacts readily at the interfaces. However, organized nanofibrillar structures are formed only when 4Rep is fused to CT. A strong interplay between the parts to direct the assembly is demonstrated. The presence of either a liquid-air or a liquid-solid interface had a surprisingly similar influence on the assembly.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Structural Biology
Identifiers
urn:nbn:se:kth:diva-237101 (URN)10.1021/acs.langmuir.8b02381 (DOI)000446543000016 ()30183309 (PubMedID)2-s2.0-85053916732 (Scopus ID)
Funder
Swedish Research Council FormasKnut and Alice Wallenberg Foundation
Note

QC 20181030

Available from: 2018-10-30 Created: 2018-10-30 Last updated: 2019-02-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0140-419X

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