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Shi, Liyang
Publications (10 of 17) Show all publications
Shi, L., Ding, P., Wang, Y., Zhang, Y., Ossipov, D. & Hilborn, J. (2019). Self-Healing Polymeric Hydrogel Formed by Metal-Ligand Coordination Assembly: Design, Fabrication, and Biomedical Applications. Macromolecular rapid communications, 40(7), Article ID 1800837.
Open this publication in new window or tab >>Self-Healing Polymeric Hydrogel Formed by Metal-Ligand Coordination Assembly: Design, Fabrication, and Biomedical Applications
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2019 (English)In: Macromolecular rapid communications, ISSN 1022-1336, E-ISSN 1521-3927, Vol. 40, no 7, article id 1800837Article in journal (Refereed) Published
Abstract [en]

Self-healing hydrogels based on metal-ligand coordination chemistry provide new and exciting properties that improve injectability, rheological behaviors, and even biological functionalities. The inherent reversibility of coordination bonds improves on the covalent cross-linking employed previously, allowing for the preparation of completely self-healing hydrogels. In this article, recent advances in the development of this class of hydrogels are summarized and their applications in biology and medicine are discussed. Various chelating ligands such as bisphosphonate, catechol, histidine, thiolate, carboxylate, pyridines (including bipyridine and terpyridine), and iminodiacetate conjugated onto polymeric backbones, as well as the chelated metal ions and metal ions containing inorganic particles, which are used to form dynamic networks, are highlighted. This article provides general ideas and methods for the design of self-healing hydrogel biomaterials based on coordination chemistry.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH, 2019
Keywords
biomaterials, coordination chemistry, hydrogels, self-healing materials
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-385569 (URN)10.1002/marc.201800837 (DOI)000467997700006 ()30672628 (PubMedID)
Funder
Swedish Research Council, 2017-04651
Available from: 2019-06-19 Created: 2019-06-19 Last updated: 2019-06-19Bibliographically approved
Lunzer, M., Shi, L., Andriotis, O. G., Gruber, P., Markovic, M., Thurner, P. J., . . . Ovsianikov, A. (2018). A Modular Approach to Sensitized Two-Photon Patterning of Photodegradable Hydrogels. Angewandte Chemie International Edition, 57(46), 15122-15127
Open this publication in new window or tab >>A Modular Approach to Sensitized Two-Photon Patterning of Photodegradable Hydrogels
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2018 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 57, no 46, p. 15122-15127Article in journal (Refereed) Published
Abstract [en]

Photodegradable hydrogels have emerged as useful platforms for research on cell function, tissue engineering, and cell delivery as their physical and chemical properties can be dynamically controlled by the use of light. The photo-induced degradation of such hydrogel systems is commonly based on the integration of photolabile o-nitrobenzyl derivatives to the hydrogel backbone, because such linkers can be cleaved by means of one-and two-photon absorption. Herein we describe a cytocompatible click-based hydrogel containing o-nitrobenzyl ester linkages between a hyaluronic acid backbone, which is photodegradable in the presence of cells. It is demonstrated for the first time that by using a cyclic benzylidene ketone-based small molecule as photosensitizer the efficiency of the two-photon degradation process can be improved significantly. Biocompatibility of both the improved two-photon micropatterning process as well as the hydrogel itself is confirmed by cell culture studies.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH, 2018
Keywords
biomaterials, hyaluronic acid, hydrogels, photochemistry, sensitizers
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-372823 (URN)10.1002/anie.201808908 (DOI)000452396800023 ()30191643 (PubMedID)
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-01-09Bibliographically approved
Porras, A. M., Shi, L., Ossipov, D. A. & Tenje, M. (2018). Chemical micropatterning of hyaluronic acid hydrogels for controlled cell adhesion. In: : . Paper presented at European Organ on Chip, Stuttgart, Germany 24-25 May, 2018.
Open this publication in new window or tab >>Chemical micropatterning of hyaluronic acid hydrogels for controlled cell adhesion
2018 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

The blood brain barrier is constituted by endothelial cells, astrocytes and pericytes; and are organized into well structured units [1]. Standard cell culture techniques cannot recapitulate this organized structure. Hydrogels are an attractive scaffold due to their mechanical and chemical properties similar to those in body tissue[2] We propose the use of a photo-crosslinkable hyaluronic acid hydrogel as cell culture scaffold. Furthermore, chemical cues can be added into the hydrogel matrix to promote and control cell adhesion using UV lithography.

National Category
Engineering and Technology Other Medical Engineering
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-368272 (URN)
Conference
European Organ on Chip, Stuttgart, Germany 24-25 May, 2018
Funder
Wallenberg Foundations, 2016-0112EU, Horizon 2020, 757444
Available from: 2018-12-05 Created: 2018-12-05 Last updated: 2018-12-11Bibliographically approved
Shi, L., Yu, Z. & Ossipov, D. A. (2018). Enzymatic degradation of hyaluronan hydrogels with different capacity for in situ bio-mineralization. Biopolymers, 109(2), Article ID e23090.
Open this publication in new window or tab >>Enzymatic degradation of hyaluronan hydrogels with different capacity for in situ bio-mineralization
2018 (English)In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 109, no 2, article id e23090Article in journal (Refereed) Published
Abstract [en]

In situ cross-linked hyaluronan (HA) hydrogels with different capacities for biomineralization were prepared and their enzymatic degradation was monitored. Covalent incorporation of bisphosphonates (BPs) into HA hydrogel results in the increased stiffness of the hydrogel in comparison with the unmodified HA hydrogel of the same cross-linking density. The rate of enzymatic degradation of HABP hydrogel was significantly lower than the rate of degradation of control HA hydrogel in vitro. This effect is observed only in the presence of calcium ions that strongly bind to the matrix-anchored BP groups and promote further mineralization of the matrix. The degradation of the hydrogels was followed by noninvasive fluorescence measurements enabled after mild and chemoselective labeling of cross-linkable HA derivatives with a fluorescent tag.

National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-334854 (URN)10.1002/bip.23090 (DOI)000428629000004 ()
Funder
EU, FP7, Seventh Framework Programme
Available from: 2017-11-28 Created: 2017-11-28 Last updated: 2018-06-04Bibliographically approved
Searle, S., Porras, A. M., Barbe, L., Shi, L., Ossipov, D. A., Trau, D. & Tenje, M. (2018). Hyaluronic acid based hydrogel droplets: A potential injectable cell culture scaffold. In: : . Paper presented at EUROoC, Stuttgart, Germany. 24 and 35 May, 2018..
Open this publication in new window or tab >>Hyaluronic acid based hydrogel droplets: A potential injectable cell culture scaffold
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2018 (English)Conference paper, Oral presentation only (Other academic)
Abstract [en]

Introduction

Cell culture scaffolds such as hydrogels give support and structure for cultured cells in 3D environments that better mimic in vivo conditions [1]. Hyaluronic acid (HA) derived hydrogels are particularly attractive scaffold materials, due to their high water content, and its high presence in the extracellular matrix of a multitude of tissues in the human body [2]. Adequate diffusion of oxygen and nutrients however, is generally limited to a depth of 200 µm in bulk hydrogels [3], heavily limiting their applicability to relatively large size constructs. We propose the use of droplet-based microfluidics to produce monodisperse HA-derived injectable microgel droplets which could enable the diffusion of nutrients and metabolites, while maintaining a size in which encapsulating sufficient cells to allow cell-cell interactions and proliferation would be possible.

 

Experimental results

Hyaluronic acid acrylamide (HA-am) was synthesized by partially modifying high molecular weight sodium hyaluronan with a N-(2-aminoethyl)acrylamide linker. Degree of modification was confirmed by NMR to be of 20%. HA-am bulk hydrogels were formed by exposing a solution of HA-am and photoinitiator Irgacure 2959 (0.4 % w/v) to a UV light source of 365 nm wavelength. Gel droplets were produced in a PDMS microfluidic device designed in a flow focusing geometry. In order to simulate cell encapsulation in the microgel, hydrogel precursor mixtures were prepared as for bulk hydrogels with the addition of polystyrene beads (10µm in diameter) at a concentration of 10 million beads ml-1. For the oil phase, a fluorinated oil (Novec 7500, 3M) with 0.5% surfactant (PicoSurf 1) was used. The flow rates for the oil phase and aqueous phase were adjusted to 15 and 5 µl min-1, respectively to produce highly monodisperse droplets of 151 µm in average diameter. Collected droplets were polymerized by exposing to UV light, washed and transferred to an aqueous solution.

 

 

Conclusion

Highly monodisperse microgels containing microbeads were obtained. We demonstrate that photocrosslinkable hydrogel droplets can be produced from HA-am in a microfluidic flow-focusing chip which could enable the encapsulation of cells and the use of the droplets as injectable cell culture scaffolds.

 

References

[1]       G. D. Nicodemus and S. J. Bryant, “Cell Encapsulation in Biodegradable Hydrogels for Tissue Engineering Applications,” Tissue Eng. Part B Rev., vol. 14, no. 2, pp. 149–165, Jun. 2008.

[2]       J. A. Burdick and G. D. Prestwich, “Hyaluronic acid hydrogels for biomedical applications,” Adv. Mater., vol. 23, no. 12, pp. 41–56, Mar. 2011.

[3]       H. Huang, Y. Yu, Y. Hu, X. He, O. Berk Usta, and M. L. Yarmush, “Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture,” Lab Chip, vol. 17, no. 11, pp. 1913–1932, 2017.

National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-357613 (URN)
Conference
EUROoC, Stuttgart, Germany. 24 and 35 May, 2018.
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-08-22Bibliographically approved
Shi, L., Yannan, Z., Qifan, X., Caixia, F., Hilborn, J., Jianwu, D. & Ossipov, D. A. (2018). Moldable Hyaluronan Hydrogel Enabled by Dynamic Metal–Bisphosphonate Coordination Chemistry for Wound Healing. Advanced Healthcare Materials, 7(5), Article ID 1700973.
Open this publication in new window or tab >>Moldable Hyaluronan Hydrogel Enabled by Dynamic Metal–Bisphosphonate Coordination Chemistry for Wound Healing
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2018 (English)In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 7, no 5, article id 1700973Article in journal (Refereed) Published
Abstract [en]

Biomaterial-based regenerative approaches would allow for cost-effective off-the-shelf solution for the treatment of wounds. Hyaluronan (HA)-based hydrogel is one attractive biomaterial candidate because it is involved in natural healing processes, including inflammation, granulation, and reepi-thelialization. Herein, dynamic metal–ligand coordination bonds are used to fabricate moldable supramolecular HA hydrogels with self-healing properties. To achieve reversible crosslinking of HA chains, the biopolymer is modified with pendant bisphosphonate (BP) ligands using carbodiimide coupling and chemoselective “click” reactions. Hydrogel is formed immediately after simple addition of silver (Ag+) ions to the solution of HA containing BP groups (HA-BP). Compared with previous HA-based wound healing hydrogels, the HA-BP·Ag+ hydrogel is highly suitable for clinical use as it can fill irregularly shaped wound defects without the need for premolding. The HA-BP·Ag+ hydrogel shows antimicrobial properties to both Gram-positive and Gram-negative bacterial strains, enabling prevention of infections in wound care. In vivo evaluation using a rat full-thickness skin wound model shows sig-nificantly lower wound remaining rate and a thicker layer of regenerated epidermis as compared with the group left without treatment. The presented moldable and self-healing supramolecular HA hydrogel with “ready-to-use” properties possesses a great potential for regenerative wound treatment.

Keywords
antibacterial, bisphosphonate, hyaluronan, moldable, wound healing
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-338080 (URN)10.1002/adhm.201700973 (DOI)000426758500016 ()
Available from: 2018-01-07 Created: 2018-01-07 Last updated: 2018-06-27Bibliographically approved
Chen, S., Shi, L., Luo, J. & Engqvist, H. (2018). Novel Fast-Setting Mineral Trioxide Aggregate: Its Formulation, Chemical-Physical Properties, and Cytocompatibility. ACS Applied Materials and Interfaces, 10(24), 20334-20341
Open this publication in new window or tab >>Novel Fast-Setting Mineral Trioxide Aggregate: Its Formulation, Chemical-Physical Properties, and Cytocompatibility
2018 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 10, no 24, p. 20334-20341Article in journal (Refereed) Published
Abstract [en]

One of the main drawbacks that limits the application of mineral trioxide aggregate (MTA) in dental field is its long setting time. Mineral trioxide aggregate with accelerated setting properties and excellent chemical-physical and biological properties is still required. In this study, an innovative mineral trioxide aggregate, which consists of calcium silicates, calcium aluminates, and zirconium oxide, was designed to obtain fast-setting property. The optimized formulation can achieve initial setting in 10 min and final setting in 15 min, which are much faster than commercial mineral trioxide aggregate. In addition, the optimized fast-setting MTA showed adequate radiopacity and good biocompatibility. The ion concentrations after storage in water for 1 day were 52.3 mg/L Ca, 67.7 mg/L Al, 48.8 mg/L Si, and 11.7 mg/L Mg. The hydration products of hardened cements were investigated by X-ray diffraction, scanning electron microscopy, and Fourier transform infrared, showing the accelerated setting time was due to the formation of honeycomb-like calcium silicate hydrate gel. The novel MTA could be a promising material for dental applications.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
Keywords
mineral trioxide aggregate, dental cements, fast setting, calcium silicates, calcium aluminates
National Category
Materials Chemistry Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-358684 (URN)10.1021/acsami.8b04946 (DOI)000436211500015 ()29873476 (PubMedID)
Available from: 2018-09-05 Created: 2018-09-05 Last updated: 2018-09-06Bibliographically approved
Searle, S., Porras, A. M., Barbe, L., Shi, L., Pohlit, H., Trau, D. & Tenje, M. (2018). Production of hyaluronic acid-acrylamide microgels as potential cell culture scaffolds. In: Micronano System Workshop, May 13-15, 2018: Book of Abstracts. Paper presented at Micronano System Workshop, Aalto University, Espoo, Finland, May 13th to 18th, 2018. (pp. 24-24).
Open this publication in new window or tab >>Production of hyaluronic acid-acrylamide microgels as potential cell culture scaffolds
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2018 (English)In: Micronano System Workshop, May 13-15, 2018: Book of Abstracts, 2018, p. 24-24Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

Hyaluronic acid (HA) derived hydrogels give support and structure for cultured cells in 3D environments that better mimic in vivo conditions 1. Adequate diffusion of oxygen and nutrients however, is generally limited to a depth of 200 µm in bulk hydrogels 2, limiting their applicability to larger size constructs. Through droplet-based microfluidics we produced monodisperse HA-derived microgel droplets. Hyaluronic acid acrylamide (HA-am) was synthesized by partially modifying high molecular weight sodium hyaluronan with a N-(2-aminoethyl)acrylamide linker to a 20% degree.

Gel droplets were produced in a PDMS microfluidic device designed in a flow focusing geometry. In this setup polystyrene beads were added to simulate cell-encapsulation into a matrix that would better reflect in vivo conditions. The hydrogel precursor mixtures were prepared with 2% solution of HA-am and a photoinitiator with the addition of polystyrene beads (10µm in diameter) at a concentration of 10 million beads per milliliter. A fluorinated oil (Novec 7500, 3M) with 0.5% surfactant (PicoSurf 1) was used as the continuous phase. Highly monodisperse droplets of 151 µm in average diameter were produced and later polymerized by exposing to a long-wave UV light source (365 nm).  

We demonstrate that photocrosslinkable hydrogel droplets can be produced from HA-am. These microgels could enable the diffusion of nutrients and metabolites, while maintaining a size in which encapsulating sufficient cells to allow cell-cell interactions and proliferation would be possible.

[1]         J. A. Burdick and G. D. Prestwich, Adv. Mater., 2011, 23, 41–56.

[2]         H. Huang, Y. Yu, Y. Hu, X. He, O. Berk Usta and M. L. Yarmush, Lab Chip, 2017, 17, 1913–1932.

National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-357608 (URN)
Conference
Micronano System Workshop, Aalto University, Espoo, Finland, May 13th to 18th, 2018.
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-10-19Bibliographically approved
Porras, A. M., Sjögren, F., Shi, L., Ossipov, D. A. & Tenje, M. (2017). Addressing the biocompatibility of photo-crosslinkable hyaluronic acid hydrogels. In: Abstract book at EMBEC 2017 & NBC 2017: . Paper presented at European Medical and Biological Engineering Conference (EMBEC ’17) co-organised with Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (NBC ’17), Tampere, Finland, June 11-15 2017 (pp. 117-117).
Open this publication in new window or tab >>Addressing the biocompatibility of photo-crosslinkable hyaluronic acid hydrogels
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2017 (English)In: Abstract book at EMBEC 2017 & NBC 2017, 2017, p. 117-117Conference paper, Oral presentation with published abstract (Refereed)
National Category
Engineering and Technology Other Physics Topics
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-335797 (URN)
Conference
European Medical and Biological Engineering Conference (EMBEC ’17) co-organised with Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (NBC ’17), Tampere, Finland, June 11-15 2017
Funder
Swedish Research Council FormasKnut and Alice Wallenberg Foundation
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2017-12-29Bibliographically approved
Shi, L., Carstensen, H., Hölzl, K., Lunzer, M., Li, H., Hilborn, J., . . . Ossipov, D. A. (2017). Dynamic Coordination Chemistry Enables Free Directional Printing of Biopolymer Hydrogel. Chemistry of Materials, 29, 5816-5823
Open this publication in new window or tab >>Dynamic Coordination Chemistry Enables Free Directional Printing of Biopolymer Hydrogel
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2017 (English)In: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 29, p. 5816-5823Article in journal (Refereed) Published
Abstract [en]

Three-dimensional (3D) printing is a promising technology to develop customized biomaterials in regenerative medicine. However, for the majority of printable biomaterials (bioinks) there is always a compromise between excellent printability of fluids and good mechanical properties of solids. 3D printing of soft materials based on the transition from a fluid to gel state is challenging because of the difficulties to control such transition as well as to maintain uniform conditions three-dimensionally. To solve these challenges, a facile chemical strategy for the development of a novel hydrogel bioink with shear-thinning and self-healing properties based on dynamic metal-ligand coordination bonds is presented. The non-covalent cross-linking allows easy extrusion of the bioink from a reservoir without changing of its bulk mechanical properties. The soft hydrogel can avoid deformation and collapse using omnidirectional embedding of the printable hydrogel into a support gel bath sharing the same cross-linking chemistry. After combination with photo-initiated covalent cross-linking, it enables manufacturing of hydrogel structures with complex shapes and precise location of chemically attached ligands. Living cells can be entrapped in the new printable hydrogel and survive the following in situ photocross-linking. The presented printable hydrogel mate-rial expands the existing tool-box of bioinks for generation of in vitro 3D tissue-like structures and direct in vivo 3D printing.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-324796 (URN)10.1021/acs.chemmater.7b00128 (DOI)000406573200011 ()
Funder
EU, European Research Council, 307701
Available from: 2017-06-19 Created: 2017-06-19 Last updated: 2018-09-03Bibliographically approved
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