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Wang, Shujiang
Publications (9 of 9) Show all publications
Wang, S., Nawale, G. N., Kadekar, S., Oommen, O. P., Jena, N. K., Chakraborty, S., . . . Varghese, O. P. (2018). Saline Accelerates Oxime Reaction with Aldehyde and Keto Substrates at Physiological pH. Scientific Reports, 8, Article ID 2193.
Open this publication in new window or tab >>Saline Accelerates Oxime Reaction with Aldehyde and Keto Substrates at Physiological pH
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 2193Article in journal (Refereed) Published
Abstract [en]

We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation reaction that could be adapted for both aldehyde and keto substrates. We found that saline accelerated the oxime kinetics in a concentration-dependent manner under physiological conditions. The reaction mechanism is validated by computational studies, and the versatility of the reaction is demonstrated by cell-surface labeling experiments. Saline offers an efficient and non-toxic catalytic option for performing the bioorthogonal-coupling reaction of biomolecules at the physiological pH. This saline mediated bioconjugation reaction represents the most biofriendly, mild and versatile approach for conjugating sensitive biomolecules and does not require any extensive purification step.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-347090 (URN)10.1038/s41598-018-20735-0 (DOI)000423787500168 ()29391582 (PubMedID)
Funder
Swedish Foundation for Strategic Research
Available from: 2018-03-26 Created: 2018-03-26 Last updated: 2018-03-26Bibliographically approved
Yan, H., Casalini, T., Hulsart Billström, G., Wang, S., Oommen, O. P., Salvalaglio, M., . . . Varghese, O. P. (2018). Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation. Biomaterials, 161, 190-202
Open this publication in new window or tab >>Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation
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2018 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 161, p. 190-202Article in journal (Refereed) Published
Abstract [en]

Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor.

National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-343820 (URN)10.1016/j.biomaterials.2018.01.041 (DOI)000427100300017 ()29421555 (PubMedID)
Funder
Swedish Foundation for Strategic Research , 139400126, 139400127EU, FP7, Seventh Framework Programme, NMP3-LA-2011-262948
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2018-03-01 Created: 2018-03-01 Last updated: 2018-05-16Bibliographically approved
Ravichandran, R., Islam, M. M., Alarcon, E. I., Samanta, A., Wang, S., Lundstrom, P., . . . Phopase, J. (2016). Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications. Journal of materials chemistry. B, 4(2), 318-326
Open this publication in new window or tab >>Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications
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2016 (English)In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 4, no 2, p. 318-326Article in journal (Refereed) Published
Abstract [en]

In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the crosslinking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.

National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-274914 (URN)10.1039/c5tb02035b (DOI)000367335200016 ()
Funder
Swedish Research Council, 621-2012-4286Swedish Research Council, 521-2012-5706
Note

Correction in: Journal of Materials Chemistry B, Volume: 5, Issue: 26, Pages: 5284-5284. DOI: 10.1039/c7tb90075a

Available from: 2016-01-27 Created: 2016-01-26 Last updated: 2019-01-21Bibliographically approved
Wang, S., Gurav, D., Oommen, O. P. & Varghese, O. P. (2015). Insights into the Mechanism and Catalysis of Oxime Coupling Chemistry at Physiological pH. Chemistry - A European Journal, 21(15), 5980-5985
Open this publication in new window or tab >>Insights into the Mechanism and Catalysis of Oxime Coupling Chemistry at Physiological pH
2015 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, no 15, p. 5980-5985Article in journal (Refereed) Published
Abstract [en]

The dynamic covalent-coupling reaction involving alpha-effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of alpha-effect by forming H-bonds with the rate-limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a similar to 14-31-fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell-surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline.

Keywords
ketones, kinetics, coupling reaction, oxime, reaction mechanisms
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-252690 (URN)10.1002/chem.201406458 (DOI)000352506500042 ()25737419 (PubMedID)
Available from: 2015-05-25 Created: 2015-05-11 Last updated: 2017-12-04Bibliographically approved
Wang, S., Oommen, O. P., Yan, H. & Varghese, O. P. (2013). Mild and Efficient Strategy for Site-Selective Aldehyde Modification of Glycosaminoglycans: Tailoring Hydrogels with Tunable Release of Growth Factor. Biomacromolecules, 14(7), 2427-2432
Open this publication in new window or tab >>Mild and Efficient Strategy for Site-Selective Aldehyde Modification of Glycosaminoglycans: Tailoring Hydrogels with Tunable Release of Growth Factor
2013 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 14, no 7, p. 2427-2432Article in journal (Refereed) Published
Abstract [en]

Aldehydes have been used as an important bioorthogonal chemical reporter for conjugation of large polymers and bioactive substances. However, generating aldehyde functionality on carbohydrate-based biopolymers without changing its native chemical structure has always persisted as a challenging task. The common methods employed to achieve this require harsh reaction conditions, which often compromise the structural integrity and biological function of these sensitive molecules. Here we report a mild and simple method to graft aldehydes groups on glycosaminoglycans (GAGs) in a site-selective manner without compromising the structural integrity of the biopolymer. This regio-selective modification was achieved by conjugating the amino-glycerol moiety on the carboxylate residue of the polymer, which allowed selective cleavage of pendent diol groups without interfering with the C2C3 diol groups of the native glucopyranose residue. Kinetic evaluation of this reaction demonstrated significant differences in second-order reaction rate for periodate oxidation (by four-orders of magnitude) between the two types of vicinal diols. We employed this chemistry to develop aldehyde modifications of sulfated and nonsulfated GAGs such as hyaluronic acid (HA), heparin (HP), and chondroitin sulfate (CS). We further utilized these aldehyde grafted GAGs to tailor extracellular matrix mimetic injectable hydrogels and evaluated its rheological properties. The composition of the hydrogels was also found to modulate release of therapeutic protein such as FGF-2, demonstrating controlled release (60%) for over 14 days. In short, our result clearly demonstrates a versatile strategy to graft aldehyde groups on sensitive biopolymers under mild conditions that could be applied for various bioconjugation and biomedical applications such as drug delivery and regenerative medicine.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-204978 (URN)10.1021/bm400612h (DOI)000321793700035 ()
Note

De två (2) första författarna delar förstaförfattarskapet.

Available from: 2013-08-16 Created: 2013-08-13 Last updated: 2017-12-06Bibliographically approved
Oommen, O. P., Wang, S., Kisiel, M., Sloff, M., Hilborn, J. & Varghese, O. P. (2013). Smart Design of Stable Extracellular Matrix Mimetic Hydrogel: Synthesis, Characterization, and In Vitro and In Vivo Evaluation for Tissue Engineering. Advanced Functional Materials, 23(10), 1273-1280
Open this publication in new window or tab >>Smart Design of Stable Extracellular Matrix Mimetic Hydrogel: Synthesis, Characterization, and In Vitro and In Vivo Evaluation for Tissue Engineering
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2013 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 23, no 10, p. 1273-1280Article in journal (Refereed) Published
Abstract [en]

The simplicity and versatility of hydrazone crosslinking has made it a strategy of choice for the conjugation of bioactive molecules. However, the labile nature of hydrazone linkages and reversibility of this coupling reaction restricts its full potential. Based on the fundamental understanding of hydrazone stability, this problem is circumvented by resonance-stabilization of a developing N2 positive charge in a hydrazone bond. A novel chemistry is presented to develop a resilient hydrazone bond that is stable and non- reversible under physiological conditions. A carbodihydrazide (CDH) type hydrazide derivative of the biomolecule forms intrinsically stabilized hydrazone-linkages that are nearly 15-fold more stable at pH 5 than conventional hydrazone. This chemoselective coupling reaction is catalyst-free, instantaneous, and virtually non-cleavable under physiological conditions, therefore can serve as a catalyst-free alternative to click chemistry. This novel crosslinking reaction is used to tailor a hyaluronan hydrogel, which delivered exceptional hydrolytic stability, mechanical properties, low swelling, and controlled enzymatic degradation. These desired characteristics are achieved without increasing the chemical crosslinking. The in vivo evaluation of this hydrogel revealed neo-bone with highly ordered collagen matrix mimicking natural bone regeneration. The proximity ligation assay or PLA is used to detect blood vessels, which highlighted the quality of engineered tissue.

Keywords
biomimetics, biomedical applications, hydrogels, tissue engineering, hyaluronic acid
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-198387 (URN)10.1002/adfm.201201698 (DOI)000316196100007 ()
Available from: 2013-04-15 Created: 2013-04-15 Last updated: 2017-12-06Bibliographically approved
Podiyan, O., Wang, S., Kisiel, M., Hilborn, J. & Varghese, O. P. (2012). Smart design of stable hydrazone crosslinked extracellular matrix mimetic hydrogel for tissue engineering application. Journal of Tissue Engineering and Regenerative Medicine, 6(suppl 1), 192-192
Open this publication in new window or tab >>Smart design of stable hydrazone crosslinked extracellular matrix mimetic hydrogel for tissue engineering application
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2012 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 6, no suppl 1, p. 192-192Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Injectable hydrogels are important biomaterials with enormous applications. They are used for various biomedical applications such as diagnostics, 3D cell culture matrix, drug reservoir, encapsulation of bioactive compounds and growth factors, scaffold for tissue engineering etc. We here present our recent development in our efforts to develop hydrogel scaffolds with enhanced rigidity, stability, swelling characteristics. Hydrazone crosslinked gels are attractive due to its simplicity and versatility which could be formed by mixing appropriate aldehyde and hydrazide functionalized hyaluronan. By fine-tuning the electronic character around the hydrazone linkage, we succeeded in developing extremely stable hydrazone bond and utilized it for developing hyaluronan (HA) based synthetic extracellular matrix (ECM) hydrogel. Among the different hydrazides tested, we identified carbonyldihydrazide (CDH) as the best candidate to deliver stable hydrazone linkage. This stability is presumably due to extensive delocalization of the positive charge across neighboring amino groups of CDH. The hydrolytic stability imparted by this group was found to be several folds under acidic, basic and physiological pH when compared to other hydrazones. This tailored hydrogel with CDH also exhibited superior swelling and mechanical properties and enzymatic stability which makes it ideal for tissue engineering application.

National Category
Medical and Health Sciences Polymer Chemistry
Research subject
Chemistry with specialization in Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-182412 (URN)10.1002/term.1586 (DOI)000308313001311 ()
Available from: 2012-10-12 Created: 2012-10-10 Last updated: 2013-02-11Bibliographically approved
Paidikondala, M., Wang, S., Yan, H., Podiyan, O., Hilborn, J., Larsson, S. & Varghese, O. P.Rational Design of Biomaterials for Growth Factor Delivery: Impact of Hydrogel Crosslinking Chemistry on the In Vitroand In VivoBioactivity of Recombinant Human Bone Morphogenetic Protein-2.
Open this publication in new window or tab >>Rational Design of Biomaterials for Growth Factor Delivery: Impact of Hydrogel Crosslinking Chemistry on the In Vitroand In VivoBioactivity of Recombinant Human Bone Morphogenetic Protein-2
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(English)Manuscript (preprint) (Other academic)
National Category
Biomaterials Science
Identifiers
urn:nbn:se:uu:diva-369656 (URN)
Available from: 2018-12-14 Created: 2018-12-14 Last updated: 2018-12-15
Wang, S., Nawale, G. N., Kadekar, S., Oommen, O. P., Jena, N. K., Chakraborty, S., . . . Varghese, O. P. Saline catalyse oxime reaction at physiological pH: overcoming a major limitation of bioorthogonal reaction.
Open this publication in new window or tab >>Saline catalyse oxime reaction at physiological pH: overcoming a major limitation of bioorthogonal reaction
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(English)In: Article in journal (Refereed) Submitted
Abstract [en]

We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation reaction that could be adapted for both aldehyde and keto substrates. We found that saline accelerated the oxime kinetics in a concentration dependent manner under physiological conditions. The reaction mechanism is validated by computational studies, and the versatility of the reaction is demonstrated by cell-surface labeling experiments. Saline offers an efficient and non-toxic catalytic option for performing the bioorthogonal-coupling reaction of biomolecules at the physiological pH. This saline mediated bioconjugation reaction represents the most bio-friendly, mild and versatile approach for conjugating sensitive biomolecules and does not require any extensive purification step.

Keywords
Oxime reaction, catalysis, kinetics, labeling
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-328905 (URN)
Available from: 2017-09-04 Created: 2017-09-04 Last updated: 2017-09-07Bibliographically approved
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