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Hong, Jaan
Publications (10 of 29) Show all publications
Basu, A., Hong, J. & Ferraz, N. (2017). Hemocompatibility of Ca2+-Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis. Macromolecular Bioscience, 1-9, Article ID 1700236.
Open this publication in new window or tab >>Hemocompatibility of Ca2+-Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis
2017 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, 1-9 p., 1700236Article in journal (Refereed) Epub ahead of print
Abstract [en]

The present work investigates Ca2+-crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood-derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet-free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.

Keyword
biocompatibility, blood coagulation, complement system, nanofibrillated cellulose, wound dressing
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-332127 (URN)10.1002/mabi.201700236 (DOI)28941135 (PubMedID)
Funder
Swedish Research Council Formas
Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2017-11-13Bibliographically approved
Ek, R. K., Hong, J., Thor, A., Backstrom, M. & Rannar, L.-E. (2017). Micro- to Macroroughness of Additively Manufactured Titanium Implants in Terms of Coagulation and Contact Activation. International Journal of Oral & Maxillofacial Implants, 32(3), 565-574.
Open this publication in new window or tab >>Micro- to Macroroughness of Additively Manufactured Titanium Implants in Terms of Coagulation and Contact Activation
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2017 (English)In: International Journal of Oral & Maxillofacial Implants, ISSN 0882-2786, E-ISSN 1942-4434, Vol. 32, no 3, 565-574 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: This study aimed to evaluate how as-built electron beam melting (EBM) surface properties affect the onset of blood coagulation. The properties of EBM-manufactured implant surfaces for placement have, until now, remained largely unexplored in literature. Implants with conventional designs and custom-made implants have been manufactured using EBM technology and later placed into the human body. Many of the conventional implants used today, such as dental implants, display modified surfaces to optimize bone ingrowth, whereas custom-made implants, by and large, have machined surfaces. However, titanium in itself demonstrates good material properties for the purpose of bone ingrowth. Materials and Methods: Specimens manufactured using EBM were selected according to their surface roughness and process parameters. EBM-produced specimens, conventional machined titanium surfaces, as well as PVC surfaces for control were evaluated using the slide chamber model. Results: A significant increase in activation was found, in all factors evaluated, between the machined samples and EBM-manufactured samples. The results show that EBM-manufactured implants with as-built surfaces augment the thrombogenic properties. Conclusion: EBM that uses Ti6Al4V powder appears to be a good manufacturing solution for load-bearing implants with bone anchorage. The as-built surfaces can be used "as is" for direct bone contact, although any surface treatment available for conventional implants can be performed on EBM-manufactured implants with a conventional design.

Place, publisher, year, edition, pages
QUINTESSENCE PUBLISHING CO INC, 2017
Keyword
bone ingrowth, coagulation, customization, electron beam melting, surface roughness
National Category
Dentistry
Identifiers
urn:nbn:se:uu:diva-330057 (URN)10.11607/jomi.5357 (DOI)000404520600022 ()
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2017-11-16Bibliographically approved
Ekdahl, K. N., Teramura, Y., Hamad, O. A., Asif, S., Duehrkop, C., Fromell, K., . . . Nilsson, B. (2016). Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation. Immunological Reviews, 274(1), 245-269.
Open this publication in new window or tab >>Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation
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2016 (English)In: Immunological Reviews, ISSN 0105-2896, E-ISSN 1600-065X, Vol. 274, no 1, 245-269 p.Article, review/survey (Refereed) Published
Abstract [en]

Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.

Keyword
coagulation, complement system, contact activation, kallikrein system, innate immunity, platelets, thromboinflammation
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-313666 (URN)10.1111/imr.12471 (DOI)000387059600017 ()27782319 (PubMedID)
Funder
Swedish Research Council, 2013-65X-05647-34-4EU, FP7, Seventh Framework Programme, 602699The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Available from: 2017-01-24 Created: 2017-01-23 Last updated: 2018-01-13Bibliographically approved
Frykstrand, S., Forsgren, J., Cheung, O., Zhang, P., Hong, J., Strømme, M. & Ferraz, N. (2016). Study of mesoporous magnesium carbonate in contact with whole human blood. RSC Advances, 6(58), 52810-52816.
Open this publication in new window or tab >>Study of mesoporous magnesium carbonate in contact with whole human blood
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2016 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 6, no 58, 52810-52816 p.Article in journal (Refereed) Published
Abstract [en]

The interaction of mesoporours magnesium carbonate (Upsalite) particles (50-100 mm) with human whole blood was investigated using an in vitro loop model and the effect on the complement system, blood coagulation and red blood cell lysis was assessed. The removal of Ca2+ by Upsalite and the possible exchange with and/or release of Mg2+ were explored as well. Upsalite was found to present anticoagulant properties, most probably due to the uptake of Ca2+ by the particles. No hemolytic activity was detected at Upsalite concentrations up to 1 mg ml(-1). Moderate to high levels of C3a and sC5b-9 were observed for Upsalite, however such levels were statistically different from the negative control only when the particle concentrations were 0.25 mg ml(-1) and 1.0 mg ml(-1), respectively. The presented findings are promising for the future development of mesoporous magnesium carbonate-based materials for biomedical applications.

National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-281465 (URN)10.1039/c6ra05679b (DOI)000378563200037 ()2-s2.0-84973390611 (Scopus ID)
Funder
Swedish Research Council
Available from: 2016-03-24 Created: 2016-03-24 Last updated: 2017-11-30Bibliographically approved
Hårdstedt, M., Lindblom, S., Hong, J., Nilsson, B., Korsgren, O. & Ronquist, G. (2015). A novel model for studies of blood-mediated long-term responses to cellular transplants. Upsala Journal of Medical Sciences, 120(1), 28-39.
Open this publication in new window or tab >>A novel model for studies of blood-mediated long-term responses to cellular transplants
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2015 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 1, 28-39 p.Article in journal (Refereed) Published
Abstract [en]

Aims

Interaction between blood and bio-surfaces is important in many medical fields. With the aim of studying blood-mediated reactions to cellular transplants, we developed a whole-blood model for incubation of small volumes for up to 48 h.

Methods

Heparinized polyvinyl chloride tubing was cut in suitable lengths and sealed to create small bags. Multiple bags, with fresh venous blood, were incubated attached to a rotating wheel at 37°C. Physiological variables in blood were monitored: glucose, blood gases, mono- and divalent cations and chloride ions, osmolality, coagulation (platelet consumption, thrombin-antithrombin complexes (TAT)), and complement activation (C3a and SC5b-9), haemolysis, and leukocyte viability.

Results

Basic glucose consumption was high. Glucose depletion resulted in successive elevation of extracellular potassium, while sodium and calcium ions decreased due to inhibition of energy-requiring ion pumps. Addition of glucose improved ion balance but led to metabolic acidosis. To maintain a balanced physiological environment beyond 6 h, glucose and sodium hydrogen carbonate were added regularly based on analyses of glucose, pH, ions, and osmotic pressure. With these additives haemolysis was prevented for up to 72 h and leukocyte viability better preserved. Despite using non-heparinized blood, coagulation and complement activation were lower during long-term incubations compared with addition of thromboplastin and collagen.

Conclusion

A novel whole-blood model for studies of blood-mediated responses to a cellular transplant is presented allowing extended observations for up to 48 h and highlights the importance of stringent evaluations and adjustment of physiological conditions.

National Category
Immunology in the medical area Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-232482 (URN)10.3109/03009734.2014.965290 (DOI)000350984700004 ()
Available from: 2014-09-18 Created: 2014-09-18 Last updated: 2018-01-11Bibliographically approved
Ekstrand-Hammarstrom, B., Hong, J., Davoodpour, P., Sandholm, K., Ekdahl, K. N., Bucht, A. & Nilsson, B. (2015). TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations. Biomaterials, 51, 58-68.
Open this publication in new window or tab >>TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations
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2015 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 51, 58-68 p.Article in journal (Refereed) Published
Abstract [en]

There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity.

Keyword
Contact system, P25, Platelets, Nanoparticles, Complement
National Category
Biomaterials Science
Identifiers
urn:nbn:se:uu:diva-258808 (URN)10.1016/j.biomaterials.2015.01.031 (DOI)000351796700007 ()25770998 (PubMedID)
Funder
Swedish Research Council FormasSwedish Research Council, 2013-65X-05647-34-4
Available from: 2015-07-23 Created: 2015-07-20 Last updated: 2017-12-04Bibliographically approved
Nordling, S., Hong, J., Fromell, K., Edin, F., Brännström, J., Larsson, R., . . . Magnusson, P. U. (2015). Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation. Thrombosis and Haemostasis, 113(6), 1312-1322.
Open this publication in new window or tab >>Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation
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2015 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 113, no 6, 1312-1322 p.Article in journal (Refereed) Published
Abstract [en]

Ischaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and in whole organ transplantation. Activation of the endothelial cells and shedding of the protective vascular glycocalyx during IRI increase the risk of innate immune activation, cell infiltration and severe thrombus formation, promoting damage to the tissue. Here, we present a novel one-step strategy to protect the vas, culature by immobilisation of a unique multi-arm heparin conjugate to the endothelium. Applying a new in vitro blood endothelial cell chamber model, the heparin conjugate was found to bind not only to primary human endothelial cells but also directly to the collagen to which the cells adhered. Incubation of hypoxic endothelial cells with freshly drawn human blood in the blood chambers elicited coagulation activation reflected by thrombin anti-thrombin formation and binding of platelets and neutrophils. Immobilisation of the heparin conjugate to the hypoxic endothelial cells created a protective coating, leading to a Significant reduction of the recruitment of blood cells and coagulation activation compared to untreated hypoxic endothelial cells. This novel approach of immobilising multi-arm heparin conjugates on the endothelial cells and collagen of the basement membrane ensures to protect the endothelium against IRI in thrombotic disorders and in transplantation.

Keyword
Blood coagulation, endothelial cells, heparin, surface modification, collagen
National Category
Cardiac and Cardiovascular Systems Hematology
Identifiers
urn:nbn:se:uu:diva-258043 (URN)10.1160/TH14-09-0724 (DOI)000355776400021 ()25740465 (PubMedID)
Funder
Swedish Research Council, 90293501, A0290401, A0290402
Available from: 2015-07-13 Created: 2015-07-10 Last updated: 2017-12-04Bibliographically approved
Hong, J., Kurt, S. & Thor, A. (2013). A Hydrophilic Dental Implant Surface Exhibit Thrombogenic Properties In Vitro. Clinical Implant Dentistry and Related Research, 15(1), 105-112.
Open this publication in new window or tab >>A Hydrophilic Dental Implant Surface Exhibit Thrombogenic Properties In Vitro
2013 (English)In: Clinical Implant Dentistry and Related Research, ISSN 1523-0899, E-ISSN 1708-8208, Vol. 15, no 1, 105-112 p.Article in journal (Refereed) Published
Abstract [en]

Background:

Surface modifications of dental implants have gained attention during several years and the thrombotic response from blood components with these materials has become more important during recent years.

Purpose:

The aims of this study were to evaluate the thrombogenic response of whole blood, in contact with clinically used dental surfaces, Sandblasted Large grit Acid etched titanium (SLA) and Sandblasted Large grit Acid etched, and chemically modified titanium with hydrophilic properties (SLActive).

Methods:

An in vitro slide chamber model, furnished with heparin, was used in which whole blood came in contact with slides of the test surfaces. After incubation (60-minute rotation at 22 rpm in a 37°C water bath), blood was mixed with ethylenediaminetetraacetic acid (EDTA) or citrate, further centrifuged at +4°C. Finally, plasma was collected pending analysis.

Results:

Whole blood in contact with surfaces resulted in significantly higher binding of platelets to the hydrophilic surface, accompanied by a significant increase of contact activation of the coagulation cascade. In addition, the platelet activation showed a similar pattern with a significant elevated release of β-TG from platelet granule.

Conclusions:

The conclusion that can be drawn from the results in our study is that the hydrophilic modification seems to augment the thrombogenic properties of titanium with implications for healing into bone of, that is titanium dental implants.

National Category
Biomaterials Science Dentistry
Identifiers
urn:nbn:se:uu:diva-171030 (URN)10.1111/j.1708-8208.2011.00362.x (DOI)000314110900014 ()21745323 (PubMedID)
Available from: 2012-03-15 Created: 2012-03-15 Last updated: 2017-12-07Bibliographically approved
Nilsson, P. H., N. Ekdahl, K., Magnusson, P. U., Qu, H., Iwata, H., Ricklin, D., . . . Teramura, Y. (2013). Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating. Biomaterials, 34(4), 985-994.
Open this publication in new window or tab >>Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating
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2013 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 34, no 4, 985-994 p.Article in journal (Refereed) Published
Abstract [en]

Activation of the thrombotic and complement systems is the main recognition and effector mechanisms in the multiple adverse biological responses triggered when biomaterials or therapeutic cells come into blood contact. We have created a surface which is auto-protective to human innate immunity by combining three fundamentally different strategies, all developed by us previously, which have been shown to induce substantial, but incomplete hemocompatibility when used separately. In summary, we have conjugated a factor H-binding peptide; and an ADP-degrading enzyme; using a PEG linker on both material and cellular surfaces. When exposed to human whole blood, factor H was specifically recruited to the modified surfaces and inhibited complement attack. In addition, activation of platelets and coagulation was efficiently attenuated, by degrading ADP. Thus, by inhibiting thromboinflammation using a multicomponent approach, we have created a hybrid surface with the potential to greatly reduce incompatibility reactions involving biomaterials and transplantation.

Keyword
Apyrase, Coagulation, Complement, Factor H-binding peptide, Poly(ethylene glycol) (PEG), Surface modification, Autoregulations, Biological response, Biomaterial surfaces, Blood contact, Complement systems, H-binding, Hemocompatibility, Hybrid surface, Innate immunity, Modified surfaces, Multicomponents, Whole blood, Biological materials, Biomaterials, Peptides, Polyethylene glycols, Surface treatment, Surfaces, 5C6 peptide, biomaterial, complement factor H, macrogol, peptide, unclassified drug, article, autoregulation, biotinylation, endothelium cell, erythrocyte, human, inflammation, multicomponent therapeutic coating, peptide synthesis, porcine aortic endothelial cell, priority journal, protein immobilization, thromboinflammation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-191995 (URN)10.1016/j.biomaterials.2012.10.040 (DOI)000313155800014 ()
Funder
Swedish Research Council, 90293501, A0290401, A0290402
Note

K.N.E., J.D.L., B.N. and Y.T. equally contributed to this paper as a supervisor.

Available from: 2013-01-24 Created: 2013-01-15 Last updated: 2017-12-06Bibliographically approved
Thor, A. L., Hong, J., Kjeller, G., Sennerby, L. & Rasmusson, L. (2013). Correlation of Platelet Growth Factor Release in Jawbone Defect Repair: A Study in the Dog Mandible. Clinical Implant Dentistry and Related Research, 15(5), 759-768.
Open this publication in new window or tab >>Correlation of Platelet Growth Factor Release in Jawbone Defect Repair: A Study in the Dog Mandible
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2013 (English)In: Clinical Implant Dentistry and Related Research, ISSN 1523-0899, E-ISSN 1708-8208, Vol. 15, no 5, 759-768 p.Article in journal (Refereed) Published
Abstract [en]

Background:

Platelet concentrate/platelet-rich plasma (PRP) has been studied extensively in various experimental models and there is some agreement among workers to its early effect in bone regeneration and healing. We have earlier showed in vitro that titanium in whole blood activates the thrombogenic response to a higher degree than PRP and that a fluoridated test surface augmented the effect compared with control.

Purpose:

We designed this study to evaluate the effect of PRP and whole blood on bone regeneration in a dog implant defect model and, in addition, the effect of a test surface modified in hydrofluoric acid. A correlation attempt between platelet count, release of growth factors, and bone regeneration was made.

Materials and Methods:

Six dogs were used and simultaneously with the experimental surgery and implant installation, autologous PRP was prepared. Defects were prepared (6 mm in diameter and 5 mm deep), and implants were installed (TiO2 gritblasted and hydrofluoric acid treated [test] or TiO2 gritblasted [control], 5 mm in diameter and 9 mm long) in defects filled with either PRP or whole blood. Randomization of sides between PRP and whole blood, and sites for test and control implants were made. Blood samples were collected from PRP and whole blood. The dogs were killed after 5 weeks of healing, and samples with implants and surrounding bone were collected and processed for analysis. Enzyme linked immunosorbent assays were used for detection of growth factors in PRP.

Results:

The mean increase of platelet count was 424% in PRP. A correlation for platelet counts and transforming growth factor β was found in each dog (r2 = 0.857). Approximately 50% of the region of interest (ROI) in the defects was filled with new bone after 5 weeks. No difference could be observed in ROI by using PRP or whole blood in the defects regarding new bone formation, bone in contact with implant, or distance to first bone contact. However, the fluoridated implants exhibited more new bone formation (p = .03) compared with control, regardless of comparing PRP or whole blood, and also displayed a shorter distance from first bone contact to the margin of the bone envelope (p = .05).

Conclusions:

Platelet concentrate/PRP failed to show more new bone regeneration in a peri-implant defect model compared with whole blood. Implants treated with hydrofluoric acid displayed higher percentages of bone fill in the defect.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-171072 (URN)10.1111/j.1708-8208.2011.00405.x (DOI)000325494400014 ()22235990 (PubMedID)
Available from: 2012-03-15 Created: 2012-03-15 Last updated: 2017-12-07Bibliographically approved
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