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1,060 results on '"Leeuwenburgh, S.C.G."'

51. The use of bisphosphonates for bone-specific drug delivery

Author

Jansen, J.A., Leeuwenburgh, S.C.G., Farbod, K., Jansen, J.A., Leeuwenburgh, S.C.G., and Farbod, K.

Abstract

Radboud University, 10 november 2016, Promotor : Jansen, J.A. Co-promotor : Leeuwenburgh, S.C.G., Contains fulltext : 160841.pdf (publisher's version ) (Open Access), The pharmacological efficacy of conventional drug formulations can be improved through the use of drug delivery systems. Controlled drug delivery systems are intended to deliver drugs locally at predetermined rates for predefined periods of time. By delivering pharmacologically high concentrations of active agents more selectively to pathological sites, drug delivery systems aim to improve the balance between efficacy and toxicity as compared to systemically administered therapeutics, thereby overcoming the shortcomings of systemic delivery of conventional drug formulations. This thesis describes the development of bone-specific delivery strategies either by linking bisphosphonates to drug delivery carriers or to chemotherapeutic platinum-based drugs. The drug delivery carriers were made of either inorganic or organic materials, and bisphosphonates were applied as the targeting moieties. These drug delivery systems were designed for use in local or non-local targeted delivery of chemotherapeutic platinum-based drugs to bone tumors.

Published
2016

52. Nanostructured carriers for the delivery of antibacterial agents

Author

Jansen, J.A., Yang, F., Leeuwenburgh, S.C.G., Song, S.J.K., Jansen, J.A., Yang, F., Leeuwenburgh, S.C.G., and Song, S.J.K.

Abstract

RU Radboud Universiteit, 22 september 2016, Promotor : Jansen, J.A. Co-promotores : Yang, F., Leeuwenburgh, S.C.G., Contains fulltext : 159479.pdf (publisher's version ) (Open Access)

Published
2016

58. A self-healable, moldable and bioactive biomaterial gum for personalised and wearable drug delivery

Author

Shahbazi, Mohammad-Ali, Shrestha, N., Pierchala, M.K., Kadumudi, F.B., Mehrali, Mehdi, Hasany, Masoud, Leeuwenburgh, S.C.G., Dolatshahi-Pirouz, A., Shahbazi, Mohammad-Ali, Shrestha, N., Pierchala, M.K., Kadumudi, F.B., Mehrali, Mehdi, Hasany, Masoud, Leeuwenburgh, S.C.G., and Dolatshahi-Pirouz, A.

Abstract

Contains fulltext : 219813.pdf (Publisher’s version ) (Closed access)

Published
2020

59. Micro- and macromechanical characterization of the influence of surface-modification of poly(vinyl alcohol) fibers on the reinforcement of calcium phosphate cements

Author

Kucko, N.W., Petre, D.G., Ruiter, M., Herber, R.P., Leeuwenburgh, S.C.G., Kucko, N.W., Petre, D.G., Ruiter, M., Herber, R.P., and Leeuwenburgh, S.C.G.

Abstract

Contains fulltext : 220688.pdf (Publisher’s version ) (Open Access), Calcium phosphate cements (CPCs) are frequently used as synthetic bone substitute materials due to their favorable osteocompatibility and handling properties. However, CPCs alone are inherently brittle and exhibit low strength and toughness, which restricts their clinical applicability to non-load bearing sites. Mechanical reinforcement of CPCs using fibers has proven to be an effective strategy to toughen these cements by transferring stress from the matrix to the fibers through frictional sliding at the interface. Therefore, tailoring the fiber-matrix affinity is paramount in designing highly toughened CPCs. However, the mechanistic correlation between this interaction and the macromechanical properties of fiber-reinforced CPCs has hardly been investigated to date. The aim of this study was to tailor the fiber-matrix interface affinity by modifying the surface of poly(vinyl alcohol) (PVA) fibers and correlate their interfacial properties to macromechanical properties (i.e. fracture toughness, work-of-fracture and tensile strength) of CPCs. Results from single fiber pullout tests reveal that the surface modification of PVA fibers increased their hydrophilicity and improved their affinity to the CPC matrix. This observation was evidenced by an increase in the interfacial shear strength and a reduction in the critical fiber embedment length (i.e. maximum embedded length from which a fiber can be pulled out without rupture). This increased interface affinity facilitated energy dissipation during fracture of CPCs subjected to macromechanical three-point flexure and tensile tests. The fracture toughness also significantly improved, even for CPCs reinforced with fibers of lengths greater than their critical fiber embedment length, suggesting that other crack-arresting mechanisms also play an important role in mechanically reinforcing CPCs. Overall, these basic insights will improve the understanding of the correlation between micro- and macromechanical characteristics of

Published
2020

60. Electrodeposited Assembly of Additive-Free Silk Fibroin Coating from Pre-Assembled Nanospheres for Drug Delivery

Author

Cheng, X., Deng, D., Chen, L., Jansen, J.A., Leeuwenburgh, S.C.G., Yang, F., Cheng, X., Deng, D., Chen, L., Jansen, J.A., Leeuwenburgh, S.C.G., and Yang, F.

Abstract

Contains fulltext : 218161.pdf (Publisher’s version ) (Open Access), Electrophoretically deposited (EPD) polymer-based coatings have been extensively reported as reservoirs in medical devices for delivery of therapeutic agents, but control over drug release remains a challenge. Here, a simple but uncommon assembly strategy for EPD polymer coatings was proposed to improve drug release without introducing any additives except the EPD matrix polymer precursor. The added value of the proposed strategy was demonstrated by developing a novel EPD silk fibroin (SF) coating assembled from pre-assembled SF nanospheres for an application model, that is, preventing infections around percutaneous orthopedic implants via local delivery of antibiotics. The EPD mechanism of this nanosphere coating involved oxidation of water near the substrate to neutralize SF nanospheres, resulting in irreversible deposition. The deposition process and mass could be easily controlled using the applied EPD parameters. In comparison with the EPD SF coating assembled in a conventional way (directly obtained from SF molecule solutions), this novel coating had a similar adhesion strength but exhibited a more hydrophobic nanotopography to induce better fibroblastic response. Moreover, the use of nanospheres as building blocks enabled 1.38 and 21 times enhancement on the antibiotic release amount and time (of 95% maximum dug release), respectively, while retaining drug effectiveness and showing undetectable cytotoxicity. This unexpected release kinetics was found attributable to the electrostatic and hydrophobic interactions between the drug and nanospheres and a negligible initial dissolution effect on the nanosphere coating. These results illustrate the promising potential of the pre-assembled strategy on EPD polymer coatings for superior control over drug delivery.

Published
2020

61. Degradation and excretion of poly(2-oxazoline) based hemostatic materials

Author

Boerman, Marcel A., Roozen, E.A., Franssen, G.M., Bender, J., Hoogenboom, R., Leeuwenburgh, S.C.G., Laverman, P., Hest, J. van, Goor, H. van, Felix Lanao, R.P., Boerman, Marcel A., Roozen, E.A., Franssen, G.M., Bender, J., Hoogenboom, R., Leeuwenburgh, S.C.G., Laverman, P., Hest, J. van, Goor, H. van, and Felix Lanao, R.P.

Abstract

Contains fulltext : 221645.pdf (postprint version ) (Open Access)

Published
2020

62. Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Author

Nadar, R., Farbod, K., Schilden, K.C. der, Schlatt, L., Crone, B., Asokan, N., Curci, A., Brand, M van den, Bornhaeuser, M., Iafisco, M., Margiotta, N., Karst, U., Heskamp, S., Boerman, O.C., Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., Nadar, R., Farbod, K., Schilden, K.C. der, Schlatt, L., Crone, B., Asokan, N., Curci, A., Brand, M van den, Bornhaeuser, M., Iafisco, M., Margiotta, N., Karst, U., Heskamp, S., Boerman, O.C., Beucken, J.J.J.P van den, and Leeuwenburgh, S.C.G.

Abstract

Contains fulltext : 220554.pdf (publisher's version ) (Open Access), Platinum-based chemotherapeutics exhibit excellent antitumor properties. However, these drugs cause severe side effects including toxicity, drug resistance, and lack of tumor selectivity. Tumor-targeted drug delivery has demonstrated great potential to overcome these drawbacks. Herein, we aimed to design radioactive bisphosphonate-functionalized platinum ((195m)Pt-BP) complexes to confirm preferential accumulation of these Pt-based drugs in metabolically active bone. In vitro NMR studies revealed that release of Pt from Pt BP complexes increased with decreasing pH. Upon systemic administration to mice, Pt-BP exhibited a 4.5-fold higher affinity to bone compared to platinum complexes lacking the bone-seeking bisphosphonate moiety. These Pt-BP complexes formed less Pt-DNA adducts compared to bisphosphonate-free platinum complexes, indicating that in vivo release of Pt from Pt-BP complexes proceeded relatively slow. Subsequently, radioactive (195m)Pt-BP complexes were synthesized using (195m)Pt(NO3)2(en) as precursor and injected intravenously into mice. Specific accumulation of (195m)Pt-BP was observed at skeletal sites with high metabolic activity using micro-SPECT/CT imaging. Furthermore, laser ablation-ICP-MS imaging of proximal tibia sections confirmed that (195m)Pt BP co-localized with calcium in the trabeculae of mice tibia.

Published
2020

63. Platinum-loaded, selenium-doped hydroxyapatite nanoparticles selectively reduce proliferation of prostate and breast cancer cells co-cultured in the presence of stem cells

Author

Barbanente, Alessandra, Nadar, R., Esposti, Lorenzo Degli, Palazzo, Barbara, Lafisco, Michele, Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., Margiotta, Nicola, Barbanente, Alessandra, Nadar, R., Esposti, Lorenzo Degli, Palazzo, Barbara, Lafisco, Michele, Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., and Margiotta, Nicola

Abstract

Contains fulltext : 218582.pdf (Publisher’s version ) (Closed access)

Published
2020

66. Preclinical evaluation of platinum-loaded hydroxyapatite nanoparticles in an embryonic zebrafish xenograft model

Author

Nadar, R., Asokan, N., Degli Esposti, L., Curci, A., Barbanente, Alessandra, Schlatt, L., Beucken, J.J.J.P van den, Bornhaeuser, M., Leeuwenburgh, S.C.G., Nadar, R., Asokan, N., Degli Esposti, L., Curci, A., Barbanente, Alessandra, Schlatt, L., Beucken, J.J.J.P van den, Bornhaeuser, M., and Leeuwenburgh, S.C.G.

Abstract

Contains fulltext : 221558.pdf (publisher's version ) (Open Access)

Published
2020

67. Pre-Clinical Evaluation of Biological Bone Substitute Materials for Application in Highly Loaded Skeletal Sites

Author

Lacerda Schickert, S. de, Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., Jansen, J.A., Lacerda Schickert, S. de, Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., and Jansen, J.A.

Abstract

Contains fulltext : 220526.pdf (publisher's version ) (Open Access), The development of bone substitute materials (BSMs) intended for load-bearing bone defects is highly complicated, as biological and mechanical requirements are often contradictory. In recent years, biological BSMs have been developed which allow for a more efficient integration of the material with the surrounding osseous environment and, hence, a higher mechanical stability of the treated defect. However, while these materials are promising, they are still far from ideal. Consequently, extensive preclinical experimentation is still required. The current review provides a comprehensive overview of biomechanical considerations relevant for the design of biological BSMs. Further, the preclinical evaluation of biological BSMs intended for application in highly loaded skeletal sites is discussed. The selected animal models and implantation site should mimic the pathophysiology and biomechanical loading patterns of human bone as closely as possible. In general, sheep are among the most frequently selected animal models for the evaluation of biomaterials intended for highly loaded skeletal sites. Regarding the anatomical sites, segmental bone defects created in the limbs and spinal column are suggested as the most suitable. Furthermore, the outcome measurements used to assess biological BSMs for regeneration of defects in heavily loaded bone should be relevant and straightforward. The quantitative evaluation of bone defect healing through ex vivo biomechanical tests is a valuable addition to conventional in vivo tests, as it determines the functional efficacy of BSM-induced bone healing. Finally, we conclude that further standardization of preclinical studies is essential for reliable evaluation of biological BSMs in highly loaded skeletal sites.

Published
2020

70. Polyester fibers can be rendered calcium phosphate-binding by surface functionalization with bisphosphonate groups

Author

Polini, A., Petre, D.G., Iafisco, M., Lacerda Schickert, S. de, Tampieri, A., Beucken, J.J. van den, and Leeuwenburgh, S.C.G.

Subjects
Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10]
Abstract

Item does not contain fulltext Fibers are often used as structural elements to improve the mechanical properties of materials such as brittle ceramic matrices by facilitating the dissipation of energy. However, this energy dissipation is mainly controlled by the interface between the two components, and a poorly designed fiber-matrix interface strongly reduces the efficacy of fiber reinforcement. Here, we present a versatile approach to control the affinity of biocompatible fibers to calcium-containing matrices to maximize the efficacy of reinforcement of calcium phosphates-based bioceramics by means of polymeric fibers. To this end, polyester fibers of tunable length were produced by electrospinning and aminolysis, followed by covalent attachment of alendronate, a bisphosphonate molecule with strong calcium-binding affinity, to the surface of the fibers. The proposed method allowed for selective control over the amount of alendronate conjugation, thereby improving the affinity of polyester fibers toward calcium phosphate bioceramics. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2335-2342, 2017. 01 augustus 2017

Published
2017
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71. Porous titanium scaffolds with injectable hyaluronic acid-DBM gel for bone substitution in a rat critical-sized calvarial defect model

Author

Houdt, C.I.A. van, Cardoso, D.A., Oirschot, B.A.J.A. van, Ulrich, D.J.O., Jansen, J.A., Leeuwenburgh, S.C.G., and Beucken, J.J.J.P van den

Subjects
Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], Women's cancers Radboud Institute for Health Sciences [Radboudumc 17]
Abstract

Contains fulltext : 177178.pdf (Publisher’s version ) (Closed access) Demineralized bone matrix (DBM) is an allograft bone substitute used for bone repair surgery to overcome drawbacks of autologous bone grafting, such as limited supply and donor-site comorbidities. In view of different demineralization treatments to obtain DBM, we examined the biological performance of two differently demineralized types of DBM, i.e. by acidic treatment using hydrochloric acid (HCl) or treatment with the chelating agent ethylene diamine tetra-acetate (EDTA). First, we evaluated the osteo-inductive properties of both DBMs by implanting the materials subcutaneously in rats. Second, we evaluated the effects on bone formation by incorporating DBM in a hyaluronic acid (HA) gel to fill a porous titanium scaffold for use in a critical-sized calvarial defect model in 36 male Wistar rats. These porous titanium scaffolds were implanted empty or filled with HA gel containing either DBM HCl or DBM EDTA. Ectopically implanted DBM HCl and DBM EDTA did not induce ectopic bone formation over the course of 12 weeks. For the calvarial defects, mean percentages of newly formed bone at 2 weeks were significantly higher for Ti-Empty compared to Ti-HA + DBM HCl, but not compared to Ti-HA + DBM EDTA. Significant temporal bone formation was observed for Ti-Empty and Ti-HA + DBM HCl, but not for Ti-HA + DBM EDTA. At 8 weeks there were no significant differences in values of bone formation between the three experimental constructs. In conclusion, these results showed that, under the current experimental conditions, neither DBM HCl nor DBM EDTA possess osteo-inductive properties. Additionally, in combination with an HA gel loaded in a porous titanium scaffold, DBM HCl and DBM EDTA showed similar amounts of new bone formation after 8 weeks, which were lower than using the empty porous titanium scaffold. Copyright (c) 2016 John Wiley & Sons, Ltd.

Published
2017
Full Text
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73. Electrosprayed coatings: from passive to active surfaces for bone implants

Author

Jansen, J.A., Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., Bosco, R., Jansen, J.A., Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., and Bosco, R.

Abstract

Radboud Universiteit Nijmegen, 10 november 2014, Promotor : Jansen, J.A. Co-promotores : Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., Contains fulltext : 131641.pdf (publisher's version ) (Open Access)

Published
2014

75. Polymer-based injectable bone substitute materials: in vitro and in vivo evaluation

Author

Jansen, J.A., Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., Bongio, M., Jansen, J.A., Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., and Bongio, M.

Abstract

Radboud Universiteit Nijmegen, 31 mei 2013, Promotor : Jansen, J.A. Co-promotores : Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., Contains fulltext : 117442.pdf (Publisher’s version ) (Open Access)

Published
2013

76. Nanostructured Colloidal Gelatin Gels for Bone Tissue Regeneration

Author

Jansen, J.A., Leeuwenburgh, S.C.G., Wang, H., Jansen, J.A., Leeuwenburgh, S.C.G., and Wang, H.

Abstract

Radboud Universiteit Nijmegen, 10 april 2013, Promotor : Jansen, J.A. Co-promotor : Leeuwenburgh, S.C.G., Contains fulltext : 106975.pdf (publisher's version ) (Open Access)

Published
2013

77. Degradation of calcium phosphate cements

Author

Jansen, J.A., Wolke, J.G.C., Leeuwenburgh, S.C.G., Felix Lanao, R.P., Jansen, J.A., Wolke, J.G.C., Leeuwenburgh, S.C.G., and Felix Lanao, R.P.

Abstract

Radboud Universiteit Nijmegen, 28 maart 2013, Promotor : Jansen, J.A. Co-promotores : Wolke, J.G.C., Leeuwenburgh, S.C.G., Contains fulltext : 106967.pdf (publisher's version ) (Open Access), Calcium Phosphate Cements (CPC) are commonly used as bone replacement materials. Rosa Félix’s reseach specifically deals with strategies to enhance CPC degradation and its subsequent replacement by newly formed bone. In order to achieve this, several materials have been used in combination with CPC to create porosity that will increase fluid-flow and cell penetration throughout the implant material and therefore facilitate implant degradation. In this doctoral thesis research, the influence of several physico-chemical properties of varoius potential CPC porogens have been investigated in order to improve CPC degration and new bone formation. In addition, the influence of bio-active factors in this process of new bone formation has also been studied.

Published
2013

78. Sterilization effects on the handling and degradation properties of calcium phosphate cements containing poly ((D,L)-lactic-co-glycolic acid) porogens and carboxymethyl cellulose

Author

Kucko, N.W., Li, Wenliang, Martinez, Marcela A.Garcia, Rehman, Ihtesham ur, Ulset, A.S., Christensen, B.E., Leeuwenburgh, S.C.G., and Herber, R.P.

Subjects
All institutes and research themes of the Radboud University Medical Center, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10]
Abstract

Item does not contain fulltext

Published
2019

79. Electrosprayed organic - inorganic coatings for bone implantology

Author

Jansen, J.A., Schoonman, J., Wolke, J.G.C., Leeuwenburgh, S.C.G., Jonge, L.T. de, Jansen, J.A., Schoonman, J., Wolke, J.G.C., Leeuwenburgh, S.C.G., and Jonge, L.T. de

Abstract

RU Radboud Universiteit Nijmegen, 29 januari 2010, Promotores : Jansen, J.A., Schoonman, J. Co-promotores : Wolke, J.G.C., Leeuwenburgh, S.C.G., Contains fulltext : 88724.pdf (Publisher’s version ) (Open Access)

Published
2010

83. Hybrid particles derived from alendronate and bioactive glass for treatment of osteoporotic bone defects

Author

Diba, M., Camargo, W.A., Zinkevich, T., Gruenewald, Alina, Detsch, R., Kabiri, Yoones, Kentgens, Arno P.M., Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., Diba, M., Camargo, W.A., Zinkevich, T., Gruenewald, Alina, Detsch, R., Kabiri, Yoones, Kentgens, Arno P.M., Beucken, J.J.J.P van den, and Leeuwenburgh, S.C.G.

Abstract

Contains fulltext : 201144.pdf (publisher's version ) (Closed access)

Published
2019

85. Alendronate-Functionalized Poly(2-oxazoline)s with Tunable Affinity for Calcium Cations

Author

Sanchez Fernandez, M.J., Immers, Mikey R., Lanao, Rosa P. Felix, Yang, F., Bender, J., Leeuwenburgh, S.C.G., Hest, J. van, Sanchez Fernandez, M.J., Immers, Mikey R., Lanao, Rosa P. Felix, Yang, F., Bender, J., Leeuwenburgh, S.C.G., and Hest, J. van

Abstract

Contains fulltext : 207002.pdf (publisher's version ) (Open Access)

Published
2019

87. Effect of mechanical loading and substrate elasticity on the osteogenic and adipogenic differentiation of mesenchymal stem cells

Author

Gungordu, H.I., Bao, M., Helvert, S. van, Jansen, J.A., Leeuwenburgh, S.C.G., Walboomers, X.F., Gungordu, H.I., Bao, M., Helvert, S. van, Jansen, J.A., Leeuwenburgh, S.C.G., and Walboomers, X.F.

Abstract

Contains fulltext : 215424.pdf (postprint version ) (Open Access), Mesenchymal stem cells (MSCs) are highly sensitive to biomechanics of their extracellular environment. Generally, a higher elasticity of culture substrates can drive cells into the osteogenic lineage, whereas low substrate elasticity results in adipogenesis. Applied mechanical loading by cyclic strain is another major variable influencing cell fate. Yet, little is known about the simultaneous effect of both cues. Therefore, the present study investigated the relative importance of both cues on differentiation. MSCs were cultured in an osteogenic and also an adipogenic environment on soft polyacrylamide (PAAm; E = 23 +/- 0.3 kPa), stiff PAAm (111 +/- 2 kPa), and polydimethylsiloxane (PDMS; E = 1,5 +/- 0.07 MPa) either unstrained or with 8% cyclic strain at 1 Hz. Without strain, the relative expression of the early osteogenic marker alkaline phosphatase (ALP) was significantly higher (78%) on PDMS than on both PAAm. With 8% cyclic strain, ALP expression increased for all groups in comparison with unstrained controls. The highest increase was observed for the soft PAAm by 36%. Moreover, relative oil red O (ORO) expression-indicating adipogenesis-was the highest for unstrained soft PAAm. On the other hand, the percentage of ORO positive cells significantly decreased by 57% and 69% for soft and stiff PAAm when strained. In conclusion, biomaterial elasticity and mechanical loading can act simultaneously on cell differentiation. Substrate elasticity is an important factor, regulating the differentiation, but cyclic strain can drive MSCs towards the osteogenesis even on the softest substrate. As such, the osteogenic effect of mechanical loading can overrule the adipogenic effect of soft substrates, thereby acting as an inhibitor.

Published
2019

88. Preclinical evaluation of injectable bone substitute materials

Author

Bongio, M., Beucken, J.J.J.P van den, Leeuwenburgh, S.C.G., and Jansen, J.A.

Subjects
Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10]
Abstract

Item does not contain fulltext Injectable bone substitutes (IBSs) represent an attractive class of ready-to-use biomaterials, both ceramic- and polymer-based, as they offer the potential benefit of minimally invasive surgery and optimal defect filling. Although in vitro assessments are the first step in the process of development, the safety and efficacy of an IBS strongly depend on validated preclinical research prior to clinical trials. However, the selection of a suitable preclinical model for performance evaluation of an IBS remains a challenge, as no gold standard exists to define the best animal model. In order to succeed in this attempt, we identified three stages of development, including (a) proof-of-principle, (b) predictive validity and (c) general scientific legitimacy, and the respective criteria that should be applied for such selection. The second part of this review provides an overview of commonly used animals for IBSs. Specifically, scientific papers published between January 1996 and March 2012 were retrieved that report the use of preclinical models for the evaluation of IBSs in situations requiring bone healing and bone augmentation. This review is meant not only to describe the currently available preclinical models for IBS application, but also to address critical considerations of such multi-factorial evaluation models (including animal species, strain, age, anatomical site, defect size and type of bone), which can be indicative but in most cases edge away from the human reality. Consequently, the ultimate goal is to guide researchers toward a more careful and meaningful interpretation of the results of experiments using animal models and their clinical applications. Copyright (c) 2012 John Wiley & Sons, Ltd.

Published
2015

89. Gelation and biocompatibility of injectable alginate-calcium phosphate gels for bone regeneration

Author

Cardoso, D.A., Beucken, J.J.J.P van den, Both, L.L., Bender, J., Jansen, J.A., and Leeuwenburgh, S.C.G.

Subjects
Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10]
Abstract

Item does not contain fulltext An emerging approach toward development of injectable, self-setting, and fully biodegradable bone substitutes involves the combination of injectable hydrogel matrices with a dispersed phase consisting of nanosized calcium phosphate particles. Here, novel injectable composites for bone regeneration have been developed based on the combination of ultrapure alginate as the matrix phase, crystalline CaP [monetite and poorly crystalline hydroxyapatite (HA)] powders as both a dispersed mineral phase and a source of calcium for cross-linking alginate, glucono-delta-lactone (GDL) as acidifier and glycerol as both plasticizer and temporary sequestrant. The composites were maximized with respect to CaP content to obtain the highest amount of osteoconductive filler. The viscoelastic and physicochemical properties of the precursor compounds and composites were analyzed using rheometry, elemental analysis (for calcium release and uptake), acidity [by measuring pH in simulated body fluid (SBF)], general biocompatibility (subcutaneous implantation in rabbits), and osteocompatibility (implantation in femoral condyle bone defect of rabbits). The gelation of the resulting composites could be controlled from seconds to tens of minutes by varying the solubility of the CaP phase (HA vs. monetite) or amount of GDL. All composites mineralized extensively in SBF for up to 11 days. In vivo, the composites also disintegrated upon implantation in subcutaneous or bone tissue, leaving behind less degradable but osteoconductive CaP particles. Although the composites need to be optimized with respect to the available amount of calcium for cross-linking of alginate, the beneficial bone response as observed in the in vivo studies render these gels promising for minimally invasive applications as bone-filling material.

Published
2014

90. In vitro response to alkaline phosphatase coatings immobilized onto titanium implants using electrospray deposition or polydopamine-assisted deposition

Author

Nijhuis, A.W.G., Beucken, J.J.J.P van den, Jansen, J.A., and Leeuwenburgh, S.C.G.

Subjects
musculoskeletal diseases, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10]
Abstract

Contains fulltext : 138268.pdf (Publisher’s version ) (Closed access) Immobilization of biomolecules onto implant surfaces is one of the most straightforward strategies to control the interaction between an implant and its biological environment. Recently, it was shown that the enzyme alkaline phosphatase (ALP) could be efficiently immobilized onto titanium implants in a single step using polydopamine. We hypothesized that such polydopamine-ALP coatings can enhance the early attachment of cells and increase mineralization. Therefore, the current study aimed at immobilization of ALP onto titanium by means of either one- or two-step polydopamine-assisted immobilization or electrospray deposition, the comparative characterization of these experimental substrates and subsequent cell behavioral analysis using primary osteoblast-like cells. Uncoated titanium and ALP-free polydopamine coatings served as controls. Despite significant ALP surface activity and lower water contact for angles ALP-containing surface modifications, only marginal effects on early cell behavior (i.e., cell spreading) and osteogenic differentiation (i.e., proliferation, differentiation and mineralization) were observed in comparison to uncoated titanium. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1102-1109, 2014.

Published
2014
Full Text
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92. Monitoring local delivery of vancomycin from gelatin nanospheres in zebrafish larvae

Author

Zhang, Xiaolin, Song, J., Klymov, A., Zhang, Y., Boer, Leonie de, Jansen, J.A., Beucken, J.J.J.P van den, Zaat, Sebastian A.J., Leeuwenburgh, S.C.G., Zhang, Xiaolin, Song, J., Klymov, A., Zhang, Y., Boer, Leonie de, Jansen, J.A., Beucken, J.J.J.P van den, Zaat, Sebastian A.J., and Leeuwenburgh, S.C.G.

Abstract

Contains fulltext : 195862.pdf (publisher's version ) (Open Access)

Published
2018

93. Self-Healing Biomaterials: From Molecular Concepts to Clinical Applications

Author

Diba, Mani, Spaans, Sergio, Ning, K., Ippel, Bastiaan D., Yang, F., Loomans, B.A.C., Dankers, Patricia Y.W., Leeuwenburgh, S.C.G., Diba, Mani, Spaans, Sergio, Ning, K., Ippel, Bastiaan D., Yang, F., Loomans, B.A.C., Dankers, Patricia Y.W., and Leeuwenburgh, S.C.G.

Abstract

Item does not contain fulltext

Published
2018

94. Composite Colloidal Gels Made of Bisphosphonate-Functionalized Gelatin and Bioactive Glass Particles for Regeneration of Osteoporotic Bone Defects

Author

Diba, M., Camargo, W.A., Brindisi, Mariateresa, Farbod, K., Klymov, A., Schmidt, Stephan, Jansen, J.A., Beucken, Jeroen J.J.P. van den, and Leeuwenburgh, S.C.G.

Subjects
All institutes and research themes of the Radboud University Medical Center, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10]
Abstract

Item does not contain fulltext

Published
2017

95. Enzymatically biomineralized chitosan scaffolds for tissue-engineering applications

Author

Dash, M., Samal, S.K., Douglas, T.E.L., Schaubroeck, D., Leeuwenburgh, S.C.G., Voort, P. van der, Declercq, H.A., and Dubruel, P.

Subjects
Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10]
Abstract

Item does not contain fulltext Porous biodegradable scaffolds represent promising candidates for tissue-engineering applications because of their capability to be preseeded with cells. We report an uncrosslinked chitosan scaffold designed with the aim of inducing and supporting enzyme-mediated formation of apatite minerals in the absence of osteogenic growth factors. To realize this, natural enzyme alkaline phosphatase (ALP) was incorporated into uncrosslinked chitosan scaffolds. The uncrosslinked chitosan makes available amine and alcohol functionalities to enhance the biomineralization process. The physicochemical findings revealed homogeneous mineralization, with the phase structure of the formed minerals resembling that of apatite at low mineral concentrations, and similar to dicalcium phosphate dihydrate (DCPD) with increasing ALP content. The MC3T3 cell activity clearly showed that the mineralization of the chitosan scaffolds was effective in improving cellular adhesion, proliferation and colonization. Copyright (c) 2015 John Wiley & Sons, Ltd. 01 mei 2017

Published
2017

96. Enzymatic mineralization of hydrogels for bone tissue engineering by incorporation of alkaline phosphatase

Author

Douglas, T.E.L., Messersmith, P.B., Chasan, S., Mikos, A.G., Mulder, E.L.W. de, Dickson, G., Schaubroeck, D., Balcaen, L., Vanhaecke, F., Dubruel, P., Jansen, J.A., and Leeuwenburgh, S.C.G.

Subjects
technology, industry, and agriculture, Tissue engineering and pathology [NCMLS 3]
Abstract

Item does not contain fulltext Alkaline phosphatase (ALP), an enzyme involved in mineralization of bone, is incorporated into three hydrogel biomaterials to induce their mineralization with calcium phosphate (CaP). These are collagen type I, a mussel-protein-inspired adhesive consisting of PEG substituted with catechol groups, cPEG, and the PEG/fumaric acid copolymer OPF. After incubation in Ca-GP solution, FTIR, EDS, SEM, XRD, SAED, ICP-OES, and von Kossa staining confirm CaP formation. The amount of mineral formed decreases in the order cPEG > collagen > OPF. The mineral:polymer ratio decreases in the order collagen > cPEG > OPF. Mineralization increases Young's modulus, most profoundly for cPEG. Such enzymatically mineralized hydrogel/CaP composites may find application as bone regeneration materials. 01 augustus 2012

Published
2012
Full Text
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97. Enzymatically induced mineralization of platelet-rich fibrin

Author

Douglas, T.E.L., Gassling, V., Declercq, H.A., Purcz, N., Pamula, E., Haugen, H.J., Chasan, S., Mulder, E.L.W. de, Jansen, J.A., and Leeuwenburgh, S.C.G.

Subjects
Tissue engineering and pathology [NCMLS 3], digestive system diseases
Abstract

Item does not contain fulltext Membranes of the autologous blood-derived biomaterial platelet-rich fibrin (PRF) were functionalized by incorporation of alkaline phosphatase (ALP), an enzyme involved in mineralization of bone, and subsequently incubated in calcium glycerophosphate (CaGP) solution to induce PRFs mineralization with calcium phosphate (CaP) to improve PRFs suitability as a material for bone replacement. Incorporated ALP retained its bioactivity and induced formation of CaP material within PRF membranes, as confirmed by SEM, EDS, FTIR, and von Kossa staining. The mass percentage attributable to CaP was quantified by lyophilization and measurement of the remaining mass fraction as well as by TGA. Cytocompatibility tests (LDH, MTT, and WST) with SAOS-2 cells showed that mineralized PRF did not release substances detrimental to cell vitality. Live/dead staining and SEM showed that mineralized PRF was colonized by cells. The results show that hydrogel biomaterials such as PRF can be mineralized through functionalization with ALP. 01 mei 2012

Published
2012

98. The osteoinductive potential of printable, cell-laden hydrogel-ceramic composites

Author

Fedorovich, N.E., Leeuwenburgh, S.C.G., Helm, Y.J. van der, Alblas, J., and Dhert, W.J.

Subjects
Tissue engineering and pathology [NCMLS 3]
Abstract

Item does not contain fulltext Hydrogels used as injectables or in organ printing often lack the appropriate stimuli to direct osteogenic differentiation of embedded multipotent stromal cells (MSCs), resulting in limited bone formation in these matrices. Addition of calcium phosphate (CaP) particles to the printing mixture is hypothesized to overcome this drawback. In this study we have investigated the effect of CaP particles on the osteoinductive potential of cell-laden hydrogel-CaP composite matrices. To this end, apatitic nanoparticles have been included in Matrigel constructs where after the viability of embedded progenitor cells was assessed in vitro. In addition, the osteoinductive potential of cell-laden Matrigel containing apatitic nanoparticles was investigated in vivo and compared with composites containing osteoinductive biphasic calcium phosphate (BCP) microparticles after subcutaneous implantation in immunodeficient mice. Histological and immunohistochemical analysis of the tissue response as well as in vivo bone formation revealed that apatitic nanoparticles were osteoinductive and induced osteoclast activation, but without bone formation. The BCP particles were more effective in inducing elaborate bone formation at the ectopic location. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2412-2420, 2012. 01 september 2012

Published
2012

99. Wet-chemical deposition of functional coatings for bone implantology

Author

Nijhuis, A.W.G., Leeuwenburgh, S.C.G., and Jansen, J.A.

Subjects
Tissue engineering and pathology [NCMLS 3]
Abstract

Contains fulltext : 87430.pdf (Publisher’s version ) (Closed access) Since the early 1980s, research on the modification of bone implant surfaces by applying coatings has mainly focused on the application of inorganic calcium phosphate (CaP) coatings using physical deposition techniques. Organic components of the extracellular bone matrix, on the other hand, play an essential role in the process of bone healing, but cannot be applied using these physical techniques. Therefore, a recent trend in biomaterials research involves development of novel wet-chemical deposition techniques for both inorganic and organic coatings. This study reviews the major wet-chemical coating techniques that are used for the deposition of inorganic CaP coatings and organic biomolecules coatings.

Published
2010
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