VU Research Portal Osteoinductive bone substitutes Liu, T. 2013 document version Publisher's PDF, also known as Version of record Link to publication in VU Research Portal citation for published version (APA) Liu, T. (2013). Osteoinductive bone substitutes. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 10. Oct. 2021 Osteoinductive Bone Substitutes Tie Liu The following institutions generously funded printing of this thesis: Academic Centre for Dentistry Amsterdam VU University Amsterdam Tie Liu Osteoinductive bone substitutes Thesis Amsterdam – With ref. – With Summary in Dutch ISBN: 978-90-5383014-7 Copyright © 2013 by Tie Liu. All Rights Reserved. No part of this book may be reproduced, stored in a retrievable system, or transmitted in any form or by any means, mechanical, photo-copying, recording or otherwise, without the prior written permission of the holder of copyright. VRIJE UNIVERSITEIT Osteoinductive bone substitutes ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad Doctor aan de Vrije Universiteit Amsterdam, op gezag van de rector magnificus prof.dr. F.A. van der Duyn Schouten, in het openbaar te verdedigen ten overstaan van de promotiecommissie van de Faculteit der Tandheelkunde op woensdag 18 september 2013 om 11.45 uur in de aula van de universiteit, De Boelelaan 1105 door Tie Liu geboren te Zhejiang, China promotoren: prof.dr. D. Wismeijer prof.dr. Z. Gu copromotor: dr. Y. Liu Dedicated to my wife Qian Lu to my parents Publications 1. Tie Liu, Bing Xia, Zhiyuan Gu. Inferior alveolar canal course: a radiographic study. Clinical Oral Implant Research, 2009; 20: 1212–1218. 2. Tie Liu, Gang Wu, Daniel Wismeijer, Zhiyuan Gu and Yuelian Liu. Deproteinized bovine bone functionalized with the slow delivery of BMP-2 for the repair of critical-sized bone defects in sheep. Bone. 2013, 56: 110–118. 3. Xin Zhang&, Tie Liu&, Yuanliang Huang, Daniel Wismeijer, and Yuelian Liu. Icariin: Does It Have An Osteoinductive Potential for Bone Tissue Engineering? Phytotherapy Research. 2013 Jul 4. doi: 10.1002/ptr.5027. [Published online] (& contributed equally) 4. Tie Liu, Gang Wu, Yuanna Zheng, Daniel Wismeijer, Vincent Everts, and Yuelian Liu. Cell-mediated BMP-2 release from a novel dual drug delivery system promotes bone formation. Clinical Oral Implant Research 2013. [under revision] 5. Yuanna Zheng, Gang Wu, Tie Liu, Yi Liu, Daniel Wismeijer, and Yuelian Liu. A novel BMP2-coprecipitated, layer-by-layer assembled biomimetic calcium phosphate particle: a biodegradable and highly-efficient osteoinducer. Clinical Implant Dentistry and Related Research, 2013 Mar 4. doi: 10.1111/cid.12050. [Published online] 6. Jingxiao Wang, Yuanna Zheng, Juan Zhao, Tie Liu, Lixia Gao, Zhiyuan Gu and Gang Wu. Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro-CT evaluation. Journal of Clinical Periodontology 2012 Jan;39(1):98-105. 7. Tie Liu, Gang Wu, Yuanna Zheng, Daniel Wismeijer, and Yuelian Liu. A biomimetic osteoinducer enhances the therapeutic effects of deproteinized bovine bone in a sheep critical-sized bone defect (Ø8×13mm) model. 2013 [submitted]. 8. Tie Liu, Gang Wu, Daniel Wismeijer, and Yuelian Liu. Osteoinductive biomimetic bone substitute for the repair of critical-sized bone defects in sheep. 2013 [submitted]. 9. Tie Liu, Gang Wu, Yuanna Zheng, Afsheen Tabassum, Daniel Wismeijer, Vincent Everts, and Yuelian Liu. A single biomimetic calcium phosphate granule as a model to deliver proteins. 2013 [submitted]. 10. Tie Liu, Sven Bakx, Gang Wu, Leo van Ruijven, Daniel Wismeijer, and Yuelian Liu. Cone-beam CT and micro-CT analysis of deproteinized bovine bone for the repair of critical-sized bone defects in sheep. 2013 [in preparation]. 11. Yuanan Zheng, Tie Liu, Zhiyuan Gu. Investigation of changes of articles on China national academic stomatological conferences in last two decades. Stomatology 2007 (12): 643-645. (Chinese) 12. Qian Lu, Tie Liu. Progressive Studies on Effects of Traditional Chinese Medicines on Differentiation, Proliferation and Bone Formation Gene Expression of Osteoblasts. Journal of Zhejiang Chinese Medical University 2012(5): 609-612. (Chinese) CONTENT Chapter 1 General introduction ……………………………………………….…1 Chapter 2 Cell-mediated BMP-2 release from a novel dual drug delivery system promotes bone formation ...…………………………….….………….9 Chapter 3 Preparation and characteristics of osteoinductive biomimetic calcium phosphate material: in vitro and in vivo study ……………………...29 Chapter 4 Osteoinductive biomimetic bone substitute for the repair of critical-sized bone defects in sheep ...……………………………….47 Chapter 5 A novel BMP2-coprecipitated, layer-by-layer assembled biomimetic calcium phosphate particle: a biodegradable and highly-efficient osteoinducer ..…………………………………...…………………...65 Chapter 6 A biomimetic osteoinducer enhances the therapeutic effects of deproteinized bovine bone in a sheep critical-sized bone defect (Ø8×13mm) model ……………………………………………….…83 Chapter 7 Deproteinized bovine bone functionalized with the slow delivery of BMP-2 for the repair of critical-sized bone defects in sheep ……………………………………………………………….101 Chapter 8 Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro-CT evaluation ……………………….…………....123 Chapter 9 Icariin: does it have an osteoinductive potential for bone tissue engineering? …………………………………………………….….137 Chapter 10 General discussion ...……………………………………………….161 Chapter 11 General summary ….……………………………………………….167 Dutch summary….………………………………………...…….….172 Acknowledgements ………..………………………………………177 Curriculum vitae ………………………...…………………………179 Abbreviations ACP amorphous calcium phosphate BCP biphasic calcium phosphate BioCaP biomimetic calcium phosphate BMP bone morphogenetic protein BMP2-cop.BioCaP BMP-2-coprecipitated biomimetic calcium phosphate BMSCs bone marrow stem cells BSA bovine serum albumin CaP calcium phosphate CDHA calcium deficient hydroxyapatite CPS calcium phosphate supersaturated solution CSBD critical-sized bone defect DBB deproteinized bovine bone EDX energy-dispersive x-ray spectroscopy FBGC foreign body giant cell HA hydroxyapatite ICA icariin MNC multinucleated giant cell OCP octacalcium phosphate OPG panoramic radiograph PBMCs peripheral blood mononuclear cell PMMA poly methylene methacrylate RANKL receptor activator for nuclear factor-κB ligand SBF supersaturated body fluids SEM scanning electron microscopy TB trabecular bone TCM traditional Chinese medicine TCP tricalcium phosphate TRACP tartrate-resistant acid phosphatase VEGF vascular endothelial growth factor XRD X-ray diffraction Chapter 1 General Introduction 1 Chapter 1 GENERAL INTRODUCTION The treatment of bone fractures and defects requires adequate volume of bone tissue which is of paramount importance to achieve an excellent restoration. When the bone defects are too large to be self-healed, bone grafting is required in order to fill the defect [1, 2]. Bone grafts fill voids and serve as scaffolds to provide support, and therefore may enhance the biological repair of the defect. Critical-sized bone defect (CSBD) is defined as the intraosseous wound with the smallest size, which cannot spontaneously heal completely without intervention [3]. Bone healing heals through the generation of new bone rather than by forming fibrotic tissue. Usually, the fibrous connective tissue regenerates faster than bone tissue and becomes dominant within the CSBD because of the faster migration mechanism of fibroblasts compared to osteoblasts. Bone grafting, as a common surgical procedure, is carried out in approximately 10% of all skeletal reconstructive surgery cases [4]. Worldwide, more than 2.2 million grafting procedures are performed annually [1, 5]. In most patients, the intervention therapies can be unproblematically executed and the outcome is generally excellent [6, 7]. However, there are still a significant number of eligible individuals with the existence of well-recognized risk factors such as diabetes, local osteoporosis and metabolic bone disorder. These risk factors are associated with poor activity of bone formation [2, 8]. Nevertheless, the expectations of patients and surgeons alike are continually rising, both aspiring to a curtailment of the recovery phase and the postoperative period of functional incapacity [9]. Consequently, these clinical, social and economic pressures make it absolutely necessary to develop a simple, efficacious and cost-effective bone substitute to expedite and augment bone formation. Bone regeneration Bone regeneration in large bone defects requires four critical elements: (i) osteogenic cells (e.g. progenitor cells or osteoblasts); (ii) osteoinductive signals (growth factors); (iii) an biocompatible, biodegradable and osteoconductive matrix (scaffold);