VRIJE UNIVERSITEIT In situ forming membranes and matrices for guided bone regeneration ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad Doctor aan de Vrije Universiteit Amsterdam, op gezag van de rector magnificus prof.dr. L.M. Bouter, in het openbaar te verdedigen ten overstaan van de promotiecommissie van de faculteit der Tandheelkunde op woensdag 11 mei 2011 om 13.45 uur in de aula van de universiteit, De Boelelaan 1105 door Ronald Ernst Jung geboren te Zurich, Zwitserland
promotor: copromotor: prof.dr. D. Wismeijer prof.dr. Ch. Hämmerle
List of included publications This thesis is based on the following publications and patent: 1. Jung, R. E., Zwahlen, R., Weber, F. E., Molenberg A., van Lenthe G. H., Hämmerle, C. H. F. Evaluation of an in situ formed synthetic hydrogel as a biodegradable membrane for guided bone regeneration. Clinical Oral Implants Research, 2006; 17: 426-433 2. Herten, M., Jung, R. E., Ferrari, D., Rothamel, D., Golubovic, V., Molenberg, A., Hämmerle, C. H. F., Becker, J., Schwarz, F. Biodegradation of different synthetic hydrogels made of polyethylene glycolhydrogel/rgd-peptide modification: An immunohistochemical study in rats. Clinical Oral Implants Research, 2009; 20: 116-125 3. Jung, R. E., Lecloux, G., Rompen, E., Ramel, C.F., Buser, D., Hämmerle, C. H. F. A feasibility study evaluating an in situ formed synthetic biodegradable membrane for guided bone regeneration in dogs. Clinical Oral Implants Research, 2009; 20: 151-161 4. Thoma, D. S., Gian Andrea Hälg, G. A., Dard, M. M., Seibl, R., Hämmerle, C. H. F, Jung, R. E. Evaluation of a new biodegradable membrane to prevent gingival ingrowth into mandibular bone defects in minipig. Clinical Oral Implants Research, 2009; 20: 7-16 5. Jung, R. E., Hämmerle, C. H. F., Kokovic, V., Weber, F. E. Bone regeneration using a synthetic matrix containing a parathyroid hormone peptide combined with a grafting material. International Journal of Oral and Maxillofacial Implants, 2007; 22: 258-266 6. Jung, R. E., Cochran, D. L., Domken, O., Seibl, R., Jones, A.A., Hämmerle, C. H. F. The effect of matrix bound parathyroid hormone on bone regeneration. Clinical Oral Implants Research, 2007; 18: 319-325 7. Valderrama, P., Jung, R. E., Thoma, D. S., Jones, A.A., Cochran, D. L. Evaluation of parathyroid hormone bound to a synthetic matrix for guided bone regeneration around dental implants: A histomorphometric study in dogs. Journal of Clinical Periodontology, 2010; 81: 737-747 8. Jung, R. E., Weber, F. E., Thoma, D. S., Ehrbar, M., Cochran, Hämmerle, C. H. F. Bone morphogenetic protein-2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapatite/tricalciumphosphate. Clinical Oral Implants Research 2008; 19: 188-195 9. Jung, R. E., Hälg, G.A., Thoma, D. S., Hämmerle, C. H. F. A randomized, controlled clinical trial to evaluate a new membrane for guided bone regeneration around dental implants. Clinical Oral Implants Research, 2009; 20: 162-168 10. Ramel, C.F., Hälg, G.A., Wismeijer, D.A., Jung, R. E. A randomized, controlled clinical trial to evaluate a synthetic gel-membrane for GBR around dental implants: 1-3 years result. International Journal of Oral and Maxillofacial Implants, 2010; submitted Invention/Patent: PEG Granulate Matrix: Fehr, D., Neidhardt, A., Molenberg, A., Jung, R.E., Hämmerle, C.H.F. (Application No.: EP 06003422.0) I
Table of content Chapter 1: General introduction and aims...1 Chapters 2 to 5: Preclinical studies: Evaluation of PEG membrane...6 Chapter 2: Evaluation of an in situ formed synthetic hydrogel as a biodegradable membrane for guided bone regeneration...7 Chapter 3: Biodegradation of different synthetic hydrogels made of polyethylene glycol hydrogel/rgd-peptide modifications: An immunohistochemical study in rats...15 Chapter 4: A feasibility study evaluating an in situ formed synthetic biodegradable membrane for guided bone regeneration in dogs...25 Chapter 5: Evaluation of a new biodegradable membrane to prevent gingival ingrowth into mandibular bone defects in minipig...36 Chapter 6 to 9: Preclinical studies: Modification of PEG material...46 Chapter 6: Bone regeneration using a synthetic matrix containing a parathyroid hormone peptide combined with a grafting material...47 Chapter 7: The effect of matrix bound parathyroid hormone on bone regeneration...56 Chapter 8: Evaluation of parathyroid hormone bound to a synthetic matrix for guided bone regeneration around dental implants: A histomorphometric study in dogs...63 Chapter 9: Bone morphogenetic protein-2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapetite/tricalciumphosphate...74 Chapter 10 and 11: Clinical studies: Human application of PEG membrane...82 Chapter 10: A randomized, controlled clinical trial to evaluate a new membrane for guided bone regeneration around dental implants...83 Chapter 11: A randomized, controlled clinical trial to evaluate a synthetic gel-membrane for GBR around dental implants: 1-3 years result...90 Chapter 12: Summary and conclusion...101 Samenvatting...106 Acknowledgments...109 Curriculum Vitae...111 II
Chapters 2 to 5 Chapters 2 to 5: Preclinical studies: Evaluation of PEG membrane Chapter 2: Evaluation of an in situ formed synthetic hydrogel as a biodegradable membrane for guided bone regeneration Jung, R. E., Zwahlen, R., Weber, F. E., Molenberg A., van Lenthe G. H., Hämmerle, C. H. F. Clinical Oral Implants Research, 2006; 17: 426-433 Chapter 3: Biodegradation of different synthetic hydrogels made of polyethylene glycol hydrogel/rgd-peptide modifications: An immunohistochemical study in rats Herten, M., Jung, R. E., Ferrari, D., Rothamel, D., Golubovic, V., Molenberg, A., Hämmerle, C. H. F., Becker, J., Schwarz, F. Clinical Oral Implants Research, 2009; 20: 116-125 Chapter 4: A feasibility study evaluating an in situ formed synthetic biodegradable membrane for guided bone regeneration in dogs Jung, R. E., Lecloux, G., Rompen, E., Ramel, C.F., Buser, D., Hämmerle, C. H. F. Clinical Oral Implants Research, 2009; 20: 151-161 Chapter 5: Evaluation of a new biodegradable membrane to prevent gingival ingrowth into mandibular bone defects in minipig Thoma, D. S., Gian Andrea Hälg, G. A., Dard, M. M., Seibl, R., Hämmerle, C. H. F, Jung, R. E. Clinical Oral Implants Research, 2009; 20: 7-16 6
Chapters 6 to 9 Chapters 6 to 9: Preclinical studies: Modification of PEG material Chapter 6 Bone regeneration using a synthetic matrix containing a parathyroid hormone peptide combined with a grafting material Jung, R. E., Hämmerle, C. H. F., Kokovic, V., Weber, F. E. International Journal of Oral and Maxillofacial Implants, 2007; 22: 258-266 Chapter 7 The effect of matrix bound parathyroid hormone on bone regeneration Jung, R. E., Cochran, D. L., Domken, O., Seibl, R., Jones, A.A., Hämmerle, C. H. F. Clinical Oral Implants Research, 2007; 18: 319-325 Chapter 8 Evaluation of parathyroid hormone bound to a synthetic matrix for guided bone regeneration around dental implants: A histomorphometric study in dogs Valderrama, P., Jung, R. E., Thoma, D. S., Jones, A.A., Cochran, D. L. Journal of Clinical Periodontology, 2010; 81: 737-747 Chapter 9 Bone morphogenetic protein-2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapetite/tricalciumphosphate Jung, R. E., Weber, F. E., Thoma, D. S., Ehrbar, M., Cochran, Hämmerle, C. H. F. Clinical Oral Implants Research, 2008; 19: 188-195 46
Chapter 10 and 11 Chapter 10 and 11: Clinical studies: Human application of PEG membrane Chapter 10 A randomized, controlled clinical trial to evaluate a new membrane for guided bone regeneration around dental implants. Jung, R. E., Hälg, G.A., Thoma, D. S., Hämmerle, C. H. F. Clinical Oral Implants Research, 2009; 20: 162-168 Chapter 11 A randomized, controlled clinical trial to evaluate a synthetic gel-membrane for GBR around dental implants: 1-3 years result. Ramel, C.F., Hälg, G.A., Wismeijer, D.A., Jung, R. E. International Journal of Oral and Maxillofacial Implants, 2010; submitted 82