Mastoid Obliteration by BMP-2/Collagen Composites: An Experimental Study Using Tissue Engineering Kazunori Nishizaki, MD,* Hidetsugu Tsujigiwa, PhD,† Yasushi Takeda, MD,* Tadashi Yoshino, MD,‡ Manabu Maeta, MD,* Kunihiro Fukushima, MD,* Hitoshi Nagatsuka, DDS,† and Noriyuki Nagai, DDS† Purpose: Several materials have been used in the application of mastoid cavity obliteration duringsurgeryforcholesteatoma;however,nothinghaswonuniversalacceptance.Through the advancement of tissue engineering, bone morphogenetic protein–2 (BMP-2)/collagen composites have been elucidated as inducers of heterogenic bone formation. This study wasperformedtoinvestigatewhetherthesecompositesarepotentiallyobliterationmaterials for use in the mastoid cavity by using an animal experimental study. Materials and Methods: The composites were implanted in the rat mastoid to investigate whether new bone would be tissue engineered in the mastoid and, if so, whether the newly formed bone was stable. The composites were examined histologically over a 24-week period. Results: The composites implanted in the rat mastoid were able to tissue engineer new bone, and the newly formed bone was stable as assessed histologically, with almost normal bone structure, that was not resorbed during the 24-week period. Adverse immunological reactions were not found during our observation. Conclusions: Bone that was tissue engineered by the BMP-2/collagen composites was stableasassessedbyhistologicalexaminationandpersistedintheratmastoid.Thepresent study shows that the composites have the potential to become real materials for use in mastoid obliteration. (Am J Otolaryngol 2003;24:14-18. Copyright 2003, Elsevier Science (USA). All rights re- served.) The prevention of recurrent cholesteatoma through surgical intervention has been a con- troversial issue among otologists. The canal down method is certainly advantageous in this point, but the mastoid problem remains to be solved. As one of the answers to this prob- lem, mastoid obliteration has often been per- formed. Historically, many obliteration mate- rials have been adopted and abandoned because of unacceptable results such as necro- sis and infection. 1 At present, soft-tissue flaps, 2 bone plate, 3 cartilage, 4 and biocompat- ible materials 5,6 continue to be used clinically for this purpose. However, each of them has disadvantages and thus competes for first place. 7 Soft-tissue flaps, like muscular flaps, atrophy with age, and a recavity is often formed. Cartilage is a material of limited sup- ply. Biocompatible materials like hydroxyap- atite sometimes cause a foreign body reaction to the surrounding tissue and subsequently extrude. Bone plate may be the current pre- ferred material but may lack enough strength to prevent recurrent cholesteatoma because of its fragility and resorption. 8 Bone plate also has a disadvantage of limited supply in cases previously operated on using the canal down technique. Thus, the real winner has not been decided yet. Recent advancements in tissue engineering provide a new concept to cope with diseases, and their clinical application is just about to be considered. BMP and insoluble bone ma- trix (mainly consisting of collagen) compos- ites are reported to induce heterotropic bone From the Departments of *Otolaryngology–Head and Neck Surgery, †Oral Pathology and Medicine, and ‡Pathological Research, Okayama University Graduate Schools, Okayama, Japan. Address correspondence to: Kazunori Nishizaki, MD, Department of Otolaryngology–Head and Neck Sur- gery, Okayama University Graduate School, 700-8558 Japan. E-mail: nishizak@cc.okayama-u.ac.jp. Copyright2003,ElsevierScience(USA).Allrightsreserved. 0196-0709/03/2401-0003$30.00/0 10.1053/ajot.2003.13 14 American Journal of Otolaryngology, Vol 24, No 1 (January-February), 2003: pp 14-18