**Human Dentin as Novel Biomaterial for Bone Regeneration**

Masaru Murata1, Toshiyuki Akazawa2, Masaharu Mitsugi3, In-Woong Um4, Kyung-Wook Kim5 and Young-Kyun Kim6

> *1Health Sciences University of Hokkaido, 2Hokkaido Organization, 3Takamatsu Oral and Maxillofacial Surgery 4Tooth Bank Co. Ltd, 5Dankook University, 6Seoul National University Bundang Hospital, 1,2,3Japan 4,5,6Korea*

### **1. Introduction**

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Human dentin autograft was reported in 2003 as a first clinical case (Murata et al., 2003), while human bone autograft was done in 1820. There was a long-long time lag between the autografts of dentin and bone. In 2009, Korea Tooth Bank was established in Seoul for the processing of the tooth-derived materials in Seoul, and an innovative medical service has begun for bone regeneration. Recently, the tooth-derived materials have been becoming a realistic alternative to bone grafting.

The regeneration of lost-parts of the skeleton has been generally carried out with fresh, autogenous bone as a gold standard. To obviate the need for harvesting of grafts and thus, to avoid morbidity resulting from it, the researches for bone substitutes (Kuboki et al., 1995; Asahina et al., 1997; Takaoka et al., 1991; Artzi et al., 2004; Kim et al., 2010) or bone production via bio-engineering have begun (Wozney et al., 1988; Wang et al., 1990; Murata et al., 1999). In the regenerative field, there is a medical need for biomaterials that both allow for bone formation and also gradually absorb as to be replaced by bone. Non-absorbable materials are never replaced by bone and thus, reveal chronic inflammation in tissues as foreign bodies.

As bone and dentin consist of fluid (10%), collagen (20%) and hydroxyapatite (70%) in weight volume, our attention for biomaterials is collagenous and ceramic materials (Murata et al., 2000; Murata et al., 2002; Akazawa et al., 2006; Murata et al., 2007). Generally, extracted teeth have been discarded as infective medical dusts in the world. We have thought the non-functional teeth as native resource for self and family (Fig. 1). Therefore, we noticed on bone-inductive, absorbable properties of dentin, and have been studying a medical recycle of human teeth as a novel graft material for bone regeneration in Japan and Korea (Akazawa et al. 2007; Kim et al. 2010). Biomaterial science should support and develop the advanced regenerative therapy using enamel and dentin matrix for patients in the near future.

Human Dentin as Novel Biomaterial for Bone Regeneration 129

Dentin and bone are mineralized tissues and almost similar in chemical components. Both DDM and DBM are composed of predominantly type I collagen (95%) and the remaining as non-collagenous proteins including small amount of growth factors (Finkelman et al., 1990). In other words, DDM and DBM can be defined as acid-insoluble collagen binding bone morphogenetic proteins (BMPs), which are member of transforming growth factor-beta (TGF-β) super-family. BMPs were discovered from bone matrix (Urist, 1965; Sampath & Reddi., 1983), and had bone-inducing property in non-skeletal site (Murata et al., 1998). Animal dentin-derived BMPs were extracted with 4M guanidine HCl, and partially purified from rat, rabbit, and bovine (Butler et al., 1977; Urist & Mizutani, 1982; Kawai & Urist, 1989; Bessho et al, 1990). In addition, the concentration of TGF-β, Insulin growth factor-I (IGF-I) and Insulin growth factor-II (IGF-II) were detected in human dentin (DDM). Briefly, the three growth factors were measured in the following concentration (ng/μg 4M guanidine hydrochloride-EDTA protein): TGF-β (0.017), IGF-I (0.06) and IGF-II (0.52). All 3 growth factors were present in concentrations lower than that in human bone (Finkelman et al., 1990). Recently, both mature and immature types of BMP-2 were detected in human dentin

and dental pulps (Ito et al., 2008).

b: bone induction by DDM at 4 weeks.

d: bone induction by DBM at 4 weeks.

a: SEM of DDM (granule size: 0.5mm), Note: smooth surface and no crack.

c: SEM of DBM (granule size: 0.5mm), Note: micro-cracks and spaces of blood vessels.

Fig. 2. Dematerialized dentin matrix (DDM) and dematerialized bone matrix (DBM)

In this chapter, human dentin will be introduced as novel biomaterial and also as carrier matrix of the recombinant human bone morphogenetic protein-2 (BMP-2) delivery for bone engineering.

a: whole appearance of molar.

b: divided tooth (E; enamel, D; dentin, P; pulp).

c: crushed tooth granules.

d: SEM photograph of calcified dentin after crushing and washing. Note; dentinal tubes

Fig. 1. Human wisdom tooth
