Topic: Preparation of functional artificial bones based on calcium phosphates

Speaker: Dr. Masanobu Kamitakahara (Graduate School of Environmental Studies, Tohoku University, Japan)

Time: 11月5日（周四）10:30-11:50

Venue: Room 468, Lee Hsun Building, IMR CAS

More details can be found at the lab homepage of Dr. Kamitakahara: http://ehtp.kankyo.tohoku.ac.jp/ioku/index.html

报告摘要

As ceramics composed of calcium phosphates show a high biological affinity to bone tissue, they have been used for the repair and regeneration of bone. Although conventional sintered hydroxyapatite (HA; Ca10(PO4)6(OH)2) ceramics and tricalcium phosphate (TCP; Ca3(PO4)2) ceramics are both widely used clinically, the ability of these materials to regenerate the bone is insufficient and their use remains limited. Highly functional artificial bones could be obtained if we made best use of the properties of calcium phosphates. This presentation shows the several our approaches to improve the functionality of artificial bones based on calcium phosphates.

1. Functional HA ceramics prepared by hydrothermal process

Porous HA ceramics are used for bone regeneration because HA is the main inorganic component of bones and possesses bone-bonding properties. However, conventional sintered HA ceramics show little bioresorbability, and their ability for bone regeneration is not high. The hydrothermal process can create HA particles with various morphologies, such as rod-like and plate-like [1]. We synthesized porous calcium-deficient HA ceramics composed of rod-like particles through a hydrothermal process, and these materials were shown to have advantages over the sintered porous HA ceramics. When the porous calcium-deficient HA ceramics composed of rod-like particles were implanted into bone defects in rabbit femurs, the implanted porous HA ceramics were quickly integrated into the natural bone and exhibited bioresorbability [2]. The entanglement of rod-shaped particles also contribute to a reduction of the brittle fracture of the porous ceramic [3].

2. Functional TCP ceramics prepared with addition of other elements

 In order to control bioresorbability of TCP, we fabricated TCP porous ceramics with a controlled a- and b-TCP ratio by the addition of Mg [4] because the addition of Mg raises the transformation temperature from b-TCP to a-TCP. We compared the in vivo degradation rate of the TCP porous ceramic consisting of biphasic a- and b-TCP (a/b-TCP) to that of TCP ceramics consisting of pure a-TCP or b-TCP, and found that the biphasic TCP porous ceramic showed good biodegradability and bone formation [5].

The addition of trace elements which enhance bone regeneration is another possible approach to improve the properties of calcium phosphate ceramics. Silicon is known as a trace element that is essential for bone formation in the body. We synthesized Si-containing TCP powder through a wet process starting from CaO, H3PO4 and Si(OCOCH3)4 [6]. The Si addition lowered the temperature of phase transition from b-TCP to a-TCP, and promoted sintering. Supplementation with Si significantly promoted osteogenesis and delayed biodegradation of a-TCP.

3. Functional octacalcium phosphate-based ceramics

Octacalcium phosphate (OCP; Ca8(HPO4)2(PO4)4·5H2O) is known as a precursor of hydroxyapatite (HA), and is reported to act as a useful bone-repairing material. OCP has a potential as a drug carrier for treating the bone cancer when anticancer drugs are incorporated in the granules. When OCP having drugs is implanted into a bone defect site, it is expected that drugs are released during the transformation of OCP to HA due to the dissolution of OCP and the difference in the adsorption properties. We investigated the transformation behavior of OCP to HA in vitro and revealed that the nucleation of HA is the rate-determining step in the transformation of OCP to HA [7]. Base on this knowledge, the OCP granules added with HA (OCP/HA granules) were designed, expecting that the transformation of OCP to HA is accelerated. We successfully prepared spherical porous OCP/HA granules by immersing spherical porous a-TCP granules in an adequate solution and revealed the potential of the granules as a drug carrier [8].

References

[1] M. Kamitakahara, C. Ohtsuki, G. Kawachi, D. Wang. K. Ioku, “Preparation of hydroxyapatite porous ceramics with different porous structures using a hydrothermal treatment with different aqueous solutions”, J. Ceram. Soc. Japan, 116, 6-9 (2008).

[2] T. Okuda, K. Ioku, I. Yonezawa, H. Minagi, Y. Gonda, G. Kawachi, M. Kamitakahara, Y. Shibata, H. Murayama, H. Kurosawa, T. Ikeda, “The slow resorption with replacement by bone of a hydrothermally synthesized pure calcium-deficient hydroxyapatite”, Biomaterials, 29, 2719-2728 (2008).

[3] S. Murakami, K. Kato, Y. Enari, M. Kamitakahara, N. Watanabe, K. Ioku, “Hydrothermal synthesis of porous hydroxyapatite ceramics composed of rod-shaped particles and evaluation of their fracture behavior”, Ceram. Int., 38, 1649-1654 (2012).

[4] M. Kamitakahara, C. Ohtsuki, M. Oishi, S. Ogata, M. Tanihara, T. Miyazaki, "Control of the microstructure of porous tricalcium phosphate: Effects of addition of Mg, Zn and Fe", J. Jpn. Soc. Powder Powder Metallury, 52, 356-359 (2005).

[5] M. Kamitakahara, C. Ohtsuki, M. Oishi, S. Ogata, T. Miyazaki and M. Tanihara, “Preparation of Porous Biphasic Tricalcium Phosphate and Its In Vivo Behavior”, Key Engineering Materials, 284-286, 281-284 (2005).

[6] Masanobu Kamitakahara, Takashi Kurauchi, Masao Tanihara, Koji Ioku and Chikara Ohtsuki, “Synthesis of Si-containing Tricalcium Phosphate and Its Sintering Behavior”, Key Engineering Materials, 361-363, 59-62 (2008).

[7] N. Ito, M. Kamitakahara, M. Yoshimura, K. Ioku, “Importance of nucleation in transformation of octacalcium phosphate to hydroxyapatite”, Mater. Sci. Eng. C, 40, 121–126 (2014).

[8] N. Ito, M. Kamitakahara, K. Ioku, Preparation and evaluation of spherical porous granules of octacalcium phosphate/hydroxyapatite as drug carriers in bone cancer treatment, Mater. Lett., 120, 94–96 (2014).