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Abstract Evaluation of Osteosynthesis in CaO-SiO 2 -P 2 O 5 -B 2 O 3 Glass-ceramics by Posterolateral Fusion of Rabbit Lumbar vertebrae Jae Hyup Lee, MD #, Kun-Woo Park, MD, Kwang Sup Song, MD, Hyun-Seung Ryu, PhD, Jun-Hyuk Seo, ME, Kug Sun Hong, PhD, Hwan Kim, PhD, Bong-Soon Chang, MD, Choon-Ki Lee, MD Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul, Korea Department of Orthopedic Surgery, Gachon Medical School, Incheon, Korea # School of Materials Science & Engineering, Seoul National University, Seoul, Korea Study Design: A comparative in vivo study between ceramics with different compositions Objectives: To compare the biodegradation and osteoconduction properties of CaO-SiO 2- P 2O 5- B 2O 3 glass-ceramics and Cerabone - A W Summary of Literature Review: Bioglass ceramics can be used as bone graft substitutes However, no study has been undertaken to investigate the possibility of CaO-S i O 2-P 2O 5-B 2O 3 glass-ceramics as a bone graft substitute Materials and Methods: Porous CSPB2 implants (4407% CaO, 4028% SiO 2, 81% P 2O 5 and 50% B 2O 3), porous CSPB3 implants (4376% CaO, 4341% SiO 2, 405% P 2O 5 and 75% B 2O 3) and porous Cerabone -AW were prepared by the polymer sponge method Single-level posterolateral spinal fusions were performed on sixty New Zealand white male rabbits The animals were divided into four groups (9 of autograft, 17 per 3 kind of porous implant group) according to the implant material used: autograft, CSPB2, CSPB3 and Cerabone -AW Radiographs were performed every two weeks All animals were sacrificed 12 weeks after surgery Manual palpation and uniaxial tensile strength were determined The proportion of the area occupied by the ceramics in the final compared to the initial radiographs was calculated Decalcified and undecalcified histological sections were evaluated by light microscopy R e s u l t s: Fifty one rabbits were evaluated The union rates were 100 (9 out of 9), 80 (8 out of 8), 811 (9 out of 11) and 909% (10 out of 11) in the autograft, Cerabone -AW, CSPB2 and CSPB3 groups, respectively The proportion of the area occupied by Cerabone - A W ( 9 0 8 %140) was significantly higher than for CSPB2 (731%115) and CSPB3 (735%100)(p=00011) The mean values of the tensile strengths of Cerabone -AW (214573N), CSPB2 (214573 N) and CSPB3 (217701 N) were not significantly different (p>005) Conclusion: CSPB2 and CSPB3 had similar tensile strengths and fusion rates of the fusion masses as those of Cerabone -AW; however, they degraded more rapidly than Cerabone -AW These findings suggest that CSPB2 and CSPB3 grafts can be used as a more ideal new bone graft substitutes than Cerabone -AW Key Words: C a O - S i O 2- P 2O 5- B 2O 3 glass-ceramics, A-W glass-ceramics, Biodegradation, Osteoconductivity, Bone graft substitute Address reprint requests to Choon-Ki Lee, MD Department of Orthopaedic Surgery, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-774, Korea Tel: 82-2-2072-2360, Fax: 82-2-764-2718, E-mail: choonki@plazasnuackr - 1 -

CaOSiO 2 B 2 O 3 CaO-SiO 2 -B 2 O 3 B 2 O 3 6,7), B 2 O 3 42 mol% CS5B, 84 mol%cs10b in 1) v i t r o (simulated body fluid) C S 10 BC e r a b o n e - A W (biodegradable), B 2 O 3 7 Hench 1971 N a 2 O - C a O - S i O 2 - P 2 O 5 ), 2-4 ), CaO-SiO 2 - P 2 O 5 C a O - S i O 2 C S 10 B ( b i o a c t i v e, CS10B glass) (hydroxyapatite, Ca 10 (PO 4 ) 6 (OH) 2, HA) 6 ( C a )( P ) ), CS10B (calcium phosphate-based ceramics), C e r a b o n e A - W ( C a O - S i O 2 - P 2 O 5 ), CaO-SiO 2 - B 2 O 3 CaO-SiO 2 -P 2 O 5 -B 2 O 3 4 - (Apatite-wollastonite glass-ceramics, A-W ) 1982Kokubo A-W (Cerabone -AW) 5) A-W CaO-SiO 2 -P 2 O 5 ( C a S i O 3 ),, 3 999% 215 MPa, 20 MPam 1/2 SiO 2, CaCO 3, CaHPO 4 2H 2 O, H 3 PO 4, MgO, CaF 2 CaO 449 wt%, SiO 2 342 wt%, P 2 O 5 163 wt%, MgO 46 wt%, CaF 2 05 wt% 200 gbatch Batch 24 ball mill 1500~1600 2 spex milling 15 1~2 m Cerabone A-W (HA), C a C O 3 (high purity chemical, 9999%, (Ca 3 (PO 4 ) 2, TCP) Japan), SiO 2 (high purity chemical, 99,9%, Japan), B 2 O 3 (high purity chemical, 999%, Japan), C a O - S i O 2 - B 2 O 3 457% CaO, 457% - 2 -

SiO 2, 86%B 2 O 3 CS10B CSPB2Cerabone -AWCS10B1:1, CaO 4407 wt%, SiO 2 4028 wt%, P 2 O 5 81 wt%, B 2 O 3 5 wt%, MgO 23 wt%, CaF 2 025 wt% CSPB3 Cerabone -AWCS10B1:3, CaO 4376 wt%, SiO 2 4341 wt%, P 2 O 5 405 wt%, B 2 O 3 75 wt%, MgO 115 wt%, CaF 2 013 wt% Cerabone A-W, CSPB2 CSPB31450 e m b o l i z a t i o n ) 5-6 2 (fusion mass) 1 polyvinyl alcohol (PVA) (45 cm 2 ), 4 10 g 3 600 ( 60 30~35 kg cm, 45 kv, 25 ma, 12 milleseconds) 60 2 60 4 9, C e r a b o n e A-W 17, CSPB2 17, CSPB3 17,, (Fig 1) c c 025 g 3 025 g 1 2 ( a i r, a 12 b 2 12 I m a g e - P r o Plus (Media Cybernetics, USA) c (ketamine hydrochloride 50 mg/ml,, 70 ) (xylazine hydrochloride 2332 mg/ml, 4, ),, 10% betadine,,, 5-6 4 cm,, 5,6 8,9) 40 mm (burr), 3 ( r o t a t i o n a l - 3 -

s t r e s s ) I n s t r o n Instron 8500, Instron corporation, USA), ( K g f ) (break point) d 5% 4 b l o c k b l o c k 4, p<005 60 51 Cerabone A-W Hematoxylin and Eosin (H & E), CSPB2C S P B 3,, -, methylmethacrylate,, ( e m b e d d i n g ),, - H & E,, 99 (100%) e, Cerabone A-W 108 Fisher's exact test (80%), CSPB2 11, 9 ( 81 8 %), CSPB3 Kruskall-Wallis 111 0 ( 90 9 %) 4 Fig 1 The calculation process using Image-Pro Plus (Media Cybernetics, USA) Left: Immediate postoperative radiograph, Right: postoperative 12 weeks radiograph - 4 -

( p > 0 05 ) (Table 1) 6 CSPB2 Cerabone A-W, 12, (Fig 4) CSPB3 12 CSPB2 (Fig 5) 12, 12 (Fig 2) Cerabone A-W, 12 12 12, 12 (Fig 3) Fig 2 Posteroanterior radiographs of a rabbit in the autograft group At 12 weeks, homogeneous fusion masses were formed Table 1 Summary of fusion rate, radiomorphometric of lumbar intertransverse process fusions, and ultimate tensile strength Fusion rate (%) Proportion of area occupied by ceramics in final X-ray (%) mean tensile strength (N) Cerabone-AW 800 908140 aa 214573 CSPB2 818 731115 aa 217661 CSPB3 909 735100 aa 217701 a & aa Indicate statistically different data by Kruskall-Wallis test, p<005-5 -

(Fig 4,5) 12, Cerabone A - W 90 8 %140, CSPB-2 73 1 %115, C S P B - 3 73 5 %1 0 0, Kruskall-Wallis, CSPB2 CSPB3B Cerabone A-W (p=00011)(table 1) A B Fig 3 Posteroanterior radiographs of a rabbit in the Cerabone A-W group At 12 weeks, fusion masses seemed to be formed, but the porous structure of the graft was maintained The proportion of the area occupied by Cerabone A-W in final radiograph over the area occupied by ceramics in the initial radiograph was almost the same (A) Immediate postoperative, (B) postoperative 12 weeks A B Fig 4 Posteroanterior radiographs of a rabbit in the CSPB2 group (A) Immediate postoperative, (B) postoperative 12 weeks - 6 -

,, Cerabone A - W 214 5 7 3 N, CSPB-2 217661N, CSPB-3 217 70 1 N CS10B Cera b o n e A - W C S P B 2 Kruskall-Wallis (Table 1), CSPB2 Cerabone A-W, Cerabone A-WCSPB2, CSPB3 (Fig 7) CSPB3 Cerabone, A-W,, Cerabone A-W, Cerabone A-W, C e r a b o n e A-W C e r a b o n e A-W, CSPB2, (Fig 6) C S P B 2, C e r a b o n e A - W A B Fig 5 Posteroanterior radiographs of a rabbit in the CSPB3 group (A) Immediate postoperative, (B) postoperative 12 weeks - 7 -

,,, 14),, (Fig 8) CaO-SiO 2 -B 2 O 3 CS10B 700, 25%, 28132063 MPa, 687105 Hv, 204404 MPa 7) (biocompatibility) ( o s t e o c o n d u c t i v i t y ) 10, 11 ), 12 ) Fig 6 Histologic results of Cerabone A-W 12 weeks after, surgery The bone is directly attached to pores, the contours of which are nearly intact (Undecalcified, H&E, staining, 40) White circles indicate the Cerabone A- 13) W implant, black arrows indicate newly formed bone Fig 7 Histologic results of CSPB2 12 weeks after surgery The bone is directly attached to pores, the contours of which are nearly intact (Undecalcified, H&E staining, 40) White circles indicates the CSPB2 implant, black arrows indicate newly formed bone Fig 8 Histologic results of CSPB3 12 weeks after surgery The bone is directly attached to pores, the contours of which are nearly intact (Undecalcified, H&E staining, 40) White circles indicates the CSPB3 implant, black arrows indicate newly formed bone - 8 -

, in vitro 90, CS10B CSPB2, CSPB3,, CaO-SiO 2 - B 2 O 3, CS10B, Cerabone A-W (92% ) CSPB2 (269% )CSPB3 (265% ) (113% ) 6 ) 6 ), CS10B,,,, C e r a b o n e A - WC a O - S i O 2 - B 2 O 3 ( 191 4335 N)C S 10 B ( 182 7 C e r- 199 N) abone A-WCS10B 4, CaO-SiO 2 - P 2 O 5 - B 2 O 3 C S P B 2C S P B 3C e r a b o n e A - W Cerabone A-W,,,,,, 100%, Cerabone A - W 80 %, CSPB2 818%, CSPB3 909% CSPB2CSPB3 Cerabone A-W,,, 70%, 15), 16,17), 12 Image-Pro Plus (Media Cybernetics, CaO- USA) S i O 2 - P 2 O 5 - B 2 O 3 C S P B 2C S P B 3 CaO-SiO 2 -B 2 O 3,, C e r a b o n e A - W,, CSPB2CSPB3B 2 O 3-9 -

, using in-vitro test J Kor Ceramic Soc 2002; 39:490-497 08) Boden SD, Schimandle JH, Hutton WC: An experimen - tal lumbar intertransverse process spinal fusion model C a O - S i O 2 - P 2 O 5 - B 2 O 3 of electromagnetic fields in a spinal fusion: A rabbit model Spine 1997; 22:2351-2365 C e r a b o n e A - W CaO-SiO 2-10) Holmes RE, Bucholz RW, Mooney V: Porous hydroxya - P 2 O 5 -B 2 O 3 Cerabone A-W patite as a bone graft substitute in diaphyseal defects: a histometric study J Orthop Res 1987; 5:114-121 Cerabone A-W 11) Uchida A, Nada SM, McCartney ER, Ching W: The use Cerabone A-W of ceramics for bone replacement A comparative study of three different porous ceramics J Bone Joint Surg 1984; 66-B:269-275 12) Eggli PS, Muller W, Schenk RK: Porous hydroxyapatite 01) Klein CP, Driessen AA, de Groot K, Van Den Hooff A: Biodegradation behavior of various calcium phosphate materials in bone tissue J Biomed Mat Res 1983;17:769-784 02) Hench LL, Wilson JW: Surface-active Biomaterial Sci - ence 1984; 226:630 03) Hench LL, Paschall HA: Histo-chemical responses at a biomaterials interface J Biomed Mater Res 1974;5:49-64 04) Hench LL: Bioceramics: From concept to clinic J Am Ceram Soc 1991; 81:1497-1510 05) Kokubo T, Ito S, Sakka S, Yamamuro T: Formation of a high-strength bioactive glass-ceramic in the system MgO-CaO-SiO 2 -P 2 O 5 J Mater Sci 1986; 21:536-540 06) Lee JH, Ha JH, Lee DH, et al: Evaluation of biodegra - dation and osteosynthesis in CaO-SiO 2-B 2O 3 glass-ceram - ics by posterolateral fusion of rabbit lumbar vertebrae J Kor Orthop Assoc 2003; 38:347-353 07) Ryu HS, Seo JH, Kim H, et al: Preparation of CaO- S i O 2 - B 2 O 3 glass-ceramics and evaluation of bioactivity Radiographic, histologic, and biomechanical healing characteristics Spine 1995; 20:412-420 09) Glazer PA, Heilmann MR, Lotz JC, Bradford DS: Use and tricalcium phosphate cylinders with two different pore size ranges implanted in the cancellous bone of rabbits Clin Orthop 1988; 232: 127-138 13) Blokhuis TJ, Termaat MF, den Boer FC, Patka P, Bakker FC, Haarman HJ: Properties of calcium phos - phate ceramics in relation to their in vivo behavior J Trauma 2000; 48(1):179-186 14) Lee JH, Lee DH, Ryu HS, et al: Porous beta-calcium pyrophosphate as a bone graft substitute in a canine bone defect model Key Eng Mat 2003; 240-242:399-402 15) Boden SD: Overview of the biology of lumbar spine fusion and principles for selecting a bone graft substitute Spine 2002; 27:S26-S31 16) Boden SD, Martin Jr GJ, Morone M, Ugbo JL, Titus L, Hutton WC: The use of coralline hydroxyapatite with bone marrow, autogenous bone graft, or osteoinductive bone protein extract for posterolateral lumbar spine fusion Spine 1999; 24:320-327 17) Bozic KJ, Glazer PA, Zurakowski D, Simon BJ, Lipson SJ, Hayes WC: In vivo evaluation of coralline hydroxyap - atite and direct current electrical stimulation in lumbar spinal fusion Spine 1999; 24:2127-2133 - 10 -

: :, CaO-SiO 2-P 2O 5-B 2O 3 CaO-SiO 2-P 2O 5-B 2O 3 Cerabone -AW : 50 mol%b 2 O 3 CaO-SiO 2 -P 2 O 5 -B 2 O 3 CSPB2, 75 mol%b 2 O 3 CaO-SiO 2 -P 2 O 5 -B 2 O 3 CSPB3 60 Autograft9, Cerabone -AW, CSPB2, CSPB3 17 5-6 3 cc 6 cc 2 12, : 6051 Cerabone -AW 214573N 10 8(80%), CSPB2 217661N 11 9(818%), CSPB3 217701N 11 10(919%), 9 9(100%) 12 C e r a b o n e - A W9 0 8140%, CSPB27 3 11 1 5 %, CSPB3735100%Cerabone -AW CSPB2CSPB3 (p=00011), : CSPB2CSPB3 Cerabone -AW Cerabone - AW Cerabone -AW : CaO-SiO 2 -P 2 O 5 -B 2 O 3, A-W,,, - 11 -