Leonardo – Biomaterial for bone grafting

PRECLINICAL and CLINICAL STUDIES on BIOACTIVE GLASS and LEONARDO – Oral surgery

1. General informations on bioactive glassesBioactive glasses are classified as ceramic biomaterials, and more precisely as bioactive ceramic materials, just like hydroxyapatite and other calcium phosphate ceramics[1]. Bioactive glasses are mainly composed of silicon dioxide (SiO2), sodium oxide (Na2O), calcium oxide (CaO) and phosphorous pentoxide (P2O5). L. L. Hench was the inventor of bioactive glass 45S5 in 1971, called Bioglass® (composed, in weigh, of 45 % SiO2, 24.5 % Na2O, 24.5 % CaO and 6 % P2O5). Since then, different types of bioactive glasses or glass-ceramic materials (glasses incorporating hydroxyapatite crystals and/or wollastonite), with different properties, have been devel-oped[1].

Bioactive glasses are effective materials for bone grafting or pros-thesis coating. They have been used in different types of surgeries: orthopedic surgery, oral surgery, cranio-facial surgery and spinal surgery. These materials are known for their excellent biocompat-ibility. In contact with body fluids, they are able to create a solid grip at the interface implant/host tissues. These biomaterials do not promote any fibrous encapsulation at the interface implant/tissue; the connection between the implant and the bone tissues is thus direct. The surface of bioactive glasses serves as a support for bone regrowth. The degree of bioactivity depends on the composition of bioactive glasses, in particular on the proportion of silica (SiO2), sodium oxide (Na2O), phosphorus pentoxide and calcium oxide (CaO)[2].

Absorbable biomaterials are known for their ability to gradual-ly degrade while being replaced by the natural host bone tissue. Hydroxyapatite is hardly soluble and its in vivo degradation rate is

3. OsteostimulationRecent in vitro studies have been led to the understanding of the mechanism of action of bioactive glass[5,6]. They show that ionic products such as silicon and calcium have an influence on the stem cells differentiation and on the growth of bone. Besides, the bone mineralization happens thanks to phosphor transit. The dissolution products of bioactive glass 45S5 develop an extracellular environ-ment that is capable of supporting osteoblast phenotype expression and extracellular matrix deposition and mineralization in vitro[6].

Preclinical studies on Leonardo granules 4. Biocompatibility evaluation4.1 Biocompatibility tests following NF EN ISO 10993-1 standard

Biocompatibility evaluation has been conducted following the tableof the NF EN ISO 10993-1 standard. Since bioactive glass is a well-known material which has been clinically used for more than 20 years, biocompatibility tests which have been conducted aim at evaluating the toxicity of manufacturing residues.

Here is the list of the tests which have been conducted and the providers involved in the study:

The set of biocompatibility tests performed show that bioactive glass 45S5 products:

are not cytotoxic do not induce irritation do not induce delayed-type hypersensitivity do not induce acute systemic toxicity are neither toxic nor mutagen are not pyrogen

Figure 1: Sequence of interfacial reactions involved in forming a bond between bone and a bioactive glass. L. L. Hench[1]

PROLIFERATION AND GROWTH OF BONE

CRYSTALLIZATION OF MATRIX

GENERATION OF MATRIX

DIFFERENTATION OF STEM CELLS

ATTACHMENT OF STEM CELLS

ACTION OF MACROPHAGES

ADSORPTION OF BIOLOGICAL MOIETIES IN HCA LAYER

CRYSTALLIZATION OF HYDROXYL CARBONATE APATITE (HCA)

ADSORPTION OF AMORPHOUS Ca+PO4+CO3

POLYCONDENSATION OF SiOH + SiOH Si-O-Si

FORMATION OF SiOH BONDS

BIOACTIVE GLASS

12

11

10

9

8

7

5

4

3

1&2

12

1020

100

6

SURF

ACE

REAC

TIO

N S

TAGE

S

LOG

TIM

E (H

OU

RS)

(A)

BIOCOMPOTIBILITY TESTS PERFORMED

PROLIFERATION AND GROWTH OF BONE

IRRITATION (ISO 10993-10)

DELAYED-TYPE HYPERSENSITIVITY (ISO 10993-10)

ACUTE SYSTEMIC TOXICITY (ISO 10993-11)

AMES TEST (ISO 10993-3)

PYROGENICITY (USP 31)

CYTOTOXICITY (ISO 10993-5)

1 L. L. Hench. The Story of Bioglass. J. Mater. Sci: Mater Med (2006) 17: p. 967-978 2 L. L. Hench. Bioceramics. J. Am. Ceram. Soc. (1998) 81: p. 1705-28

3 L. L. Hench, G. P. Latorre. Reaction kinetics of bioactive ceramics. PartIV: effect of glass and solution composition. Bioceramics (1992) 5: p. 67-744 A. E. Clark, C. G. Pantano, L. L. Hench. Auger spectroscopy analysis of bioglass corrosion films. J. Am. Ceram. Soc. (1976) 59: p. 37-39

very low, but can vary with pH. Tricalcium phosphate ß (ß-TCP) is much more soluble than HA and degrades rapidly in vivo. Bioactive glass 45S5 can be considerate as perfectly absorbable since it com-pletely dissolves in order to form carbonated hydroxyapatite. Its degradation rate depends on its composition.

2. Description of mechanism of bioactivityA cascade of physical and chemical reactions occurs at the periph-ery of bioactive glasses in contact with body fluids. A hydrolytic degradation of bioactive glass happens[2], followed by numerous and complex reactions. Figure 1 below summarizes the cascade of the 11 reactions occurring at the surface of bioactive glass during the formation of a solid grip with the bone.

The five first reactions take place in the periphery of bioactive glass and do not depend on the presence of tissue. This reactions has been studied and could take place in distilled water or buffer solution like TRIS or SBF[3,4]. These reactions make up a layer of crystallized carbon hydroxyapatite at the top of material. The implant fastens down with the tissue for the step 6 to 11 like as growth of bone.

5 I. D. Xynos et al. Bioglass 45S5 Stimulates Osteoblast Turnover and Enhances Bone Formation In Vitro: Implications and Applications for Bone Tissue Engineering. Calcif Tissue Int (2000) 67:3216 Olga Tsigkou et al. Differentiation of fetal osteoblasts and formation of mineralized bone nodules by 45S5 Bioglass conditioned medium in the absence of osteogenic supplements. Biomaterials 30 (2009) 3542–3550

| 2 3 |

4.2 Implantation of different bone grafting materials on rabbits: global evaluation of NORAKER products

An implantation study has been conducted on rabbits in order to evaluate the biological response of tissues to different bone graft-ing materials, including bioactive glass 45S5. This study has been conducted in adaptation to the ISO 10993-6 norm. Bioactive glass 45S5 product is compared to a ß-TCP control material. Granules are implanted in 5 animals for each time, in the area of the femoral epiphysis (either distal or proximal). Observation times are 4, 12 and 24 weeks.

surface of the material, 4/ degradation of the material (with differ-ent rates), and replacement by mature bone.

The picture shows a normal marrow without any sign of residual ossification. Some Bioactive glass 45S5 residues can be observed, under granuled shapes (BG) in very isolated trabeculae.

After 12 weeks, Bioactive glass 45S5 granules quickly resorbed whereas control material (ß-TCP) had a slowier degradation.

Outside the cortical area, the picture shows a heap of bioactive glass 45S5 particulates. They are included in a soft conjonctive tis-sue which is denser at the interface with particulates. In the medul-lar implantation area, some trabeculae remain. They seam to result from the presence of the particulates.

Bioactive glass 45S5 granules (material) are of particle shapes. We can see numerous monocyte cells in the existing soft connective tissue, between the ossified areas, only at the surface of the parti-cles (dark blue).

After 4 weeks, at histological observation, both materials (bioactive glass 45S5 and control) have a bioactive appearance. They went through different successive stages: 1/ invasion by monocyte cells, 2/ by a soft connective tissue, 3/ osteoblasts differentiation at the

1. Literature review A literature review including products similar to Leonardo has been realised using PubMed database.

The following products, composed of bioactive glass 45S5, are marketed: PerioGlas® (oral surgery), NovaBone® (orthopaedic sur-gery) and NovaBone-C/M® (Skull-maxillo-facial surgery) marketed by NovaBone (developped by US biomaterials) and Biogran® (de-velopped by Orthovita). One can also find bioactive glass 53S4 or S53P4 (Vivoxid, Finlande) with a different composition to 45S5: 53 % of SiO2, 23 % of Na2O, 20 % of CaO and 4 % de P2O5. Another product contains 60 % of SiO2 who is called 60S. A mix of bioac-tive glass and wollastonite called Cerabone A/W is also available on the market. Addition of wollastonite to the ceramic gives better mechanical properties. This product is used for hip and spine surgery.

Medical device vigilance has been conducted on bioactive glass products available in the market. One alert has been had as a conse-quence a hospitalization of patient despite the relationship between inflammation and Perioglas use was established.

Figure 3:Histological section in the

implantation area of bioactive glass 45S5

at 12 weeks (section by microtome/Giemsa)

Figure 4:Histological section in the implantation area of Bioactive glass 45S5 at 24 weeks (section by microtome/Giemsa)

Clinical Data

BIOAKTIVE GLASS 45S5: PERIOGLAS (NOVABONE)

NOVABONE (NOVABONE)

BIOGRAN (ORTHOVITA/BIOMET 3i)

BIOACTICE GLASS S53P4: BONALIVE (VIVOXID)

BIOACTIVE GLASS AW: CERABONE (AAP)

PRODUCTS EQUIVALENT

TO LEONARDO (MIX OF Ca, Na, Si, P)

Figure 2:Histological section in the implantation area of bioactive glass 45S5 at 4 weeks (section by microtome/Giemsa)

After 24 weeks, materials have the following biological characteristics: Materials are in particle form and damage. No reactions to foreign body are visible. Materials are totally inserted to the bone.

Bioactive glass 45S5 and ß-TCP materials can be considered as bio-active implants which contribute bone remodeling. At first, they are colonized by monocyte cells, then by a soft conjonctive tissue. Osteoblasts then differentiate at their surface and are responsible for the synthesis of immature bone matrix. Finally, the immature matrix is remodelled, repaced by mature bone. During this final stage, implants are damaged with variable-speed. 12 weeks the materialimplantation, bioactive glass 45S5 was more damaged than the ß-TCP control materialß-TCP. After 24 weeks, both materials were damaged and totally integrated to the bone. No foreign body was visible in the implantation sites.

| 4 5 |

Repair of orbital fl oor fractures with bioactive glass implants [EC1]

Aitasalo et al.

J oral maxillo-facial surg 2001, vol 59:12, page 1390

Orbital fl oor fracturesUse of bioactive glass S53P4 implants

36 patients from 1995 to 1999

Clinical and radio-locical follow-up of 28 patients at one-year

Bioactive glass implants were well-to-lerated. No foreign body reaction and no infl ammation. New bone formation around the implants.

Using 45S5 Bioglass cones as endosseous ridge maintenance implants to prevent alveolar ridge resorption: a 5-year evaluation [EC2]

Stanley et al.

Int J Oral Maxillofac Implants 12 (1), 95 (1997)

Use of bioactive glass 45S5 cones after removal of tooth roots to delay the resorp-tion of alveolar ridges.

168 implants in 20 recalled patients

Clinical follow up at fi ve-years

Good results. Only 7.7 % of the implants required recontouring. High rate of bioactive glass cone retention (85.7 % ) after 5 years. The authors recommend their placement into fresh sockets to maintain the alveolar ridge.

Effects of pretreatment clinical parameters on bioactive glass implantati-on in intrabony periodon-tal defects [EC3]

Park et al.

J Periodontol 72 (6), 730 (2001)

Clinical effects of bioactive glass 45S5 implanta-tion in intrabony periodontal defects.

38 intrabony defects from 38 patients

Evaluation of preoperati-ve and postoperative pro-bing depth (PD), clinical attachment level (CAL), bone probing depth (BPD) and gingival recession at 6 months after surgery

Use of a bone substitute in a fl ap ope-ration resulted in signifi cantly greater improvements in CAL and BPD over fl ap operation alone and seemed to have positive effects in postoperative PD, CAL, BPD in those cases with more severe preoperative CAL and BPD.

Clinical comparison of bioactive glass bone repla-cement graft material and expanded polytetrafl uo-roethylene barrier mem-brane in treating human mandibular molar class II furcations [EC4]

Yukna et al.

J Periodontol 72 (2), 125 (2001)

Treatment problems of man-dibulaire Class II furcations

27 pairs of mandibulaire molars in 27 patients (27 molars with Perioglas (granules from 0.09 to 0.71 mm) and 27 molars with ePTFE membrane)

Follow up during 6 months: clinical attach-ment level, bone probing depth and gingival recession

Equal clinical results with bioactive glass bone replacement graft material and e-PTFE barriers in mandibular molar Class II furcations. Bioactive glass required no additional material removal procedures.

Bioabsorbable membrane and bioactive glass in the treatment of intrabony defects in patients with generalized aggressive periodontitis: results of a 5-year clinical and radio-logical study [EC5]

Mengel et al.

J Periodontol 77 (10), 1781 (2006)

Bioactive glass in the treatment of intrabony peri-odontal defects

16 patients: 22 intrabony defects treated with the Resolut XT membrane and 20 tre-ated with Perioglas 45S5 bioactive glass

Clinical and radiological prospective 5-year study

No signifi cant difference between the two groups. Both regenerative materi-als gave good results in the treatment of intrabony periodontal defects.

Clinical evaluation of an enamel matrix protein derivative combined with a bioactive glass for the treatment of intrabony periodontal defects in humans [EC6]

Sculean et al.

J Periodontol 73 (4), 401 (2002)

Treatment of deep intrabony defects

28 patients: 14 in each group Perioglas + Emdogain or Perioglas alone

Clinical study at 1 years with evaluation of probing depth, clinical attachment level and gingival recession

No signifi cant improvements of the investigated clinical parameters after 1 year. Both therapies led to signifi cant improvements of the investigated clinical parameters, and the combina-tion of enamel matrix derivative and bioactive glass does not seem to addi-tionally improve the clinical outcome of the therapy.

Clinical evaluation of bioactive glass in the treatment of periodontal osseous defects in human [EC7]

Lovelace et al.

J Periodontol 69 (9), 1027 (1998)

Treatment of hu-man periodontal osseous defects

15 patients: 30 osseous defects treated: 15 with Perioglas and 15 with DFDBA(demineralised freeze-dried bone allograft)

Clinical follow-up at 6 months with evaluation of probing depth, clinical attachment level and gingival recession

No statistical difference was found when comparing bioactive glass to DF-DBA. The study suggests that bioactive glass is capable of producing results in the short term similar to DFDBA.

Bioactive glass S53P4 in frontal sinus obliterati-on: a long-term clinical experience [EC8]

Peltola et al.

Head Neck 28 (9), 834 (2006)

Osteoplastic frontal sinus operations on patients suffering from chronic frontal sinusitis

42 patientsUse of bioactive glass S53P4 (granules from 0.5 to 1 mm)

Clinical and radiological prospective after 1, 6 and 12 months

Accurate obliteration of sinuses was achieved in 39 patients. Uneventful recovery and clinical outcome were seen in 92 % of the patients. Bioactive glass S53P4 appears to be a reliable frontal sinus obliteration material.

Bioactive glass granules as a bone adjunctive material in maxillary sinus fl oor augmentation [EC9]

Turunen et al.

Clin Oral Implants Res 15 (2), 135 (2004)

Bilateral sinus fl oor augmentati-on procedure

17 patientsUse of bioactive glass S53P4 (granule from 0.8 to 1 mm) mixed with autologous bone or bone alone.

62 weeks of Clinical follow-up. Biopsies for histological analyses were studied.

Similar results between two groups. Bioactive glass granules can be used together with autologous bone chips for sinus augmentation procedure, thus decreasing the amount of bone needed.

Title Authors Journal Indication Patients Follow-up Conclusion

Title Authors Journal Indication Patients Follow-up Conclusion2. Publications on bioactive glassOnly the clinical studies with more than 12 patients have been selected. They can be found in the table below, named [EC1] to [EC18].

| 6 7 |

Maxillary sinus fl oor augmentation using bioactive glass granules and autogenous bone with simultaneous implant placement [EC10]

Cordioli et al.

Clin Oral Implants Res 12 (3), 270 (2001)

Maxillary sinus augmentation with simulta-neous implant placementbiogran 70–80 % (orthovita) + 20–30% autolo-gous bone

12 patients: unilateral or bilateral sinus augmentation with grafting of 27 implants

Radiography and histo-logical studies (CT) bet-ween 9 and 12 months. Biopsies for histological analyses were taken

Biogran with autologous bone graft combination used in one-stage sinus augmentation yields suffi cient quality and volume of mineralized tissue for predictable simultaneous implant placement in patients with 3–5 mm of bone height prior to grafting. 26 implants were stable 12 months post loading.

reconstruction of orbital fl oor fractures using bioactive glass [EC11]

Kinnunen et al.

J Cranioma-xillofac Surg 28 (4), 229 (2000)

Repair of orbital fl oor defects after trauma.

28 patients: 14 with bioactive glass S53P4 et 14 with autologous bone

Clinical and radiography follow-up between 2 and 5 years

Bioactive glass implants are well-tole-rated and seem to be a promising re-pair material for orbital fl oor fractures as well as use of autologous bone

Four-year results of a prospective-controlled clinical study evaluating healing of intrabony de-fects following treatment with an enamel matrix protein derivative alone or combined with a bioactive glass [EC12]

Sculean et al.

J Clin Perio-dontol 34 (6), 507 (2007)

Regenerative pe-riodontal surgery at intra-bony de-fects with either a combination of an enamel matrix protein derivative and bioactive glass or with protein alone

25 patients: 12 using enamel matrix protein and bioactive glass, 13 treated with enamel matrix protein alone

Following therapy at 1 and 4 years. Evaluation of clinical attachment level, probing depth and gingival recession

Results indicate that the clinical improvements obtained with both regenerative modalities can be maintained over a period of 4 years.

Alveolar ridge reconstruc-tion and/or preservation using root form bioglass cones [EC13]

Yilmaz et al.

J Clin Perio-dontol 25 (10), 832 (1998)

Filling of the alveolar ridge after extraction in order to avoid deformities of the residual alveolar ridge in the maxillary anterior region.

16 patients, 3 groups: bioactive glass 45S5 cones, artifi cial sockets, fresh extraction sockets

Clinical and radiography studies until 12 months

After 12 months, no dehiscences were detected and the differences in height between the groups remained signifi cant. Results indicate that this procedure is effi cient in reconstructing alveolar ridges deformed as a result of extraction.

Particulate bioglass as a grafting material in the treatment of periodontal intrabony defects [EC14]

Zamet et al.

J Clin Peri-odontol 24 , 410 (1997)

Treatment of periodontal intra-bony defects

20 patients: 44 sites (22 sites with Perioglas and 22 fl as surgery)

Follow-up was the carried out weekly and at 3, 6, 9 months and 1year post-surgery. Recording of probing pocket depth, probing attachment level and gingival recession. Radiography evaluation.

Bioactive glass is as effective as an adjunct to conventional surgery in the treatment of intrabony defects.

A bioactive glass particu-late in the treatment of molar furcation invasions [EC15]

Anderegg et al.

J Periodontol 70 (4), 384 (1999)

Treatment of molar furcation invasion defects

15 patientsreceived surgical therapy using bioactive glass compared to open fl ap debridement alone in human mandibular molar furcation defects

Follow-up at 3 and 6 months and evaluation of probing depth probing attachment level and bleeding

The study revealed the benefi ts of bioactive glass in the treatment of Class II furcation defects. study proves that the use of bioactive glass as a bone grafting material is safe and gives good results that are similar to the use of autologous bone.

Comparison of Bioactive glass synthetic bone graft particles and open debri-dement in the treatment of human periodontal defects. A clinical study [EC16]

Froum et al.

J Periodontol 69 (6), 698 (1998)

Repair response of bioactive glass synthetic bone graft particles and open debri-dement in the treatment of hu-man periodontal osseous defects

16 patients: 32 bone defects with Périoglas and 27 with fl ap surgery

Clinical Follow-up at 6, 9 and 12 months, evalua-tion of probing depth, probing attachment level and gingival recession

Bioactive glass showed signifi cant improvements in clinical parameters compared to open fl ap debridement.

Histological observations on biopsies harvested following sinus fl oor elevation using a bioactive glass material of narrow size range [EC17]

Tadjoedin et al.

Clin Oral Implants Res 11 (4), 334 (2000)

Bone augmen-tation capacity of bioactive glass particles in human sinus fl oor elevations

10 patients: bilateral grafting using a mixture of autogenous bone particles and bioactive glass 45S5 or bone particles.

Histomorphometrical methods at 4, 6 et 16 months from bone biopsiesv

All bioactive glass particles had di-sappeared by resorption at 16 months after grafting and had been replaced by bone tissue: mixture of autogenous bone and bioactive glass particles seems a promising alternative to autogenous bone only.

Clinical evaluation of platelet-rich plasma and bioactive glass in the treatment of intra-bony defects [EC18]

Demir et al.

J Clin Perio-dontol 34 (8), 709 (2007)

Filling intrabony defects

29 patients:15 patients treated with bioactive glass+ PRP (platelet rich plasma) and 14 treated with bioactive glass only

Clinical evaluation of probing depth, probing attachment level and gingival recession at 9 months

Both PRP and bioactive glass combina-tion and bioactive glass alone are effective in the treatment of intra-bony defects. Using PRP with bioactive glass has no additional benefi ts.

Title Authors Journal Indication Patients Follow-up Conclusion Title Authors Journal Indication Patients Follow-up Conclusion

combined with a bioactive glass [EC12]

and bioactive glass or with protein alone

Alveolar ridge reconstruc-tion and/or preservation using root form bioglass cones [EC13]

Yilmaz et al.

J Clin Perio-dontol 25 (10), 832 (1998)

Filling of the alveolar ridge after extraction in order to avoid deformities of the residual alveolar ridge in the maxillary anterior

16 patients, 3 groups: bioactive glass 45S5 cones, artifi cial sockets, fresh extraction sockets

Clinical and radiography studies until 12 months

maxillary anterior region.

| 8 9 |

3. Evaluation of the clinical dataEvaluation of clinical publications on bioactive glass is based on the literature review already published. The previous table sums up scientific studies where bioactive glass is used in oral clinical sur-geries. This paragraph is devised in two parts: ■ Preclinical and clinical studies on bioactive glass resorption ■ Clinical studies in oral surgery.

3.1 Bioactive glass resorption

Bioactive glass particles are composed of an amorphous mixture of calcium, silicon, phosphate and sodium. The resorption by ionic dissolution improves the contact surface of the material, allowing a better blood circulation and increasing the cells anchoring.

Different in vivo studies assessed bioactive glass resorption. A his-tomorphometrical study[7] conducted on rabbits showed the disso-lution capacities of three different types of bioactive glasses. The authors observed that 45S5 bioactive glass had the most important kinetics of bone fixation and the faster resorption rate. Oonishi’s study[8] showed that the he major part of bioactive glass particles is absorbed between 8 to 12 months after implantation in femoral condyles of rabbits. Particles could not be identified at further times of observation.

Ducheyne[9] evaluated the elimination of bioactive glass resorption products and showed that silicon oxide elimination was included into the acceptable limits for the tested animals. The approximate time of silicon oxide elimination is 2.4 mg/day and 100 % of implan-

ted silicon oxide is eliminated after 19 days. Another study [EC15] concerning human-beings follow-up has been studying the rate of silicon in the blood. 25 patients had graft surgery using bioactive glass or autologous bone after tumors resection. Blood analyses have been realised at different times until 36 months. Results showed that there is no significant difference in the patients’ blood silicon concentration between the group treated with bioactive glass only and the group treated with autologous bone. Besides, the quantity of implanted bioactive glass, which depends on the volume of the defect to fill, has no influence on the silicon concentration in blood.

Moreover, studies have proved that silicon is involved in bone remo-delling. Indeed, Reffitt [d] has showed that addition of orthosilicic acid in osteoblast cell culture stimulated type I collagen synthesis and osteoblastic differentiation. We can think that silicon released by bioctive glass could have a positive effect on bone remodelling.

3.2 Clinical studies in oral surgery

There are numerous clinical studies related to the use of bioactive glass in oral surgery, with a follow-up at different levels: clinical parameters, radiographs, biopsies. The main clinical studies in previ-ous table deal with the treatment of periodontal defects.

Diagnostic of periodontal diseases is made on clinical signs such as redness, oedema or inflammation. Periodontal clinical examination has to evaluate presence and quantity of bacterium blotch, bloo-ding, probe depth, probe attachment level and mobility. Three diffe-rent surgical techniques have been identified: flap surgery, guided tissue regeneration technique, and bone grafting treatment.

Three comparative and randomized studies compare two first techniques to bone grafting using bioactive glass. Zamet [EC14] showed that bone grafting with bioactive glass is better than flap surgery from bone remodelling aspect. Froum [EC16] and Park [EC3]

showed that bone grafting with bioactive glass is the best: the pro-bing depth was better and attachment level too.

3.3 Literature review conclusion

Clinical data showed that the use of bioactive glass for bone graf-ting in oral surgery gives good results, similarly to autologous bone. The majority of these published studies are randomised and compa-rative studies with a little number of patients. A clinical study with more patients could improve the scientific evidence of effectiveness of bioactive glass.

This great number of studies proves that the use of bioactive glass as a bone grafting material is safe and gives good results that are similar to the use of autologous bone.

This evaluation of clinical studies is completed with the clinical follow-up of Bioactive glass 45S5 product.

7 Vogel, M., et al., In vivo comparison of bioactive glass particles in rabbits. Biomaterials, 2001. 22(4): p. 357–62.8 Oonishi, H., et al., Particulate bioglass compared with hydroxyapatite as a bone graft substitute. Clin Orthop Relat Res, 1997(334): p. 316–25.9 Lai, W., et al., Excretion of resorption products from bioactive glass implanted in rabbit muscle. J Biomed Mater Res A, 2005. 75(2): p. 398–407

| 10 11 |

Im Rott 8 – 69493 Hirschberg – GermanyTel.: +49 (0) 6201 8 44 38 27Fax: +49 (0) 5624 92 60 79