BONITmatrix® Bone remodeling – as perfect as nature

medical implant solutions

Biomaterials

Nature is setting the benchmark

3

The goal of all treatment methods forbone regeneration is the “Restitutio adintegrum”. To achieve this, bone graftsubstitutes have to be completely inte-grated via natural processes. In the idealcase the material should thus haveosteogenic, osteoconductive and osteo-inductive properties. So far only auto-graft bone transplant, the so called goldstandard, fulfils these functions. The disadvantage of this method is the need for a second operation, which isnecessary to harvest the autologous bonetissue. This intervention leads to morerisks for the patients, functional inter-ference and increased costs. Replacingthe autologous bone by the use of allo-genic or xenogenic materials can induceimmunological response. Furthermorehuman or animal transplants involve therisk of potential disease transmission.The limited availability of autologous tissue and the inherent risks of humanand animal based materials have lead tothe increased use of synthetic materialsin both orthopaedic and dental surgery. Crucial to the success of synthetic bonegraft substitutes is, that the materialshould be a bioactive material which iscompletely integrated into the naturalregeneration process of the bone.

Most synthetic bone graft materials aremade up of “structured” inorganic com-pounds. In combination with their struc-ture they serve as osteoconductive scaf-folds which guide bone growth. The ma-terials most frequently used are calciumphosphate-compounds (e.g. Hydroxylapatite), because they are most similar tothe naturally occurring inorganic or hardcomponent of the bone matrix. However,osteoconduction alone is no guaranteefor success. Deficits in the compositionof the material may considerably affectthe surgical success rate. One reason forthis is the hampering of physiologicalprocesses.

Moreover; certain manufacturing pro-cesses may substantially affect the suit-ability of a specific material. A good bone graft substitute should al-low physiological activities at a cellularlevel. It should support the formation ofbone and be simultaneously resorbed in a controlled manner.

Bone defect filling Accelerated osteogenesisMixed with autologous blood

BONITmatrix® - innovation for successfulbone regeneration

BONITmatrix® is a synthetic bone graftsubstitute for reconstruction of bonedefects.BONITmatrix® consists of a mixture ofthe two calcium phosphates hydroxy-apatite (HA) and ß-Tricalciumphosphate(ß-TCP) in the clinically proven ratio of 60/40. In contrast to conventional HA and ß-TCP based ceramics and bio-glasses BONITmatrix® is manufacturedin a sol-gel-process without sintering(patented sol-gel-procedure DE 100 03824). In this process nanocrystalline calcium phosphates are embedded in abiological active Silicon dioxide-matrix.

Utilising this special low temperatureprocess leads to a high interconnectingporosity inside the granules. The pore sizes are in the nano- and micrometerrange ensuring the products very largeinternal surface of approx. 90 m2/g. After mixing with autologous blood or bone marrow the granules are veryform-stable. Because of the simple and

safe surgical applicability and firm im-plantation site retention, BONITmatrix®is recommended for use in larger anddifficult to access dental defects(>1cm3).

Good biocompatibilityBONITmatrix® has a good biocompa-tibility and does not hinder wound healing. This and the surgical safety has been confirmed in biocompatibility,toxicology and clinical studies.

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Indications• Defects following the

exstirpation of bone cysts• Defects related to correction

osteotomies• Other polymural alveolar bone

defects• Parodontal defects• Defects after excision of

submerged third-molar teeth • Defects following root end

resection• Extraction defects for later

implant therapy• Sinus base augmentation and

elevation• Peri-implant defects• Defects after removal of

autologous bone

HA ß-TCP SiO2

60 : 40

87% 13 %

Nano-90 nm 400 nm porous

matrix

Production:Patented Sol-Gel procedurewithout sintering (DE 100 03 824)

BONITmatrix®- bone graft material: optimal composition

0,3 mm granulate 4,0 mm granulate

BONITmatrix® is available in various granulate and

package sizes (see page 11)

Specific to BONITmatrix® is the additionof the element Silicon in a biologicallyactive form. It is well-known that Sili-con has a regulating and stimulating influence on the natural mineralisationprocess [1, 2].The novel manufacturing process pro-duces a hydrated Silicon dioxide matrix.This results in a very important propertyrequired for osteogenesis, namely: theability to form a nano-crystalline apa-tite substrate on the material after in-sertion into a physiological environment(left Fig. P. 7). The FTIR-spectrum clearly shows theformation of an in vitro produced,superficial apatite phase layer with synthetic micro-crystalline hydroxy-apatite (centre fig. P. 7). BONITmatrix® serves as a catalyst forthe newly formed layer, which is com-parable to that found in young bone. Inthe scientific literature reprecipitationon to an unsintered silicon dioxide sur-face has been frequently described andinvestigated as a requirement for rapidbone formation [3, 4].

A complimentary effect is that thisnewly formed bioactive layer controlsthe dissolution speed of the underlyingsilicon dioxide matrix.

Controlled Ca-releaseThe embedding of the two calciumphosphates HA and ß-TCP into the silicon dioxide xerogel matrix causes an enduring locally increased ion concentration in the defect site (right fig. P. 7). Thereby supporting accelerated osteogenesis and increasedbone remodelling [5].

Accelerated bio-mineralisation by an innovative Silicon calcium phosphate composite

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FTIR-spectrum of the BONITmatrix® surface (blue line) comparedto that of synthetic micro-crystalline hydroxyl apatite (red line)after 90 minutes incubation in physiological saline

Precipitation of apatite onto the BONITmatrix® surface (substrate formation)

Ca-release (cumulative) by 24 hourly exchanges/day in Tris-HCl-buffer pH 7,3

Interconnecting pore systemBONITmatrix® has an implanted porosityof approx. 80%, whereas the single granules have a porosity of approxi-mately 60%. The interconnecting poresystem in the nano- and micrometerrange with its high capillarity and the adsorptive capacity of the surface allowfor the diffusion of biological fluids. The surface binding of important growthfactors present in blood etc. supportsosteogenesis. The material is osteocon-ductive and acts as a scaffold duringthe osteogenesis.

Results andCell culture studies have demonstratedthat BONITmatrix® is particularly effec-tive in supporting the growth and thefunctional performance of developingbone cells (osteoblasts and osteoclasts)[6].

in vivoin vitro

A randomised clinical study of BONIT-matrix® compared to a conventionallysintered bone graft material showed afaster osteogenesis and less post opera-tive wound inflammation. The investi-gators concluded that BONITmatrix®was simple and safe in the dental appli-cations reviewed [7].

Excellent absorption capacity through high porosity

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REM 1,000x magnification.Round cutout: REM 10,000x magnification

REM 2,000x magnification.Mesenchymal stem cell

REM 80x magnification

Application step by stepBONITmatrix® is suitable for the filling ofbone defects of different sizes. The bonegraft material is mixed with autologousblood and if possible with autologousbone marrow and or bone chips. The re-sulting malleable mass is simply placedinto the defect. The form stability and

good packing in the defect helps to pre-vent micro-motion. After the augmenta-tion the defect area should be coveredwith a periosteal flap or a membrane, toprevent the infiltration of fibrous tissueduring the healing phase.

[5] S. Overgaard “Calcium phosphate coatings for fixation of bone implants.”Acta Orthop Scand (2000), Suppl. 297 (71): 1-74

[6] F. Lüthen et al. „Adhesion and gene expression in osteoblasts on sol-gel-derived calcium phophate coatings.“Proceedings ESB 2003 Stuttgart P 081

[7] Mitteilungsblatt der Zahnärztekammer und der KZVMecklenburg-Vorpommern 1/2005: 20-22

Granulate and package sizes BONITmatrix®

From simple defect treatment to unhindered wound healing

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BONITmatrix® - advantages at a glance• Accelerated bone

regeneration• Practically complete

resorption• Totally synthetic• Unhindered wound healing• Good biocompatibility with

no foreign body reaction reported

• interconnecting nano- and micro-pore system

• High capillary effect• No electrostatic charge • Simple and safe handling

(form-stable, retained in the defect)

Literature:

[1] E.M. Carlisle „Silicon as a trace nutrient.”Sci Total Environ (1988), 73 (1-2): 95-106

[2] S. Hidaka, Y. Okamoto, K. Abe „Possible regulatory rolesof silicic acid, silica and clay minerals in the formationof calcium phosphate precipitates.”Arch Oral Biol (1993), 38 (5): 405-413

[3] P. Li, C. Ohtsuki, T. Kokubo, K. Nakanishi, N. Soga „Apatite formation induced by silica gel in simulated bodyfluid.” J Am Ceram Soc (1992), 75: 2094-2097

[4] S. Radin, S. Falaize, MH Lee, P. Ducheyne „In vitro bioactivity and degradation behaviour of silicaxerogels intended as controlled release materials.“Biomaterials (2002), 23: 3113-3122

Opening and debridement of the defect area Mixing with autologous bloodPre-operative surgical planning

Placement of a membrane over the augmented site Wound closure

4A

1 2 3

Order number Package size Granulate size

BM01.06.40.0025 0,25g 0,6 x 4 mmBM01.06.40.005 0,5g 0,6 x 4 mmBM01.06.40.010 1,00g 0,6 x 4 mmBM01.06.03.0025 0,25g 0,6 x 0,3 mm

4B 5 6

Filling of a defect with the BONITmatrix® autologous blood mixture

We look forward to working for you

DOT GmbHCharles-Darwin-Ring 1a18059 RostockGermany

Tel: +49 (0)381- 4 03 35-0Fax: +49(0)381- 4 03 35-99info@dot-coating.dewww.dot-coating.de

medical implant solutions B-BM

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DOT – Specialist for dental and orthopedic implants

DOT is one of Europe's leading providers of medical coating solutions for orthopedicand dental implants, instruments and also their cleanroom packaging.

We also manufacture implants and products for regenerative medicine, dental andorthopedic applications.

Our comprehensive supply chain concept makes us an ideal medical technologypartner. Our activities help restore the health of patients worldwide and thus make amajor contribution to the improvement of their quality of life.