Bone Substitute MaterialsOverview

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What can patients and surgeons expect from us? Reliable products, and expertise, which ensures secure application. Moreover, develop-ments needed in the future.

Biomet is one of the leading orthopaedic companies worldwide. We develop and produce products for orthopaedic and trauma surgery. Our predominant competence enables us to accompany our clients continuously in clinical surgeries.

This vicinity has an impact: We take impulses in, and our own Research and Development Department is a direct contact partner for new ideas. Here we connect the clinically documented quality of our implants with the future orientated possibilities of bioactive materials. Through this we become an innovation force and are able to face the continuous devel-opments in our markets more flexibly.

The results are products and performances, that aid the surgeons’ community, to support the healing process of their patients in a medically optimal, scientifically proven, and cost-effective manner.

Content

Introduction 3Overview 4Endobon 6Calcium Phosphate 8Calcibon Paste 10Calcibon Granules 12Ordering Information 14References 16

Legal noticeThis material is intended for educational purposes only. Any medical information included herein is for information purposes and shall not be used in any way as substitute for professional advice provided by a physician or other health care provider.

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Bone Substitute Materials from Biomet

Time-tested ProductsAutologous graft, bone bank or bone substitute material? The first criterion when treating a bone defect is always a rapid recovery process, without as few complications for the patient as possible. More over economical and technical aspects are essential. The treatment with bone substitutes proves to be well suited for the treatment of bone defects with respect to availability, duration of surgery and incurred costs, linked with excellent compatibility and documented treatment achievements.

Quality and Unlimited Quantity Biomet developed a portfolio of bone substitute materials (based on mainly hydroxyapatite calcium phosphates). Un-like autologous material, they have the advantage to have a rapid availability in constant quality and unlimited quantity. Furthermore, the application of bone substitute materials avoids a second surgery for harvesting autologous material: The duration of the surgery and the anesthesia are reduced and patients are not faced with possible complications and pain at the donor site.Bone substitute materials have advantages in compari-son to bone bank materials: There are no logistics issues in providing the materials for surgery and they are available in adequate quantity.

A Solution for Each IndicationNot all bone substitute materials are the same: For each separate indication, suitable bone substitute materials were thoroughly researched and developed. Particularly the utilisation of different substances with specific characteristics and functionalities supports the healing process in the long run. Biomet's bone substitute ma-terials have proven to be of high quality for a number of years already. Their excellent biocompatibility and their clinical success are documented extensively. Praxis- orientated trainings and consulting services aid to support surgeons and their personnel in order to ensure consistent successful application.

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Overview Bone Substitute Materials: A Solution for Each Indication

A precondition for successful clinical use of bone substitu-tes are the exact indication and the correct application. They are suitable for non-infected, metaphyseal, cancellous bone defects. Bone substitutes should only be implanted into a vital bony bed. When utilizing bone substitute materials, it is always vital to carry out a correct reposition and an adequate osteosynthesis.

Product Endobon Calcibon Calcibon Granules

Blocks, Cylinder, Granules

Paste (liquid & powder)

Granules

Basic Material Hydroxyapatite (ceramic) Calciumdeficient hydroxyapatite Calciumdeficient hydroxyapatite

Material Properties BiologicalStable osseous integrationReady-to-useAugmentablePorous

SyntheticStable osseous integration

SyntheticStable osseous integrationReady-to-useAugmentablePorous

Characteristics Osteoconductive OsteoconductiveBiodegradable

OsteoconductiveBiodegradable

Indications 1. Tibia plateau fractures2. Osteotomies

1. Distal radius fractures 2. Calcanus fractures3. Tibia plateau fractures

1. Mixing with spongiosa2. Large bone defects, e.g. hip revision

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Product Endobon Calcibon Calcibon Granules

Blocks, Cylinder, Granules

Paste (liquid & powder)

Granules

Basic Material Hydroxyapatite (ceramic) Calciumdeficient hydroxyapatite Calciumdeficient hydroxyapatite

Material Properties BiologicalStable osseous integrationReady-to-useAugmentablePorous

SyntheticStable osseous integration

SyntheticStable osseous integrationReady-to-useAugmentablePorous

Characteristics Osteoconductive OsteoconductiveBiodegradable

OsteoconductiveBiodegradable

Indications 1. Tibia plateau fractures2. Osteotomies

1. Distal radius fractures 2. Calcanus fractures3. Tibia plateau fractures

1. Mixing with spongiosa2. Large bone defects, e.g. hip revision

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Endobon

Primary stable

Osteoconductive

Interconnecting pore system

Augmentable

Endobon is a natural hydroxyapatite ceramic (HA ceramic), which is particularly suitable as a bone graft substitute. It is of biological origin and osteoconductive. The newly formed bone can grow directly onto the ceramic surface and into the implant. The interconnecting pore system of Endobon allows the new bone to grow through the whole implant.

Indications Endobon is an excellent bone substitute material for impression fractures close to the joint, like tibia and radius fractures, for fractures of the calcaneus and for osteotomies.

Material Properties Endobon is a primary stable hydroxyapatite ceramic. The inner structure with its interconnecting system of macro and micro pores with pore sizes of 100 to 1,500 μm allows the newly formed bone to grow through the whole implant. This finally leads to a stable osseous integration of the Endobon implant.Endobon has a porosity of 45-85 Vol.% and a density of 0.4 to 1.6 g/cm3 resembling the values of natural bone.

Quality and Production Endobon is manufactured in a two-stage high-tempera-ture process: • 1. Pyrolysis above 900°C • 2. Sintering above 1,200°C This leads to a complete combustion and ablation of all bacteria, viruses, and prions from the original material. Endobon has been successfully used in clinical applications for more than 15 years.

UsageEndobon is available in the form of blocks, cylinders, or granules of different sizes. The latter are especially suited for augmentation of autologous bone chips.All forms are easily and rapidly usable during surgery.The blocks and cylinders are especially suitable for fractures below load bearing joints, e.g. tibia plateau fractures. The granules should be used for filling irregularly formed defects.

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6 Weeks Post-operatively 6 weeks after the implantation of Endobon, integration of the implant with the surrounding vital bony bed can be seen on the microscopic analysis.

3 Months Post-operatively After 3 months, the microscopic analysis shows a nearly complete osseous integration of the implant.

6 Months Post-operatively After 6 months, the histological slide shows direct contact of the newly formed bone (1) and the ceramic surface (2).

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Calcium Phosphate – The Calcibon Family

Synthetic

Primary stable

Osteoconductive

Biodegradable

Calcibon is a synthetic, biodegradable bone substitute material. It belongs to the family of calcium phosphates, a group of osteoconductive bone substitutes. The cured Calcibon material is a micro-crystalline, calciumdeficient hydroxyapatite. The chemical composition and the crystal-line structure of the cured material mimic the mineral part of natural bone.

Material Properties Calcibon powder is synthesized from calcium and phosphate salts. Its different components are Tri-calcium-phosphate, calcium-hydrogen-phosphate and calcium carbonate.

The Biodegradability Calcibon has the potential to be biodegraded by the surrounding vital bony bed through remodelling. Calcibon is thereby broken down by osteoclasts and the new bone is reconstructed by osteoblasts. The remodelling process depends on the individual and the environment where Calcibon is implanted. A vital bony bed, close contact with the surrounding bone, and a func-tional stimulation improve the rate of the remodelling.

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• Osteoclasts recognize bone mineral like surface

• Osteoclasts start degradation

• Osteoclasts release differentiating factors and thereby induce differentiation

and activation of pre-osteoblasts

• Differentiation of mesenchymal stem cells

• Activation of pre-osteoblasts

• Osteoblasts synthesis and deposit new bone matrix with subsequent mineralization

Mechanical stimulation Mesenchymal stem cells

Pre-osteoblasts

New bone matrix

Differentiating factors

Osteoblasts

Calcibon – Two Products: Paste or Granules The synthetic calcium-phosphate material Calcibon is available in two different forms: as a paste, mixed from a liquid and a powder component, or ready-to-use as granules.

Despite identical origins the two products, Calcibon and Calcibon Granules differ in their properties regarding further processing. Both products are introduced in more detail on the following pages.

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Calcibon Paste

Calcibon consists of two components: Calcibon liquid and Calcibon powder. Mixing these two components results in a smooth and malleable paste ideal for filling bone defects. The paste hardens at body temperature in-situ and reaches a very high compressive strength.

Processing The Calcibon paste is mixed directly before application. Calcibon liquid is an aqueous di-sodium-hydrogen-phos-phate solution, which initiates the curing process within the paste.

The processing cycle of Calcibon has been optimized in consideration of the Operating Room environment:

• Short mixing time 1 minute • Sufficient application time 4 minutes • Acceptable final setting time 5 minutes

Overall required time 10 minutes

The Compressive Strength One of the outstanding properties of Calcibon is its extremely high compressive strength. In-vitro testing shows that after 6 hours, the cured final material shows a com-pressive strength of approximately 15 MPa, already in the range of the strength of cancellous bone (10-20 MPa). This compressive strength continues to increase over time and results in a final strength of up to 45 MPa after 3 days. Thus, the compressive strength is in the area of cortical bone (25-100 MPa).

15 MPa = 6 hours

45 MPa = 3 days

60

40

20

0 50 100

Co

mp

ress

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stre

ngth

(M

Pa)

Time (h)

Compressive strength versus timeAfter 6 hours the compressive strength of Calcibon is comparable to that of cancellous bone. After 3 days the final compressive strength of up to 45 MPa is reached.

High compressive strength

Good clinical results

Easy handling

Hardens in aqueous environment

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24 weeks post-operatively Continued biodegradation of Calcibon and subsequent bone in-growth. The new bone is mature and cannot be discerned from original trabecu-lar bone.

16 weeks post-operatively Parts of the Calcibon implant material have been biodegraded followed by bone in-growth. Remodelling activity at the interface, as characterised by the presence of remodelling lacunae (RL) and osteoclast-like cells (black arrows), was still seen.

2 weeks post-operatively Detailed picture of the bone formation at the contact site Calcibon im-plant-bone. The Calcibon surface is covered with an osteoid-layer (*).

Osteoblasts

Osteocyte

Calcibon

Bone

Calcibon

Calcibon

Indications Calcibon is indicated for refilling of noninfected, meta- physeal, cancellous bone defects caused either by trauma, benign tumour, surgery, or congenital. Calcibonmay also be used to refill cavities created in connection with kyphoplasty, if classified as fracture type A1 (according to Magerl classification).

The most common indications for the clinical use of Calcibon are distal radius fractures, tibia plateau fractures, and calcaneus fractures.

Usage The cohesion time of Calcibon is extremely short. Already after mixing, the binding forces inside the paste are high enough to ensure the form stability of the material, even in an aqueous environment.

Even though Calcibon should be implanted into a dry and blood-free environment, the short cohesion time allows an implantation into a wet bony bed, where the material will keep its form and harden adequately.

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Calcibon Granules

Refilling of lange bone defects

Porosity supports remodelling process

Augmentation with other material

Utilization in revision surgery

Calcibon Granules are a line extension of the existing Calcibon product range. Like the paste, the granules are also manufactured synthetically, are biodegradable and biocompatible. The main differences: The granules are ready-to-use, however, due to their porosity the compres-sive strength is reduced. In addition they are highly suita-ble to be used for augmentation in combination with other materials.

Material Properties The production process of Calcibon Granules is at first glance identical to the one of the Calcibon powder. Never-theless, the mixing of the two components already takes place during production. The granules are hence a com-pletely hardened material. Due to a special manufacturing technique porous granules with micro and macro pores are produced.

The porous Calcibon Granules have macro pores of 150-550 µm. These allow cells, e.g., osteoclasts and osteo-blasts, to migrate into the granules. The activities of these cells enable the cellular biodegradation of the Calcibon Granules and the formation of new autologous bone.

The macro pores are separated from each other by thin walls, which in turn consist of a micro porous network. These micro pores allow the cells involved in the remodel-ling process to be supplied with nutrients.

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Scanning electron microscope image of the interconnecting micro pore system. Magnification x 3,000

2 ml Calcibon Granules mixed with 1 ml PRP (Platelet-Rich-Plasma of Biomet Biologics)

Indications Generally, Calcibon Granules are intended for filling and reconstructing large, non-infected, metaphyseal, cancel-lous bone defects. The origin of these defects can vary greatly; from e.g., trauma, benign tumour, surgery, to congenital.

Calcibon Granules can be used as filling material for revision hip surgery, e.g., for the reconstruction of the acetabulum and to fill the shaft. Moreover, the granules can be used as filling material for cages in spinal surgery.

Use Calcibon Granules are ready-to-use. No mixing time has to be taken into account.

Calcibon Granules can be applied directly to the aseptic bone bed or augmented with other material, such as bone marrow, bone grafts, blood, and PRP (Platelet-Rich-Plasma, extracted with the GPS III System).

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Ordering Information

Calcibon Synthetic calcium-phosphateProduct Description Quantity Art. Nr.

Calcibon 5 g circa 4 ml paste 30 3005 0001

Calcibon 10 g circa 8 ml paste 30 3010 0001

Calcibon 20 g circa 16 ml paste 30 3020 0001

Calcibon Granules 10 10 ml Granules 30 3210 0001

Calcibon Granules 20 20 ml Granules 30 3220 0001

Calcibon Granules 50 50 ml Granules 30 3250 0001

Product Description Granules size Art. Nr.

Granules I 5 ml 1.5 - 2.8 mm 30 2034 0001

Granules II 5 ml 2.8 - 5.6 mm 30 2035 0001

Granules II 10 ml 2.8 - 5.6 mm 30 2069 0001

Endobon HydroxyapatiteProduct Description Size Art. Nr.

Block 5 5.0 x 5.0 x 10.0 mm 30 2037 0001

Block 12.5 12.5 x 12.5 x 10.0 mm 30 2030 0001

Block 20 20 x 20 x 10.0 mm 30 2031 0001

Product Description Size Art. Nr.

Cylinder 9 Ø 8.50 x 20 mm 30 2022 0001

Cylinder 10 Ø 9.55 x 20 mm 30 2023 0001

Cylinder 11 Ø 10.60 x 20 mm 30 2024 0001

Cylinder 12 Ø 11.70 x 20 mm 30 2025 0001

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Notes

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Worldwide distributorBiomet Deutschland GmbHGustav-Krone-Str. 2D-14167 BerlinTel.: +49 / 30 / 845 81-0Fax: +49 / 30 / 845 81-110www.biomet.de

Responsible manufacturers:Calcibon, Calcibon GranulesBiomet Deutschland GmbHGustav-Krone-Str. 2D-14167 Berlin

www.biomet.de

EndobonBiomet France S.A.R.L.58 Avenue de LautagneB.P. 75F-26903 Valence Cedexwww.biomet.fr 04590123

Calcibon and Calcibon Granules

1. Driessens F.C.M., Boltong M.G., Wenz R.: „Calcium phosphate bone cements: State of the art 2000”. 12th Conference of the European Society of Biomechanics, Dublin, Ireland, 27–30th August 2000.

2. Hillmeier J., Meeder P.J., Nöldge G., Kasperk C.: „Minimally invasive reduction and internal stabilization of osteoporotic vertebral body fractures (Balloon Kyphoplasty)”. Operat. Orthop. Traumatol 2003; 15: 343–362.

3. Hillmeier J., Meeder P.J., Nöldge G., Kock H.J., Da Fonseca K., Kasperk C.: „Augmentation von Wirbelkörperfrakturen mit einem neuen Calciumphosphat-Zement nach Ballon-Kyphoplastie”. Orthopäde 2004; 33: 31–39.

4. Hillmeier J., Grafe I., Da Fonseca K., Meeder P.J., Nöldge G., Libicher M., Kock H.J., Haag M., Kasperk C.: „Die Wertigkeit der Ballonkyphoplastie bei der osteoporotischen Wirbelkörperfraktur”. Orthopäde 2004; 33: 893–904.

5. Linhart W., Briem D., Peters A., Lehmann W., Windolf J., Rueger J.M.: „Resorbierbare Kalziumphosphatzemente”. Trauma Berufskrankheit 2004; online: 29. Oktober.

6. Ooms E.M., Wolke J.G.C., van der Waerden J.P.C.M., Jansen J.A.: „Trabecular bone response to injectable calcium phosphate (Ca-P) cement”. J-Biomed-Mater Res 2002; 61: 9–18.

7. Ooms E.M., Wolke J.G.C., van de Heuvel M.T., Jeschke B., Jansen J.A.: „Histological evaluation of the bone response to calcium phosphate implanted in cortical bone”. Biomaterials 2003; 24: 989–1000.

8. Ooms E.M., Egglezos E.A., Wolke J.G.C., Jansen J.A.: „Soft-tissue response to injectable calcium phosphate cements”. Biomaterials 2003; 24: 749–757.

9. Schnettler R., Stahl J.P., Alt V., Pavlidis T., Dingeldein E., Wenisch S.: „Calcium phosphate-based bone substitutes“. Europ. J. Trauma 2004; 30: 219–229.

Endobon

1. Baer W., Schaller P., Carl H.D.: „Spongy hydroxyapatite in hand surgery – A five year follow-up". J. Hand. Surg. (Br) 2002; 27B: 101–103.

2. Briem D., Linhart W., Lehmann W., Meenen N.M., Rueger J.M.: „Langzeitergebnisse nach Anwendung einer porösen Hydroxyapatitkeramik (Endobon) zur operativen Versorgung von Tibiakopffrakturen”. Unfallchirurg 2002; 105: 128–133.

3. Großpeter A.S., Pretzsch M., Frh. van Salis-Soglio G.: „Die Behandlung knöcherner Defekte mit der Hydroxylapatitkeramik Endobon – Eine mittelfristige klinische und radiologische Verlaufsbeobachtung bei 58 Patienten”. Orthopädische Praxis 2004; 40: 290–294.

4. Helber M.U., Ulrich C.: „Metaphysärer Defektersatz mit Hydro- xylapatitkeramik – 3- bis 4 Jahresnachuntersuchungsergebnisse”. Unfallchirurg 2000; 103: 749–753.

5. Kehr P., Gosset F.: „Endobon as a bone substitute in spine surgery. Preliminary study in 11 patients”. Europ. J. Orthop. Surg. Traumatol 2000; 10: 217–221.

6. Khodadadyan-Klostermann C., Liebig T., Melcher I., Raschke M., Haas N.P.: „Osseous integration of hydroxyapatite grafts in meta- physeal bone defects of the proximal tibia” (CT-Study). Acta. Chir. Orthop. Traumatol Cech. 2002; 69(1): 16– 21.

7. Müller-Mai C., Voigt C., Hering A., Rahmanzadeh R., Gross U.: „Madreporische Hydroxylapatitgranulate zur Füllung ossärer Defekte”. Unfallchirurg 2001; 104: 221–229.

8. Sailer R., Lutz M., Zimmermann R., Hackl W., Gabl M., Blauth M.: „Minimalinvasive Therapie der dislozierten distalen metaphysären Radiuskompressionsfraktur: klinische und radiologische Ergebnisse nach gedeckter Reposition, Stiftfixation und stabiler Defektauffüllung mit einer porösen Hydroxylapatitkeramik”. Akt. Traumatol 2003; 33: 26-30.

References

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