**4.1.3 Dental filling materials**

66 Biomaterials – Physics and Chemistry

ray, and three questions regarding subjective symptoms were put to patients: 1. Have you had any persistent symptoms? 2. Do you know which tooth was treated? 3. Can you feel

In 13 of the 17 treated patients the diagnosis was chronic perapical osteitis (c p o). These were treated with retrograde root filling (rf) therapy. Three patients suffered from trauma or chronic perapical destruction, and these patients were treated with orthograde therapy. Out of 17 patients (22 teeth) treated, 16 patients (21 teeth) were examined with follow-up x-ray after treatment and also after two years or more. The additional patient was asked about symptoms. The results of both the clinical examination and the subjective symptoms were graded into different groups related to the success of the therapy. The results of the 2-year

> 2 Incomplete healing

Fig. 9. Tooth 21 (patient14) a) condensing with a Gutta-percha pointer, b) just after treatment

Fig. 10. Tooth 21 (patient 9) at treatment (left) and at two year control (middle) and at 5 year

In summary 21 out of 22 treated teeth have acceptable results being either symptom free or judged healed after clinical examination. The single failure can probably not be attributed to

 2-year 5-year 2-year 5-year 2 year 5-year 2-year 5-year Nos. of teeth 18 14 3 2 0 0 1 0 Percentage 82 87 14 13 0 0 4 0 Table 14. Summary of the results (Score 1 and 2 considered successful, score 3 and 4 failure) Figures 9-10 show examples of the X-ray examination of orthograde and retrograde

3 Uncertain 4 Failure

any symptoms at the tooth apex?

treatments.

and c) at two year control

control (right)

and the 5-year study are shown in Table 14.

1 Complete healing

> An important feature of the hydration mechanisms of the Ca-aluminate based materials is the nanostructural integration with and the high shear strength developed towards dental tissue. This makes both undercut (retention) technique and bonding techniques redundant. The Ca-aluminate approach to dental filling technique is new. With this technique, the chemical reactions cause integration when the bioceramic material is placed in the oral cavity at body temperature and in a moist treatment field. Figure 11 shows a TEM (transmission electron microscopy) illustration of the interface between the CA-based material and dentine. This establishes a durable seal between bioceramic and tooth. Whereas amalgam attaches to the tooth by mechanical retention and resin-based materials attach by adhesion, using bonding agents, etchants, light-curing or other complementary techniques, the CA-materials integrate with the tooth without any of these, delivering a quicker, simpler and more robust solution.

Fig. 11. Nanostructural integration of CAPH-material with dentine (gray particles in the biomaterial are glass particles)

The general aspects of Ca-aluminate based materials have been presented in two Ph D Thesis-publications. Important aspects of Ca-aluminate materials as dental filling materials are dealt with, such as dimensional stability, acid corrosion and wear resistance, and biocompatibility and mechanical properties (Kraft 2002, Lööf et al 2003).

#### **4.1.4 Coatings on dental implant and augmentation**

For successful implantation of implants in bone tissue, early stabilisation is of great importance (Ellingsen and Lyngstaadas, 2003). This includes both orthopaedic and dental

Nanostructural Chemically Bonded Ca-Aluminate Based Bioceramics 69

Fig. 12. High-resolution TEM of Ti – CA-paste interface, nano-mechanical integration, bar =

Within orthopedics the following areas for Ca-aluminate based materials have been identified; percutaneous vertebroplasty (PVP) and kyphoplasty (KVP), trauma and general

The benefits of the injectable ceramic biomaterials based on CA related to orthopaedic

 High radiopacity allows for superior visibility of the cement during and increases the probability to detect potential leakages during injection (See Figs. 13-14 below)

During the surgical procedure (Engqvist et al, 2005, Lööf et al 2008)

Fig. 13. Percutaneous vertebroplasty using a CA-material.

Fig. 14. Vertebral compression factures, restored by CA-material.

10 nm.

augmentation.

applications are

**4.2 Orthopaedic applications** 

implants. Even small gaps may lead to relative micro-motions between implant and the tissue, which increases the risk of implant loosening over time due to formation of zones of fibrous tissues at the implant-tissue interface. Early loading of implants is of particular interest for dental implants (Vercaigne et al, 1998). The use of surface coatings technology is today an established method to reduce the problem with poor interfacial stability for implants. With coatings technology, structural characteristics of the implant (e.g. strength, ductility, low weight or machinability) may be combined with surface properties promoting tissue integration. There are several established coating deposition techniques, e.g. physical vapour deposition (sputtering) and thermal spraying techniques. Coatings based on calcium phosphates are the most used ones.

This section deals with coatings deposited with established methods, with the aim of improving particularly the early stage anchoring of metal implants to bone tissue by exploring *in vivo* hydration of coatings or pastes based on chemically curing ceramics. The study focuses on calcium aluminate in the form of coatings and paste. Results are presented from an implantation study with flame-sprayed coating on titanium implants and uncoated implants augmented with a calcium aluminate paste in the hind legs of rabbits. Implants were applied with the paste composed of a mixture of CaO·Al2O3 and CaO·2Al2O3. The paste was applied manually as a thin layer on the threaded part of the implant just before implantation. The uncoated and coated implants were sterilised with hot dry air at 180 ºC for 2 hrs. Female albino adult New Zealand White rabbits with a body weight around 2.5 kg were used. Each animal received four implants, two in each hind leg. Implants were placed in the distal femoral metaphysis as well as in the proximal tibial metaphysis. Surgery followed standard procedure. The implants were screwed into predrilled and threaded cavities. Necropsy took place after 24 hrs, 2 and 6 weeks (Axen et al, 2005).

No negative effects of the implants on the general welfare of the animals were observed. The healing progressed in a normal and favourable way. As for the removal torque recordings, all calcium aluminate coatings types provided an improved implant anchoring to bone tissue after *in vivo* hydration, as compared to that of the pure metal implants. Implants on the tibia and femur side of the knee gave similar removal torques. Table 15 provides average values from both tibia and femur sides.


Table 15. Removal torque (Ncm) for dental implants in rabbit hind legs (tibia and femur).

24 hrs after implantation, calcium aluminate in-between the implant and tissue increased the removal torque to about double that of the uncoated reference implants, independently of means of application (coatings or paste). This is considered to be attributable to the pointwelding according to integration mechanism 6 above. Two weeks after implantation, implants combined with paste augmentation provide the highest removal torque; flame sprayed coatings also improve the torque relative to the uncoated system. Six weeks after implantation, all systems are relatively similar (considering the uncertainty due to scatter and statistics), apart from the sprayed system which shows significantly higher values.

Fig. 12. High-resolution TEM of Ti – CA-paste interface, nano-mechanical integration, bar = 10 nm.

#### **4.2 Orthopaedic applications**

68 Biomaterials – Physics and Chemistry

implants. Even small gaps may lead to relative micro-motions between implant and the tissue, which increases the risk of implant loosening over time due to formation of zones of fibrous tissues at the implant-tissue interface. Early loading of implants is of particular interest for dental implants (Vercaigne et al, 1998). The use of surface coatings technology is today an established method to reduce the problem with poor interfacial stability for implants. With coatings technology, structural characteristics of the implant (e.g. strength, ductility, low weight or machinability) may be combined with surface properties promoting tissue integration. There are several established coating deposition techniques, e.g. physical vapour deposition (sputtering) and thermal spraying techniques. Coatings based on calcium

This section deals with coatings deposited with established methods, with the aim of improving particularly the early stage anchoring of metal implants to bone tissue by exploring *in vivo* hydration of coatings or pastes based on chemically curing ceramics. The study focuses on calcium aluminate in the form of coatings and paste. Results are presented from an implantation study with flame-sprayed coating on titanium implants and uncoated implants augmented with a calcium aluminate paste in the hind legs of rabbits. Implants were applied with the paste composed of a mixture of CaO·Al2O3 and CaO·2Al2O3. The paste was applied manually as a thin layer on the threaded part of the implant just before implantation. The uncoated and coated implants were sterilised with hot dry air at 180 ºC for 2 hrs. Female albino adult New Zealand White rabbits with a body weight around 2.5 kg were used. Each animal received four implants, two in each hind leg. Implants were placed in the distal femoral metaphysis as well as in the proximal tibial metaphysis. Surgery followed standard procedure. The implants were screwed into predrilled and threaded

No negative effects of the implants on the general welfare of the animals were observed. The healing progressed in a normal and favourable way. As for the removal torque recordings, all calcium aluminate coatings types provided an improved implant anchoring to bone tissue after *in vivo* hydration, as compared to that of the pure metal implants. Implants on the tibia and femur side of the knee gave similar removal torques. Table 15 provides average

Implant type 24 hrs (n) 2 weeks (n) 6 weeks (n) Flame spraying 7.0 (8) 7.0 (8) 25 (6) Paste augmentation 6.6 (8) 15 (6) 13 (4) Rf-PVD 12 (4) - - 10 (4) Uncoated reference 3.8 (8) 5.7 (6) 14 (4) Table 15. Removal torque (Ncm) for dental implants in rabbit hind legs (tibia and femur).

24 hrs after implantation, calcium aluminate in-between the implant and tissue increased the removal torque to about double that of the uncoated reference implants, independently of means of application (coatings or paste). This is considered to be attributable to the pointwelding according to integration mechanism 6 above. Two weeks after implantation, implants combined with paste augmentation provide the highest removal torque; flame sprayed coatings also improve the torque relative to the uncoated system. Six weeks after implantation, all systems are relatively similar (considering the uncertainty due to scatter and statistics), apart from the sprayed system which shows significantly higher values.

cavities. Necropsy took place after 24 hrs, 2 and 6 weeks (Axen et al, 2005).

phosphates are the most used ones.

values from both tibia and femur sides.

Within orthopedics the following areas for Ca-aluminate based materials have been identified; percutaneous vertebroplasty (PVP) and kyphoplasty (KVP), trauma and general augmentation.

The benefits of the injectable ceramic biomaterials based on CA related to orthopaedic applications are

During the surgical procedure (Engqvist et al, 2005, Lööf et al 2008)

 High radiopacity allows for superior visibility of the cement during and increases the probability to detect potential leakages during injection (See Figs. 13-14 below)

Fig. 13. Percutaneous vertebroplasty using a CA-material.

Fig. 14. Vertebral compression factures, restored by CA-material.

Nanostructural Chemically Bonded Ca-Aluminate Based Bioceramics 71

material, he microstructure of the additional particles for drug incorporation, and additives

The loading of the drug can be performed in several ways. The drug may be included, either partially or fully, in the powder or in the hydration liquid. Time and temperature for hydration are selected with regard to the drug and drug loading and to the selected release criteria. The manufacturing of the carrier can be done completely before or during loading of the drug. This renders a controlled release time to be selected from a few hours to days

The drug is introduced in the carrier by mixing the drug into the precursor powder, or the hydrated CBCs or other porous phases. The material can be formed into a paste by mixing it with a water-based hydration liquid. The powder can also be pressed into pellets, which thereafter are soaked in the liquid. The paste or the soaked pellets start to develop the microstructure that to a great extent will contribute to the controlled release of the drug. The time and temperature after the mixing will determine the degree of hydration, i.e. the porosity obtained. The porosity can be controlled within a broad interval of open porosity.

The Ca-aluminate technology provides a platform upon which Ca-aluminate based materials may work as a general biomaterial and as a complement to other chemically bonded ceramics based on phosphates, silicates or sulphates. Identified areas are in the first place within the dental and orthopedic areas, where injectable stable biomaterials are required. These include also properties as bioactivity related to apatite formation, antibacterial properties as well as nanostructural features useful for carriers for controlled

 Nano-structural integration and apatite formation provide important benefits to both the dentist and patient, notably minimal micro-leakage, perfect seal at the interface

 The potential use of the Ca-aluminate materials for implant applications is based on the following features: nanostructural integration with tissue, possible apatite formation, and a mass increase yielding early point welding between the biomaterial and

 The following product areas have been identified based on experimental material data, pre-clinical studies, pilot studies and on-going clinical studies: dental cement, endodontic products (orthograde and retrograde), sealants, restoratives, underfillings,

 Consequences of nanostructural contact integration of the Ca-aluminate system are reduced risk of secondary caries and restoration failure, and reduced post-operative

 The Ca-aluminate material can be used as a vehicle for transport and delivery of the medicament and as an injectable implant. The combination of the material as carrier and implant material makes site-specific placement of drugs and implants possible. By introducing optional additives, or by changing the w/c ratio, the release time can be controlled from short time periods (a few hours) to prolonged time periods (day and weeks). The release time is also dependant upon where the drug is placed. In cortical

drug delivery. The studies presented in this paper can be summarised as follows;

between tooth and material and as a result longer-lasting treatment results.

and pastes for augmentation and dental implant coatings.

bone a release time of months seems possible.

to ensure complementary porosity.

and months.

**5. Conclusion** 

surrounding.

sensitivity.


#### **4.3 Drug carrier for drug delivery**

General aspects of ceramics for use in drug delivery of drugs are presented by Ravaglioli et al and by Lasserre and Bajpaj (Ravaglioli et al, 2000, Lasserre and Bajpaj, 1998). A short description of carrier materials for drug delivery using chemically bonded ceramics, especially Ca-aluminate and/or Ca-silicate systems are given below. The CBC carrier material based on CA and CS structures exhibit some attractive features. The manufacturing procedure at low temperatures, where no or limited degradation of the medicaments occur, and the microstructure developed with open porosity as nano-sized channels as described above, are the basic features that open up a possibility for controlled release of medical agents. The precursor powder cures as a result of hydration reactions, between a ceramic oxide powder, primarily Ca-silicates and/or Ca-aluminates, and water. Through the hydration, new phases of hydrates are formed, which to a great part establish the microstructures needed to control the release of drugs incorporated in the injectable precursor material. An injectable material is formed into a paste by mixing it with a waterbased hydration liquid, which is then ready to be injected. Directly after the injection, the paste starts to develop the final microstructure. The water-based liquid may also comprise viscosity-controlling additives. These may be loaded with the drug before preparation of the final injectable paste. A couple of unique reaction conditions related to the production of materials yields materials with a variety of possible microstructures with porosities from the nanoscale to the microscale. variety of possible microstructures with porosities from the nanoscale to the microscale. 3) pore size and pore channel size, and 4) combination of different porosity structures (Hermansson, 2010). Porosity generated during the hydration of the Ca-aluminates and Ca-silicates is open porosity due to the reaction mechanism, and can be in the interval of 5-60 vol.-%. The average pore channel size (i.e. the diameter of the pores formed between the particles of the hydrated material) may be 1-10 nm. The crystal size of the reacted hydrates is in the interval 10-50 nm. This was established by BETmeasurements, where the specific surface area of dried hydrated CA was determined to be in the interval 400-500 m2, corresponding to a particle size of approximately 25 nm, and by HRTEM [7], Fig. 1 below. When short hydration time and/or low amount of water, or moisture at relative humidity > 70 %, are used, additional porosity is achieved with pore sizes in the interval 0.1-1 micrometer due to incomplete reaction. The different pore sizes obtained can be utilized for controlled release of drugs, when the Ca-aluminate implant material also works as a carrier of medicaments.

#### **Drug loading and controlled release of drugs**

The following properties are of significance with regard to the carrier for controlling the drug release; Type of ceramic precursor for producing the chemically bonded ceramic, grain size distribution of the precursor powder particles and general microstructure of the material, he microstructure of the additional particles for drug incorporation, and additives to ensure complementary porosity.

The loading of the drug can be performed in several ways. The drug may be included, either partially or fully, in the powder or in the hydration liquid. Time and temperature for hydration are selected with regard to the drug and drug loading and to the selected release criteria. The manufacturing of the carrier can be done completely before or during loading of the drug. This renders a controlled release time to be selected from a few hours to days and months.

The drug is introduced in the carrier by mixing the drug into the precursor powder, or the hydrated CBCs or other porous phases. The material can be formed into a paste by mixing it with a water-based hydration liquid. The powder can also be pressed into pellets, which thereafter are soaked in the liquid. The paste or the soaked pellets start to develop the microstructure that to a great extent will contribute to the controlled release of the drug. The time and temperature after the mixing will determine the degree of hydration, i.e. the porosity obtained. The porosity can be controlled within a broad interval of open porosity.
