![BACKGROUND The congenital malformations, arthritis, osteoporosis, traumatic accidents, spinal deformities, among others are the basis for need bone and cartilage replacements. The chronic pain, inflammation or discomfort of these diseases translates into a significant impact on patients’ and hospital treatments costs. There is yet no solution that meets the structural and functional requirements of definitive implants. In the case of trauma, for example, treatment often consists of bone joining or even implants in a nonpermanent situation, that is, requiring more than one surgical intervention which causes pain and discomfort to the patient besides the costs involved. Therefore, the development of low cost, durable, compatible and functional solutions is needed. Namely bone substitutes that can be perfectly integrated, morphologically and anatomically biocompatible, with complex structure and a material that mimics native bone and encourages cell migration, proliferation and differentiation. Ideally a bone substitute has original three-dimensional anatomical shape the trabecular zone is dense and has Young’s modulus in the range of 0.01-0.5 GPa and compressive strength values of 4-12 MPa while the cortical region is porous with compressive strength values in the range 130-225 MPa and modulus Young from 3-30GPa. The development of bone implants represents an area of medicine attracting growing interest in recent years. Most used implants are made of noble metals such as titanium. This material, although with good biocompatibility, strength and durability characteristics, faces often body rejection problems. To avoid that, the metal is coated with a biocompatible ceramic material (zirconia, hydroxyapatite, etc.). Despite their good performance, titanium implants have a much higher Young’s modulus than bone, which leads to localized stress phenomena, increase of osteoblast activity and may lead to periprosthetic osteolysis and consequent implant failure. The 3D printing techniques provided opportunities for the development of customized pieces. Ceramics, plastics and metals are all possible to printing in three dimensions by additive or subtractive techniques. In particular subtractive techniques are already used to perform ceramic teeth for dentistry. A piece of dense ceramic material is mechanically dug until the desired form is obtained. However, the dense ceramic implant behaves most likely the metal implants as it doesn’t allow the body fluids to flow through it. Compared to other techniques, the great advantage of pastes extrusion technique is the facility to mimic the graded porosity of implants while a specific design according to patient needs, reaching the mechanical properties close to those of the native bone, as well as their adequate, porosity, permeability to cells, biocompatibility and durability. The goal of the NOVA researchers is to develop low cost production ceramic implants, permanent, conformal and compatible with the specific needs of patients, mimicking resistance and bioactivity. This approach was achieved in preliminary results focused in 3D printed pieces of ceramics powders, achieving mechanical properties in the range of cortical bone, the most demanding in terms of mechanical strength. Indeed, the cortical mechanical resistance values were achieved just printing pieces layer-by-layer with pastes made with inorganic and organic compounds. The required biocompatibility and osteointegration was also tested in-vivo. TECHNOLOGY OVERVIEW The obtained background data show a real possibility to implement this technology in the veterinary area special to horses, dogs and cats in a first phase. This will open then possibilities and verification to further human applications. From left to right: Sample draw; printed samples after sintering for compression test; geometry and dimensions to tension tests; samples geometry for flexure tests. The mechanical strength obtained from axial compression, the tension and the flexure tests are summarized in table 1, where the obtained values are compared to the trabecular and cortical bone values obtained from literature. Comparison of mechanical teste with bone (values from literature).[1][2] Density and porosity compared to bone. The in-vitro tests were made with SAOS 2 cellules tinted for alkaline phosphatase with naphthol AS-MX phosphate and fast red violet and images of cell proliferation obtained for day 5 (left image) and 11 day (right image) of culture are shown in Figure 2. Figure 2: Image of SAOS 2 cells on the top a PIC sample for day 5 (left) and day 11 (right). The graph shows the evolution of cells growth along 9 days. The in-vivo tests were performed in rabbit being implanted two different samples S1 and S2 and the radiography images obtained after 2, 4 and 12 weeks are shown in Figure 3. Figure 3: Image of the implant (left). The graph represents the % of the bone-to-implant contact (BIC) evolution for two different composition samples. There was no adverse response, either local or systemic. No clinical symptoms of exaggerated inflammation, edema or infection were identified. No extensive bone resorption of the surrounding bone tissue is identified STAGE OF DEVELOPMENT The Technology Readiness Level (TRL) is 4. BENEFITS The main advantage of this technology is to allow the printing of a customized bone according to the needs of replacement. It enables the production of bone with gradient of density, in the exterior, properties similar to cortical bone, and, in the interior, density and properties of trabecular bone. Adding to that, the good osteointegration of the material, will allow a giant step towards bone’s mimicking especially for implants in animals, as a first step. Avoiding the need for a second operation for removing metallic parts, or due to rejection problems. APPLICATIONS The potential market is the implants in animals, horses, dogs and cats. There is a huge market for pets, which will allow also to consolidate the technology before it can be implemented in humans. OPPORTUNITY The NOVA team is looking for a co-development partner or a licensee for the implementation of this technology. IP STATUS Know-how based SEEKING Development partner Licensing](https://novainnovation.unl.pt/wp-content/uploads/2021/02/tech_image_2.7ccfbcf1.jpg)
3D printing of bone-like structures for bone replacement in animals [NI-TECH-2020-17]
3D printable ceramics compatible with cortical bones which have demonstrated good osseointegration in in vivo tests
BACKGROUND
The congenital malformations, arthritis, osteoporosis, traumatic accidents, spinal deformities, among others are the basis for bone and cartilage replacements. The chronic pain, inflammation or discomfort of these diseases translates into a significant impact on patients’ and hospital treatments costs. There is yet no solution that meets the structural and functional requirements of definitive implants. In the case of trauma, for example, treatment often consists of bone joining or even implants in a non-permanent situation, that is, requiring more than one surgical intervention which causes pain and discomfort to the patient besides the costs involved. Therefore, the development of low cost, durable, compatible and functional solutions is needed. Namely bone substitutes that can be perfectly integrated, morphological and anatomically biocompatible, with complex structure and a material that mimics native bone and encourages cell migration, proliferation and differentiation.
Ideally a bone substitute has original three-dimensional anatomical shape the trabecular zone is dense and has Young’s modulus in the range of 0.01-0.5 GPa and compressive strength values of 4-12 MPa while the cortical region is porous with compressive strength values in the range 130-225 MPa and modulus Young from 3-30GPa.
The development of bone implants represents an area of medicine attracting growing interest in recent years. Most used implants are made of noble metals such as titanium. This material, although with good biocompatibility, strength and durability characteristics, often faces body rejection problems. To avoid that, the metal is coated with a biocompatible ceramic material (zirconia, hydroxyapatite, etc.). Despite their good performance, titanium implants have a much higher Young’s modulus than bone, which leads to localized stress phenomena, increase of osteoblast activity and may lead to periprosthetic osteolysis and consequent implant failure.
The 3D printing techniques provided opportunities for the development of customized pieces. Ceramics, plastics and metals are all possible to printing in three dimensions by additive or subtractive techniques. In particular subtractive techniques are already used to perform ceramic teeth for dentistry. A piece of dense ceramic material is mechanically dug until the desired form is obtained. However, the dense ceramic implant behaves most likely the metal implants as it doesn’t allow the body fluids to flow through it. Compared to other techniques, the great advantage of pastes extrusion technique is the facility to mimic the graded porosity of implants while a specific design according to patient needs, reaching the mechanical properties close to those of the native bone, as well as their adequate, porosity, permeability to cells, biocompatibility and durability.
The goal of the NOVA researchers is to develop low cost production ceramic implants, permanent, conformal and compatible with the specific needs of patients, mimicking resistance and bioactivity. This approach was achieved in preliminary results focused in 3D printed pieces of ceramics powders, achieving mechanical properties in the range of cortical bone, the most demanding in terms of mechanical strength. Indeed, the cortical mechanical resistance values were achieved just printing pieces layer-by-layer with pastes made with inorganic and organic compounds. The required biocompatibility and osteointegration was also tested in vivo.
TECHNOLOGY OVERVIEW
The obtained background data shows a real possibility to implement this technology in the veterinary area special to horses, dogs and cats in a first phase. This will open possibilities and verification to further human applications.
The mechanical strength obtained from axial compression, the tension and the flexure tests are summarized in table 1, where the obtained values are compared to the trabecular and cortical bone values obtained from literature.
![Comparison of mechanical teste with bone (values from literature).[1][2]](https://novainnovation.unl.pt/wp-content/uploads/2021/02/tech_image_2_2.7d2cd816.png)
The in vitro tests were made with SAOS 2 cells tinted for alkaline phosphatase with naphthol AS-MX phosphate and fast red violet and images of cell proliferation obtained for day 5 (left image) and 11 day (right image) of culture are shown in Figure 2.
The in vivo tests were performed in rabbit being implanted two different samples S1 and S2 and the radiography images obtained after 2, 4 and 12 weeks are shown in Figure 3.
- There was no adverse response, either local or systemic.
- No clinical symptoms of exaggerated inflammation, edema or infection were identified.
- No extensive bone resorption of the surrounding bone tissue is identified
STAGE OF DEVELOPMENT
TRL 4 – Technology validated in laboratory.
BENEFITS
The main advantage of this technology is to allow the printing of a customized bone according to the needs of replacement. It enables the production of bone with gradient of density, in the exterior, properties similar to cortical bone, and, in the interior, density and properties of trabecular bone. Adding to that, the good osteointegration of the material, will allow a giant step towards bone’s mimicking especially for implants in animals, as a first step. Avoiding the need for a second operation for removing metallic parts, or due to rejection problems.
APPLICATIONS
The potential market is the implants in animals, horses, dogs and cats. There is a huge market for pets, which will allow also to consolidate the technology before it can be implemented in humans.
OPPORTUNITY
The NOVA team is looking for a co-development partner or a licensee for the implementation of this technology.
INTELLECTUAL PROPERTY
- Know-how based
SEEKING
- Development partner
- Licensing
