Researchers at Germany’s Fraunhofer Institute have optimised the surface structures of implants to promote cell adhesion and developed materials for bone tissue engineering.
By: P. Imgrund, S. Hein and V. Friederici; Fraunhofer-Institut für Fertigungstechnik und Angewandte Materialforschung IFAM, Bremen, Germany
Novel developments
| Figure 1: Interference screws are injection moulded from PLA (left), hydroxyl apatite (centre), and 316L stainless steel (right). |
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Injection moulding is a known and viable net-shape process for manufacturing medical devices and implants. This technology is adaptable to a range of materials: in addition to polymers, metals such as stainless steel or titanium and ceramics such as hydroxyapatite (HA) can be processed. Furthermore, process modifications can tailor the material’s density, porosity and surface topography. Potential applications include scaffolds for tissue engineering and implants such as interference screws for ligament fixation (Figure 1). Two novel developments in powder injection moulding technology involving the surface microstructuring of implant materials and processing of bioresorbable composites are presented in this article.
Using μ-MIM to produce micropatterns
Surface topography has a significant influence on implant integration. The presence of nano- and micrometre scale surface patterns has been proven to directly modulate cell behaviour at the implant-bone interface. Careful application of such surface features can result in enhanced immediate postoperative implant fixation and long-term biomechanical stability.1 Consequently, most metal surfaces for implantation undergo a secondary process to produce micron-scale surface roughness.2 However, current processing methods for the modification of implant surface topography are mainly based on multistep downstream mechanical or chemical surface treatments.3, 4 These processes are suited for rapid and large-scale surface modification, but downstream surface processing often yields increased production costs.
In recent years, micro metal injection moulding (μ-MIM) has emerged as a cost-effective tool for the serial production of net-shape, functionalised micro parts and micro-structured surfaces.5, 6, 7 The technique has also been used for the fabrication of orthodontic-grade metallic components.8
| Figure 2: A sample with a hemispheric surface micro pattern is pictured. Different mould inserts were used to prepare surface patterns with 5-, 30- and 50-μm diam hemispheres positioned at an equidistance of 20 μm. |
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The μ-MIM process calls for the production of a homogeneous feedstock consisting of micrometre-scale metal particles and organic binders. The feedstock is then injected into a micro patterned mould cavity to replicate a defined surface patterned green part. Finally, the moulded green part is sintered at an elevated temperature and the final metal part is obtained as a result of metal particle fusion (Figure 2).
The µ-MIM method eliminates secondary processes to enable single-step implant production. Additionally, the process allows replication of complex and well-defined micrometer-scale patterns on implant surfaces. In our study, grade 316L stainless steel is used to process a feedstock that contains a mixture of nano- and micro-sized powder particles. Because of the very fine powder particles and grain boundary formation, a secondary micrometre and submicrometre structure evolved on the surface of the μ-MIM processed parts in addition to the hemispheric micropattern.
Thus far, our investigation shows that the size and distribution of the microstructure can be controlled by varying the processing parameters, powder characteristics and sintering programme. For example, the inclusion of nanometre-scale particles in a stainless-steel feedstock regulates grain growth of the sintered product (the sintering temperature also plays a role). Interestingly, as the grain size decreases, the submicrometre surface topography is affected, provoking increased surface roughness values. This is visualised using atomic force microscope imaging (Figure 3). The nature of these topographical features is controlled by the ratio of nanometre/micrometre feedstock particle content.
| Figure 3: Atomic force microscope images reveal surface roughness variations due to nano particle additions in the feedstock, confirming a topological component of the microstructure modulation. |
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The mechanical properties of the sintered parts are within the range of conventionally produced stainless steel (yield strength >200 MPa and tensile strength >500 MPa); the finer grain microstructures lead to a significantly increased yield and ultimate tensile strength of 530 and 730 MPa, respectively.
The hemispheric surface patterning also seems to have an effect on cell behaviour. Osteoblast cells seeded on the stainless-steel samples tend to spread out between the hemispheres, as seen in Figure 4. Investigations of cell performance as a function of submicrometre structure are currently under way.
A further goal in making micropatterning by µ-MIM viable for implant production is the ability to process biocompatible titanium samples. In this case, purity is even more relevant than it is for stainless steel. Elevated oxygen content (>0.12 wt%), for example, leads to severely diminished mechanical properties. Because of the high affinity of micrometre-sized titanium Grade-1 particles for light elements such as oxygen, carbon and nitrogen, a special setup for mixing feedstock under inert atmospheric conditions was developed. Also, variations in binder compositions were necessary to reduce polymer content in order to eliminate a source of contamination during the sintering process. With these preparations, it was possible to process titanium samples with reduced oxygen and carbon contamination levels, corresponding to Grade-2 titanium suitable for medical implant components. Further investigation will focus on the enhanced mouldability of surface micropatterns as well as grain-refinement of the titanium material using fractions of nanometre-scale particles, analogous to the stainless-steel samples.
Mouldable PLA/HA composite material
| Figure 4: An SEM image of a stainless-steel surface shows an osteoblast cell spread out between the hemispheres. |
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In addition to optimising the surface structures of metallic implants for cell adhesion, another focus of research is on the development and processing of resorbable materials that can degrade within the body and be replaced by the body’s own tissue—for example, when the replacement of part of a bone after a fracture is medically preferable. This approach, called bone tissue engineering (BTE), has certain advantages over conventional autografting and allografting methods. Autografting involves harvesting the patient’s own bone material, normally from the iliac crest, for use as a bone graft. The disadvantages of this method are pain, cost and limited supply. Allografting uses bone tissue from other natural sources, but incompatibility as well as disease transmission can occur.9 Therefore, the use of materials that are replaced by the patient’s own tissue within a certain amount of time is a very promising approach. As the bone itself is an organic-inorganic composite with calcium phosphate–based minerals as the inorganic component, it is reasonable to use a representative of this material class in a composite; in our case, we used hydroxyapatite (HA). The organic component of our material is polylactic acid (PLA), a biocompatible and resorbable biopolymer.10
PLA is deposited onto the HA particles homogeneously. The resulting powder consists of HA particles with a thin PLA coating. This powder represents the starting material for dense or porous components, processible by injection moulding.
| Figure 5: Porosity in these PLA/HA composite scaffolds increases from 0% (left) to 52% (right). |
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In a manner similar to the µ-MIM process described above, a feedstock consisting of a powder and binder system is produced. The PLA-coated HA powder is mixed with a suitable binder, which acts as a flowing agent during injection moulding and can be removed later by solvent extraction. The process leads to nearly fully dense specimens after fusion of the composite by sintering of the PLA. In the finished components, ceramic contents up to 71% by volume fraction were achieved. In order to produce porous specimens, salt was added to the feedstock as a space holder. The salt particles are washed out during the debinding process, leaving behind a porous structure. Depending on the amount of space holder used, up to 52% porosity by volume can be obtained (Figure 5).
Initial tests of the composite scaffolds confirm that the mechanical properties of the dense material are in accord with the properties of human bone (Table I). Further developments will include optimisation of the pore size and porosity as well as research concerning in-vitro degradability and biocompatibility.
| Table I: Mechanical properties of dense mouldable PLA/HA composites. |
| Mechanical property |
Dense PLA/HA composite |
Human bone |
| Compression strength |
>130 N/sq mm |
130 – 180 N/sq mm10 |
| Compression modulus |
>13,000 N/sq mm |
12,000 – 18,000 N/sq mm10 |
| Compression strain |
1.8 % |
1 – 2 %11 |
| Vickers hardness |
45 HV |
35.18 HV12 |
|
References
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3. J. Lausmaa, “Mechanical, Thermal, Chemical and Electrochemical Surface Treatment of Titanium,” in D.M. Brunette, P. Tengvall, M. Textor, P. Thomson, Eds., Titanium in Medicine, 231-266. Springer-Verlag, Berlin, Heidelberg, Germany (2001).
4. L. Le Guéhennec et al., Dental Materials, 23, 844-854 (2007).
5. A. Rota, “New Features in Material Issues for Metallic Micro Components by MIM,” in V. Arnhold Ed., Proceedings of the 2002 World Conference on Powder Metallurgy & Particulate Materials, Orlando, FL, 10/49-10/57, Metal Powder Industries Federation, Princeton, NJ, USA (2002).
6. P. Imgrund et al., Journal of Materials Processing Technology, 200: 259-264, (2008).
7. C. Quinard et al., Powder Technology, 190, 123–128, (2009).
8. T. Eliades, American Journal of Orthodontics and Dentofacial Orthopedics, 131, 253-262 (2007).
9. B. Stevens et al., Biomed Mater Res Part B: Appl Biomater, 85B, 573-582. (2008).
10. K. Rezwan, Biomaterials, 27, 3413-3431 (2006).
11. D.T. Reilly et al., J. Bone Joint. Surg. Am.,1974, 56: 1001-1022.
12. E. Dall’Ara et al., Journal of Biomechanics, 2007, 40: 3267-3270.
Dr.-Ing. Philipp Imgrund
is Head of the department of Biomaterials Technology at Fraunhofer-Institut für
Fertigungstechnik und Angewandte
Materialforschung IFAM, Wienerstraße 12, D-28359 Bremen, Germany
tel: + 49 4212 246 216
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