Joined at the hip - optimising implant biocompatibility
An in vitro approach for optimising implant biocompatibility has been developed by Damian Marshall, Principal Scientist for Cell Biology at LGC, and Paul Tomlins, Principal Scientist for biomaterials at NPL, both Teddington, UK, who outline the process.
The surface texture and chemical composition of implants play a key role in successful clinical integration. Despite this knowledge, it remains difficult to predict the exact role that surface characteristics will have on implant integration, particularly over an extended period of time.
To address this, LGC, in collaboration with the UK’s National Physical Laboratory (NPL), has developed an in vitro approach which enables cell responses to be quantified rapidly using a variety of surface textures and chemistries that replicate the machining techniques used in implant manufacture.
Every year, thousands of hip and knee replacements, coronary stent insertions, and other surgical interventions are performed to replace or augment damaged or diseased tissue. In each case, the surgery will ideally use materials with properties that relate to their clinical function, such as resistance to corrosion and wear under physiological conditions, promotion of optimal interaction with surrounding cells, or a modulus of elasticity similar to the tissue they are augmenting.
Considering the frequency with which these procedures are performed, it is surprising that fewer than 20 materials are used within the body. This limitation is primarily due to problems of bio-incompatibility, which vary depending upon the type of material used, its application within the body and the physiologies of the individuals receiving the implant. The challenge is to enhance the degree of biocompatibility to extend the implant’s durability and reduce the patient’s needs for repeat procedures. Many attempts to improve this have been made, however, the efficacy of these different approaches is difficult to quantify unless the implant fails or the recipient dies. This makes clinical optimisation of a particular coating or finish extremely challenging.
Cut to the bone
Devices that are intended to integrate with bone are one of the largest groups of surgical implants and have applications ranging from the repair of fractured bones to dental implants and joint replacements. The majority of these implants are coated with titanium and its alloys, which have been shown, in both clinical and in vivo models, to have good biocompatibility. Nonetheless, exactly how titanium-coated implants interact with the in vivo cellular environment remains largely unknown, and creating an optimal implant interface with a clinically desirable response is, for the most part, time-consuming and expensive.
In addition to biocompatibility, the processes used during product manufacture can produce surface characteristics at the micro- and nanoscales that influence the behaviour of cells in unexpected ways. For example, in the titanium prosthesis used for hip replacement or resurfacing, the manufacturing process can leave a characteristic periodic or random texture (see image, above) on both the acetabular cup (see image, above, label B) and the stem (see image, above, label C). These features can impact the way the implant interacts with the surrounding tissue and, in extreme cases, lead to implant failure.
Reducing implant failure rates requires a better understanding of the way that different materials and manufacturing techniques can be manipulated to influence cell behaviour. This cannot be achieved through retrospective analysis of failed clinical implants and using data from expensive in vivo models. Therefore, an in vitro approach is required that allows high throughput screening of cellular responses to different materials, mimicking the surface topography induced by different machining techniques.
Development of an in vitro system to measure the
Scientists from LGC and NPL have developed an in vitro screening system to predict implant integration. They quantify cell attachment to a variety of surface textures. The system uses commercially available nickel comparator plates, which are used in engineering to quantify surface features. The plates have an array of textures that increase in surface roughness, mimicking different machining or metal processing techniques used in implant manufacture, such as spark erosion or shot blasting (see boxes A and B, right).
A simple measure of the surface roughness of the comparator plates is given by an Ra value, which is defined as the arithmetical mean deviation of the absolute ordinate values, z(x) of the profile from a midline. Additionally, the surface chemistry of the comparator plates can be modified by, for example, sputter coating or plasma vapour deposition, to produce a range of different metal or metallic alloy finishes, and can be modified for use in cell culture assay plates.
Developing metrics to measure the interaction of cells with the different engineered surfaces is challenging. However, the processes that cells undergo in vivo for both bone remodelling and their interactions with implant materials, can be used to develop quantitative in vitro measurements.
This information has resulted in a series of methods for rapid quantitative analysis, using cell line (MC3T3-E1). This can, given the right chemical signals, differentiate into osteoblast-like cells that manufacture bone nodules. The controlled differentiation process is broken down into a series of steps, which can be measured using fluorescent markers – a technique widely used in cell biology – allowing different measurements to be made, ranging from cell attachment (see box C), through to more complex measurements of how cells develop and form new bone in response to surface features (see box D).
The advantage with this in vitro system is its applicability for high throughput screening, enabling cell responses to be measured rapidly and quantified on a large variety of surface textures and chemistries.
Dr Damian Marshall, LGC, Queens Road, Teddington, TW11 0LY, UK. Tel: +44 (0)20 8943 8951. Email: firstname.lastname@example.org
Thanks to co-authors Paul Tomlins from NPL and Louise Dean from LGC. This work was funded by the UK National Measurement System.