Bioactive orthopaedic implants using nanopatterned 3D materials

Today we live longer and longer, and at the same time we have a more active life than ever before. This means that younger and younger patients are now facing partial or total hip replacement. This combined with a longer life expectancy increases the possibility of revision surgery as the life span of prostheses is shorter than the patients? life expectancy. This possesses several problems. Firstly, the success of a hip replacement is lower for younger patients and as a result such surgical procedures are often being delayed by the surgeons. Secondly, revision surgery is significantly less successful and the lifetime of the prostheses is greatly reduced. A major step forward to increase the lifetime of a prosthesis has been for cementless implants. Here the surface of the implant has been roughened thus providing a better locking with the ingrowing bone. Nonetheless, there is still space for significant improvements of current implants.

The bone marrow is a rich source of stem cells which can, provided the correct stimuli, become bone forming cells. When a hip implant in fitted during the surgical procedure it will come in direct contact with the bone marrow. We have discovered a specific nanopattern which promotes the stem cells from the bone marrow to become bone forming cells. This project will take our remarkable discovery from a Petri dish and turn the results into a new generation of orthopaedic implants with improved properties over current ones. To realise this ambitious goal we have devised a clear technology development plan combined with the necessary biological experiments to bring our technology to a large animal stage. Our initial results have been performed on patterned plastic surfaces. However, plastics do not have the required mechanical properties (strength) to be used for prostheses. Such load bearing implants are commonly made in titanium and we will develop methods to pattern such metal implants.

To the best of our knowledge this will be a world s first to develop osseoinductive process (development of immature cells to bone forming cells) on an orthopaedic metal implant surface.

Current orthopaedic procedures have moved from cemented to cementless implants (held in place by osteointegration). When first implanted there is only 20% contact between the bone and the implant. As osteointegration occurs over a period of several weeks it is essential that the implant fits tightly and that micromotion is minimal post surgery. To increase the bone growth on the implant and increase the life time of the implant, the surface is now coated with hydroxyapetite giving an osteoconductive surface. However, the roughened and coated surfaces do not control the fate of the progenitor cells which will be present after the surgical procedure and importantly during the healing process. Primary cementless total hip arthroplasty results are still worse than cemented shown by national joint registry data (UK and Australian -2% revision at 3 years). However, cementing is technically demanding and therefore not reproducible without a long training curve and will remain intraoperatively more time consuming and therefore an expensive procedure. We know from cadaveric studies that even the best present day cementless prosthesis obtain only a 25% bony on/ingrowth and consequently less than ideal physiological loading. Also, even the best performing smooth taper, cemented stems are associated with abnormal physiological loading (Scottish arthroplasty project shows a ten years fracture rate of 1.7 % for primary THA). We have discovered a unique nanopattern which exactly provides this cue in vitro. A slightly irregular nanopattern of nanosized pits (100 nm diameter and an average of 300 nm centre-to-centre spacing) specifically differentiates skeletal stem cells into bone forming cells with the use of any hormones or growth factors but only driven by the surface topography. In this project we have devised an ambitious plan to translate our in vitro findings into a new generation of orthopaedic implants. To reach this goal, we will develop a number of new patterning methods which will enable us to pattern titanium implants with our unique nanopattern. In a series of ex vivo and in vivo experiments we will move from organotypic cultures to segmental mouse defects. In essence this will bring our technology from the Petri dish to a pre-clinical stage.

This is an ambitions project and to the best of our knowledge this will be a world s first to develop osseoinductive metal implant surface for load bearing implants.