Future Perspective
The Potential for Topographical 'Zoning' of Implants & Additional Modifications
In the next 5–10 years, it is likely that we will begin to see the development and use oalleviating infection issues and increasing the likelihood of clinical success following implantation (discussed further if multistructured topographically patterned Ti implants with distinct combinations of micro- and nano-topographical cues that have been tuned and selected to initiate a more tailored cell response. These implants are likely to incorporate 'zones' of different topographies with specialized functionalities appropriate to each region. In applications where unwanted bone resorption can be an issue, for example, in aseptic loosening of orthopedic devices, elements that could reduce osteoclastic adhesion or activity would be highly advantageous. The incorporation of features to retain the multipotency of MSCs could also promote the establishment or retention of a 'pool' of stem and progenitor cells that could gradually be increased in number to populate the implant surface in a therapeutically useful manner.[46] The expansion of such immature cell types would be beneficial prior to the induction of differentiation, where cell division slows or ceases as the cells become committed to an osteoblastic lineage and mature. Cues such as the highly ordered arrangement of nanopit features[54] could potentially be interspersed with other areas of topographical cues such as the osteogenic 15-nm high titania nanopillars discussed in[58,99] or the slightly disordered arrangement of nanopits discussed in.[53] Figure 6 shows an example of a potential future 'zoned' knee prosthesis, featuring topographically modified regions to promote implant stability and maximal integration with (and regeneration of) the appropriate host tissues, including bone, tendon and cartilage, while minimizing cell adhesion on the articulating surfaces.
Figure 6.
Potential future 'zoned' knee prosthesis. Indicates the potential for use of different types of topographical features on the same implant to maximize the functionality and lifetime of the device, including areas that should encourage ingrowth of depleted bone ('bone regeneration topography'; e.g., 15-nm titanium nanopillars), ongrowth and integration with the surrounding bone stock ('osseointegration topography'; e.g., 15-nm titanium nanopillars), promote appropriate attachment of tendons (e.g., using microgrooves to align the tenocytes) and encourage regeneration of the articulating cartilage and discourage cell adhesion around articulating surfaces (e.g., using a low-adhesion topography, such as the hexagonal arrangement of nanopits discussed in [124], if an equivalent surface can be produced in titanium). It would be anticipated that the combinations of nano- and microtopography would also be distinct; for example, there may be grooves to encourage migration of the stem cells and osteoprogenitors along the device from the surrounding tissue in the 'bone regeneration' zones, whereas there could be alternative features promoting in situ differentiation in the 'osseointegration' regions.Images of topographies reprinted from [58] © (2011), with permission from Elsevier, and reprinted from [124] © (2007), with permission from Wiley Periodicals Inc.
Image of nanopits courtesy of N Gadegaard, University of Glasgow, UK.
Development of topographies for implant patterning that directly reduce or prevent bacterial adhesion would be particularly useful for alleviating infection issues and increasing the likelihood of clinical success following implantation (discussed further in [116]). Ideally, such patterns would also promote osseointegration, but could perhaps be interspersed with other feature types to increase the overall osseoinductive properties of the surface. Decreasing the favorability of the surface to bacteria could potentially also be facilitated by doping surfaces with silver, for its antibacterial properties (although this could present additional toxicity issues for patients), or employing UV photocatalysis to generate reactive oxygen species and reduce bacterial numbers at the time of implantation.[117] Controlled release approaches for the delivery of antibiotic to the implant surface or surrounding tissue[118] could prove a useful intermediate step.
Protein and chemical cues would be more likely to become more rapidly denuded from the surface than physical (topographical) cues. Clinical application of protein cues could be problematic due to sterility issues and the protein source, but a combination of defined topographical features and chemical cues could be advantageous in providing initial cues for cell activation and implant zoning. For example, Sun et al. showed that MSCs from older patients had less proliferative capacity and less tendency to differentiate into bone, but interestingly, this appeared to be related to the age of the ECM, since the culture of the older MSCs on ECM derived from younger donors could 'reactivate' the older cells, improving proliferation and differentiation.[119] Thus, allogeneic transfer of cells or ECM may also provide a useful intermediate stage. Similarly, Nayan et al. postulated that use of allogeneic 'young' MSCs may be clinically beneficial (compared with the use of autologous MSCs from older patients) in repairing myocardial infarcts based on their in vivo research in a rodent model,[120] and it is possible that similar approaches could also be useful in improving the cell stock aspects of orthopedic operations. Such strategies could be complementary to a topographical surface modification approach and may help provide an intermediary step in the improvement of biological implant fixation. This is likely to be particularly beneficial for challenging clinical presentations, such as patients with poor bone stock, while 'smarter,' more efficient topographical surfaces are under development, which could have the ability to stimulate both the in situ proliferation and differentiation of bone lineage cells and thus enhance bone quality.
Nanomedicine. 2013;8(1):89-104. © 2013 Future Medicine Ltd.
