Aseptic loosening is the most common cause of failure in load bearing orthopaedic implants. This is most often attributed to stress shielding, which is caused by a mismatch in mechanical properties between the implant and bone, predominantly stiffness. The implant causes a redistribution of the forces through the bone leading to localised tissue resorption in low stress areas and over time loosening of the implant. To address this, the implant design may be modified to introduce porous structures that reduced overall stiffness. Conventional methods of creating porous structures include the space holder method and gas foaming, although these allow control of the pore size and volume fraction, the position of the voids is random and potentially non-uniform, creating unpredictable mechanical properties. Using additive manufacture predictable porous lattice structures can be built. Two methods for creating lattice structure are explored here: controlled stochastic lattices, and layers of repeating unit cells. Due to the predictable nature of these design methods the mechanical properties can be tailored to suit the needs of the implants. In addition to mechanical optimisation the porous lattice structures can be optimised for osseointegration properties. The ability of the tissue to grow into the implant are affected by; the size of the pores, how interconnected the pores are, the overall void fraction (porosity), the shape and roughness of the pores, and whether the structure is coated. Although additive manufacture allows great design freedoms, there are also some manufacturing constraints to consider including resolution which is determined by powder and laser spot size, and strut angle since these cannot be too close to horizontal or they will collapse during the build unless supported. This preliminary work uses Finite Element Analysis to model the compressive properties of lattice structures with different design parameters, with the intention to optimise for mechanical, osseointegration and manufacturability properties. Cylinders of the lattice structures were generated in Simpleware ScanIP (Synopsys, Exeter, UK) and their compression was modelled in Ansys Workbench 18.2 (Canonsburg, PA, USA) in accordance with ISO 13314. Stress distributions for each lattice structure were produced which showed the stochastic lattice did not undergo banded deformation unlike the repeating unit cell based lattices. Future work will physically test the lattices and feed that data back into the model for further optimisation. Other relevant mechanical testing will be modelled and performed in order to choose the optimal lattice design for future implants.
Heterotopic ossification is the formation of lamellar bone in soft tissues and is a common complication of high-energy combat injury. This disabling condition can cause pain, joint ankylosis, and skin ulceration in the residua of amputees. This project is aimed at developing a novel treatment to dissolve hydroxyapatite in heterotopic ossification and prevent the crystallisation of this this mineral at sites of ectopic bone formation. Previously reported results demonstrated that hexametaphosphate could dissolve hydroxyapatite at physiological pH. Further work has been undertaken to investigate the mechanism of this dissolution and establish a means of temporal control of action. In addition, physicochemical analyses of samples of human heterotopic ossification have yielded important insights into the nature of this pathological tissue. Techniques include mapped micro X-ray fluorescence, mapped Raman spectroscopy, scanning electron microscopy, and micro computed tomography. Formulation engineering work has begun in order to develop an appropriate delivery vehicle for this agent. This includes rheological testing and hexametaphosphate elution profiles. Finally, micro CT analysis has shown that hexametaphosphate is able to dissolve human heterotopic ossification tissue. In summary, this work has moved us closer towards our goal of a novel injectable agent for the treatment and prevention of heterotopic ossification.
Over the last 10 years atypical femoral fractures (AFFs) have become recognised as a complication of standard-dose bisphosphonate use. In 2014 the American Society for Bone and Mineral Research published updated diagnostic criteria for AFF. We undertook a 5-year retrospective analysis of the trauma admission database at a major trauma centre to establish the incidence of this problem in our patient population. Initial screening was performed using keyword-matching methodology to produce a shortlist of patients with low-energy femoral fractures. These patients’ case notes, radiographs, and electronic discharge summaries were reviewed to discriminate AFF from typical femoral fractures. Initial filtering identified a total of 112 low energy femoral fractures. Of these, 12 were confirmed as AFFs. 58% (7/12) of the AFF group were on bisphosphonates compared to 15% (15/100) of the typical femoral fracture group. This finding was statistically significant (p = 0.0004). These data show that there is a link between bisphosphonate use and AFF. However, a causal relationship cannot be inferred. The incidence of AFF in our study is broadly in line with the published data.
Heterotopic ossification (HO) is the formation of bone in extraskeletal sites. It is a major problem for combat-related casualties with 64% of such patients showing radiological evidence of the disease. Of these, 19% require surgical excision. Current prophylaxis is problematic due to poor efficacy and unsuitability in a military setting. Our novel anti-HO strategy is to use an inorganic reagent to inhibit the deposition of HA and disperse any pre-formed mineral. Literature review identified several potentially effective agents. These were tested for their ability to disperse solid monoliths of HA. In addition, a standard HA synthetic reaction was performed in the presence of each agent to establish their inhibiting activity. One reagent (a condensed phosphate) dispersed a solid monolith of HA by 38% (mass loss) over 30 days. This reagent was also shown to inhibit HA crystal synthesis yield by 28%. Early work on a hydrogel delivery system has produced favourable results. These preliminary data demonstrate proof of concept that HA may be dispersed and its formation inhibited by a non-toxic polyphosphate. This work will form the justification for development into
