Objectives

Osteoporosis and osteomalacia lead to increased fracture risk. Previous studies documented dysregulated osteoblast and osteoclast activity, leading to a high-turnover phenotype, reduced bone mass and low bone mineral content. Osteocytes, the most abundant bone cell type, are involved in bone metabolism by enabling cell to cell interaction. Osteocytes presence and viability are crucial for bone tissue homeostasis and mechanical integrity. Osseo-integration and implant degradation are the main problems in developing biomaterials for systemically diseased bone. This study examines osteocyte localisation, morphology and on the implant surface and at the implant bone interface. Furthermore, the study investigates ECM proteins regulation correlated to osteocytes and mechanical competence in an ovariectomised rat model with a critical size metaphyseal defect.

Background

Multiple Myeloma is a hematological malignancy of terminally differentiated plasma cells associated with increased osteoclast activity and decreased osteoblast functions. Systemic antiproliferative treatment includes proteasome inhibitors such as bortezomib, a clinical potent antimyeloma agent. Local delivery of biological active molecules via biomaterial composite implants to the site of the lesion has been shown to be beneficial for bone and implant-associated infections. In anticancer treatment local delivery of anticancer agents to the neoplasia via biomaterial carriers has never been reported before. The purpose of the current is to present the concepts and the first in vivo results for proteasome inhibitor composite biomaterials for local delivery of bortezomib to proliferative multiple myeloma bone lesions including concentration measurements at different anatomical regions in a rat model.

Implant loosening is one of the primary mechanisms of failure for hip, knee, ankle and shoulder arthroplasty. Many established implant fixation surfaces exist to achieve implant stability and fixation. More recently, additive manufacturing technology has offered exciting new possibilities for implant design such as large, open, porous structures that could encourage bony ingrowth into the implant and improve long-term implant fixation. Indeed, many implant manufacturers are exploiting this technology for their latest hip or knee arthroplasty implants. The purpose of this research is to investigate if the design freedoms offered by additive manufacturing could also be used to improve initial implant stability – a precursor to successful long-term fixation. This would enable fixation equivalent to current technology, but with lower profile fixation features, thus being less invasive, bone conserving and easier to revise.

250 cylindrical specimens with different fixation features were built in Ti6Al4V alloy using a Renishaw AM250 additive manufacturing machine, along with 14 specimens with a surface roughness similar to a conventional titanium fixation surface. Pegs were then pushed into interference fit holes in a synthetic bone material using a dual-axis materials testing machine equipped with a load/torque-cell (figure 1). Specimens were then either pulled-out of the bone, or rotated about their cylindrical axis before being pulled out to quantify their ability to influence initial implant stability.

It was found that additively manufactured fixation features could favourably influence push-in/pull-out stability in one of two-ways: firstly the fixation features could be used to increase the amount pull-out force required to remove the peg from the bone. It was found that the optimum fixation feature for maximising pull-out load required a pull-out load of 320 N which was 6× greater than the least optimum design (54 N) and nearly 3× the maximum achieved with the conventional surface (120 N). Secondly, fixation features could also be used to decrease the amount of force required to insert the implant into bone whilst improving fixation (figure 2). Indeed, for some designs the ratio of push-in to pull-out was as high as 2.5, which is a dramatic improvement on current fixation surface technology, which typically achieved a ratio between 0.3–0.6 depending on the level of interference fit. It was also found that the additively manufactured fixation features could influence the level of rotational stability with the optimum design resisting 3× more rotational torque compared to the least optimum design.

It is concluded that additive manufacturing technology could be used to improve initial implant stability either by increasing the anchoring force in bone, or by reducing the force required to insert an implant whilst maintaining a fixed level of fixation. This defines a new set of rules for implant fixation using smaller low profile features, which are required for minimally invasive device design.

Summary Statement

The present study demonstrates the beneficial effects of strontium (Sr) modified calcium phosphate cement to improve new bone formation in a metaphyseal osteoporotic fracture defects in rats compared to calcium phosphate cement and empty defects. Keywords: strontium, fracture, calcium phosphate, bone formation