Orthopedic Implant Used as Drug Delivery System: Clinical Situation and State of the Research

Abstract

Abstract:A partial review is proposed on the existing literature for the research performed in orthopedic implant used as drug delivery system. In the first part, an evaluation is given on the clinical need to deliver a drug in the surrounding of an implant. Secondly, a review of the clinical situation is developed for implants already used as drug delivery system. Experimental works performed for local delivery are reported. In particular, a description is given on the in vitro and in vivo studies where the implant is coated with different proteins or drugs. Finally, a conclusion is proposed on the next step in the development of orthopedic implant as drug delivery system mentioning also the industrial situation.Keywords: Orthopedic implant, local delivery, drug, bone remodelling. IS THERE A CLINICAL NEED FOR LOCAL DELIVERY OF DRUG AROUND ORTHOPEDIC IMPLANT?Orthopedic practice recently enters a new area by considering use of drugs to enhance the fixation of implants. The rational behind this approach is to keep the bone around the implant as the trend observed clinically is a peri-implant bone resorption for hip or knee implants. Studies over the past 2 decades have strongly implicated osteoclasts as the major cause of the bone lysis leading to implant failure [1,2]. Different activation pathways of osteoclasts have been identified and in particular the RANKL/OPG/RANK pathway has been given much interest [3]. Decreasing the catabolic bone activity would then be a good strategy to avoid peri-implant bone loss. The drug of choice so far is of bisphosphonate type and several clinical trials have been performed and effectively show a reduction of peri-implant bone loss in treated groups [4][5][6]. Systemic injections of a drug may then be potentially interesting to control the bone remodeling around orthopedic implant, however this mode of delivery may not be optimal.The failure of an orthopedic implant is strongly correlated to its bone fixation [7]. When an implant is used without cement, stability immediately after the surgery must be obtained, a process called primary fixation, followed by a long-term fixation, a process called secondary fixation. A race on fixation quality is then engaged with the concept that the faster the secondary implant fixation is obtained, the better will be the implant outcome. The primary fixation being insured by the press-fit technique, the drug should then target the secondary fixation with the goal of reducing the bone loss. We should not be mislead by the term secondary fixation which is indeed already happening during the first months following the surgery. This has been shown in a clinical study where up to 14% bone loss arose during the first three months after total hip arthroplasties [8]. In parallel, rapid early migrations have been detected by roentgen stereophotogrammetry in many asymptotic hips, often as early as four months postoperatively [9]. The migrations have been found to predict an increased risk of clinical loosening.Systemic delivery of bisphosphonate by sever...

In vivo assessment of local effects after application of bone screws delivering bisphosphonates into a compromised cancellous bone site

“…Indeed, orthopedic implants designed to locally deliver bisphosphonates have been demonstrated to increase their fixation in animal studies (Wermelin et al, 2008a), even in osteoporotic bone (Peter et al, 2006) or very recently for dental implant in human (Abtahi et al, 2010). Several reviews have been recently published supporting the idea that a general positive effect is observed on bone volume fraction and implant fixation when an implant is used as local bisphosphonate delivery (Aspenberg, 2009;Pioletti et al, 2008). In particular, increase in bone volume fraction and pull-out force was observed as early as 2 to 3 weeks in rats after insertion of the implant coated with bisphosphonate (Peter et al, 2005;Wermelin et al, 2008b).…”

A fully functional drug-eluting joint implant

“…A strategy to address this is to deliver antibiotics locally by incorporating them into orthopaedic implant materials [9, 10]. The current treatments incorporate antibiotics into poly methyl-methacrylate bone cement [10], ceramic bone graft substitutes [11], or resorbable polymeric systems [12].…”

Controlled Delivery Systems: From Pharmaceuticals to Cells and Genes

“…Two main approaches were used to obtain a drug-implant complex. The drugs were either coated on the implant surface or directly incorporated into the polymeric implant (9). These implants were extensively used in the field of orthopedics (9,10).…”

“…The drugs were either coated on the implant surface or directly incorporated into the polymeric implant (9). These implants were extensively used in the field of orthopedics (9,10). However, the complications generated by the presence of these devices (toxicity, inflammation, infection, pharmacological side effects), together with the need for additional surgical intervention for implant removal, have been pointed out as important disadvantages of these systems.…”