Leading opinionThe future of biologic coatings for orthopaedic implants
Introduction
Orthopaedic implants are used routinely worldwide for fixation of long bone fractures and non-unions, for correction and stabilization of spinal fractures and deformities, for replacement of arthritic joints, and for other orthopaedic and maxillofacial applications. The primary aim of these devices is to provide mechanical stabilization so that optimal alignment and function of bone can be maintained during physiologic loading of bones and joints. In this way, the implants facilitate the relief of pain and more normal use of the injured limb or body part, and thus foster earlier return to function. By providing stability to bone fractures for example, orthopaedic implants indirectly assist in the biological aspects of bone healing by decreasing unwanted shear stress [1]. Similarly, devices that minimize micromotion at the bone-implant interface of cementless joint replacements, and unwanted movements between opposed bone surfaces in spinal fusion will enhance bone formation and remodelling [2], [3], [4]. The mechanical and biological aspects of bone healing are closely inter-related and ultimately determine final clinical outcome.
Historically, the design of orthopaedic fixation and reconstructive devices has focused primarily on the mechanical properties and function of the implant. In fracture fixation for example, this concept purports that bone will “heal by itself” if appropriately stabilized. However, this approach is shortsighted. Indeed in the USA, there are approximately 600,000 fractures with delayed union and 100,000 cases of nonunion each year [5]. Cementless joint replacements do not always osseointegrate with the surrounding bone, which may lead to implant migration and possible loosening [6]. Spinal fusion is not always a certainty [4].
The ultimate purpose of surgery employing a device is to help obtain, restore, or improve pre-morbid function. This goal may be compromised due to many potential factors including patient characteristics (e.g. chronic systemic metabolic disease, chemotherapy, smoking, excessive alcohol use, diabetes, medications, poor compliance with rehabilitation), local factors (e.g. difficult anatomical site and high degree of comminution of fractures, extensive injury to the soft tissue bed, infection, poor vascular supply, irradiation), and surgical and implant factors (suboptimal bone reduction, surgical technique, or application of the implant, inadequate implant characteristics) [5]. These facts have stimulated research into how the biological milieu of the implant bed could be modulated in order to help ensure a more robust bone healing response. The potential advantages are readily apparent: more vigorous, and expeditious bone healing would allow earlier rehabilitation and return of function. Although systemic pharmacological treatments to accomplish this goal have been considered, local strategies have several advantages including local targeted anatomic delivery of one or more biologics to the injury site, lower overall dosage requirements, and mitigation of potentially serious systemic side effects. This review will address strategies to improve bone healing (for example of fractures, non-unions, spinal fusion) and implant osseointegration for joint replacement via local delivery of molecules via implant coatings.
Orthopaedic devices may function in an appropriate fashion mechanically and biologically, however acute and chronic infection are potential dreaded complications that may necessitate further surgery. Infections of orthopaedic fracture and reconstructive devices occur in approximately 5% of cases and total about 100,000 cases per year in the USA alone [7], [8]. For primary total hip replacement, the surgical site infection rate varies from about 0.2% to 2.2% [9]. Despite a comprehensive infection surveillance program, the rate of deep surgical site infection for primary hip replacement in the Kaiser Permanente registry in the USA was recently reported to be 0.51% [9]. Infections in spine surgery occur in approximately 2%–5% of cases [10]. Implant infections are a substantial cause of morbidity and even mortality, and are very costly to the patient and society in general [8].
Implant infections are not only a consequence of host factors (such as obesity and chronic medical conditions) and surgical technique [9]. The anatomical site and characteristics of the implanted device including size, shape, material, topography and intended use are important variables [7]. The use of prophylactic systemic antibiotics has been shown to dramatically reduce the incidence of implant related infections [11], [12]. However, there are additional opportunities for local delivery of antibiotics and other anti-infective agents. Antibiotic containing bone cements appear to reduce the risk of infection in joint replacement surgery, although this point is controversial [12], [13]. Thus there are ongoing opportunities to coat the implant directly with antibiotics or other biomolecules to reduce implant related infections [10], [14].
This opinion paper reviews methods to coat prostheses implanted into bone in order to enhance osseointegration and mitigate adverse events associated with the foreign body response or infection. These implants of the future will hopefully modulate the local environment in a favourable manner with minimal risks, to improve patient outcome.
Section snippets
Mechanism of action and clinical results
Bone is a composite structure composed of cells, protein (mainly collagen and other signalling proteins) and mineral. The inorganic mineral phase of bone constitutes about 50% of its weight and is mainly composed of carbonated hydroxyapatite (HA). Coating the surface with HA has been shown to improve osseointegration of a cementless metallic prosthesis within bone [15], [16]. HA is chemically similar to the apatite of the host's bone, and is a source of calcium and phosphate to the bone-HA
The foreign body reaction to implants or osteoclasts
Bone, like other tissues, responds to acute injury by a series of events that constitute an acute inflammatory reaction. Insertion of an implant of any type within the body including bone evokes an inflammatory and (usually) limited foreign body reaction [56]. During use of an orthopaedic implant, wear particles and other byproducts are generated from the bearing surfaces of joint replacements, and non-articulating implant surfaces that impinge or fret (e.g. screws in a plate for fracture
Infection of orthopaedic implants
Orthopaedic implant-associated infection (OII) is one of the most common complications associated with devices for fracture fixation, joint replacement and spine surgery. Bacterial colonization and biofilm formation on the implanted device may lead to acute and chronic infection of the underlying bone and the adjacent soft tissues [71]. Biofilm on the implant surface protects the microorganisms from the host immune system and antibiotic therapy [13], [72], [73], [74], [75] which may lead to
Discussion and conclusion
The use of orthopaedic implants has grown dramatically in all subspecialities in orthopaedic surgery. These mechanical devices are used routinely to stabilize fractures, non-unions, and arthrodeses, for reconstruction of arthritic joints during total joint arthroplasty, for correction of spinal deformities and in other orthopaedic conditions. Recently, the coating of implants has engendered much interest in order to improve osseointegration, and prevent adverse tissue reactions such as
Acknowledgements
This work has been funded in part by NIH grants 2R01AR055650-05 and 1R01AR063717-01 and the Ellenburg Chair in Surgery, Stanford University (SBG), and the McCormick Faculty Award and Bio-X Interdisciplinary Initiative Grant (FY).
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