ReviewMultifunctional coatings to simultaneously promote osseointegration and prevent infection of orthopaedic implants
Introduction
Orthopaedic implant use for joint replacements has been on the rise, with significant increases still projected over the next 15 years [1]. The majority of procedures are knee and hip replacements, with over 700,000 knee and 300,000 hip replacements done annually in the United States [2]. While these surgeries have a track record of decades of positive outcomes, approximately 10% of these implants fail prematurely, within the first 10–20 years, thereby affecting many tens of thousands of patients annually [3]. Furthermore, as the US population continues to age and as life expectancy continues to increase, premature failures are not the only concern; many patients are now outliving their implants. This combination of factors leads to projections of a dramatic increase in implant failures in the near future.
The two leading causes of implant failure are aseptic loosening and infection. While the reported rates of these failures vary depending on the study, approximately 18% of implant failures are due to aseptic loosening while 20% of failures are attributed to infection [4], [5]. Additionally, these issues become even more prevalent in revised total joint arthroplasties. Aseptic loosening can originate from a variety of sources. These include micromotion of the implant relative to the bone during loading, the generation of implant wear particles that lead to inflammation and bone resorption, and poor osseointegration – the functional interface between the implant and the patient's bone [6]. Implant site infections occur as microbes, particularly bacteria, become sessile and adhere to implant surfaces. These solid interfaces provide surfaces for bacterial attachment, proliferation, and biofilm formation, in which the adherent bacteria produce a protective, polymeric, extracellular substance, rendering these bacteria substantially more difficult to eradicate than individual suspended planktonic bacteria floating around the body [7], [8]. A wide variety of bacteria can infect an implant, but a small subset of species makes up the majority of pathogens. Staphylococcus bacteria, most prominently Staphylococcus aureus and Staphylococcus epidermidis, account for close to 70% of orthopaedic implant infections, while Pseudomonas aeruginosa accounts for another 8% of infections [9].
Aseptic loosening and implant infection appear to be mutually exclusive, particularly given the use of the word ‘aseptic’. However, recent studies point to the potential connection between implants that have been reported to fail aseptically and latent occult infections that may have been missed prior to the time of diagnosis [10]. Therefore, even in cases of implant failure where infection was not the primary cause, microbial presence may still play a critical role in initiating or accelerating the failure pathway.
Independently, the problems of aseptic loosening and infection are pressing for the orthopaedics field, and many excellent review articles cover the fields of osseointegration and infection prevention individually [11], [12], [13], [14], [15], [16], [17], [18]. However, the two issues are intimately related, as laid out by Gristina in his description of the “race for the surface”; if the host's cells can reach and occupy the implant surface first, not only will stronger tissue integration be achieved, but a defensive barrier will also be established against microbial attachment and colonization [19]. Strong osseointegration and prevention of infection are both required for a successful implant, necessitating that implant designs consider both criteria simultaneously. In this review we describe several of the specific underlying mechanisms that lead to implant failure either by aseptic loosening or infection and potential design strategies to address these challenges (summarized in Table 1). In particular, with recent progress in understanding the connections between aseptic loosening and infection, this article will highlight recent works that address both problems in concert.
Section snippets
Challenges and potential solutions for osseointegration
Implant osseointegration relies on two distinct requirements. The first is obtaining initial implant stability during surgery, which then lays the groundwork for subsequent osseointegration of the implant as the patient heals. Ensuring implant stability is largely the responsibility of the surgeon and her/his team. Even technological solutions to improve initial implant fit, including automated imaging and robotic arm assistance platforms only assist, rather than replace, the surgery team. The
Challenges and potential solutions for bacterial infection of implants
Infection of orthopaedic implants can have a plethora of consequences, including hospitalization and costly revision surgery [11]. Implant infection has been reported to be the new leading cause of orthopaedic implant removal, overtaking aseptic loosening [4], [72], [73], [74]. Despite the biocompatibility of titanium and its alloys used for implants, bacteria easily and readily colonize these surfaces. Once bacteria adhere to the surface, they begin to proliferate, eventually reaching a high
Future direction
Addressing the clinical challenges of aseptic loosening and implant infection have clearly drawn much attention from the research community. While significant advances have been made in coating technologies to reduce failure either by loosening or infection, the development of technologies to address both challenges simultaneously is ongoing. A clear future direction for the field is the development of multifunctional implant coatings that can effectively balance osseointegration and microbial
Conclusions
Orthopaedic implants are widely used and highly successful treatments for musculoskeletal issues. Their success can be undermined by poor osseointegration and infection, the two leading causes of implant failure and revision surgeries. A variety of strategies have been studied to improve osseointegration and to prevent infection, though typically proposed solutions have only addressed one of the two issues. In this review, we highlighted technologies that have the potential to address these
Acknowledgments
We acknowledge the Robert L. and Mary Ellenburg Professorship at Stanford University (SBG) and funding from the National Science Foundation (DMR 0846363 to SCH) and the National Institutes of Health (U19 AI116484–01, R21 EB018407–01, R21 AR062359-01 to SCH).
References (152)
- et al.
The significance of infection related to orthopedic devices and issues of antibiotic resistance
Biomaterials
(2006) - et al.
A review of the biomaterials technologies for infection-resistant surfaces
Biomaterials
(2013) - et al.
Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces
Acta Biomater.
(2011) - et al.
Recent progress in inorganic and composite coatings with bactericidal capability for orthopaedic applications
Nanomedicine
(2011) - et al.
The future of biologic coatings for orthopaedic implants
Biomaterials
(2013) - et al.
The use of Roentgen stereophotogrammetry to study micromotion of orthopaedic implants
ISPRS J. Photogramm. Remote Sens.
(2002) - et al.
Fabrication methods of porous metals for use in orthopaedic applications
Biomaterials
(2006) - et al.
Critical overview of nitinol surfaces and their modifications for medical applications
Acta Biomater.
(2008) - et al.
Mandibular defect repair by TGF-beta and IGF-1 released from a biodegradable osteoconductive hydrogel
J. Craniomaxillofac. Surg.
(2005) - et al.
Hydrogels for tissue engineering: scaffold design variables and applications
Biomaterials
(2003)
Improvement of corrosion resistance and antibacterial effect of NiTi orthopedic materials by chitosan and gold nanoparticles
App Surf. Sci.
Antibacterial and biological characteristics of silver containing and strontium doped plasma sprayed hydroxyapatite coatings
Acta Biomater.
Enhancing the antibacterial activity of biomimetic HA coatings by incorporation of norvancomycin
J. Orthop. Sci.
Osteogenic and antimicrobial nanoparticulate calcium phosphate and poly-(D,L-lactide-co-glycolide) powders for the treatment of osteomyelitis
Mater. Sci. Eng. C Mater. Biol. Appl.
Micromotion and friction evaluation of a novel surface architecture for improved primary fixation of cementless orthopaedic implants
J. Mech. Behav. Biomed. Mater.
Preclinical trial of a novel surface architecture for improved primary fixation of cementless orthopaedic implants
Clin. Biomech. Bristol. Avon.
Promoting bone mesenchymal stem cells and inhibiting bacterial adhesion of acid-etched nanostructured titanium by ultraviolet functionalization
J. Mater. Sci. Technol.
Review of bioactive glass: from Hench to hybrids
Acta Biomater.
Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential
App. Surf. Sci.
Toward 3D printed bioactive titanium scaffolds with bimodal pore size distribution for bone ingrowth
Procedia CIRP
A multifunctional streptococcal collagen-mimetic protein coating prevents bacterial adhesion and promotes osteoid formation on titanium
Acta Biomater.
Silk-functionalized titanium surfaces for enhancing osteoblast functions and reducing bacterial adhesion
Biomaterials
Gentamicin and bone morphogenic protein-2 (BMP-2)-delivering heparinized-titanium implant with enhanced antibacterial activity and osteointegration
Bone
Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells
Blood
Stem cell homing in musculoskeletal injury
Biomaterials
Balancing osteoblast functions and bacterial adhesion on functionalized titanium surfaces
Biomaterials
Staphylococcus aureus adhesion to titanium oxide surfaces coated with non-functionalized and peptide-functionalized poly(L-lysine)-grafted-poly(ethylene glycol) copolymers
Biomaterials
The effect of incorporating RGD adhesive peptide in polyethylene glycol diacrylate hydrogel on osteogenesis of bone marrow stromal cells
Biomaterials
Influence of engineered titania nanotubular surfaces on bone cells
Biomaterials
Nanocolumnar coatings with selective behavior towards osteoblast and Staphylococcus aureus proliferation
Acta Biomater.
Antibacterial nano-structured titania coating incorporated with silver nanoparticles
Biomaterials
Biological actions of silver nanoparticles embedded in titanium controlled by micro-galvanic effects
Biomaterials
Cellular responses to titanium successively treated by magnesium and silver PIII&D
Surf. Coat. Tech.
Electron storage mediated dark antibacterial action of bound silver nanoparticles: smaller is not always better
Acta Biomater.
Synergistic effects of dual Zn/Ag ion implantation in osteogenic activity and antibacterial ability of titanium
Biomaterials
Chitosan: a versatile biopolymer for orthopaedic tissue-engineering
Biomaterials
Therapeutic potential of chitosan and its derivatives in regenerative medicine
J. Surg. Res.
Chitosan – a versatile semi-synthetic polymer in biomedical applications
Prog. Polym. Sci.
Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030
J. Bone Jt. Surg. Am.
Prevalence of primary and revision total hip and knee arthroplasty in the United States from 1990 through 2002
J. Bone Jt. Surg. Am.
The epidemiology of revision total knee arthroplasty in the United States
Clin. Orthop. Relat. Res.
The epidemiology of revision total hip arthroplasty in the United States
J. Bone Jt. Surg. Am.
Aseptic loosening, not only a question of wear: a review of different theories
Acta Orthop.
Bacterial biofilms: a common cause of persistent infections
Science
Bacterial biofilms: from the natural environment to infectious diseases
Nat. Rev. Microbiol.
Does endotoxin contribute to aseptic loosening of orthopedic implants?
J. Biomed. Mater. Res. B Appl. Biomater.
Antibacterial coatings on titanium implants
J. Biomed. Mater. Res. B Appl. Biomater.
New strategies in the development of antimicrobial coatings: the example of increasing usage of silver and silver nanoparticles
Polymers
Osseointegration in skeletal reconstruction and rehabilitation: a review
J. Rehabil. Res. Dev.
Cited by (543)
Improvement of micro/nano-structure and corrosion resistance of TiCu alloy by addition of tin and their Sr-hydroxyapatite coating
2024, Journal of Alloys and CompoundsMultifunctional nanocoating for enhanced titanium implant osseointegration
2023, Colloids and Surfaces B: Biointerfaces