The use of biomaterials and implants for joint replacement, fracture fixation, spinal stabilization and other orthopedic indications has revolutionized patient care by reliably decreasing pain and improving function. These surgical procedures always invoke an acute inflammatory reaction initially, that in most cases, readily subsides. Occasionally, chronic inflammation around the implant develops and persists; this results in unremitting pain and compromises function. The etiology of chronic inflammation may be specific, such as with infection, or be unknown. The histological hallmarks of chronic inflammation include activated macrophages, fibroblasts, T cell subsets, and other cells of the innate immune system. The presence of cells of the adaptive immune system usually indicates allergic reactions to metallic haptens. A foreign body reaction is composed of activated macrophages, giant cells, fibroblasts, and other cells often distributed in a characteristic histological arrangement; this reaction is usually due to particulate debris and other byproducts from the biomaterials used in the implant. Both chronic inflammation and the foreign body response have adverse biological effects on the integration of the implant with the surrounding tissues. Strategies to mitigate chronic inflammation and the foreign body response will enhance the initial incorporation and longevity of the implant, and thereby, improve long-term pain relief and overall function for the patient. The seminal research performed in the laboratory of Dr. James Anderson and co-workers has provided an inspirational and driving force for our laboratory's work on the interactions and crosstalk among cells of the mesenchymal, immune, and vascular lineages, and orthopedic biomaterials. Dr. Anderson's delineation of the fundamental biologic processes and mechanisms underlying acute and chronic inflammation, the foreign body response, resolution, and eventual functional integration of implants in different organ systems has provided researchers with a strategic approach to the use of biomaterials to improve health in numerous clinical scenarios.
- Klíčová slova
- acute and chronic inflammation, foreign body response, implants, orthopedic biomaterials, osseointegration,
- MeSH
- biokompatibilní materiály * chemie MeSH
- lidé MeSH
- ortopedie metody MeSH
- protézy a implantáty škodlivé účinky MeSH
- reakce na cizí těleso * patologie MeSH
- zánět * patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biokompatibilní materiály * MeSH
PURPOSE OF REVIEW: Joint replacement has revolutionized the treatment of end-stage arthritis. We highlight the key role of macrophages in the innate immune system in helping to ensure that the prosthesis-host interface remains biologically robust. RECENT FINDINGS: Osteoimmunology is of great interest to researchers investigating the fundamental biological and material aspects of joint replacement. Constant communication between cells of the monocyte/macrophage/osteoclast lineage and the mesenchymal stem cell-osteoblast lineage determines whether a durable prosthesis-implant interface is obtained, or whether implant loosening occurs. Tissue and circulating monocytes/macrophages provide local surveillance of stimuli such as the presence of byproducts of wear and can quickly polarize to pro- and anti-inflammatory phenotypes to re-establish tissue homeostasis. When these mechanisms fail, periprosthetic osteolysis results in progressive bone loss and painful failure of mechanical fixation. Immune modulation of the periprosthetic microenvironment is a potential intervention to facilitate long-term durability of prosthetic interfaces.
- Klíčová slova
- Inflammation, Innate immune system, Joint replacement, Macrophage, Osteoimmunology, Periprosthetic osteolysis, Prosthesis,
- MeSH
- artroplastiky kloubů * MeSH
- lidé MeSH
- makrofágy MeSH
- osteolýza * MeSH
- protézy kloubů * MeSH
- selhání protézy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
Introduction: Total joint replacement is one of the most common, safe, and efficacious operations in all of surgery. However, one major long-standing and unresolved issue is the adverse biological reaction to byproducts of wear from the bearing surfaces and modular articulations. These inflammatory reactions are mediated by the innate and adaptive immune systems.Areas covered: We review the etiology and pathophysiology of implant debris-associated inflammation, the clinical presentation and detailed work-up of these cases, and the principles and outcomes of non-operative and operative management. Furthermore, we suggest future strategies for prevention and novel treatments of implant-related adverse biological reactions.Expert opinion: The generation of byproducts from joint replacements is inevitable, due to repetitive loading of the implants. A clear understanding of the relevant biological principles, clinical presentations, investigative measures and treatments for implant-associated inflammatory reactions and periprosthetic osteolysis will help identify and treat patients with this issue earlier and more effectively. Although progressive implant-associated osteolysis is currently a condition that is treated surgically, with further research, it is hoped that non-operative biological interventions could prolong the lifetime of joint replacements that are otherwise functional and still salvageable.
- Klíčová slova
- Joint replacement, hip, joint arthroplasty, knee, osteolysis, particles, wear,
- MeSH
- chemokiny metabolismus MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- protézy kloubů škodlivé účinky MeSH
- selhání protézy * MeSH
- výsledek terapie MeSH
- zánět diagnóza diagnostické zobrazování etiologie patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- chemokiny MeSH
Clinical studies, as well as in vitro and in vivo experiments have demonstrated that byproducts from joint replacements induce an inflammatory reaction that can result in periprosthetic osteolysis (PPOL) and aseptic loosening (AL). Particle-stimulated macrophages and other cells release cytokines, chemokines, and other pro-inflammatory substances that perpetuate chronic inflammation, induce osteoclastic bone resorption and suppress bone formation. Differentiation, maturation, activation, and survival of osteoclasts at the bone-implant interface are under the control of the receptor activator of nuclear factor kappa-Β ligand (RANKL)-dependent pathways, and the transcription factors like nuclear factor κB (NF-κB) and activator protein-1 (AP-1). Mechanical factors such as prosthetic micromotion and oscillations in fluid pressures also contribute to PPOL. The treatment for progressive PPOL is only surgical. In order to mitigate ongoing loss of host bone, a number of non-operative approaches have been proposed. However, except for the use of bisphosphonates in selected cases, none are evidence based. To date, the most successful and effective approach to preventing PPOL is usage of wear-resistant bearing couples in combination with advanced implant designs, reducing the load of metallic and polymer particles. These innovations have significantly decreased the revision rate due to AL and PPOL in the last decade.
The type of tissue response to implant by-products can be determined by examination of periprosthetic tissues. However, little is known about the most suitable location for tissue sampling. The main goal of this study was to evaluate the extent of variability in tissue response in relation to location of tissue sampling, implant fixation, age and sex in total joint arthroplasties with metal-on-polyethylene or ceramic-on-polyethylene bearing pairs. We processed 236 histology slides from 21 patients and focused on the association between the location of tissue samples and histological features. The presence of the synovial hyperplasia showed a significant association with the particular sampling site. A higher density of high endothelial cell venules was seen in the samples from around the joint, and polyethylene particles were more abundant in noncemented TJA but both findings did not show statistically significant association with the sampling site. The results showed a relatively small variance in the tissue response to prosthetic by-products among tissues sampled from the same patient. Our findings indicate that tissue samples retrieved from similar distance from around the TJA during the revision operation show comparable results of histological analysis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2008-2018, 2018.
- Klíčová slova
- aseptic loosening, histology, interindividual variability, intraindividual variability, total joint replacement,
- MeSH
- keramika * škodlivé účinky chemie MeSH
- kyčelní protézy * MeSH
- lidé středního věku MeSH
- lidé MeSH
- náhrada kyčelního kloubu * MeSH
- polyethylen * škodlivé účinky chemie MeSH
- protézy - design * MeSH
- retrospektivní studie MeSH
- rozhraní kost/implantát patologie MeSH
- selhání protézy * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- polyethylen * MeSH
Inflammation, an essential tissue response to extrinsic/intrinsic damage, is a very dynamic process in terms of complexity and extension of cellular and metabolic involvement. The aim of the inflammatory response is to eliminate the pathogenic initiator with limited collateral damage of the inflamed tissue, followed by a complex tissue repair to the preinflammation phenotype. Persistent inflammation is a major contributor to the pathogenesis of many musculoskeletal diseases including ageing-related pathologies such as osteoporosis, osteoarthritis, and sarcopaenia. Understanding the mechanisms of inflammation and its resolution is therefore critical for the development of effective regenerative, and therapeutic strategies in orthopaedics.
- Klíčová slova
- fibroblasts, inflammation, innate lymphoid cells, macrophages, neutrophils, proresolving mediators,
- Publikační typ
- časopisecké články MeSH
Normal usage of total joint replacements results in the production of wear debris and other byproducts. In particular, polyethylene particles are heavily involved in the stimulation of local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone resorption (osteolysis), and eventually implant loosening. As sentinels of the innate immune system, cells of the monocyte/macrophage lineage initiate the inflammatory cascade that lead to osteolysis. The biological processes involved are complex, based on the unique properties of the monocytes/macrophages, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The interaction with wear debris triggers the release of pro-inflammatory factors such as tumor necrosis factor-α, interleukin-1, and others; pro-osteoclastic factors such as RANKL; and chemokines such as MCP-1 and MIP-1, all of which are crucial to the recruitment, migration, differentiation, and ultimately activation of bone-resorbing osteoclasts. In parallel, other distinct macrophage populations inhibit inflammation and mitigate its consequences on the bone-implant interface. Here, the role of the monocyte/macrophage cell lineage in the initiation and maintenance of the host inflammatory response to wear debris and subsequent periprosthetic osteolysis is presented.
- Publikační typ
- časopisecké články MeSH
The innate immune system consists of functionally specialized "modules" that are activated in response to a particular set of stimuli via sensors located on the surface or inside the tissue cells. These cells screen tissues for a wide range of exogenous and endogenous danger/damage-induced signals with the aim to reject or tolerate them and maintain tissue integrity. In this line of thinking, inflammation evolved as an adaptive tool for restoring tissue homeostasis. A number of diseases are mediated by a maladaptation of the innate immune response, perpetuating chronic inflammation and tissue damage. Here, we review recent evidence on the cross talk between innate immune sensors and development of rheumatoid arthritis, osteoarthritis, and aseptic loosening of total joint replacements. In relation to the latter topic, there is a growing body of evidence that aseptic loosening and periprosthetic osteolysis results from long-term maladaptation of periprosthetic tissues to the presence of by-products continuously released from an artificial joint.
- MeSH
- lektiny typu C metabolismus MeSH
- lidé MeSH
- osteoartróza imunologie patofyziologie MeSH
- osteolýza patofyziologie MeSH
- přirozená imunita fyziologie MeSH
- protézy kloubů škodlivé účinky MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory cytoplazmatické a nukleární metabolismus MeSH
- receptory imunologické metabolismus MeSH
- revmatoidní artritida imunologie patofyziologie MeSH
- signální adaptorové proteiny Nod metabolismus MeSH
- toll-like receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- lektiny typu C MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory cytoplazmatické a nukleární MeSH
- receptory imunologické MeSH
- signální adaptorové proteiny Nod MeSH
- toll-like receptory MeSH
Macrophages derive from human embryonic and fetal stem cells and from human bone marrow-derived blood monocytes. They play a major homeostatic role in tissue remodeling and maintenance facilitated by apoptotic "eat me" opsonins like CRP, serum amyloid P, C1q, C3b, IgM, ficolin, and surfactant proteins. Three subsets of monocytes, classic, intermediate, and nonclassic, are mobilized and transmigrate to tissues. Implant-derived wear particles opsonized by danger signals regulate macrophage priming, polarization (M1, M2, M17, and Mreg), and activation. CD14(+) monocytes in healthy controls and CD16(+) monocytes in inflammation differentiate/polarize to foreign body giant cells/osteoclasts or inflammatory dendritic cells (infDC). These danger signal opsonins can be pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), but in aseptic loosening, usually are damage-associated molecular patterns (DAMPs). Danger signal-opsonized particles elicit "particle disease" and aseptic loosening. They provide soluble and cell membrane-bound co-stimulatory signals that can lead to cell-mediated immune reactions to metal ions. Metal-on-metal implant failure has disclosed that quite like Ni(2+), its neighbor in the periodic table Co(2+) can directly activate toll-like receptor 4 (TLR4) as a lipopolysaccharide-mimic. "Ion disease" concept needs to be incorporated into the "particle disease" concept, due to the toxic, immune, and inflammatory potential of metal ions.
