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Multifunctional Coatings to Simultaneously Promote Osseointegration and Prevent Infection of Orthopaedic Implants
Abstract
The two leading causes of failure for joint arthroplasty prostheses are aseptic loosening and periprosthetic joint infection. With the number of primary and revision joint replacement surgeries on the rise, strategies to mitigate these failure modes have become increasingly important. Much of the recent work in this field has focused on the design of coatings either to prevent infection while ignoring bone mineralization or vice versa, to promote osseointegration while ignoring microbial susceptibility. However, both coating functions are required to achieve long-term success of the implant; therefore, these two modalities must be evaluated in parallel during the development of new orthopaedic coating strategies. In this review, we discuss recent progress and future directions for the design of multifunctional orthopaedic coatings that can inhibit microbial cells while still promoting osseointegration.
... Several growth and differentiation factors have been shown to enhance osseointegration, including bone morphogenic proteins BMP-2 and BMP-7 [28], osteogenic protein-1 (OP-1) [29], platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), and transforming growth factor-beta 1 (TGFβ-1) [12]. A recently proposed strategy to enhance osseointegration consisted of actively recruiting osteogenic cells through the creation of a chemotactic gradient using released signaling molecular factors [30]. One of the most well-studied recruitment factors is the cytokine stromal-derived growth factor-1 (SDF-1α), also known as CXC chemokine ligand-12 (CXCL-12) [30]. ...
... A recently proposed strategy to enhance osseointegration consisted of actively recruiting osteogenic cells through the creation of a chemotactic gradient using released signaling molecular factors [30]. One of the most well-studied recruitment factors is the cytokine stromal-derived growth factor-1 (SDF-1α), also known as CXC chemokine ligand-12 (CXCL-12) [30]. SDF-1α-bound CXCR4 is crucial in directing the migration of hematopoietic cells during embryogenesis [31], recruiting endothelial progenitor cells for angiogenesis in adulthood [32], influencing tumor metastasis [33], and acting as a chemotactic factor for mesenchymal stem cells (MSCs) [34,35]. ...
... Aseptic loosening of the implant results in pain and instability [40]. Enhancing osseointegration by actively recruiting mesenchymal stem cells has been proposed recently to secure initial mechanical stability and to increase long-term implant survival [30]. ...
Background: Active recruitment of osteogenic cells by secreted signaling factors, such as stromal-cell-derived factor 1 (SDF-1), has recently been proposed as a novel strategy to enhance osseointegration. However, the intrinsic importance of the SDF-1/C-X-C chemokine receptor type 4 (CXCR4) axis in promoting osseointegration is unknown. To study the role of SDF-1/CXCR4 in osseointegration, we blocked the SDF-1/CXCR4 pathway in a murine tibial implant model through repeated administrations of an antibody against SDF-1. Methods: Using our previously described murine tibial implant model (N = 24), mice were randomized into an anti-SDF-1 group and a control group (N = 12/group). Intraperitoneal injections of CXCL12/SDF-1 monoclonal antibody (84 µg/mouse) or mouse IgG1 isotype were administered on days 2, 4, 7, 10, 13, 16, 19, 22, and 25 post-surgery. Mice were euthanized 4 weeks post-surgery. Peri-implant bone mass and architecture were determined through microcomputed tomography (µ-CT). Bone implant strength was detected through implant pull-out testing. Results: Inhibition of the SDF-1/CXCR4 pathway significantly reduced host bone–implant interface strength but did not significantly change the cancellous architecture surrounding the implant. Conclusion: SDF-1/CXCR4 is an important pathway to achieve maximum implant osseointegration. However, inhibition of the pathway did not completely eliminate osseointegration.
... Strategies aimed at reducing PJI and the resultant lack of osseointegration should improve the success of TJA and increase implant longevity [33]. It has been shown in vitro that EM-eluting coaxial PCL/PLGA-PVA NF coating (EM-NF) had a sustained and controlled drug delivery with prolonged bacterial growth inhibition, and the degradation of the NFs matches the period of an implant's osseointegration [32]. ...
... An ex vivo porcine bone implantation model [33] was used to determine whether the EM-NF coating remained intact during implantation. Fresh-frozen porcine knee specimens were purchased from a local slaughterhouse and stored at −20 °C. ...
Implant surface nanofiber (NF) coatings represent an alternative way to prevent/treat periprosthetic joint infection (PJI) via local drug release. We developed and characterized a coaxial erythromycin (EM)-doped PLGA/PCL-PVA NF coating. The purpose of this study was to determine the efficacy of EM-NF coatings (EM0, no EM, EM100 (100 mg/mL), and EM1000 (1000 mg/mL) wt/wt) in a rat PJI model. A strong bond of the EM-NF coating to the surface of titanium (Ti) pins was confirmed by in vitro mechanical testing. Micro-computed tomography (mCT) analysis showed that both EM100 and EM1000 NF effectively reduced periprosthetic osteolysis compared to EM0 at 8 and 16 weeks after implantation. Histology showed that EM100 and EM1000 coatings effectively controlled infection and enhanced periprosthetic new bone formation. The bone implant contact (BIC) of EM100 (35.08%) was higher than negative controls and EM0 (3.43% and 0%, respectively). The bone area fraction occupancy (BAFO) of EM100 (0.63 mm2) was greater than controls and EM0 (0.390 mm2 and 0.0 mm2, respectively). The BAFO of EM100 was higher than that of EM1000 (0.3 mm2). These findings may provide a basis for a new implant surface fabrication strategy aimed at reducing the risks of defective osseointegration and PJI.
... [177] Recent attention has been given to immunomodulation-based strategies aimed at manipulating the immune microenvironment in soft tissues surrounding metal implants. [178][179][180] Chen et al. showcased that PDA/IL-4 -coated titanium alloy implants, aimed at pro-healing M2 macrophage polarization, successfully enhanced gingival cell response and in vivo soft tissue-metal implant integration. Their research also highlighted that the M2 immune microenvironment contributed to improved cell proliferation, anchoring, and spreading capabilities, along with increased hemidesmosome formation and the upregulation of proteins linked to cell adhesion ( Figure 5). ...
... Their research also highlighted that the M2 immune microenvironment contributed to improved cell proliferation, anchoring, and spreading capabilities, along with increased hemidesmosome formation and the upregulation of proteins linked to cell adhesion ( Figure 5). [179] 7 | HYBRID MULTIFUNCTIONAL COATINGS Multifunctional coatings for titanium implants are a significant leap in biomaterials due to their capability to concurrently enhance various facets of implant performance, providing a comprehensive solution to diverse implant-related challenges. Unlike single-function coatings, multifunctional coatings address the complexity of biological environments, such as resisting bacterial infections, enhancing osseointegration, and simultaneously promoting tissue regeneration. ...
Dental and orthopedic titanium implants are successfully and widely used but still face challenges due to complications leading to high treatment cost, morbidity, and even mortality. This review focuses on the hybrid coatings designed to prevent and mitigate implant failure by integrating multiple strategies and materials. The forms of manufacturing and synthesizing hybrid coatings were first discussed. We then categorize these coatings based on their biological functions: antibacterial coatings, which are essential for preventing difficult‐to‐treat infection; coatings designed to promote osseointegration, crucial for the mechanical stability of implants; coatings that encourage soft tissue attachment, contributing to the overall success and esthetics of implant. We summarize the state of the art in multifunctional coatings that integrate multiple biological functions as an alternative, holistic approach for reducing implant complications. The review culminates in a discussion on future directions in the field, emphasizing the potential and notable challenges these biofunctional hybrid coatings face toward obtaining commercial success in patients. Together, our article provides a comprehensive overview of current developments and a glimpse into the future of hybrid coatings for potentially revolutionizing dental and orthopedic implants.
... Therefore, the number of primary total hip replacement surgeries is projected to increase, and the number of such surgeries will continue to increase as the population ages [2]. In addition, the prevalence of diabetes, the increase in the number of people with excess body weight due to unhealthy lifestyle and other health problems lead to an increasing number of young patients suffering from joint and bone defects, which threatens their health and significantly reduces the quality of human life in general [3,4]. If the reason for the deterioration in the quality of life of a sick person is a damaged or diseased joint that causes severe pain and limited mobility, then surgical replacement of the joint with an appropriate implant may be necessary to treat this condition. ...
The paper presents new results of manufacturing coatings by magnetron sputtering to improve the functional properties of joint endoprostheses. The antibacterial properties of Ti-Cu and Ta-Cu coatings deposited by DC multi-magnetron sputtering on Ti6Al4V alloy substrates subjected of gas-abrasive treatment have been investigated. The roughness of the substrate was measured by optical profilometry. The coating hardness and elastic modulus were estimated by nanoindentation methods; the adhesion characteristics were assessed by Rockwell test. Scanning electron microscopy with energy-dispersive X-ray analysis verified the application of coatings with 25 at.% Cu, at thicknesses of 2 μm and 10 μm to roughened Ti6Al4V alloy. All coatings demonstrated sufficient adhesion, whereas Ta-Cu coatings generally revealed higher hardness, while the elastic modulus decreased with increasing coating thickness. Staphylococcus aureus strains were used for in vitro study of the antibacterial properties of Ti-Cu and Ta-Cu coatings. The largest zones of inhibition of bacteria S. aureus 23 mm were observed for 10 µm Ta-Cu coating thickness. The release dynamics of Cu ions from Ta-Cu and Ti-Cu coatings into physiological solution analyzed over seven days via inductively coupled plasma mass spectrometry, matched the inhibition zone growth. The Ti-Cu and Ta-Cu coatings of 2 µm thickness provided weaker antibacterial effect. The optimal parameters of magnetron sputtering of antibacterial Ti-Cu and Ta-Cu coatings on Ti6Al4 alloy substrates were selected. These findings support the potential of these coatings in developing endoprosthesis implants with enhanced antimicrobial and wear-resistant properties
... To prevent bacterial infection of BG implants it is essential to discourage initial adhesion of bacterial cells on implant surfaces. For this, several approaches including impregnation of implants with antibiotics, coating with antibacterial metals such as copper or silver [6,7], chemical treatments [8] , plasma-assisted modification [9], coating with self-assembled monolayer [10], and manipulating surface topography [11] [15]. Recently, Prabhakar et. ...
Bacterial attachment and biofilm formation on implant surface has been a major concern in hospital and industrial environment. Prevention of bacterial infections of implant surface through surface treatment could be a potential solution and hence this has become a key area of research. In the present study, the antibacterial and biocompatible properties of femtosecond laser surface treated 45S5 bioactive glass (BG) have been investigated. Adhesion and sustainability of both gram positive S. aureus and gram negative P.aeruginosa and E. coli nosocomial bacteria on untreated and laser treated BG samples has been explored. An imprint method has been used to visualize the growth of bacteria on the sample surface. We observed complete bacterial rejection potentially reducing risk of biofilm formation on laser treated surface. This was correlated with surface roughness, wettability and change in surface chemical composition of the samples before and after laser treatment. Biocompatibility of the laser treated BG was demonstrated by studying the anchoring and growth of human cervix cell line INT407. Our results demonstrate that, laser surface modification of BG enables enhanced bacterial rejection without affecting its biocompatibility towards growth of human cells on it. These results open a significantly potential approach towards use of laser in successfully imparting desirable characteristics to BG based bio-implants and devices.
... Bacterial infections could exacerbate this risk, and this can lead to implant failure [4]. Therefore, in order to minimize the risk of possible implant failure and achieve durable implant-bone contact [5,6], the surface characteristics of the implant need to be carefully designed to promote a strong structural and functional connection between the bone tissue and the implant [7][8][9][10]. Among all feasible implants, PEEK has become a promising choice due to its similar mechanical moduli to the human cortical bone, natural x-ray transparency, and excellent corrosion resistance [11]. ...
Polyetheretherketone (PEEK) emerges as a highly promising biopolymer due to its mechanical properties and elastic modulus akin to those of human cortical bone. Despite these advantages, the clinical utilization of PEEK is often hindered by its limited bioactivity and suboptimal capability for bone integration. Herein, we introduce a facile and expeditious method for enhancing the osseointegration efficacy of PEEK substrates by depositing polydopamine (PDA) chelated with magnesium ions at varying concentrations (0.02, 0.1, and 0.5 M) as a surface coating (PDA‐Mg). This PDA‐Mg‐modified PEEK surface exhibits distinctive properties, including antibacterial properties (antibacterial rate of 93.267%), improved vascular regeneration, and osteogenic promotion (ALP activity increased by 239.5%). Moreover, the Mg²⁺ ions are released in a regulated way, and the impact of Mg²⁺ concentration on the aforementioned properties has been thoroughly examined. Our study demonstrates that PDA‐Mg‐modified PEEK offers a highly promising prospect for clinical applications. Specifically, these implants stand out as exceptional candidates for bone graft materials, with the potential to significantly improve patient outcomes and accelerate recovery processes.
... Eradicating these infections is challenging once biofilms form on the implant surface. Bacterial endotoxins activate macrophages, triggering Toll-like receptor activation and ultimately leading to infection-mediated osteolysis [81]. These complications result in implant failure and necessitate subsequent surgeries. ...
The simple oxides like titania, zirconia, and ZnO are famous with their antibacterial (or even antimicrobial) properties as well as their biocompatibility. They are broadly used for air and water filtering, in food packaging, in medicine (for implants, prostheses, and scaffolds), etc. However, these application fields can be broadened by switching to the composite multicomponent compounds (for example, titanates) containing in their unit cell, together with oxygen, several different metallic ions. This review begins with a description of the synthesis methods, starting from wet chemical conversion through the manufacturing of oxide (nano)powders toward mechanosynthesis methods. The morphology of these multicomponent oxides can also be very different (like thin films, complicated multilayers, or porous scaffolds). Further, we discuss in vitro tests. The antimicrobial properties are investigated with Gram-positive or Gram-negative bacteria (like Escherichia coli or Staphylococcus aureus) or fungi. The cytotoxicity can be studied, for example, using mouse mesenchymal stem cells, MSCs (C3H10T1/2), or human osteoblast-like cells (MG63). Other human osteoblast-like cells (SaOS-2) can be used to characterize the cell adhesion, proliferation, and differentiation in vitro. The in vitro tests with individual microbial or cell cultures are rather far away from the real conditions in the human or animal body. Therefore, they have to be followed by in vivo tests, which permit the estimation of the real applicability of novel materials. Further, we discuss the physical, chemical, and biological mechanisms determining the antimicrobial properties and biocompatibility. The possible directions of future developments and novel application areas are described in the concluding section of the review.
... [12a] However, the current traditional implants are limited to a single function, failing to meet the comprehensive therapeutic requirements. [60] To address the issue, researchers have tried to develop diverse implant coatings for the treatment of implant infections or myeloma and promote bone integration and regeneration management. For instance, Li et al. constructed a multifunctional implant coating inspired by mussels and tissue biosubstrates. ...
The rise of antibiotic resistance poses a critical threat to global health, necessitating the development of novel antibacterial strategies to mitigate this growing challenge. Biomimetic materials, inspired by natural biological systems, have emerged as a promising solution in this context. These materials, by mimicking biological entities such as plants, animals, cells, viruses, and enzymes, offer innovative approaches to combat bacterial infections effectively. This review delves into the integration of biomimicry with materials science to develop antibacterial agents that are not only effective but also biocompatible and less likely to induce resistance. The study explores the design and function of various biomimetic antibacterial materials, highlighting their therapeutic potential in anti‐infection applications. Further, the study provides a comprehensive summary of recent advancements in this field, illustrating how these materials have been engineered to enhance their efficacy and safety. The review also discusses the critical challenges facing the transition of these biomimetic strategies from the laboratory to clinical settings, such as scalability, cost‐effectiveness, and long‐term stability. Lastly, the study discusses the vast opportunities that biomimetic materials hold for the future of antibacterial therapy, suggesting that continued research and multidisciplinary collaboration will be essential to realize their full potential.
... Since just the chemical composition and relief govern the properties of implants, the surfaces of biomaterials are functionalized by antibacterial agents with a pronounced biocide action, such as silver, to solve this problem [4][5][6]. According to [6][7][8][9][10][11], the antibacterial properties of silver are related with the dynamics of metal release to biological fluid when control of the dose of silver dissolved from the surface is critically important for a human being [8]. It is found that silver dissolution dynamics is affected by the metal concentration, nanoparticle shape and size, and the composition of the surface on which silver structures are deposited [5-7, 11, 12]. ...
... This can be considered consistent with previous experimental results where the reported bridgeable gap was smaller than 250 μm [52,66], although, given the variability in bone types and experimental conditions, a direct comparison should be taken with caution. The bridgeable distance is expected to increase with osteoinductive coatings [67][68][69], and a similar procedure can be applied to consider this increased ability. ...
The risk of aseptic loosening in cementless hip stems can be reduced by improving osseointegration with osteoinductive coatings favoring long-term implant stability. Osseointegration is usually evaluated in vivo studies, which, however, do not reproduce the mechanically driven adaptation process. This study aims to develop an in silico model to predict implant osseointegration and the effect of induced micromotion on long-term stability, including a calibration of the material osteoinductivity with conventional in vivo studies. A Finite Element model of the tibia implanted with pins was generated, exploiting bone-to-implant contact measures of cylindrical titanium alloys implanted in rabbits’ tibiae. The evolution of the contact status between bone and implant was modeled using a finite state machine, which updated the contact state at each iteration based on relative micromotion, shear and tensile stresses, and bone-to-implant distance. The model was calibrated with in vivo data by identifying the maximum bridgeable gap. Afterward, a push-out test was simulated to predict the axial load that caused the macroscopic mobilization of the pin. The bone-implant bridgeable gap ranged between 50 μm and 80 μm. Predicted push-out strength ranged from 19 N to 21 N (5.4 MPa–3.4 MPa) depending on final bone-to-implant contact. Push-out strength agrees with experimental measurements from a previous animal study (4 ± 1 MPa), carried out using the same implant material, coated, or uncoated. This method can partially replace in vivo studies and predict the long-term stability of cementless hip stems.
... Bioceramics, polymers, metals and their composites have been studied for their ability and biocompatibility to support the construction of bone substitutes. Ceramic materials are key elements in biomaterial applications [61][62][63][64]. Bioceramics are ceramics intended for bonding with tissue [65][66][67]. ...
Bone is the second organ of the human body that has the most transplants. The concept of bone repair has evolved over the past five decades and is known as the third generation of biomaterials. During the integration of nanotechnology with bioceramics, an emerging research field called nanobioceramics has been born within the third generation of biomaterials. Due to the chemical similarity with the mineral content of human bone, nanobioceramics are included in the definition of a new generation of biomaterials whose main purpose is to create a microenvironment to improve cellular responses leading to osteogenesis. Hydroxyapatite is a member of the calcium phosphate family. This substance, which is a bioactive and biocompatible compound, is considered the main mineral component of bone tissue. Due to the chemical and structural similarity of this compound with bone, it is widely used in the field of bone tissue repair and dental and orthopedic applications. Many of the basic properties of hydroxyapatite can be improved and improved by changing the scale of its particles to nanoparticles. Therefore, in recent years, various methods for the synthesis of nanohydroxyapatite have been reported. Using different characterization methods, the quality of synthesized nanostructures can be checked. In addition to bone-related fields, nanohydroxyapatite is also used as a carrier in the transfer of various materials, including drugs, vitamins, and proteins. In this article, in modern times, advances in the field of biomedical research focusing on the use of bioceramics in the treatment of various diseases, the function of vital organs, and tissue engineering have brought new hopes to regenerative medicine. Various methods are being investigated to synthesize bioceramic materials using natural and synthetic materials. There are several challenges to enable cost-effective material synthesis and minimize the rejection of bioceramics in biological systems. One of the major challenges in incorporating foreign materials into body systems is to improve their acceptance and reduce their rejection by humans and other organisms by studying their immune responses. When developing biocompatible ceramic materials, the mechanical and chemical properties of the ceramic material are one of the most important parameters for their acceptance in humans. The evaluation criteria of mechanical, chemical and biological properties of bioceramics using various existing approaches play a crucial role in validating the use of bioceramics. State-of-the-art techniques for synthesis and evaluation of bioceramic properties can improve their biomedical applications.
... Al can cause neurological pathology and V has been reported to exert cytotoxic effects in the body's environment. [7][8][9][10][11][12] The implants leak incompatible metal ions into the body as a result of their limited wear and corrosion resistance in bodily fluids. It is discovered that the liberated ions result in harmful and allergic responses. ...
Titanium alloys (Ti−6Al−4V) are being used in many biomedical applications due to their unique properties of bioactivity, excellent mechanical properties, low toxicity, biocompatibility, and long‐term implant application for their satisfactory corrosion resistance. We have developed a new two‐step fabrication process of zirconium oxide (ZrO2) and Chitosan/Mg−Zn−HAP (Chitosan/M−HAP) bilayer layer coating on Ti alloy for biomedical applications. Flower‐structured bilayers were coated by the electrochemical deposition method. Electrochemically deposited bilayer‐coated Ti alloy specimens were characterized by various analytical techniques like field‐emission scanning electron microscope (FE‐SEM), X‐ray diffraction (XRD), and EDS mapping analysis. Furthermore, the developed bilayer (Chitosan/Mg−Zn−HAP/ZrO2) coated Ti alloy samples improved mechanical properties such as adhesion strength (20.1±0.4 MPa) and hardness (446±4 Hv), compared to other coatings. An investigation of polarization curves showed a positive shift in the polarization values (Ecorr, and Icorr) of the Chitosan/M−HAP/ZrO2 bilayer coatings on Ti alloy. Bilayer‐modified Ti alloy samples show good antimicrobial response toward Gram‐negative and Gram‐positive bacteria. Meanwhile, the cell viability and proliferation of the bilayer‐coated samples were evaluated and the exhibited result improved cell proliferation, and bioactivity compared to other coated materials. From the results, it can be evident that the developed Chitosan/Mg−Zn−HAP/ZrO2 bilayer‐coated Ti alloy could be a good potential candidate for biomedical applications.
... As shown in Fig. 5d, the ΔT of PTP-5 coating is almost unchanged over three cycles, indicating the excellent photothermal stability of PTP-5 coating. It is important to note that the bone implants need to stay in the body for up to a year or even decades once implanted, which necessitates that the functional coating on the surface of the implant be able to maintain stable properties [48]. For example, if a bone implant has loosened after a few months (such as aseptic inflammation-induced bone loosening), an on-demand treatment can be implemented via the stable photothermal effect of the implant's surface coating. ...
Mild thermal stimulation plays an active role in bone tissue repair and regeneration. In this work, a bioactive polydopamine/Ti3C2/poly(vinylidene fluoride trifluoroethylene) (PDA/Ti3C2/P(VDF-TrFE)) nanocomposite coating with excellent near-infrared light (NIR)-triggered photothermal effect was designed to improve the osteogenic ability of implants. By incorporating dopamine (DA)-modified Ti3C2 nanosheets into the P(VDF-TrFE) matrix and combining them with alkali initiated in situ polymerization, the resulting PDA/Ti3C2/P(VDF-TrFE) nanocomposite coating gained high adhesion strength on Ti substrate, excellent tribological and corrosion resistance properties, which was quite important for clinical application of implant coatings. Cell biology experiments showed that NIR-triggered mild thermal stimulation on the coating surface promoted cell spreading and growth of BMSCs, and also greatly upregulated the osteogenic markers, including Runt-Related Transcription Factor 2 (RUNX2), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN). Simultaneously, the synthesis of heat shock protein 47 (HSP47) was significantly promoted by the mild thermal stimulation, which strengthened the specific interaction between HSP47 and collagen Ⅰ (COL-Ⅰ), thereby activating the integrin-mediated MEK/ERK osteogenic differentiation signaling pathway. In addition, the results also showed that the mild thermal stimulation induced the polarization of macrophages towards M2 phenotype, which can attenuate the inflammatory response of injured bone tissue. Antibacterial results indicated that the coating exhibited an outstanding antibacterial ability against S. aureus and E. coli. Conceivably, the versatile implant bioactive coatings developed in this work will show great application potential for implant osseointegration.
... 12,13 Approximately 18% of implant failures are reported to be attributable to aseptic loosening due to inadequate osseointegration, while 20% are attributed to bacterial infection, and some are attributed to both. 14,15 Therefore, in order to achieve better clinical results, there is an urgent need to develop implants with both antimicrobial and osteogenic properties. ...
Background
Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals.
Purpose
To study the antibacterial activity and bone induction ability of titanium–copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration.
Methods
We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining.
Results
Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects.
Conclusion
NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.
... The primary reasons for the premature failure of joint arthroplasty are aseptic loosening and periprosthetic joint infection [12,15]. Aseptic loosening can occur due to various factors, including implant micromotion within the bone during loading, the presence of corundum wear particles from grit-blasted surfaces, including the taper, generation of wear particles leading to inflammation and bone resorption, and subsequent formation of a suboptimal functional interface (osteointegration) between the implant and the patient's bone [21][22][23][24][25][26]. ...
We investigated micro-threaded stem taper surface and its impact on premature failures, aseptic loosening, and infection in cementless hip endoprostheses. Our study focused on the fretting, and crevice corrosion of micro-threaded tapers, as well as the characterization of the microstructure and surface properties of two new and three retrieved Zweymüller stem tapers. The retrieved samples were selected and examined based on the head–stem taper interface being the sole source of modularity with a metallic component, specifically between the Ti alloy taper stem and the ceramic head. To determine the surface chemistry and microstructures of both new and retrieved hip endoprostheses stem taper titanium alloy, scanning -electron microscopy (SEM) was employed for morphological and microstructural analyses. Energy dispersive spectroscopy (EDS) was utilized for characterizing chemical element distribution, and electron backscattered diffraction (EBSD) was used for phase analysis. The roughness of the micro-threated stem tapers from different manufacturers was investigated using an optical profilometer, with standard roughness parameters Ra (average surface roughness) and Rz (mean peak to valley height of the roughness profile) being measured. Electrochemical studies revealed no fretting corrosion in retrieved stem tapers with ceramic heads. Consequently, three retrieved tapers and two new ones for comparison underwent potentiodynamic measurements in Hank’s solution to determine the corrosion rate of new and retrieved stem taper surfaces. The results showed a low corrosion rate for both new and prematurely failed retrieved samples due to aseptic loosening. However, the corrosion rate was higher in infected and low-grade infected tapers. In conclusion, our study suggests that using ceramic heads reduces taper corrosion and subsequently decreases the incidence of premature failures in total hip arthroplasty.
... A direct structural and functional connection between living bone tissue and the surface of a load-bearing implant is made possible by osseointegration [16][17] [18]. In amputated limbs, this direct osseointegration interface enables a more stable connection, enhancing osseoperception while eradicating issues with the bone implants like pain and skin irritation and improving the overall quality of life [19][20] [21][22] [23]. Many suture anchors and screws are still in use for clinical applications and surgical procedures, including soft tissue reattachment, soft tissue reconstruction, repairing osteochondral defects, deformity corrections, and internal fracture fixation [24] [25]. ...
Mechanical vibration can be defined as the regular or irregular repetitive movement that makes the body leave its resting state. Mechanical vibrations have an important role in keeping the bones and joints healthy. This review study aimed to investigate the importance of mechanical vibration in the evaluation and replacement of bone cement-anchored implants in human bone. The empirical studies related to mechanical vibrations and bone cement-anchored implants were searched on Google Scholar. The combinations used to search for studies related to the topic included mechanical vibrations, evaluation, replacement, bone, cement-anchored implants, and human bone. The details of the ten studies are summarized in Table 1. The reviewed studies show that mechanical vibration, either local or whole-body, promotes bone growth in and around the implant. The stimulation of bone growth is important for the strength and durability of cement-anchored bone implants. Through the reviewed studies, it was concluded that local or whole-body mechanical vibration improves the stability and durability of bone and bone implants. Mechanical vibration achieves this effect by increasing bone formation in and around the implants and by improving the contact between the implant and the bone.
... Aseptic loosening and periprosthetic joint infection are the main causes of the premature failure of joint arthroplasty [12,15]. Aseptic loosening can be induced by different causes, such as the micromotion of the implant in the bone during loading, corundum wear particles from grit-blasted 3 surfaces, including taper, wear-particle generation, causing inflammation and bone resorption, and consequently the formation of a poor functional interface (osteointegration) between the implant and the patient's bone [22][23][24][25][26][27]. ...
We investigated the micro-threaded stem taper surface and the impact on premature failures, aseptic loosening, and infection. We have focused on the fretting, and crevice corrosion of micro-threaded tapers, as well as the characterization of microstructure and surface properties of two new and three retrieved Zweymüller stem tapers of cementless hip endoprostheses selected from a set of 45 stems. The retrievals examined were those in which the sole source of modularity with a metallic component was the head-stem taper interface between the Ti alloy taper stem and the ceramic head. To determine the surface chemistry and microstructures of both new and retrieved hip endoprostheses stem taper titanium alloy, scanning electron microscopy (SEM) was employed for morphological and microstructural analyses. At the same time, energy dispersive spectroscopy (EDS) was utilized for characterizing chemical element distribution, and electron backscattered diffraction (EBSD) was used for phase analysis. The micro-threated stem taper’s roughness for different manufacturers was investigated using an optical profilometer. Standard roughness pa-rameters Ra (average surface roughness) and Rz (mean peak to valley height of the roughness pro-file) were used in this investigation.Additionally, profile depth and peak spacing for different samples were investigated. The surface roughness results indicate no significant difference in roughness associated with varying survivorship times, ranging from 3 to 239 months, and across different manufacturers. Electrochemical studies revealed no fretting corrosion in retrieved stem tapers (ceramic head) that prematurely failed due to aseptic loosening after 239 months, infection after 3 months, and low-grade infection after a 32-month lifetime. Therefore, three retrieved ta-pers and two new ones for comparison underwent potentiodynamic measurements in Hank’s so-lution to ascertain the corrosion rate of new and retrieved stem taper surfaces. The results show a low corrosion rate for both new and retrieved samples that failed prematurely due to aseptic loosening. However, the corrosion rate of infected and low-grade infected tapers was higher. In conclusion, our study aligns with existing literature, suggesting that the use of ceramic heads de-creases the problem of taper corrosion and subsequently reduces premature failures in total hip arthroplasty.
... There was a 113% increase in spinal fusion procedures from 1998 to 2011 and a total of 1,390,611 spinal procedures in 2011 according to the HCUP Nationwide Inpatient Sample (NIS) [1]. However, up to 10% of these implants experience failure due to causes such as poor osseointegration, infection, and failure/breakage [2][3][4][5]. Osseointegration is the direct connection between living bone and the surface of an implant and is crucial for the long-term success of an implant [6]. Successful osseointegration into an implant interface is mainly influenced by material stiffness and porosity ranging in size from 100 to 600 µm; thus, it is critical to find the appropriate material and apply a surface modification, which will be conducive to enhanced osseointegration [6][7][8]. ...
The materials traditionally used for implant applications, such as titanium alloys, cobalt chromium, and zirconium, often require surface modifications to achieve the desired osseointegration. These materials still have the problematic stress-shielding effect. To limit stress shielding, PEEK is the superior alternative to fulfill implant needs. However, the traditional methods of modifying and functionalizing the surface of PEEK are often expensive, time consuming, and are not easily translated into commercialization. Sulfonation is a process, which is dependent on controllable factors. Thus far, no research has been performed to optimize the sulfonation process. Our data suggest that the process factors can be controlled and optimized. Cellular activity was examined on the optimized PEEK surfaces through testing with pre-osteoblast MC3T3-E1 cells through cell viability (MTT assay), cell proliferation (DNA assay), cell differentiation (ALP assay), and cell mineralization (Alizarin red assay). Overall, sulfonated and heat-treated PEEK exhibited a statistically significant increase in DNA content over the course of 21 days, indicating more cell proliferation and viability for that surface. In vitro testing results showed that the optimized sulfonated and heat-treated PEEK exhibited superior cell proliferation and mineralization performance over smooth PEEK and sulfonated-only PEEK.
... Consequently, the properties of materials such as medical devices that can provide a highly cell-friendly environment are required [35,36]. The previous reports mentioned above indicated that, similar to our cell biocompatibility results, the PEEK-PDA showed good cell proliferation as compared with other groups due to its enhanced hydrophilicity. ...
The occurrence of bone diseases has been increasing rapidly, in line with the aging population. A representative spinal fusion material, polyetheretherketone (PEEK), is advantageous in this regard as it can work in close proximity to the elastic modulus of cancellous bone. However, if it is used without surface modification, the initial osseointegration will be low due to lack of bioactivity, resulting in limitations in surgical treatment. In this study, we aimed to modify the surface of PEEK cages to a hydrophilic surface by coating with polyethylene glycol (PEG), hyaluronic acid (HA), and polydopamine (PDA), and to analyze whether the coated surface exhibits improved bioactivity and changes in mechanical properties for orthopedic applications. Material properties of coated samples were characterized and compared with various PEEK groups, including PEEK, PEEK-PEG, PEEK-HA, and PEEK-PDA. In an in vitro study, cell proliferation was found to be enhanced on PDA-coated PEEK; it was approximately twice as high compared to the control group. In addition, mechanical properties, including static and torsion, were not affected by the presence of the coating. Thus, the results suggest that PEEK-PDA may have the potential for clinical application in fusion surgery for spinal diseases, as it may improve the rate of osseointegration.
... Prosthesis loosening has been linked to nearly half of all implant failures in previous decades. 5 This condition is caused by poor osseointegration between the implant and bone tissue. 6 Osseointegration is a complicated healing process that involves bone, blood vessels, and implants. ...
For decades, titanium implants have shown impressive advantages in bone repair. However, the preparation of implants with excellent antimicrobial properties as well as better osseointegration ability remains difficult for clinical application. In this study, black phosphorus nanosheets (BPNSs) were doped into hydroxyapatite (HA) coatings using electrophoretic deposition. The coatings' surface morphology, roughness, water contact angle, photothermal properties, and antibacterial properties were investigated. The BP/HA coating exhibited a surface roughness of 59.1 nm, providing an ideal substrate for cell attachment and growth. The water contact angle on the BP/HA coating was measured to be approximately 8.55°, indicating its hydrophilic nature. The BPNSs demonstrated efficient photothermal conversion, with a temperature increase of 42.2°C under laser irradiation. The BP/HA composite coating exhibited a significant reduction in bacterial growth, with inhibition rates of 95.6% and 96.1% against Staphylococcus aureus and Escherichia coli. In addition, the cytocompatibility of the composite coating was evaluated by cell adhesion, CCK8 and AM/PI staining; the effect of the composite coating in promoting angiogenesis was assessed by scratch assay, transwell assay, and protein blotting; and the osteoinductivity of the composite coating was evaluated by alkaline phosphatase assay, alizarin red staining, and Western blot. The results showed that the BP/HA composite coating exhibited superior performance in promoting biological functions such as cell proliferation and adhesion, antibacterial activity, osteogenic differentiation, and angiogenesis, and had potential applications in vascularized bone regeneration.
Ceramics have long been recognized for their exceptional properties, ranging from mechanical stability to biocompatibility, making them highly promising candidates for various medical and healthcare innovations. The chapter elucidates the essential processes involved in ceramic synthesis, from precursor selection to material shaping and different heat treatments. It delves into diverse synthesis methods, including traditional solid-state reactions and advanced techniques like sol–gel and hydrothermal routes. The discussion extends to the crucial principles underlying ceramic synthesis, including crystallography, phase transformations, and microstructural development. These principles serve as the cornerstone for designing ceramics with optimal properties for biomedical applications. The chapter explores how variations in synthesis parameters influence material characteristics, leading to tailored properties such as mechanical strength, surface reactivity, and porosity for their applications in tissue engineering, drug delivery, and medical diagnostics. By synergistically addressing the synthesis intricacies and the biomedical landscape, this chapter provides a comprehensive resource for harnessing the potential of ceramics to revolutionize healthcare technologies. Ultimately, it underscores how a deep understanding of synthesis processes and principles lays the groundwork for unlocking the transformative capabilities of ceramics in the dynamic field of biomedicine as well.
Aseptic inflammation and osteolysis triggered by the phagocytosis of implant wear particles by macrophages are important reason for aseptic loosening (AL) in total joint replacement which ultimately leads to implant...
Ti and its alloys, widely utilized in orthopedic and dental implants, inherently lack antibacterial properties, posing significant infection risks, especially in the context of growing antibiotic resistance. This review critically evaluates non-antibiotic antibacterial strategies, with a particular focus on surface modifications and micro/nano-structured surfaces. Micro/nano-structured surfaces, inspired by natural topographies, utilize physical mechanisms to eradicate bacteria. Despite their potential, the antibacterial efficacy of these surfaces remains insufficient for clinical application. Titanium dioxide (TiO2), known for its excellent photocatalytic antibacterial activity and biocompatibility, is emerging as an ideal candidate for enhancing micro/nano-structured surfaces. By combining the photocatalytic antibacterial effects of TiO2 with the mechanical bactericidal properties of micro/nano-structured surfaces, superior antibacterial performance can be achieved. The hydrothermal method is frequently employed to fabricate TiO2 micro/nano-structured surfaces, and this area of research continues to thrive, particularly in the development of antibacterial strategies. With demonstrated efficacy, combined antibacterial strategies based on TiO2 micro/nano-structured surfaces have become a prominent focus in current research. Consequently, the integration of physical stimulation and chemical release mechanisms may represent the future direction for TiO2 micro/nano-structured surfaces. This review aims to advance the study of TiO2 micro/nano-structured surfaces in antibacterial applications and to inspire more effective non-antibiotic antibacterial solutions.
Polypropylene imine (PPI) dendrimer has antimicrobial efficiency, bioactivity, and enhanced biocompatibility. Scandium dioxide (Sc2O3) has cell viability, cell growth, cell proliferation, and biostability. Sc2O3-PPI dendrimer nanocomposite-coated Ti substrate was studied for its bioactivity by immersing in Kokubo’s simulated body fluid for 21 days at 36.5oC (pH: 7.4). The physio-chemical and electrochemical characterization revealed a high level of crystallinity and exhibited superior adhesion and biostability to the Ti substrate. Vickers microhardness test under various loads (50 gm) confirmed the mechanical stability of the coatings. SEM-EDS studies demonstrated that the formation of a homogenous apatite layer on the surface of the coatings was produced by the interaction of the Sc2O3-PPI dendrimer nanocomposite coating and simulated body fluid. In vitro antibacterial and in vitro cytotoxicity tests were used to evaluate the antibacterial properties and toxic effects of the Sc2O3-PPI dendrimer nanocomposite coatings. The coating excellently inhibited bacterial activity, and the highest zone of inhibition was obtained for S. aureus (gram-positive bacteria) and P. aeruginosa (gram-negative bacteria). Moreover, employing the theoretical studies of a small model system, stability of Sc2O3-PPI dendrimer composite is also explained by the existence of a hydrogen bond as well as Sc and O interaction. Preferential doping of PPI dendrimer into Sc2O3 proved high bioactivity, effective antibacterial properties, great mechanical stability of the coating, and no evidence of cytotoxic effect, suggesting that the Sc2O3-PPI dendrimer nanocomposite coating is expected to be a promising bioactive long-term orthopedic implant.
Implant-related infections pose significant challenges to orthopedic surgeries due to the high risk of severe complications. The widespread use of bioactive prostheses in joint replacements, featuring roughened surfaces and tight integration with the bone marrow cavity, has facilitated bacterial proliferation and complicated treatment. Developing antibacterial coatings for orthopedic implants has been a key research focus in recent years to address this critical issue. Researchers have designed coatings using various materials and antibacterial strategies. In this study, we fabricated 3D-printed porous titanium rods, incorporated vancomycin-loaded mPEG750-b-PCL2500 gel, and coated them with a PCL layer. We then evaluated the antibacterial efficacy through both in vitro and in vivo experiments. Our coating passively inhibits bacterial biofilm formation and actively controls antibiotic release in response to bacterial growth, providing a practical solution for proactive and sustained infection control. This study utilized 3D printing technology to produce porous titanium rod implants simulating bioactive joint prostheses. The porous structure of the titanium rods was used to load a thermoresponsive gel, mPEG750-b-PCL2500 (PEG: polyethylene glycol; PCL: polycaprolactone), serving as a novel drug delivery system carrying vancomycin for controlled antibiotic release. The assembly was then covered with a PCL membrane that inhibits bacterial biofilm formation early in infection and degrades when exposed to lipase solutions, mimicking enzymatic activity during bacterial infections. This setup provides infection-responsive protection and promotes drug release. We investigated the coating’s controlled release, antibacterial capability, and biocompatibility through in vitro experiments. We established a Staphylococcus aureus infection model in rabbits, implanting titanium rods in the femoral medullary cavity. We evaluated the efficacy and safety of the composite coating in preventing implant-related infections using imaging, hematology, and pathology. In vitro experiments demonstrated that the PCL membrane stably protects encapsulated vancomycin during PBS immersion. The PCL membrane rapidly degraded at a lipase concentration of 0.2 mg/mL. The mPEG750-b-PCL2500 gel ensured stable and sustained vancomycin release, inhibiting bacterial growth. We investigated the antibacterial effect of the 3D-printed titanium material, coated with PCL and loaded with mPEG750-b-PCL2500 hydrogel, using a rabbit Staphylococcus aureus infection model. Imaging, hematology, and histopathology confirmed that our composite antibacterial coating exhibited excellent antibacterial effects and infection prevention, with good safety in trials. Our results indicate that the composite antibacterial coating effectively protects vancomycin in the hydrogel from premature release in the absence of bacterial infection. The outer PCL membrane inhibits bacterial growth and prevents biofilm formation. Upon contact with bacterial lipase, the PCL membrane rapidly degrades, releasing vancomycin for antibacterial action. The mPEG750-b-PCL2500 gel provides stable and sustained vancomycin release, prolonging its antibacterial effects. Our composite antibacterial coating demonstrates promising potential for clinical application.
Implant infections are a major challenge for the healthcare system. The biofilm formation and increasing antibiotic resistance of common bacteria causing implant infections, leads to an urgent need of alternative...
This review highlights recent advancements in the synthesis, processing, properties, and applications of 2D‐material integrated hydrogels, with a focus on their performance in bone‐related applications. Various synthesis methods and types of 2D nanomaterials, including graphene, graphene oxide, transition metal dichalcogenides, black phosphorus, and MXene are discussed, along with strategies for their incorporation into hydrogel matrices. These composite hydrogels exhibit tunable mechanical properties, high surface area, strong near‐infrared (NIR) photon absorption and controlled release capabilities, making them suitable for a range of regeneration and therapeutic applications. In cancer therapy, 2D‐material‐based hydrogels show promise for photothermal and photodynamic therapies, and drug delivery (chemotherapy). The photothermal properties of these materials enable selective tumor ablation upon NIR irradiation, while their high drug‐loading capacity facilitates targeted and controlled release of chemotherapeutic agents. Additionally, 2D‐materials ‐infused hydrogels exhibit potent antibacterial activity, making them effective against multidrug‐resistant infections and disruption of biofilm generated on implant surface. Moreover, their synergistic therapy approach combines multiple treatment modalities such as photothermal, chemo, and immunotherapy to enhance therapeutic outcomes. In bio‐imaging, these materials serve as versatile contrast agents and imaging probes, enabling their real‐time monitoring during tumor imaging. Furthermore, in bone regeneration, most 2D‐materials incorporated hydrogels promote osteogenesis and tissue regeneration, offering potential solutions for bone defects repair. Overall, the integration of 2D materials into hydrogels presents a promising platform for developing multifunctional theragenerative biomaterials.
The urgency to address skeletal abnormalities and diseases through innovative approaches has led to a significant interdisciplinary convergence of engineering, 3D printing, and design in developing individualised bioceramic bioscaffolds. This review explores into the recent advancements and future trajectory of non-antibiotic antibacterial bioceramics in bone tissue engineering, an importance given the escalating challenges of orthopaedic infections, antibiotic resistance, and emergent pathogens. Initially, the review provides an in-depth exploration of the complex interactions among bacteria, immune cells, and bioceramics in clinical contexts, highlighting the multifaceted nature of infection dynamics, including protein adsorption, immunological responses, bacterial adherence, and endotoxin release. Then, focus on the next-generation bioceramics designed to offer multifunctionality, especially in delivering antibacterial properties independent of traditional antibiotics. A key highlight of this study is the exploration of smart antibacterial bioceramics, marking a revolutionary stride in medical implant technology. The review also aims to guide the ongoing development and clinical adoption of bioceramic materials, focusing on their dual capabilities in promoting bone regeneration and exhibiting antibacterial properties. These next-generation bioceramics represent a paradigm shift in medical implant technology, offering multifunctional benefits that transcend traditional approaches.
One of the leading causes of hospitalization, disability and mortality of 50% of women and 20% of men over the age of 50 are bone fractures and their complications caused by diseases of the musculoskeletal system. In this regard, an active search for a solution to the problem associated with the limitations of the use of auto-, allo-, and xenografts in the clinic to replace bone defects initiated the development of a regenerative approach based on the gradual replacement of artificial material with growing bone tissue. Promising in this regard are materials based on calcium phosphates, which act as an active source of chemical elements (calcium, phosphorus, etc.), which can optimize the process of bone defect fusion and ensure the replacement of the implant with new bone tissue. The review summarizes literature data on local biological activity, target cells, and molecular effects of calcium phosphates. It has been shown that calcium phosphate materials are biocompatible, capable of adsorbing regulatory proteins and cells, influencing their genetic and secretory apparatus and triggering the process of MSC differentiation in the osteogenic direction. At the same time, the successful implementation of local mechanisms of osseointegration at the “bone/implant” interface reduces the risk of periprosthetic infection (PJI) and rejection of artificial devices. Further study and use of calcium phosphate materials will make it possible to make a significant breakthrough in solving modern problems of bone tissue regeneration associated with an accurate (digital) bioengineering approach based on additive technologies and artificial intelligence.
Constructing surface topography with a certain roughness is a widely used, non-toxic, cost-effective and effective method for improving the microenvironment of cells, promoting the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs), and promoting the osseointegration of grafts and further improving their biocompatibility under clinical environmental conditions. SIRT1 plays an important regulatory role in the osteogenic differentiation of bone marrow-derived MSCs (BM-MSCs). However, it remains unknown whether SIRT1 plays an important regulatory role in the osteogenic differentiation of BM-MSCs with regard to surface morphology. Polydimethylsiloxane (PDMS) with different surface morphologies were prepared using different grits of sandpaper. The value for BMSCs added on different surfaces was detected by cell proliferation assays. RT-qPCR and Western blotting were performed to detect SIRT1 activation and osteogenic differentiation of MSCs. Osteogenesis of MSCs was detected by alkaline phosphatase (ALP) and alizarin red S staining. SIRT1 inhibition experiments were performed to investigate the role of SIRT1 in the osteogenic differentiation of MSCs induced by surface morphology. We found that BM-MSCs have better value and osteogenic differentiation ability on a surface with roughness of PDMS-1000M. SIRT1 showed higher gene and protein expression on a PDMS-1000M surface with a roughness of 13.741 ± 1.388 µm. The promotion of the osteogenic differentiation of MSCs on the PDMS-1000M surface was significantly decreased after inhibiting SIRT1 expression. Our study demonstrated that a surface morphology with certain roughness can activate the SIRT1 pathway of MSCs and promote the osteogenic differentiation of BMSCs via the SIRT1 pathway.
Aseptic loosening and bacterial infection pose significant challenges in the clinical application of titanium (Ti) orthopedic implants, which are primarily caused by insufficient osseointegration and bacterial contamination. To address these issues, a responsive coating on Ti surface is constructed, which achieves enhanced osseointegration and infection elimination by on‐demand release of therapeutic gas hydrogen sulfide (H2S) and antibiotic. TiO2 nanotubes (TNT) are anodized on the Ti surface to enhance its bioactivity and serve as reservoirs for the antibiotic. An infection microenvironment‐responsive macromolecular H2S donor layer is coated on top of TNT to inhibit premature leakage of antibiotic. This layer exhibits a sustained release of low‐dosage H2S, which is capable of promoting the osteogenic differentiation and migration of cells. Moreover, the compactness of the macromolecular H2S donor layer could be broken by bacterial invasion, leading to rapid antibiotic release thus preventing infection. In vitro antibacterial experiments validates significant antibacterial activity of the coating against both Gram‐negative (Escherichia coli) and Gram‐positive bacteria (Staphylococcus aureus). Crucially, this coating effectively suppresses implant‐associated infection with 98.7% antibacterial efficiency in a rat femoral bone defect model, mitigates inflammation at the defect site and promotes osseointegration of the Ti orthopedic implant.
Mechanical vibration can be defined as the regular or irregular repetitive movement that makes the body leave its resting state. Mechanical vibrations have an important role in keeping the bones and joints healthy. This review study aimed to investigate the effect of mechanical vibration in the evaluation and replacement of bone cement-anchored implants in human bone. The empirical studies related to mechanical vibrations and bone cement-anchored implants were reviewed. The combinations used to search for studies related to the topic included mechanical vibrations, evaluation, replacement, bone, cement-anchored implants, and human bone. The reviewed studies show that mechanical vibration, either local or whole-body, promotes bone growth in and around the implant. The stimulation of bone growth is important for the strength and durability of cement-anchored bone implants. Through the reviewed studies, it was concluded that local or whole-body mechanical vibration improves the stability and durability of bone and bone implants. Mechanical vibration achieves this effect by increasing bone formation in and around the implants and by improving the contact between the implant and the bone.
By staged regulation for antibacterial activity in the early stage and the M2 activation mediated osteogenic activity in the late stage, Zn–Sr/TiO 2 prevented implant-related infection and promoted excellent osseointegration.
Nanotechnology‐based approaches are promising for the treatment of musculoskeletal (MSK) disorders, which present significant clinical burdens and challenges, but their clinical translation requires a deep understanding of the complex interplay between nanotechnology and MSK biology. Organ‐on‐a‐chip (OoC) systems have emerged as an innovative and versatile microphysiological platform to replicate the dynamics of tissue microenvironment for studying nanotechnology‐biology interactions. This review covers first recent advances and applications of MSK OoCs and their ability to mimic the biophysical and biochemical stimuli encountered by MSK tissues. Next, by integrating nanotechnology into MSK OoCs, cellular responses and tissue behaviors may be investigated by precisely controlling and manipulating the nanoscale environment. Analysis of MSK disease mechanisms, particularly bone, joint, and muscle tissue degeneration, and drug screening and development of personalized medicine may be greatly facilitated using MSK OoCs. Finally, we outline future challenges and directions for the field, including advanced sensing technologies, integration of immune‐active components, and enhancement of biomimetic functionality. By highlighting the emerging applications of MSK OoCs, this review aims to advance our understanding of the intricate nanotechnology‐MSK biology interface and its significance in MSK disease management, and the development of innovative and personalized therapeutic and interventional strategies.
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Peri-prosthetic infections are notoriously difficult to treat as the biomaterial implant is ideal for bacterial adhesion and biofilm formation, resulting in decreased antibiotic sensitivity. Previously, we reported that vancomycin covalently attached to a Ti alloy surface (Vanc-Ti) could prevent bacterial colonization. Herein we examine the effect of this Vanc-Ti surface on Staphylococci epidermidis, a Gram-positive organism prevalent in orthopaedic infections. By direct colony counting and fluorescent visualization of live bacteria, S. epidermidis colonization was significantly inhibited on Vanc-Ti implants. In contrast, the gram-negative organism Escherichia coli readily colonized the Vanc-Ti rod, suggesting retention of antibiotic specificity. By histochemical and SEM analysis, Vanc-Ti prevented S. epidermidis biofilm formation, even in the presence of serum. Furthermore, when challenged multiple times with S. epidermidis, Vanc-Ti rods resisted bacterial colonization. Finally, when S. epidermidis was continuously cultured in the presence of Vanc-Ti, the bacteria maintained a Vanc sensitivity equivalent to the parent strain. These findings indicate that antibiotic derivatization of implants can result in a surface that can resist bacterial colonization. This technology holds great promise for the prevention and treatment of periprosthetic infections.
Aim: A meta-analysis was performed on prospective observational trials to test compare early failure rates of short (minimum length: 7 mm) and longer dental implants (≥ 10 mm).
Material and Methods: Following systematic electronic and hand searches and having additional data supplied by authors, a total of 54 publications (19,083 implants) were included in this meta-analysis.
Results: In the mandible no increased failure rate of short implants could be observed within the first year of prosthetic loading. In the maxilla a significant impact of implant length could be found only for machined implants, while short rough-surfaced implants did not demonstrate incrased failure. Implant diameter and type of prothetic rehabilitation did not influence failure rates of short implants.
Conclusion: Short dental implants may be used to obviate invasive bone graft surgery. Implant diameter increase may not compensate for length resduction.
Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver-resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings has yet to be observed. Here we identified the first strains of clinical bacteria expressing silver-resistance at a level that could significantly impact wound care and the use of silver-based dressings. Screening of 859 clinical isolates confirmed 31 were harboring at least 1 silver-resistant gene. Despite the presence of these genes, minimal inhibitory concentration (MIC) testing revealed most of the bacteria displayed little or no increase in resistance to ionic silver (200 - 300μM Ag(+)). However, 2 isolates (Klebsiella pneumonia and Enterobacter cloacae) were capable of robust growth at exceedingly high silver concentrations with MIC values reaching 5,500μM Ag(+). DNA sequencing of these two strains revealed the presence of genes homologous to known genetic determinants of heavy metal resistance. Darkening of the bacteria's pigment was observed after exposure to high silver concentrations. Scanning Electron Microscopy images showed the presence of silver nanoparticles embedded in the extracellular polymeric substance of both isolates. This finding suggested the isolates may neutralize ionic silver via reduction to elemental silver. Antimicrobial testing revealed both organisms to be completely resistant to many commercially available silver-impregnated burn and wound dressings. Taken together, these findings provide the first evidence of clinical bacteria capable of expressing silver resistance at levels that could significantly impact wound management.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Three-dimensional (3D) printing represents the direct fabrication of parts layer-by-layer, guided by digital information from a computer-aided design file without any part-specific tooling. Over the past three decades, a variety of 3D printing technologies have evolved that have transformed the idea of direct printing of parts for numerous applications. Three-dimensional printing technology offers significant advantages for biomedical devices and tissue engineering due to its ability to manufacture low-volume or one-of-a-kind parts on-demand based on patient-specific needs, at no additional cost for different designs that can vary from patient to patient, while also offering flexibility in the starting materials. However, many concerns remain for widespread applications of 3D-printed biomaterials, including regulatory issues, a sterile environment for part fabrication, and the achievement of target material properties with the desired architecture. This article offers a broad overview of the field of 3D-printed biomaterials along with a few specific applications to assist the reader in obtaining an understanding of the current state of the art and to encourage future scientific and technical contributions toward expanding the frontiers of 3D-printed biomaterials.
The long-term success of an orthopedic implant largely depends on the extent of its osseointegration in the surrounding bone. During recent decades, there have been several attempts to develop porous structures and coatings in order to maximize the bone ingrowth on prosthesis surfaces. Innovative additive manufacturing technologies, such as electron beam melting (EBM), which are based upon building components by adding layers of material rather than by removing material from a raw shape, can provide a breakthrough solution, both to overcome the major limitations of the actual technologies and to significantly enhance the performance of porous scaffolds. This article reviews the latest developments in EBM technology applied to the preparation of highly biocompatible porous materials such as Trabecular Titanium and the production of orthopedic prostheses with enhanced characteristics.
Bacterial colonization and biofilm formation on orthopedic implants is one of the worst scenarios in orthopedic surgery, in terms of both patient prognosis and healthcare costs. Tailoring the surfaces of implants at the nanoscale to actively promote bone bonding while avoiding bacterial colonization represents an interesting challenge to achieving better clinical outcomes. Herein, a Ti6Al4V alloy of medical grade has been coated with Ti nanostructures employing the glancing angle deposition technique by magnetron sputtering. The resulting surfaces have a high density of nanocolumnar structures, which exhibit strongly impaired bacterial adhesion that inhibits biofilm formation, while osteoblasts exhibit good cell response with similar behavior to the initial substrates. These results are discussed on the basis of a "lotus leaf effect" induced by the surface nanostructures and the different sizes and biological characteristics of osteoblasts and Staphylococcus aureus.
Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Dental implants with proper antibacterial ability as well as ideal osseointegration are being actively pursued. The antimicrobial ability of titanium implants can be significantly enhanced via modification with silver nanoparticles (Ag NPs). However, the high mobility of Ag NPs results in their potential cytotoxicity. The silver plasma immersion ion-implantation (Ag-PIII) technique may remedy the defect. Accordingly, Ag-PIII technique was employed in this study in an attempt to reduce the mobility of Ag NPs and enhance osseointegration of sandblasted and acid-etched (SLA) dental implants. Briefly, 48 dental implants, divided equally into one control and three test groups (further treated by Ag-PIII technique with three different implantation parameters), were inserted in the mandibles of six Labrador dogs. Scanning electron microscopy, X-ray photoelectron spectroscopy, and inductively coupled plasma optical emission spectrometry were used to investigate the surface topography, chemical states, and silver release of SLA- and Ag-PIII-treated titanium dental implants. The implant stability quotient examination, Microcomputed tomography evaluation, histological observations, and histomorphometric analysis were performed to assess the osseointegration effect in vivo. The results demonstrated that normal soft tissue healing around dental implants was observed in all the groups, whereas the implant stability quotient values in Ag-PIII groups were higher than that in the SLA group. In addition, all the Ag-PIII groups, compared to the SLA-group, exhibited enhanced new bone formation, bone mineral density, and trabecular pattern. With regard to osteogenic indicators, the implants treated with Ag-PIII for 30 minutes and 60 minutes, with the diameter of the Ag NPs ranging from 5–25 nm, were better than those treated with Ag-PIII for 90 minutes, with the Ag NPs diameter out of that range. These results suggest that Ag-PIII technique can reduce the mobility of Ag NPs and enhance the osseointegration of SLA surfaces and have the potential for future use.
After nearly half a century of development under the guidance of osseointegration theory, the major dilemmas for current implant dentistry are the implant associated infection and insufficient osseointegration. Moreover, biological aging of titanium (Ti) implant also brings great uncertainty to clinical results. In the present study, a novel nano-micro-hierarchical topography pattern is created by sandblasting and dual acid-etchings on Ti surface. The optimized nano-micro-hierarchical Ti surface exhibits surprisingly topography-dependent antibacterial capacity via inhibiting bacterial adhesion of several species in the early stage and excellent osteogenesis ability. Aging study demonstrates that, compared with the surface with microscale structure, the nano-micro-hierarchical Ti surface has greater anti-aging ability manifested as being more capable to retain hydrophilicity and bioactivity during aging. Furthermore, the present study reveals that the biological aging of the Ti implant is attributed to two decisive factors during aging period: the progressively thickened amorphous TiO2 layer by autoxidation and the unavoidable accumulation of hydrocarbons on Ti implant surface.
Background and purpose — It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival.
Patients and methods — We identified 152,410 THA procedures using uncemented stems that were performed between 1995 and 2011 and registered in the Nordic Arthroplasty Register Association (NARA) database. We excluded 19,446 procedures that used stem brands less than 500 times in each country, procedures performed due to diagnoses other than osteoarthritis or pediatric hip disease, and procedures with missing information on the type of coating. 22 stem brands remained (which were used in 116,069 procedures) for analysis of revision of any component. 79,192 procedures from Denmark, Norway, and Sweden were analyzed for the endpoint stem revision. Unadjusted survival rates were calculated according to Kaplan-Meier, and Cox proportional hazards models were fitted in order to calculate hazard ratios (HRs) for the risk of revision with 95% confidence intervals (CIs).
Results — Unadjusted 10-year survival with the endpoint revision of any component for any reason was 92.1% (CI: 91.8–92.4). Unadjusted 10-year survival with the endpoint stem revision due to aseptic loosening varied between the stem brands investigated and ranged from 96.7% (CI: 94.4–99.0) to 99.9% (CI: 99.6–100). Of the stem brands with the best survival, stems with and without HA coating were found. The presence of HA coating was not associated with statistically significant effects on the adjusted risk of stem revision due to aseptic loosening, with an HR of 0.8 (CI: 0.5–1.3; p = 0.4). The adjusted risk of revision due to infection was similar in the groups of THAs using HA-coated and non-HA-coated stems, with an HR of 0.9 (CI: 0.8–1.1; p = 0.6) for the presence of HA coating. The commonly used Bimetric stem (n = 25,329) was available both with and without HA coating, and the adjusted risk of stem revision due to aseptic loosening was similar for the 2 variants, with an HR of 0.9 (CI: 0.5–1.4; p = 0.5) for the HA-coated Bimetric stem.
Interpretation — Uncemented HA-coated stems had similar results to those of uncemented stems with porous coating or rough sand-blasted stems. The use of HA coating on stems available both with and without this surface treatment had no clinically relevant effect on their outcome, and we thus question whether HA coating adds any value to well-functioning stem designs.
The deficient osseointegration and implant-associated infections are pivotal issues for the long-term clinical success of endosteal Ti implants, while development of functional surfaces that can simultaneously overcome these problems remains highly challenging. This study aimed to fabricate sophisticated Ti implant surface with both osteogenic inducing activity and inherent antibacterial ability simply via tailoring surface topographical features. Micro/submciro/nano-scale structure was constructed on Ti by three cumulative subtractive methods, including sequentially conducted sandblasting as well as primary and secondary acid etching treatment. Topographical features of this hierarchical structure can be well tuned by the time of the secondary acid treatment. Ti substrate with mere micro/submicro-scale structure (MS0-Ti) served as a control to examine the influence of hierarchical structures on surface properties and biological activities. Surface analysis indicated that all hierarchically structured surfaces possessed exactly the same surface chemistry as that of MS0-Ti, and all of them showed super-amphiphilicity, high surface free energy, and high protein adsorption capability. Biological evaluations revealed surprisingly antibacterial ability and excellent osteogenic activity for samples with optimized hierarchical structure (MS30-Ti) when compared with MS0-Ti. Consequently, for the first time, a hierarchically structured Ti surface with topography-induced inherent antibacterial capability and excellent osteogenic activity was constructed.
Osseointegration is a good indication of the clinical success of titanium implants referring to the direct anchorage of such implants to the surrounding host bone. Despite the high success rate of endosseous dental implants, they do fail. A lack of primary stability, surgical trauma, and infection seem to be the most important causes of early implant failure. Early signs of infection may be an indication of a much more critical result than if the same complications occur later, because of disturbance of the primary bone healing process. Occlu-sal overload and periimplantitis seem to be the most important factors associ-ated with late failure. Suboptimal implant design and improper prosthetic constructions are among those risk factors responsible for implant complica-tions and failure. This concise review highlights the main causes associated with early and late implant failure, as thorough knowledge of this unavoidable clini-cal fact is essential in the field of oral implantology.
To endow a Ti-based implant with enhanced osteogenic activity and antibacterial property, we herein modified nano-grained (NG) and coarse-grained (CG) Ti surface layers by the implantation of Ca and/or Ag ions, which were derived by surface mechanical attrition treatment (SMAT). The cellular adhesion, proliferation, differentiation (as marked by the osteogenesis-related gene expression, ALP activity and specific protein content) and extracellular matrix mineralization of hFOB1.19 osteoblasts, as well as the bacterial adhesion of Staphylococcus aureus and Escherichia coli on as-SMATed and different ion-implanted surfaces, were also investigated. The obtained results show that Ca and/or Ag ion implantation almost does not significantly alter the surface roughness and topography of the SMATed layers; moreover, it has little influence on the microstructure of the SMAT-achieved Ti nanograins. Furthermore, the implanted Ca and Ag are in the form of CaTiO3 and metallic Ag nanoparticles (NPs), respectively, and are embedded tightly in the Ti matrix. Significant enhancements of osteoblast functions are exhibited on the NG and ion-implanted NG surfaces compared to the CG and ion-implanted CG surfaces, which is related to the grain size and hydrophilicity of the surfaces. Although the Ca and Ag dual-ion implanted CG surface can simultaneously enhance the osteogenic activity and antibacterial properties compared to the CG surface, the enhancement of dual functions is more pronounced on the dual-ion implanted NG surface because the NG surface is more beneficial to the implantation of Ag and Ca ions compared to the CG surface. Although surface chemistry and hydrophilicity are responsible for the various antibacterial properties of the surfaces, the Ag NPs in the ion-implanted surfaces play a dominant role in the bactericidal ability compared to the hydrophilicity. Our study provides a promising means for designing biomaterial surfaces such that their osteoblast functions and antibacterial activity are perfectly balanced.
Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent developments in material science and cell biology have seen the development of new orthopaedic implant coatings to address these issues. Coatings consisting of bioceramics, extracellular matrix proteins, biological peptides or growth factors impart bioactivity and biocompatibility to the metallic surface of conventional orthopaedic prosthesis that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. Furthermore, coatings such as silver, nitric oxide, antibiotics, antiseptics and antimicrobial peptides with anti-microbial properties have also been developed, which show promise in reducing bacterial adhesion and prosthetic infections. This review summarizes some of the recent developments in coatings for orthopaedic implants.
Genetic engineering techniques were used to design and biosynthesise an extracellular matrix (ECM) analogue. This was designed with a well-defined molecular architecture comprising different functional domains. The structural base is a elastin-derived repeating unit, which confers an adequate elastic characteristic. Some of these elastin domains have been modified to contain lysine; this amino acid can be used for crosslinking purposes. The polymer also contain periodically spaced fibronectin CS5 domains enclosing the well-known cell attachment sequence REDV. Finally, the polymer has target sequences for proteolitic action. These sequences are those found in the natural elastin and are introduced to help in the bioabsorption of the polymer. In addition, these proteolitic sequences were chosen in a way that, after proteolitic action, the released fragments will be bioactive. These fragments are expected to promote cell proliferation activity, angiogenesis and other bioactivities of interest for tissue growing, repairing and healing. After purification, the resulting polymers proved to be of high purity and correct sequence. Glutaraldehyde has shown to be a cross-linking agent for this polymer, yielding insoluble hydrogel matrices. This work is framed in a long term project aimed to exploit the power of genetic engineering for the design and bioproduction of complex ECM analogues showing the rich complexity and multi (bio)functionality of the natural matrix.
The presence of interconnected macro pores is important in tissue engineering scaffolds for guided tissue regeneration. This study reports in vivo biological performance of interconnected macro porous tricalcium phosphate (TCP) scaffolds due to the addition of SrO and MgO as dopants in TCP. We have used direct three dimensional printing (3DP) technology for scaffold fabrication followed by microwave sintering. Mechanical strength was evaluated by scaffolds with 500 µm, 750 µm, and 1000 µm interconnected designed pore sizes. Maximum compressive strength of 12.01 ± 1.56 MPa was achieved for 500 µm interconnected designed pore size Sr-Mg doped scaffold. In vivo biological performance of the microwave sintered pure TCP and Sr-Mg doped TCP scaffolds was assessed by implanting 350 µm designed interconnected macro porous scaffolds in rat distal femoral defect. Sintered pore size of these 3D printed scaffolds were 311 ± 5.9 µm and 245 ± 7.5 µm for pure and SrO-MgO doped TCP scaffolds, respectively. These 3D printed scaffolds possessed multiscale porosity, i.e., 3D interconnected designed macro pores along with intrinsic micro pores. Histomorphology and histomorphometric analysis revealed a significant increase in osteoid like new bone formation, and accelerated mineralization inside SrO and MgO doped 3D printed TCP scaffolds as compared to pure TCP scaffolds. An increase in osteocalcin and type I collagen level was also observed in rat blood serum with SrO and MgO doped TCP scaffolds compared to pure TCP scaffolds. Our results show that these 3D printed SrO and MgO doped TCP scaffolds with multiscale porosity contributed to early healing through accelerated osteogenesis.
This study aimed at investigating if a coating of hydroxyapatite nanocrystals would enhance bone healing over time in trabecular bone. Sandblasted and acid etched titanium implants with and without a submicron thick coat of hydroxyapatite nanocrystals (nano-HA) were implanted in rabbit femur with healing times of 2, 4, and 9 weeks. Removal torque analyses and histological evaluations were performed. The torque analysis did not show any significant differences between the implants at any healing time. The control implant showed a tendency of more newly formed bone after 4 weeks of healing and significantly higher bone area values after 9 weeks of healing. According to the results from this present study, both control and nano-HA surfaces were biocompatible and osteoconductive. A submicron thick coating of hydroxyapatite nanocrystals deposited onto blasted and acid etched screw shaped titanium implants did not enhance bone healing, as compared to blasted and etched control implants when placed in trabecular bone.
Biocomposite consists of gold nanoparticles (AuNPs) and a natural polymer as Chitosan (CS) was electrodeposited over NiTi alloy to improve biocompatibility, biostability, surface corrosion resistance and antibacterial effect for orthopedic implantation. The forming process and surface morphology of this biocomposite coats over NiTi alloy were studied. The results showed that the nm-scale gold particles were embedded in the composite forming compact, thick and smooth coat. Elemental analysis revealed significant less Ni ion release from the coated NiTi alloy compared with the uncoated one by 20 fold. Furthermore, the electrochemical corrosion measurements indicated that AuNPs/CS composite coat was effective for improving corrosion resistance in different immersion times and at all pH values, which suggests that the coated NiTi alloys have potential for orthopedic applications. Additionally, the efficiencies of the biocomposite coats for inhibiting bacterial growth indicate high antibacterial effect.
To assess the failure rate of cemented, uncemented, hybrid, and reverse hybrid total hip replacements in patients aged 55 years or older.
Register study.
Nordic Arthroplasty Register Association database (combined data from Sweden, Norway, Denmark, and Finland).
347 899 total hip replacements performed during 1995-2011.
Probability of implant survival (Kaplan-Meier analysis) along with implant survival with revision for any reason as endpoint (Cox multiple regression) adjusted for age, sex, and diagnosis in age groups 55-64, 65-74, and 75 years or older.
The proportion of total hip replacements using uncemented implants increased rapidly towards the end of the study period. The 10 year survival of cemented implants in patients aged 65 to 74 and 75 or older (93.8%, 95% confidence interval 93.6% to 94.0% and 95.9%, 95.8% to 96.1%, respectively) was higher than that of uncemented (92.9%, 92.3% to 93.4% and 93.0%, 91.8% to 94.0%), hybrid (91.6%, 90.9% to 92.2% and 93.9%, 93.1% to 94.5%), and reverse hybrid (90.7%, 87.3% to 93.2% and 93.2%, 90.7% to 95.1%) implants. The survival of cemented (92.2%, 91.8% to 92.5%) and uncemented (91.8%, 91.3% to 92.2%) implants in patients aged 55 to 64 was similar. During the first six months the risk of revision with cemented implants was lower than with all other types of fixation in all age groups.
The survival of cemented implants for total hip replacement was higher than that of uncemented implants in patients aged 65 years or older. The increased use of uncemented implants in this age group is not supported by these data. However, because our dataset includes only basic information common to all national registers there is potential for residual confounding.
Bone is formed by a series of complex events involving the mineralization of extracellular matrix proteins rigidly orchestrated by cells with specific functions of maintaining the integrity of the bone. Bone, similar to other calcified tissues, is an intimate composite of the organic (collagen and non-collagenous proteins) and inorganic or mineral phases. The bone mineral idealized as calcium hydroxyapatite, Ca-10(PO4)(6)(OH)(2), is a carbonate-hydroxyapatite, approximated by the formula: (Ca,X)(10)(PO4,HPO4,CO3)(6)(OH,Y)(2), where X are cations (magnesium, sodium, strontium ions) that can substitute for the calcium ions, and Y are anions (chloride or fluoride ions) that can substitute for the hydroxyl group. The current author presents a brief review of CaP biomaterials that now are used as grafts for bone repair, augmentation, or substitution. Commercially-available CaP biomaterials differ in origin (natural or synthetic), composition (hydroxyapatite, beta-tricalcium phosphate, and biphasic CaP), or physical forms (particulates, blocks, cements, coatings on metal implants, composites with polymers), and in physicochemical properties. CaP biomaterials have outstanding properties: similarity in composition to bone mineral; bioactivity (ability to form bone apatitelike material or carbonate hydroxyapatite on their surfaces), ability to promote cellular function and expression leading to formation of a uniquely strong bone-CaP biomaterial interface; and osteoconductivity (ability to provide the appropriate scaffold or template for bone formation). In addition, CaP biomaterials with appropriate three-dimensional geometry are able to bind and concentrate endogenous bone morphogenetic proteins in circulation, and may become osteoinductive (capable of osteogenesis), and can be effective carriers of bone cell seeds. Therefore, CaP biomaterials potentially are useful in tissue engineering for regeneration of hard tissues.
Human bone marrow contains a population of cells capable of differentiating along multiple mesenchymal cell lineages. Recently, techniques for the purification and culture-expansion of these human marrow-derived Mesenchymal Stem Cells (MSCs) have been developed. The goals of the current study were to establish a reproducible system for the in vitro osteogenic differentiation of human MSCs, and to characterize the effect of changes in the microenvironment upon the process. MSCs derived from 2nd or 3rd passage were cultured for 16 days in various base media containing 1 to 1000 nM dexamethasone (Dex), 0.01 to 4 mM L-ascorbic acid-2-phosphate (AsAP) or 0.25 mM ascorbic acid, and 1 to 10 mM beta-glycerophosphate (beta GP). Optimal osteogenic differentiation, as determined by osteoblastic morphology, expression of alkaline phosphatase (APase), reactivity with anti-osteogenic cell surface monoclonal antibodies, modulation of osteocalcin mRNA production, and the formation of a mineralized extracellular matrix containing hydroxyapatite was achieved with DMEM base medium plus 100 nM Dex, 0.05 mM AsAP, and 10 mM beta GP. The formation of a continuously interconnected network of APase-positive cells and mineralized matrix supports the characterization of this progenitor population as homogeneous. While higher initial seeding densities did not affect cell number of APase activity, significantly more mineral was deposited in these cultures, suggesting that events which occur early in the differentiation process are linked to end-stage phenotypic expression. Furthermore, cultures allowed to concentrate their soluble products in the media produced more mineralized matrix, thereby implying a role for autocrine or paracrine factors synthesized by human MSCs undergoing osteoblastic lineage progression. This culture system is responsive to subtle manipulations including the basal nutrient medium, dose of physiologic supplements, cell seeding density, and volume of tissue culture medium. Cultured human MSCs provide a useful model for evaluating the multiple factors responsible for the step-wise progression of cells from undifferentiated precursors to secretory osteoblasts, and eventually terminally differentiated osteocytes.
Metal implants are widely used to provide structural support and stability in current surgical treatments for bone fractures, spinal fusions, and joint arthroplasties as well as craniofacial and dental applications. Early implant-bone mechanical fixation is an important requirement for the successful performance of such implants. However, adequate osseointegration has been difficult to achieve especially in challenging disease states like osteoporosis due to reduced bone mass and strength. Here, we present a simple coating strategy based on passive adsorption of FN7-10, a recombinant fragment of human fibronectin encompassing the major cell adhesive, integrin-binding site, onto 316-grade stainless steel (SS). FN7-10 coating on SS surfaces promoted α5β1 integrin-dependent adhesion and osteogenic differentiation of human mesenchymal stem cells. FN7-10-coated SS screws increased bone-implant mechanical fixation compared to uncoated screws by 30% and 45% at 1 and 3 months, respectively, in healthy rats. Importantly, FN7-10 coating significantly enhanced bone-screw fixation by 57% and 32% at 1 and 3 months, respectively, and bone-implant ingrowth by 30% at 3 months compared to uncoated screws in osteoporotic rats. These coatings are easy to apply intra-operatively, even to implants with complex geometries and structures, facilitating the potential for rapid translation to clinical settings.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Surface-initiated polymerizations represent a versatile toolbox to generate densely grafted assemblies of chain end-tethered polymers. At sufficiently short interchain distances, surface-grafted polymers are forced into an extended chain conformation, which forms the basis of several unique properties, including their ability to withstand efficiently biofouling or to act as low friction coatings. While the effect on materials properties is well-established, only relatively recently first reports have appeared describing that chain stretching in surface-grafted polymer films also impacts chemical stability/reactivity. This Viewpoint presents surface-initiated polymerization as an alternative polymer mechanochemical tool. The absence of an external force field to induce chain elongation and the possibility to modulate chain stretching by varying brush molecular weight and grafting density, in conjunction with electrostatic interactions and nanoinclusions that may be present inside the polymeric grafts, make surface-initiated polymerization an attractive tool to both study and understand the effects of polymer chain conformation on the stability/reactivity of surface-grafted polymers.
The chemokine, stromal cell-derived factor-1 (SDF-1), and its receptor, CXCR-4, play an important role in tissue repair and regeneration in various organs including the bone. SDF-1 is indispensable for bone morphogenetic protein-2 (BMP-2)-induced osteogenic differentiation. However, SDF-1 is not needed after the osteogenic induction has been activated. Since the precise condition for the additive effects of combined DF-1 and BMP-2 in bone healing had not fully investigated, we aimed to determine the optimal conditions for SDF-1- and BMP-2-mediated bone regeneration. We examined the in vitro osteoblastic differentiation and cell migration after sequential treatments with SDF-1 and BMP-2. Based on the in vitro additive effects of SDF-1 and BMP-2, the critical-sized defects of mice calvaria were treated with these cytokines in various sequences. PBS-, SDF-1-, or BMP-2-soaked collagen scaffolds were implanted into the calvarial defects (n=36). Periodic percutaneous injections of PBS or the cytokine SDF-1 and BMP-2, into the implanted scaffolds were performed on days 3 and 6 post-operatively. Six experimental groups were used according to the types and sequences of the cytokine treatments. After 28 days, the mice were euthanized and bone formation was evaluated with micro-CT and histology. The molecular mechanism of the additive effect of SDF-1 and BMP-2 was evaluated by analyzing intracellular signal transduction via Smad and Erk phosphorylation. The in vitro experiments revealed that, among all the treatments, the treatment with BMP-2 after SDF-1 showed the strongest osteoblastic differentiation and enhanced cell migration. Similarly, in the animal model, the treatment with SDF-1 followed by BMP-2 treatment showed the highest degree of new bone regeneration than any other groups including the one with continuous BMP-2 treatment. This new bone formation can be partially explained by the activation of Smad and Erk pathways and enhanced cell migration. These results suggest that sequential treatment with the cytokines, SDF-1 and BMP-2, may be a promising strategy for accelerating bone regeneration in critical-sized defects.
According to the long-standing definition, septic and aseptic total joint replacement loosening are two distinct conditions with little in common. Septic joint replacement loosening is driven by bacterial infection whereas aseptic loosening is caused by biomaterial wear debris released from the bearing surfaces. However, recently it has been recognized that the mechanisms that drive macrophage activation in septic and aseptic total joint replacement loosening resemble each other. In particular, accumulating evidence indicates that in addition to mediating bacterial recognition and the subsequent inflammatory reaction, toll-like receptors (TLRs) and their ligands, pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPS), play a key role in wear debris-induced inflammation and macrophage activation. In addition, subclinical bacterial biofilms have been identified from some cases of seemingly aseptic implant loosening. Furthermore, metal ions released from some total joint replacements can activate TLR signaling similar to bacterial derived PAMPs. Likewise, metal ions can function as haptens activating the adaptive immune system similar to bacterial derived antigens. Thus, it appears that aseptic and septic joint replacement loosening share similar underlying pathomechanisms and that this strict dichotomy to sterile aseptic and bacterial-caused septic implant loosening is somewhat questionable. Indeed, rather than being two, well-defined clinical entities, peri-implant osteolysis is, in fact, a spectrum of conditions in which the specific clinical picture is determined by complex interactions of multiple local and systemic factors.
The demand for hip and knee replacement surgery is substantial and growing. Unfortunately, most joint replacement surgeries will fail within 10-25 years, thereby requiring an arduous, painful, and expensive revision surgery. To address this issue, a novel orthopedic implant coating material (“eXalt”) has been developed. eXalt is comprised of super elastic nitinol wire that is knit into a three-dimensional spacer fabric structure. eXalt expands in vivo to conform to the implantation site and is porous to allow for bone ingrowth. The safety and efficacy of eXalt were evaluated through structural analysis, mechanical testing, and a rabbit implantation model. The results demonstrate that eXalt meets or exceeds the performance of current coating technologies with reduced micromotion, improved osseointegration, and stronger implant fixation in vivo.
Protein adsorption and blood coagulation play important roles in the early stages of osseointegration and are strongly influenced by surface properties. We present a systematic investigation of the influence of different surface properties on the adsorption of the blood proteins fibrinogen and fibronectin and the degree of early blood coagulation. Experiments on custom-made and commercially available, micro-roughened hydrophobic titanium (Ti) surfaces (Ti SLA-Hphob), hydrophilic (Hphil) micro-roughened Ti surfaces with nanostructures (Ti SLActive-HphilNS), and on bimetallic titanium zirconium alloy (TiZr, Roxolid®) samples were performed, in order to study the biological response in relation to the surface wettability and the presence of nanostructures. Protein adsorption on the different substrates showed a highly significant effect of surface nanostructures. Hydrophilicity alone did not significantly enhance protein adsorption. Overall, the combination of nanostructures and hydrophilicity led to the highest adsorption levels, independent of whether Ti or TiZr were used: Hydrophilicity induced a strong effect on blood coagulation, whereas the effect of nanostructures alone was weak. The combination of both surface characteristics led to early and most pronounced blood-coagulation. Therefore nanostructured, hydrophilic Ti and TiZr surfaces may perform better in terms of osseointegration due to continuous protein adsorption and the formation of a layer of blood components on the implant surface. This article is protected by copyright. All rights reserved.
Infections associated with implanted medical devices are a major cause of nosocomial infections, with serious medical and economic repercussions. A variety of silver-containing coatings have been proposed to decrease the risk of infection by hindering bacterial adhesion and biofilm formation. However, the therapeutic range of silver is relatively narrow and it is important to minimize the amount of silver in the coatings, in order to keep sufficient antibacterial activity without inducing cytotoxicity. In this study, the antibacterial efficiency and biocompatibility of nanocoatings with minimal silver loading (∼0.65 nmol cm−2) was evaluated in vitro and in vivo. Titanium substrates were coated by grafting mercaptododecylphosphonic acid (MDPA) monolayers followed by post-reaction with AgNO3. The MDPA/AgNO3 nanocoatings significantly inhibited Escherichia coli and Staphylococcus epidermidis adhesion and biofilm formation in vitro, while allowing attachment and proliferation of MC3T3-E1 preosteoblasts. Moreover, osteogenic differentiation of MC3T3 cells and murine mesenchymal stem cells was not affected by the nanocoatings. Sterilization by ethylene oxide did not alter the antibacterial activity and biocompatibility of the nanocoatings. After subcutaneous implantation of the materials in mice, we demonstrated that MDPA/AgNO3 nanocoatings exhibit significant antibacterial activity and excellent biocompatibility, both in vitro and in vivo, after postoperative seeding with S. epidermidis. These results confirm the interest of coating strategies involving subnanomolar amounts of silver exposed at the extreme surface for preventing bacterial adhesion and biofilm formation on metallic or ceramic medical devices without compromising their biocompatibility.
Dip coating is a simple old way of depositing onto a substrate, especially small slabs and cylinders, a uniform thin film of liquid for solidification into a coating. The basic flow is steady, and in it film thickness is set by the competition among viscous force, capillary (surface tension) force and gravity. Thickness and uniformity can be sensitive to flow conditions in the liquid bath and gas overhead. The faster the substrate is withdrawn, the thicker the film deposited. This can be countered by using volatile solutes and combining rapid enough drying with the basic liquid flow. Then the physics grows more complicated, theoretical prediction of process performance more difficult, and control of the process more demanding. Outside product R&D labs it is far less often used in precision coating manufacture than a variety of premetered coating methods.
Spin coating is a more recently developed way of getting onto piecemeal substrates, especially small flat disks, a uniform thin liquid film for the same end. The basic flow is unsteady radial drainage in which centrifugal and viscous forces so compete that ordinary (Newtonian) liquid of constant viscosity tends toward a uniform film that grows ever thinner ever more slowly. Volatile solvents are commonly used because conditions can often be found that adequately separate thinning by spin-off from later thinning and solidification by drying. Thickness and uniformity, today theoretically predictable, are sensitive to speed, gas conditions, and rheology of concentrating, solidifying liquid. For the rheology of photoresist coating in microelectronics, spin coating works well. For that of suspension coatings in magnetic disk technology the process demands more careful control; actually it is often modified.
Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, drug-eluting chitosan-bioactive glass coatings were fabricated by a single-step electrophoretic deposition technique. Drug-loading and -releasing capacity of the composite coatings were carried out using the vancomycin antibiotic. Uniform coatings with a thickness of ∼55 μm containing 23.7 wt% bioactive glass particles and various amounts of the antibiotic (380–630 μg/cm2) were produced. The coatings were bioactive in terms of apatite-forming ability in simulated body fluid and showed favorable cell adhesion and growth. In vitro biological tests also indicated that the composite coatings had better cellular affinity than pristine chitosan coatings. The in vitro elution kinetics of the composite coating revealed an initial burst release of around 40% of the drug within the first elution step of 1 h and following by a continuous eluting over 4 weeks, revealing long-term drug-delivering potential. Antibacterial tests using survival assay against Gram-positive Staphylococcus aureus bacteria determined the effect of vancomycin release on reduction of infection risk. Almost no bacteria were survived on the coatings prepared from the EPD suspension containing ≥0.5 g/l vancomycin. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduce infection risk.