Nanoparticles to overcome bacterial resistance in orthopedic and dental implants

Document Type : Review Paper


1 Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran

2 Department of Prosthodontics, Dental Materials Research Center, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran

3 Bone And Joint Disease Center of Shiraz University of Medical Sciences, Orthopeadic Department, Shiraz, Iran

4 Department of Oral and Maxillofacial Surgery, School of Dentistry,Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Dentist, Student Research Committee, School of Dentistry, Kerman University of Medical Sciences, Kerman, Iran

6 Pharmaceutics Reseach center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran


An implant is a device for replacing a damaged or deformed joint, bone, or cartilage. Considering the aging population and developing culture of active lifestyles, orthopedic and dental implants have found their stance as a fundamental component of medical sector, which is envisioned to be continuous. Reducing the rate of failures, particularly in cases of bacterial infection, is a necessity for meeting the extending demands for implants. One of the major risk factors of this field is implant infection, which can reduce the effectiveness of treatment, as well as increase the need for corrective surgery or extend the chances of mortality. Traditional antibiotics are incapable of providing the desired effects due to the difficulties of bacterial resistance. The exertion of nanotechnology-based approaches can overcome most of the limitations and obstacles of implants. Nanostructures and nanoparticles can facilitate the production of implant coatings, provide suitable materials for making implants, and function as carriers for the release of antibiotics. There are a number of different nanostructures available for this purpose. Nanoparticles and microstructures contain a larger number of effective bactericidal properties than smooth surfaces due to their significantly increased level of adhesion. This study attempted to investigate the antibacterial properties of nanoparticles in dental and orthopedic implants.


The development of implant industry, especially orthopedic and dental implants, is growing at an incredible rate. The application of over 300 000 hip and knee implants, as well as 100 000 and 300 000 dental implants, are reported every year in the United States for replacing or restoring the functionality of injured and damaged tissues [1, 2]. As a matter of fact, the clinical utilization of implant designs throughout the recent years was quiet predictable. The purpose of designing implants is to provide a distinct interfacial layer and a biomechanically effective bone matrix. Despite being an external substance, the applied biomaterials in implants are required to exhibit biological compatibility and proper functionality in human system, as well as contain applicable mechanical, abrasion, and corrosion qualities. The progress of biomedical implants in orthopedic and dental implementations can be confined by a deficient bone-implant integration and implant-related infections [3]. Unfortunately, the weak design of some implants demands for improvements and better bone implants. Considering the unexpected outcomes of failures, many implant operations necessitate a corrective surgery to recover from a failed implant. One of the related statistics is about the average life expectancy, since the average lifespan of a joint replacement is only about 10-15 years[4-6]. The long-term fixation of load bearing implants (Especially metal implants) in bony tissues has remained as a challenge. Clearly, the insufficient lifetime of implants will lead to the need for many revision surgeries to remove failing implants, especially during the lives of young patients. Numerous factors contribute to implant failure, which include inadequate initial bone growth on the surface of implant that requires to be integrated into juxtaposed bone, the generation of wear debris by implant articulating components that turn into lodges among the implant and nearby tissue and cause the death of bone cells, and the inducement of implant loosening and eventual fracture by stress and strain imbalances throughout the implant and neighboring tissue, as well as device-related obstacles including insufficient integration, local tissue inflammation, and infection [7-10]. Implant-associated infections has remained as one of the principal causes of failure implications. Biofilm formation is assumed as the most essential pathogenic coincidence throughout the progress of infections, which is instantly triggered subsequent to bacterial adhesion on an implant to provide an efficient protection for microorganisms from the immune system and systemic antibiotics [11]. Post-surgery infections are the most challenging complication of orthopedic and dentistry fields. In the last few decades, the incorporation of antibiotics into bone cements was considered as an attempt throughout primary and revision surgery for preventing and treating orthopedic implant infections. However, not everyone believes in the therapeutic usefulness of antibiotic-releasing bone cements, since the long-term exposure of patients to low dosages of antibiotic-releasing bone cements has led to the current possibility of antibiotic resistance to medicine [12]. The local delivery of antibiotics is clearly more effective in transferring medicines to the affected area without causing any risks of systemic toxicity. [13]. Nanotechnology can overcome these limitations by facilitating the construction of surface structures for cell engineering and enhancing the surface structure of implants to promote osseous integration. Most of the reasons behind implant failures can be surpassed through the amazing potential of nanostructured coatings. In addition, the unique features of nanomaterials can provide the manufacturing of suitable coatings and implants as well [14, 15]. This work attempted to present a summary on the exertion of nanoparticles for controlling and enhancing the rate of implants while focusing on improved antimicrobial purposes. In this regard, we reviewed recent researches on the impacts of nanostructured biomaterials and particles for the antibacterial applications of orthopedic and dental implants to present a robust framework for understanding the basic interactions that control and prevent antibacterial processes.

The property requirement of a modern-day implant can be divided into three equally significant categories[16]:

Safety and compatibility 
The applied materials in the manufacturing of implants are required to be compatible with human body. Next to orthopedic and dental implants, safety concerns should include all of the implant devices as well. Specifications and standards are meant to assist producers, users, and consumers in providing safety for their products. The reaction of tissues towards the introduction of a foreign material is understandable, however, it is intolerable for the accompanying alterations in mechanical, physical, and chemical features throughout the localized surrounding to cause local detrimental changes or hazardous systemic impacts. Biological, mechanical, and morphological compatibilities are the major compatibility factors that are essential for the bio integration of implants with the receiving hard tissue and the subsequent biofunctionality[17, 18].

appealing balance of mechanical and physical qualities
An implant can achieve promising outcomes by accommodating the needed balance in mechanical and physical features. The kind and action of the particular implant portion can configure the optimization of qualities, which include elasticity, yield stress, ductility, time-dependent deformation, ultimate strength, fatigue strength, hardness, and wear resistance. As a universal requirement, the ability of implants to establish a suitable mechanical unit with the nearby hard or soft tissues must remain activated throughout the entire body. The functionality of a loose (or unstable) implant may be weakened, completely prevented, or result in an excessive tissue response, while causing discomfort and pain for the patients[19-21].

 simple fabrication and reproducibility
An appealing device is required to contain a simple fabrication, reproducibility, consistency, and compliance  with every technological and biological parameter. Meanwhile, there are possible limitations to be concerned, such as the design of techniques for producing outstanding surface finish or texture, the capacity of materials for obtaining adequate sanitation, and manufacturing costs, as well as having repairing methods for the cases of failure[16, 22, 23].

Implants can be defined as devices that are designed for replacing a damaged or deformed joint, bone, or cartilage. Synovial joints, such as the pelvis, knee, and shoulders, can operate as a result of this combined effort. A nourishing fluid is released by articular cartilage, which is a bearing connector tissue responsible for covering the bones of joints[24, 25]. However, these joints are prone to degenerative and inflammatory disorders throughout the common area and lead to the inducement of joint pain and stiffness. The common joint cartilage caries (softening of cartilage) are caused as a result of aging, as well as other disorders such as osteoarthritis (bone inflammation), osteoporosis, rheumatoid arthritis (synovial membrane inflammation), and chondromalacia. Interestingly, 90% of people over the age of 40 suffer from such destructive diseases [16, 26-28]. Degeneration is mainly originated by three factors including the deficiency of joint biomaterial features, overload conditions, and the collapse of common repair mechanisms [29-31]. Although minor surgical procedures are carried out, there is a definitive agreement to provide temporary support for a large number of patients, implicating inefficient Joints for pain relief and long-term mobility as the natural replacement phase. In severe situations, implants can replace or heal human joints. The complicated and elegant construction of human joints is abled to operate in life-threatening situations, therefore, the development of site-specific implants that would be applicable in human body is a major issue for surgeons and scientists [32-35]. Implants are widely exerted in the fields of surgery, orthopedics, and dentistry, while their other applications include ophthalmology, cardiovascular, cochlear, and maxillofacial implementations[36-38]. 

orthopedics and dentistry implants
Millions of people around the world suffer from degenerative and inflammatory bone and joint diseases. In affluent countries, people aged over 50 years old are accounted for half of all the chronic diseases These disorders are in the frequent need of surgery, as well as total joint replacement in the cases of natural joint deterioration. Furthermore, a variety of bone fractures, low back pain, osteoporosis, scoliosis, and other musculoskeletal issues demand for treatments with the exertion of permanent, temporary, or biodegradable devices. As a result, orthopaedic biomaterials are designed to be implanted as the components of a device in human body to perform particular biological functionalities through the replacement or repairing of various tissues such as bone, cartilage, ligaments, and tendons, which can also act as a guidance for bone repairs in specific situations [39, 40]. A range of orthopedic prosthetic implants are exerted by orthopedists for the purposes of replacing missing joints and bones, or to provide support for a damaged bone. Orthopedists most typically utilize knee and hip prostheses to restore the complete range of motion for patients in a relatively pain-free and short period of time. Prosthetic materials can be incorporated with a healthy bone to replace the sick or damaged bone in some circumstances, whereas prosthesis can completely replace certain parts of a joint bone [41, 42]. The method of tooth extraction subsequent to an immediate implant placement is the most typically applied surgical practice in recent years. The objective of modern dentistry is to revive the normal function, speech, health, and appearance of patients, regardless of stomatognathic system atrophy, disease, or damage. Considering this goal, dental implants can serve as an ideal choice in the cases of patients with a lost tooth (or teeth) due to periodontal diseases, injuries, or other conditions. Subperiosteal implants, endosseous implants with fibrous encapsulation, and endosseous implants with direct bone-to-implant contact (BIC) are included among the implant systems that are utilized for replacing missing teeth. Dental implants (also known as artificial tooth roots) are biocompatible metal anchors that are surgically positioned underneath the gums of jaw bone (also known as medically traumatised bone) to support the artificial crown of places where natural teeth are missing. The healing period of non-union (due to traumatization) bone can range from three to six months or more upon the usage of root form implants ( as the closest sample in shape and size to the natural tooth root), which also undergoes the occurrence of osseointegration. The growth of bone in and around the implant provides a strong structural support for the upcoming attached or screw-tightened superstructure  [15, 43, 44]. The rate of implants usage in the oral and maxillofacial skeleton is being constantly increased. For instance, the placement of 300,000 dental implants are estimated to occur each year in United States. The application of implants can facilitate a replacement for missing teeth, repair the craniofacial skeleton, provide anchorage during orthodontic treatments, and even aid the formation of new bones in the course of distraction osteogenesis process[45-47].

Risk Factors related to Failure of Dental and orthopaedic Implants
The provision of informed consent is a necessity for every clinical treatment, which refers to the patients permission for taking the proposed treatment subsequent to understanding the nature of illness, procedure description, risks and benefits, and treatment alternatives that include the option of no treatment. Although a written consent does not always stand for a informed consent, but in comparison to discussion and verbal consent, this format is easier to comprehend and recall at a later date, while providing proof for consent considerations. Treatment is contraindicated upon the patients lack of acceptance or agreement with the recommendations. In addition, implant therapy may be unsuitable for patients who are incapable or reluctant to maintain active oral diseases, as well as those with absurd treatment expectations [48-50].
Since their introduction by Branemark in 1970s, dental implants found their popularity as an appealing treatment for missing teeth rehabilitation. Nevertheless, there are limitations to this procedure that include the reports on the rate of dental implant failure ranging from 1% to 19% . Based on the connected abutment, these collapses can be classified in the two categories of early failure and late failure. Early failures take place in prior to applying the functional loading, whereas the progress of late failures can be observed subsequent to the occlusal loading or the first removal of temporary restoration in the cases of immediate implant loading. Early failure refers to the failure of dental implants in maintaining osseointegration, whereas late failure expresses the collapse of either established osseointegration or performance of dental implants. Considering how the early failure is mainly caused by biological complications, the occurrence of late failure can be possibly related to both biological and mechanical complications. Peri-implantitis commonly implicate the resorption of soft and hard tissue, while its inducement is associated with biological difficulties. Mechanical complications may occur as a consequence of incorrect implant loading design and lead to the fracture of implant body, screw body, or implant supra-structure[51-54]. Next to including a larger percentage of bone loss, the time interval between diagnosis and removal of a dental implant in late failure is substantially longer than the cases of early failure. Treatment planning for the entire dentition should be completed in prior to the surgical planning for implant placement. Systemic diseases impose the usual limits on minor surgical operations, which involve implant placement as well. There is a paucity of evidence to support systemic illnesses as a contraindication to oral implant therapy [52, 55].
Uncontrolled hypertension is a condition of blood pressure that regularly reaches higher than 160/90 mm Hg. This disorder requires immediate treatment due to the risks of high blood pressure for the patient, which include the occurrence of stroke, heart failure, myocardial infarction, and renal failure. Patients with a history of heart attack in their last six months should be prevented from implant surgery, while the cases that suffer from angina must be provided with glyceryl trinitrate tablets or sublingual sprays throughout the procedure[48, 55]. implant failure is associated with smoking, diabetes, autoimmune illnesses, osteoporosis, bisphosphonates, periodontitis-related tooth loss, genetic factors, local anatomy, and radiotherapy. Periodontal disease and smoking are considered as crucial risk factors for the late failure of implants [56-61]. Other prevalent late fracture risk factors are categorized into three sections based on (1) patients history (radiation therapy, periodontitis, gritted teeth, and premature implant failure), (2) clinical characteristics, or (3) both (posterior implant position, and bone grade), while considering the question of were there any(4) or (5) doctor’s decisions? (low initial stability, more than one implant in the course of surgery, inflammation at the surgical site during the first year, or usage of a cone-type overdenture). It is necessary for the doctors to remain cautious from the initial stages of evaluation up to treatment planning, surgery, and prosthesis selection to reduce the chance of late dental implant failure [62]. A delay in cleaning the infections at surgical site after spinal deformity surgery results in the need for the removal of implant. Patients may be required to repeat the instrumentation and fusion upon the development of exceeding deformity or symptomatic pseudoarthrosis subsequent to the implants removal [63].
Surgical site infections account for nearly 3% and up to one-third, of all the nosocomial infections. The consequences of induced complications by these infections in the implantation of a prosthesis, such as a hip replacement, can be devastating. Joint replacement infections commonly affect 0.5–5% of patients. Nevertheless, providing treatment for these infections in the course of retaining the position of prosthetic remains as a difficulty  [64].

Risk factors associated with implant infections
Infection is known as another serious side effect of implant surgery, which can lead to long-term clinical consequences and significantly increase the difficulty and cost of therapy [65]. Biomaterial-associated infection is a common impact of modern orthopaedic surgery with the potential of inducing long-term pain and functional loss in patients. Facing infection in an orthopedic surgery can be a disaster for the patient and the surgeon, while surgical site infections (SSIs) are very common in this kind of surgery. According to current estimations, periprosthetic joint infection complicates up to 2.5 percent of primary hip and knee arthroplasties and up to 20% of revision arthroplasties Prosthetic joint infection (PJI). Although modern facilities and aseptic procedures have reduced the incidence of this obstacle, yet its prevalence remained significant in developing countries. The consequences of this severe condition include increased antibiotic usage, prolonged stay in hospital, repeated debridements, longer period of rehabilitation, and increased morbidity and mortality. Furthermore, eradication is another challenging problem due to the pathophysiology of infection in fracture-fixation devices that is attributed to growing microorganisms in biofilm. The three stages of infection include early (less than two weeks), delayed (two to ten weeks), and late (more than ten weeks) infections[66-69]. Staphylococcus accounts for up to two-thirds of every existing microorganism throughout orthopedic implant infections, which stands as the primary cause behind the two principal forms of bone infections, septic arthritis and osteomyelitis, both of which implicate inflammatory joint and bone damage. Bacterial adherence is recognized as the first and most crucial step of implant infection. This complex process can be affected by various factors such as environmental conditions, bacterial characteristics, material surface qualities, and the presence of serum or tissue proteins [41].
Similar to other body implants, dental implants can collapse by the increasing accumulation of plaque that is mostly generated by the two pathogens of Streptococcus mutans and Porphyromonas gingivalis. The placement of dental implants in the contaminated surgical field of oral cavity can exceed the risk of implant failure [70, 71]. Implant infections are frequently caused by bacterial adhesion, while proliferation Caries and periodontitis are both generated through the bacterial adherence to tooth surfaces. The existing biofilms on the surfaces of dental implant can induce inflammatory lesions in peri-implant mucosa, which can result in the inhibition of osseointegration, leading to the loss of nearby bone substances and in worst-case scenario, cause a total implant failure. According to the majority of case studies, these biofilm-forming bacteria promote colonization on the fixed appliances of prosthodontic therapy, which damages the periodontal tissues. In addition, facing instability or mismatch conditions in the implant-abutment contact is another common cause of failures in dental implant treatments. The presence of microcracksmicrocracks on the joint surface of two-piece implants, which contain variable fluid flow, can facilitate the infiltration of bacteria and inflammatory cells and lead to the inducement of bone resorption in the surrounding area. Periodontitis-associated germs can colonize the bacterium throughout the early minutes of its implantation . This fixture-abutment gap (FAI) is a suitable environment for the growth of bacteria, resulting in a bacterial reservoir and inducing the inflammation of soft tissues at the fixture-abutment junction [72-74]. The production of biofilm is triggered right after bacterial adhesion on an implant, which provides an efficient protection for microorganisms from the immune system and systemic antibiotics. This process is considered as a crucial pathogenic event in the generation of implant-related infections. In the form of bacterial groups, biofilms  are accountable for the majority of chronic and recurrent infections. Next to the recurrence of about 65–80 percent of biofilm-related infection cases, the rate of antibiotic resistance is also high among the associated bacteria with biofilms. In laboratory studies, bacteria with antibiotic resistance have displayed a considerably reduced susceptibility to antimicrobials as a result of certain processes such as altered drug absorption, changing drug target, and drug inactivation; these observations were in accordance with the standard view of antibiotic resistance[75, 76]. Considering these facts, it is questionable that is there a way to overcome this problem?

Nanotechnology implicates the investigation and exertion of materials propertied that were dramatically changed in nanoscale (1–100 nm or 10-9–10-7 m) or atomic scale. This field has succeeded in exhibiting a great potential in the fields of medical science and biomedical engineering[77]. Polymer nanoparticles, magnetic nanoparticles, liposomes, carbon nanotubes, quantum dots, dendrimers, metal nanoparticles, and non-polymer nanoparticles can be listed among the examples of nanotechnology-based systems that are classified as pharmaceutical nanoparticles[78-81]. NPs are gifted with unique physical and chemical characteristics due to their high surface area and nanoscale size, while their reactivity, toughness, and other features are also affected by their distinctive size, shape, and structure [82, 83]. The accommodation of these properties has created suitable candidates for a variety of commercial, diagnostic, and medicinal applications including catalysis, imaging, cancer therapy, antimicrobial, medicinal, energy-based research, and environmental implementations[81, 83-87]. The ability to study compounds at molecular level has guided the search of materials with exceptional qualities for medical applications. The usage of these unique materials has spawned a new study field known as nanobiotechnology, which can be applied to disease diagnosis, drug design and delivery, and implant design [88]. Considering the aging population and developing culture of active lifestyles, orthopaedic and dental implants turned into one of the staples of medical industry and this trend is expected to be continuous. In response to the exceeding demands for implants, it is necessary to reduce the rate of failures, especially those that are generated by bacterial infection[89, 90]. Potential bacteria carriers include the implant itself, surgical tools, the operating room, and contaminated disinfectants. Implant materials are an appealing location for the adhesion of bacteria, which can compromise the patients immunity and heighten the risk of bacterial infection. The existing bacteria [mostly Pseudomonas aeruginosa (P. aeruginosa), including Staphylococcus aureus (S. aureus), and Staphylococcus epidermidis (S. epidermidis)], tend to adhere to the surface of implants and produce a layer of preprosthetic biofilm with resistance properties to antibacterial treatment. The infection may progress into local inflammation or spread throughout the body and lead to the inducement of a chronic infection. Nevertheless, the early replacement of an implant can prevent amputation or death. [41]. Some of the consequences of this severe condition include prolonged hospitalization, long-term antibiotic therapy, bacterial resistance, the emergence of superbugs, revision surgery, or death. The approach of antibiotics and antibacterial coatings were designed in the last two decades for reducing the chances of revision surgery and rates of infection-related death. The rapid spreading of bacterial resistance to antibiotics over the world has turned into a major public health concern, which seems to be unsolvable due to the numerous resistance mechanisms. Overexpression of relative efflux pump activity is reported to be a common and important source of bacterial resistance. Efflux transporters in the membranes of resistant bacteria may contain a crucial functionality in inhibiting intracellular drug intake and obstructing drug activities. The ineffectiveness of these methods prompted the conduction of research on the design of nano-textured surfaces to mimic the bactericidal capabilities and topographical characteristics of various animal, plant, and insect species [89, 91]. Researches tended to focus on the production of materials with nanostructured surfaces for limiting the growth of bacteria, biofilm formation, and ultimately bacterial infection without causing side effects, with the aim of reducing the chances of requiring revision surgery. Considering their wide application as encapsulating materials, nanoparticles (NPs) have the potential to boost intracellular drug accumulation and efficiently inhibit the activity of transporters [92]. Postoperative infection caused by medical implants emerged as a formidable but crucial obstacle in implant surgery, which sparked a flurry of nanotechnology research. The main applications of nanotechnology in implant therapy include bone replacement materials and implant coatings (production of biocompatible surfaces, for example, by implicating immobilized antimicrobial agents). Aside from antibiotics and nano particle  [93, 94], the contact to adhesion area of nano and microstructures is significantly increased, which leads to the generation of more effective bactericidal properties than flat surfaces. The height, radius, and spacing of a structure can affect the bactericidal efficiency of surfaces. Bactericidal or anti-biofouling surfaces have the ability to repel the adherence of bacteria. Moreover, anti-biofouling surfaces can inhibit the inducement of cell attachment due to their surface chemistry or undesirable surface topography, whereas bactericidal surfaces cause the disturbance and ultimately annihilation of cells[95, 96]. Current antibiotic treatments are still incapable of targeting bone infection sites and eventually result in ineffective therapeutic outcomes. However, the design of nanostructures gave rise to the possibility of targeted therapy[97]. As a matter of fact, nanoparticles bind to bacterial cells due to their small size to disrupt and damage their membrane, which consequently results in bacterial cell death. The antibacterial properties of nanoparticles were proved to be effective against Both gram-positive and gram-negative bacteria. These materials can contribute to bacterial death by releasing ions with the ability to attack many parts of bacteria, such as enzymes, DNA, proteins, Cytomembranes, and etc. At the same time, nanoparticles have the potential to boost the production of bacterial reactive oxygen species (ROS) that can cause oxidative destruction in cellular components[98-102] ( Figs. 1). Denaturation is the result of nanoparticles interaction with ribosomes in particular, which leads to the inhibition of translation and protein synthesis. Furthermore, the effective interaction of nanoparticles with carboxyl and thiol groups of -galactosidase has the potential to inhibit intracellular biological activities and induce cell death [103]. Nanoparticles can damage the cytoplasmic membrane of bacteria and impair cell respiration by preventing the entry of oxygen to cells, which leads to the suffocation and death of bacteria [104-106]. 
The weak penetration of these biomolecules is due to their lack of water solubility, which may be resolvable through the synthesis of antimicrobial nanoparticles for improving their activity[70]. In comparison to native biomolecules, nanoparticles can be more effective as a result of their superior dispersion ability and access to deeper tissues. They can ensure the delivery of biomolecules deep within the body and release the bioactive chemicals at the desired location, succeeding in causing high levels of bactericidal effects upon the release[70, 107, 108]. Tables 1 and 2 present the types of applied nanostructures in orthopedic and dental implants that contain antibacterial properties and can take a role in reducing or preventing infections caused by implants.

The presented studies exhibited a perspective of using different nanostructures in dental and orthopedic implants and described their antimicrobial activity. The introduced innovations in this work discovered a new vector of development for the dental and orthopedic materials and composites with the aim of improving the quality of patients lives. The ongoing assessment of researchers on dental and orthopedic nanomaterials is focused on their capability to maintain their antimicrobial effects, low cytotoxicity, and high strength over time. These nanomaterials can lead to promising horizons for having better performances and consequently improve the quality of patients lives.

The figure was designed on the BioRender website. The authors thank the designers of this

Te authors declare no conflicts of interest.

  1. Karlsson, J., et al., Atomically resolved tissue integration. Nano letters, 2014. 14(8): p. 4220-4223.
  2. Ratner, B.D., A pore way to heal and regenerate: 21st century thinking on biocompatibility. Regenerative biomaterials, 2016. 3(2): p. 107-110.
  3. Liu, Z., X. Liu, and S. Ramakrishna, Surface engineering of biomaterials in orthopedic and dental implants: Strategies to improve osteointegration, bacteriostatic and bactericidal activities. Biotechnology journal, 2021. 16(7): p. 2000116.
  4. Berjano, P., et al., Failures and revisions in surgery for sagittal imbalance: analysis of factors influencing failure. European Spine Journal, 2013. 22(6): p. 853-858.
  5. Sato, M. and T.J. Webster, Nanobiotechnology: implications for the future of nanotechnology in orthopedic applications. Expert review of medical devices, 2004. 1(1): p. 105-114.
  6. Wilson, C.J., et al., Knee instability as the primary cause of failure following total knee arthroplasty (TKA): a systematic review on the patient, surgical and implant characteristics of revised TKA patients. The Knee, 2017. 24(6): p. 1271-1281.
  7. Jin, W. and P.K. Chu, Orthopedic implants. Encyclopedia of Biomedical Engineering, 2019. 1: p. 3.
  8. Renouard, F. and D. Nisand, Impact of implant length and diameter on survival rates. Clinical oral implants research, 2006. 17(S2): p. 35-51.
  9. Yang, H., et al., Alloying design of biodegradable zinc as promising bone implants for load-bearing applications. Nature communications, 2020. 11(1): p. 1-16.
  10. Tobin, E.J., Recent coating developments for combination devices in orthopedic and dental applications: a literature review. Advanced Drug Delivery Reviews, 2017. 112: p. 88-100.
  11. Romanò, C.L., et al., Antibacterial coating of implants in orthopaedics and trauma: a classification proposal in an evolving panorama. Journal of orthopaedic surgery and research, 2015. 10(1): p. 1-11.
  12. Belt, H.v.d., et al., Infection of orthopedic implants and the use of antibiotic-loaded bone cements: a review. Acta Orthopaedica Scandinavica, 2001. 72(6): p. 557-571.
  13. Geuli, O., et al., Synthesis, coating, and drug-release of hydroxyapatite nanoparticles loaded with antibiotics. Journal of Materials Chemistry B, 2017. 5(38): p. 7819-7830.
  14. Jäger, M., et al., Significance of nano-and microtopography for cell-surface interactions in orthopaedic implants. Journal of Biomedicine and Biotechnology, 2007. 2007.
  15. Noronha Oliveira, M., et al., Can degradation products released from dental implants affect peri‐implant tissues? Journal of periodontal research, 2018. 53(1): p. 1-11.
  16. Narayan, R., Fundamentals of medical implant materials. ASM handbook, 2012.
  17. Oshida, Y., et al., Dental implant systems. International journal of molecular sciences, 2010. 11(4): p. 1580-1678.
  18. Winter, L., et al., Parallel transmission medical implant safety testbed: Real‐time mitigation of RF induced tip heating using time‐domain E‐field sensors. Magnetic Resonance in Medicine, 2020. 84(6): p. 3468-3484.
  19. Li, S., et al., Surface porous poly-ether-ether-ketone based on three-dimensional printing for load-bearing orthopedic implant. Journal of the Mechanical Behavior of Biomedical Materials, 2021. 120: p. 104561.
  20. Rafieerad, A., et al., Mechanical properties, corrosion behavior and in-vitro bioactivity of nanostructured Pd/PdO coating on Ti–6Al–7Nb implant. Materials & Design, 2016. 103: p. 10-24.
  21. Torres, Y., J. Pavón, and J. Rodríguez, Processing and characterization of porous titanium for implants by using NaCl as space holder. Journal of Materials Processing Technology, 2012. 212(5): p. 1061-1069.
  22. Bamford, J.A., et al., The fabrication, implantation, and stability of intraspinal microwire arrays in the spinal cord of cat and rat. IEEE transactions on neural systems and rehabilitation engineering, 2016. 25(3): p. 287-296.
  23. Omori, M., et al., A biomechanical investigation of mandibular molar implants: reproducibility and validity of a finite element analysis model. International journal of implant dentistry, 2015. 1(1): p. 1-13.
  24. Baker, M.I., et al., A review of polyvinyl alcohol and its uses in cartilage and orthopedic applications. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2012. 100(5): p. 1451-1457.
  25. Van Dijk, C.N., et al., Osteochondral defects in the ankle: why painful? Knee Surgery, Sports Traumatology, Arthroscopy, 2010. 18(5): p. 570-580.
  26. Belluzzi, E., et al., Contribution of infrapatellar fat pad and synovial membrane to knee osteoarthritis pain. BioMed research international, 2019. 2019.
  27. Kubicek, J., et al., Segmentation of knee cartilage: A comprehensive review. Journal of Medical Imaging and Health Informatics, 2018. 8(3): p. 401-418.
  28. Rezuș, E., et al., The link between inflammaging and degenerative joint diseases. International journal of molecular sciences, 2019. 20(3): p. 614.
  29. Lobanova, E.S., et al., Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration. Proceedings of the National Academy of Sciences, 2013. 110(24): p. 9986-9991.
  30. Musumeci, G., et al., Osteoarthritis in the XXIst century: risk factors and behaviours that influence disease onset and progression. International journal of molecular sciences, 2015. 16(3): p. 6093-6112.
  31. Tedesco, F.S., et al., Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells. The Journal of clinical investigation, 2010. 120(1): p. 11-19.
  32. Arbab, D. and D.P. König, Atraumatic femoral head necrosis in adults: epidemiology, etiology, diagnosis and treatment. Deutsches Ärzteblatt International, 2016. 113(3): p. 31.
  33. Bornstein, M.M., et al., Cone beam computed tomography in implant dentistry: a systematic review focusing on guidelines, indications, and radiation dose risks. International journal of oral & maxillofacial implants, 2014. 29.
  34. Gibon, E., et al., The biological response to orthopedic implants for joint replacement. II: Polyethylene, ceramics, PMMA, and the foreign body reaction. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2017. 105(6): p. 1685-1691.
  35. Khow, Y.Z., et al., Coronal alignment of fixed-bearing unicompartmental knee arthroplasty femoral component may affect long-term clinical outcomes. The Journal of Arthroplasty, 2021. 36(2): p. 478-487.
  36. Abe, M., et al., A case of odontogenic infection by Streptococcus constellatus leading to systemic infection in a Cogan’s syndrome patient. Case Reports in Dentistry, 2014. 2014.
  37. Baino, F. and I. Potestio, Special Applications of Bioactive Glasses in Otology and Ophthalmology. Biocompatible Glasses, 2016: p. 227-248.
  38. Niparko, J.K., et al., Spoken language development in children following cochlear implantation. Jama, 2010. 303(15): p. 1498-1506.
  39. Bartolomeu, F., et al., Additive manufactured porous biomaterials targeting orthopedic implants: A suitable combination of mechanical, physical and topological properties. Materials Science and Engineering: C, 2020. 107: p. 110342.
  40. Lin, X., et al., Orthopedic implant biomaterials with both osteogenic and anti-infection capacities and associated in vivo evaluation methods. Nanomedicine: Nanotechnology, Biology and Medicine, 2017. 13(1): p. 123-142.
  41. Ribeiro, M., F.J. Monteiro, and M.P. Ferraz, Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions. Biomatter, 2012. 2(4): p. 176-194.
  42. Staiger, M.P., et al., Magnesium and its alloys as orthopedic biomaterials: a review. Biomaterials, 2006. 27(9): p. 1728-1734.
  43. Campos, F.E., et al., Effect of drilling dimension on implant placement torque and early osseointegration stages: an experimental study in dogs. Journal of Oral and Maxillofacial Surgery, 2012. 70(1): p. e43-e50.
  44. Prados-Privado, M., et al., Influence of bone definition and finite element parameters in bone and dental implants stress: A literature review. Biology, 2020. 9(8): p. 224.
  45. Puleo, D.A. and M.V. Thomas, Implant surfaces. Dental Clinics, 2006. 50(3): p. 323-338.
  46. Vignoletti, F., et al., Ridge alterations after implant placement in fresh extraction sockets or in healed crests: An experimental in vivo investigation. Clinical Oral Implants Research, 2019. 30(4): p. 353-363.
  47. Zanetti, E.M., et al., Clinical assessment of dental implant stability during follow-up: what is actually measured, and perspectives. Biosensors, 2018. 8(3): p. 68.
  48. Bryant, S., S. Koka, and I. Matthew, Local and systemic health considerations. Osseointegration: on continuing synergies in surgery, prosthodontics and biomaterials. Zarb GA, ed. Chicago: Quintessence, 2008.
  49. Jowett, N. and L. Cabot, Patients with cardiac disease: considerations for the dental practitioner. British dental journal, 2000. 189(6): p. 297-302.
  50. Little, J.W., The impact on dentistry of recent advances in the management of hypertension. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 2000. 90(5): p. 591-599.
  51. Clark, D. and L. Levin, Dental implant management and maintenance: How to improve long-term implant success. Quintessence Int, 2016. 47(5): p. 417-423.
  52. Manor, Y., et al., Characteristics of early versus late implant failure: a retrospective study. Journal of Oral and Maxillofacial Surgery, 2009. 67(12): p. 2649-2652.
  53. Romeo, E., et al., Long‐term clinical effectiveness of oral implants in the treatment of partial edentulism: Seven‐year life table analysis of a prospective study with ITI® Dental Implants System used for single‐tooth restorations. Clinical Oral Implants Research, 2002. 13(2): p. 133-143.
  54. Sakka, S., K. Baroudi, and M.Z. Nassani, Factors associated with early and late failure of dental implants. Journal of investigative and clinical dentistry, 2012. 3(4): p. 258-261.
  55. Liddelow, G. and I. Klineberg, Patient‐related risk factors for implant therapy. A critique of pertinent literature. Australian dental journal, 2011. 56(4): p. 417-426.
  56. Anderson, L., et al., The influence of radiation therapy on dental implantology. Implant dentistry, 2013. 22(1): p. 31-38.
  57. Bornstein, M.M., N. Cionca, and A. Mombelli, Systemic conditions and treatments as risks for implant therapy. Int J Oral Maxillofac Implants, 2009. 24(Suppl): p. 12-27.
  58. Chen, H., et al., Smoking, radiotherapy, diabetes and osteoporosis as risk factors for dental implant failure: a meta-analysis. PloS one, 2013. 8(8): p. e71955.
  59. Kumar, P.S., Systemic risk factors for the development of periimplant diseases. Implant Dentistry, 2019. 28(2): p. 115-119.
  60. Moy, P.K., et al., Dental implant failure rates and associated risk factors. International Journal of Oral & Maxillofacial Implants, 2005. 20(4).
  61. Savage, N., Oral medicine in Australia 2000–2010. A publications overview. Australian Dental Journal, 2010. 55: p. 3-8.
  62. Do, T.A., et al., Risk factors related to late failure of dental implant—A systematic review of recent studies. International journal of environmental research and public health, 2020. 17(11): p. 3931.
  63. Hedequist, D., et al., Failure of attempted implant retention in spinal deformity delayed surgical site infections. Spine, 2009. 34(1): p. 60-64.
  64. Choong, P.F., et al., Risk factors associated with acute hip prosthetic joint infections and outcome of treatment with a rifampinbased regimen. Acta Orthopaedica, 2007. 78(6): p. 755-765.
  65. Cordero, J. and E. Garcia-Cimbrelo, Mechanisms of bacterial resistance in implant infection. Hip International, 2000. 10(3): p. 139-144.
  66. Cats-Baril, W., et al., International consensus on periprosthetic joint infection: description of the consensus process. Clinical Orthopaedics and Related Research®, 2013. 471(12): p. 4065-4075.
  67. Khan, M.S., et al., Infection in orthopedic implant surgery, its risk factors and outcome. J Ayub Med Coll Abbottabad, 2008. 20(1): p. 23-5.
  68. Lentino, J.R., Prosthetic joint infections: bane of orthopedists, challenge for infectious disease specialists. Clinical Infectious Diseases, 2003. 36(9): p. 1157-1161.
  69. Ming, P.C., T.Y.Y. Yan, and L.H. Tat, Risk factors of postoperative infections in adults with complicated appendicitis. Surgical Laparoscopy Endoscopy & Percutaneous Techniques, 2009. 19(3): p. 244-248.
  70. Divakar, D.D., et al., Enhanced antimicrobial activity of naturally derived bioactive molecule chitosan conjugated silver nanoparticle against dental implant pathogens. International journal of biological macromolecules, 2018. 108: p. 790-797.
  71. Parnia, F., et al., Overview of nanoparticle coating of dental implants for enhanced osseointegration and antimicrobial purposes. Journal of Pharmacy & Pharmaceutical Sciences, 2017. 20: p. 148-160.
  72. Yamada, R., et al., Ag nanoparticle–coated zirconia for antibacterial prosthesis. Materials Science and Engineering: C, 2017. 78: p. 1054-1060.
  73. Yang, Y., et al., Safety and efficacy of PLGA (Ag-Fe3O4)-coated dental implants in inhibiting bacteria adherence and osteogenic inducement under a magnetic field. International journal of nanomedicine, 2018. 13: p. 3751.
  74. Yin, I.X., et al., The antibacterial mechanism of silver nanoparticles and its application in dentistry. International journal of nanomedicine, 2020. 15: p. 2555.
  75. Smith, A.W., Biofilms and antibiotic therapy: is there a role for combating bacterial resistance by the use of novel drug delivery systems? Advanced drug delivery reviews, 2005. 57(10): p. 1539-1550.
  76. Venkatesan, N., G. Perumal, and M. Doble, Bacterial resistance in biofilm-associated bacteria. Future microbiology, 2015. 10(11): p. 1743-1750.
  77. Sun, H., et al., Nanotechnology-enabled materials for hemostatic and anti-infection treatments in orthopedic surgery. International journal of nanomedicine, 2018. 13: p. 8325.
  78. Bhatia, S., Nanoparticles types, classification, characterization, fabrication methods and drug delivery applications, in Natural polymer drug delivery systems. 2016, Springer. p. 33-93.
  79. Abdollahii, S., et al., Adverse Effects of some of the Most Widely used Metal Nanoparticles on the Reproductive System. Journal of Infertility and Reproductive Biology, 2020. 8(3): p. 22-32.
  80. Hassanzadeh, A., et al., Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities. Stem cell research & therapy, 2021. 12(1): p. 1-22.
  81. Mosleh-Shirazi, S., et al., Biosynthesis, simulation, and characterization of Ag/AgFeO2 core–shell nanocomposites for antimicrobial applications. Applied Physics A, 2021. 127(11): p. 1-8.
  82. Beheshtkhoo, N., et al., A review of COVID-19: the main ways of transmission and some prevention solutions, clinical symptoms, more vulnerable human groups, risk factors, diagnosis, and treatment. J Environmental Treat Tech, 2020. 8: p. 884-893.
  83. Beheshtkhoo, N., M.A.J. Kouhbanani, and F. sadat Dehghani, Fabrication and Properties of Collagen and Polyurethane Polymeric Nanofibers Using Electrospinning Technique for Tissue Engineering Applications. Journal of Environmental Treatment Techniques, 2019. 7(4): p. 802-807.
  84. Kouhbanani, M.A.J., et al., Green synthesis of spherical silver nanoparticles using Ducrosia anethifolia aqueous extract and its antibacterial activity. Journal of Environmental Treatment Techniques, 2019. 7(3): p. 461-466.
  85. Kouhbanani, M.A.J., et al., The inhibitory role of synthesized nickel oxide nanoparticles against Hep-G2, MCF-7, and HT-29 cell lines: The inhibitory role of NiO NPs against Hep-G2, MCF-7, and HT-29 cell lines. Green Chemistry Letters and Reviews, 2021. 14(3): p. 444-454.
  86. Nakhaei, P., et al., Liposomes: Structure, Biomedical Applications, and Stability Parameters With Emphasis on Cholesterol. Frontiers in Bioengineering and Biotechnology, 2021. 9.
  87. Nasirmoghadas, P., et al., Nanoparticles in cancer immunotherapies: an innovative strategy. Biotechnology progress, 2021. 37(2): p. e3070.
  88. Ramos, A.P., et al., Biomedical applications of nanotechnology. Biophysical reviews, 2017. 9(2): p. 79-89.
  89. Jaggessar, A., et al., Bio-mimicking nano and micro-structured surface fabrication for antibacterial properties in medical implants. Journal of nanobiotechnology, 2017. 15(1): p. 1-20.
  90. Wang, W., Y. Ouyang, and C.K. Poh, Orthopaedic implant technology: biomaterials from past to future. Annals of the Academy of Medicine-Singapore, 2011. 40(5): p. 237.
  91. Ferraris, S. and S. Spriano, Antibacterial titanium surfaces for medical implants. Materials Science and Engineering: C, 2016. 61: p. 965-978.
  92. Chopra, D., K. Gulati, and S. Ivanovski, Understanding and optimizing the antibacterial functions of anodized nano-engineered titanium implants. Acta Biomaterialia, 2021. 127: p. 80-101.
  93. Min, J., et al., Designer dual therapy nanolayered implant coatings eradicate biofilms and accelerate bone tissue repair. ACS nano, 2016. 10(4): p. 4441-4450.
  94. Sullivan, M., et al., Nanotechnology: current concepts in orthopaedic surgery and future directions. The bone & joint journal, 2014. 96(5): p. 569-573.
  95. Ivanova, E.P., et al., The multi-faceted mechano-bactericidal mechanism of nanostructured surfaces. Proceedings of the National Academy of Sciences, 2020. 117(23): p. 12598-12605.
  96. Li, X., Bactericidal mechanism of nanopatterned surfaces. Physical Chemistry Chemical Physics, 2016. 18(2): p. 1311-1316.
  97. Yeh, Y.-C., et al., Nano-based drug delivery or targeting to eradicate bacteria for infection mitigation: a review of recent advances. Frontiers in chemistry, 2020. 8: p. 286.
  98. Rasoulzadehzali, M. and H. Namazi, Facile preparation of antibacterial chitosan/graphene oxide-Ag bio-nanocomposite hydrogel beads for controlled release of doxorubicin. International journal of biological macromolecules, 2018. 116: p. 54-63.
  99. Gusev, A., et al., Effect of GO on bacterial cells: Role of the medium type and electrostatic interactions. Materials Science and Engineering: C, 2019. 99: p. 275-281.
  100. Li, C., et al., The antifungal activity of graphene oxide–silver nanocomposites. Biomaterials, 2013. 34(15): p. 3882-3890.
  101. Song, Z., et al., Synergistic antibacterial effects of curcumin modified silver nanoparticles through ROS-mediated pathways. Materials Science and Engineering: C, 2019. 99: p. 255-263.
  102. Wang, X., et al., GO-AgCl/Ag nanocomposites with enhanced visible light-driven catalytic properties for antibacterial and biofilm-disrupting applications. Colloids and Surfaces B: Biointerfaces, 2018. 162: p. 296-305.
  103. You, C., et al., The progress of silver nanoparticles in the antibacterial mechanism, clinical application and cytotoxicity. Molecular biology reports, 2012. 39(9): p. 9193-9201.
  104. Andrusishina, I., Metal nanoparticles: production methods, physicochemical properties, experimental procedures, and toxicity assessment. Suchasn. Probl. Toksikol, 2011(3): p. 5-14.
  105. Chwalibog, A., et al., Visualization of interaction between inorganic nanoparticles and bacteria or fungi. International Journal of Nanomedicine, 2010. 5: p. 1085.
  106. Olenin, A.Y., Y.A. Krutyakov, and G. Lisichkin, Formation mechanisms of anisotropic silver nanostructures in polyol synthesis. Nanotechnologies in Russia, 2010. 5(5): p. 421-426.
  107. Rai, M., A. Yadav, and A. Gade, Silver nanoparticles as a new generation of antimicrobials. Biotechnology advances, 2009. 27(1): p. 76-83.
  108. Zhang, Q., et al., Functionalized mesoporous silica nanoparticles with mucoadhesive and sustained drug release properties for potential bladder cancer therapy. Langmuir, 2014. 30(21): p. 6151-6161.
  109. Kisterskaya, L., et al., Antibacterial Surfaces Formed by Silver Nanoparticles on Bone Implants with Bioactive Coatings. Powder Metallurgy and Metal Ceramics, 2019. 58(3): p. 189-196.
  110. Yang, Y., et al., A bifunctional bone scaffold combines osteogenesis and antibacterial activity via in situ grown hydroxyapatite and silver nanoparticles. Bio-Design and Manufacturing, 2021. 4(3): p. 452-468.
  111. Wang, Y., et al., Multifunctional HA/Cu nano-coatings on titanium using PPy coordination and doping via pulse electrochemical polymerization. Biomaterials science, 2018. 6(3): p. 575-585.
  112. Chen, K., et al., Fabrication of core–shell Ag@ pDA@ HAp nanoparticles with the ability for controlled release of Ag+ and superior hemocompatibility. Rsc Advances, 2017. 7(47): p. 29368-29377.
  113. Shuai, C., et al., A strawberry-like Ag-decorated barium titanate enhances piezoelectric and antibacterial activities of polymer scaffold. Nano Energy, 2020. 74: p. 104825.
  114. Zhao, L., et al., Antibacterial nano-structured titania coating incorporated with silver nanoparticles. Biomaterials, 2011. 32(24): p. 5706-5716.
  115. Fazel, M., et al., Osteogenic and antibacterial surfaces on additively manufactured porous Ti-6Al-4V implants: Combining silver nanoparticles with hydrothermally synthesized HA nanocrystals. Materials Science and Engineering: C, 2021. 120: p. 111745.
  116. Xie, C.-M., et al., Silver nanoparticles and growth factors incorporated hydroxyapatite coatings on metallic implant surfaces for enhancement of osteoinductivity and antibacterial properties. ACS applied materials & interfaces, 2014. 6(11): p. 8580-8589.
  117. Sobolev, A., et al., Bioactive coating on Ti alloy with high osseointegration and antibacterial Ag nanoparticles. ACS applied materials & interfaces, 2019. 11(43): p. 39534-39544.
  118. Cheng, H., et al., Long‐lasting in vivo and in vitro antibacterial ability of nanostructured titania coating incorporated with silver nanoparticles. Journal of biomedical materials research Part A, 2014. 102(10): p. 3488-3499.
  119. Memarzadeh, K., et al., Nanoparticulate zinc oxide as a coating material for orthopedic and dental implants. Journal of Biomedical Materials Research Part A, 2015. 103(3): p. 981-989.
  120. Grenho, L., et al., Antibacterial activity and biocompatibility of three-dimensional nanostructured porous granules of hydroxyapatite and zinc oxide nanoparticles—An in vitro and in vivo study. Nanotechnology, 2015. 26(31): p. 315101.
  121. Seil, J.T. and T.J. Webster, Reduced Staphylococcus aureus proliferation and biofilm formation on zinc oxide nanoparticle PVC composite surfaces. Acta Biomaterialia, 2011. 7(6): p. 2579-2584.
  122. Guo, Y., et al., A multifunctional polypyrrole/zinc oxide composite coating on biodegradable magnesium alloys for orthopedic implants. Colloids and Surfaces B: Biointerfaces, 2020. 194: p. 111186.
  123. Mousa, H.M., et al., A multifunctional zinc oxide/poly (lactic acid) nanocomposite layer coated on magnesium alloys for controlled degradation and antibacterial function. ACS Biomaterials Science & Engineering, 2018. 4(6): p. 2169-2180.
  124. Li, Y., et al., Construction of N-halamine labeled silica/zinc oxide hybrid nanoparticles for enhancing antibacterial ability of Ti implants. Materials Science and Engineering: C, 2017. 76: p. 50-58.
  125. Gunputh, U.F., et al., Multilayered composite coatings of titanium dioxide nanotubes decorated with zinc oxide and hydroxyapatite nanoparticles: controlled release of Zn and antimicrobial properties against Staphylococcus aureus. International Journal of Nanomedicine, 2019. 14: p. 3583.
  126. Horprasertkij, K., et al., Spray coating of dual antibiotic-loaded nanospheres on orthopedic implant for prolonged release and enhanced antibacterial activity. Journal of Drug Delivery Science and Technology, 2019. 53: p. 101102.
  127. Mattioli-Belmonte, M., et al., Characterization and cytocompatibility of an antibiotic/chitosan/cyclodextrins nanocoating on titanium implants. Carbohydrate polymers, 2014. 110: p. 173-182.
  128. Feng, W., et al., Controlled release behaviour and antibacterial effects of antibiotic-loaded titania nanotubes. Materials Science and Engineering: C, 2016. 62: p. 105-112.
  129. Pawar, V., H. Topkar, and R. Srivastava, Chitosan nanoparticles and povidone iodine containing alginate gel for prevention and treatment of orthopedic implant associated infections. International journal of biological macromolecules, 2018. 115: p. 1131-1141.
  130. Sharma, S., et al., Silk fibroin nanoparticles support in vitro sustained antibiotic release and osteogenesis on titanium surface. Nanomedicine: Nanotechnology, Biology and Medicine, 2016. 12(5): p. 1193-1204.
  131. Li, D., et al., The immobilization of antibiotic-loaded polymeric coatings on osteoarticular Ti implants for the prevention of bone infections. Biomaterials science, 2017. 5(11): p. 2337-2346.
  132. Ballarre, J., et al., Versatile bioactive and antibacterial coating system based on silica, gentamicin, and chitosan: Improving early stage performance of titanium implants. Surface and Coatings Technology, 2020. 381: p. 125138.
  133. Aydemir, T., et al., Functional behavior of chitosan/gelatin/silica-gentamicin coatings by electrophoretic deposition on surgical grade stainless steel. Materials Science and Engineering: C, 2020. 115: p. 111062.
  134. Huo, S., et al., Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection. Bioactive Materials, 2022.
  135. Perni, S., et al., Prolonged antimicrobial activity of PMMA bone cement with embedded gentamicin-releasing silica nanocarriers. ACS Applied Bio Materials, 2019. 2(5): p. 1850-1861.
  136. Ordikhani, F., M. Dehghani, and A. Simchi, Antibiotic-loaded chitosan–Laponite films for local drug delivery by titanium implants: Cell proliferation and drug release studies. Journal of Materials Science: Materials in Medicine, 2015. 26(12): p. 1-12.
  137. Letchmanan, K., et al., Mechanical properties and antibiotic release characteristics of poly (methyl methacrylate)-based bone cement formulated with mesoporous silica nanoparticles. Journal of the mechanical behavior of biomedical materials, 2017. 72: p. 163-170.
  138. Varshney, S., et al., Antibacterial, Structural, and Mechanical Properties of MgO/ZnO Nanocomposites and its HA-Based Bio-Ceramics; Synthesized via Physio-Chemical Route for Biomedical Applications. Materials Technology, 2022: p. 1-14.
  139. Abdulkareem, E.H., et al., Anti-biofilm activity of zinc oxide and hydroxyapatite nanoparticles as dental implant coating materials. Journal of dentistry, 2015. 43(12): p. 1462-1469.
  140. Vergara-Llanos, D., et al., Antibacterial and cytotoxic evaluation of copper and zinc oxide nanoparticles as a potential disinfectant material of connections in implant provisional abutments: An in-vitro study. Archives of Oral Biology, 2021. 122: p. 105031.
  141. Goel, S., et al., Co-sputtered antibacterial and biocompatible nanocomposite Titania-Zinc oxide thin films on Si substrates for dental implant applications. Materials Technology, 2019. 34(1): p. 32-42.
  142. Fullriede, H., et al., pH-responsive release of chlorhexidine from modified nanoporous silica nanoparticles for dental applications. BioNanoMaterials, 2016. 17(1-2): p. 59-72.
  143. Qi, S., et al., Chemical stability and antimicrobial activity of plasma-sprayed cerium oxide–incorporated calcium silicate coating in dental implants. Implant dentistry, 2019. 28(6): p. 564-570.
  144. Kulshrestha, S., et al., A graphene/zinc oxide nanocomposite film protects dental implant surfaces against cariogenic Streptococcus mutans. Biofouling, 2014. 30(10): p. 1281-1294.
  145. Fialho, L., et al., Porous tantalum oxide with osteoconductive elements and antibacterial core-shell nanoparticles: A new generation of materials for dental implants. Materials Science and Engineering: C, 2021. 120: p. 111761.
  146. Lee, J.-H., et al., Nano-graphene oxide incorporated into PMMA resin to prevent microbial adhesion. Dental Materials, 2018. 34(4): p. e63-e72.
  147. Karatepe, U.Y. and T. Ozdemir, Improving mechanical and antibacterial properties of PMMA via polyblend electrospinning with silk fibroin and polyethyleneimine towards dental applications. Bioactive materials, 2020. 5(3): p. 510-515.
  148. Chen, S.-G., et al., TiO2 and PEEK reinforced 3D printing PMMA composite resin for dental denture base applications. Nanomaterials, 2019. 9(7): p. 1049.
  149. Nayak, A.K., et al., Calcium fluoride-based dental nanocomposites. Applications of nanocomposite materials in dentistry, 2019: p. 27-45.
  150. Swetha, D.L., et al., Antibacterial and mechanical properties of pit and fissure sealants containing zinc oxide and calcium fluoride nanoparticles. Contemporary Clinical Dentistry, 2019. 10(3): p. 477.
  151. Kulshrestha, S., et al., Calcium fluoride nanoparticles induced suppression of Streptococcus mutans biofilm: an in vitro and in vivo approach. Applied microbiology and biotechnology, 2016. 100(4): p. 1901-1914.
  152. Yadav, S. and S. Gangwar, The effectiveness of functionalized nano-hydroxyapatite filler on the physical and mechanical properties of novel dental restorative composite. International Journal of Polymeric Materials and Polymeric Biomaterials, 2019.
  153. Besinis, A., T. De Peralta, and R.D. Handy, The antibacterial effects of silver, titanium dioxide and silica dioxide nanoparticles compared to the dental disinfectant chlorhexidine on Streptococcus mutans using a suite of bioassays. Nanotoxicology, 2014. 8(1): p. 1-16.
  154. Boutinguiza, M., et al., Synthesis and deposition of silver nanoparticles on cp Ti by laser ablation in open air for antibacterial effect in dental implants. Materials Letters, 2018. 231: p. 126-129.
  155. Guo, C., et al., Poly-l-lysine/sodium alginate coating loading nanosilver for improving the antibacterial effect and inducing mineralization of dental implants. ACS omega, 2020. 5(18): p. 10562-10571.