Artificial implants have consistently been recognized as the most effective clinical strategy for repairing bone fractures and defects, particularly in orthopedics and stomatology. Nowadays, the focus of bone repair has shifted from basic fixation and structural restoration to the reconstruction of multifunctional "live" tissue to mimic the natural bone microenvironment. However, developing the smart implants with ideal osteogenesis-related multi-functions remains challenging, as the effects of physicochemical properties of implant materials on intracellular signaling, stem cell niches, and tissue regeneration are not yet fully understood. Herein, we systematically explore recent advancements in innovative strategies for bone repair and regeneration, revealing the significance of the smart implants that closely mimic the natural structure and function of bone tissue. Adaptation to patient-oriented osteogenic microenvironments, dynamic osteoblastogenesis-osteoclastogenesis balance, antibacterial/bactericidal capacity, vascularization, and osteoimmunomodulatory capacity and their regulatory mechanisms achieved by biomaterials design and functional modifications are thoroughly summarized and analyzed. Notably, the popular research on multifunctional platforms with synergetic interactions between different functions and treatment of complex clinical issues, including the emerging neurogenic bone repair, is also significantly discussed for developing more intelligent implants. By summarizing recent research efforts, this review proposes the latest multifunctional strategies and synergistic mechanisms of smart bone implants, aiming to provide better bone defect repair applications that more closely mimic the natural bone tissue.

Titanium (Ti) is commonly employed therapeutically in many medical sectors associated with bone healing because of its superior mechanical properties and capacity to osseointegrate in the host bone tissue. The titanium surfaces may now be functionalized to offer additional and potentially valuable features. This review article discusses many titanium implant surface modifications, emphasizing their biological significance and the challenges that each one mainly addresses. Before reviewing the genuine reason for titanium surface modification in implanted devices, we briefly explore the process of osseointegration, enhancement of antibacterial properties, biocompatibility, and the historical significance of titanium as an implantable material, and the significant challenges involved. The various physical and chemical alterations that could take place on Ti surfaces are next examined. The rest of our talk will focus on creating inorganic and organic coatings for implanted Ti devices. Finally, we present a synopsis of the surface modification strategies currently being evaluated in clinical settings.

This systematic review aims to evaluate research on titanium implants with significant surface modifications, coatings, and antibacterial capabilities.

Following the PRISMA paradigm, we searched for three electronic databases (Web of Science, PubMed Central, and Google Scholar) using the keywords "titanium implants," "titanium surface modification," and "titanium osseointegration," and "titanium antibacterial activity."

We identified 1,39,336 articles overall that were published between 2012 and 2021, and we then focused on 8917 articles that concentrated on a particular topic. Clear inclusion and exclusion criteria were used in a rigorous screening procedure. Articles that didn't meet certain requirements (were irrelevant, used incorrect techniques, had unsuitable data values, or were only brief letters or communications) were eliminated. Finally, 120 research publications in total are taken into account for this extensive systematic review.

The report summarises current information on titanium implants with significant surface modifications, antibacterial activity, and coatings. It also gives some strong recommendations for future study topics.

Cementless knee implants achieve initial fixation through an interference fit, where the tibial implant is press-fitted into an undersized bone cavity. The dimensions between the implant and bone cuts must be carefully balanced to achieve an optimal interference fit, ensuring good primary stability, which is crucial for long-term fixation and successful osseointegration. However, the ideal interference fit remains uncertain. Excessive interference fit may lead to bone plastic deformation, while insufficient fit can result in large micromotions, small movements at the bone-implant interface, that compromise stability. This study evaluates how interference fit affects bone plasticity and micromotions, and how different loading conditions influence primary stability using finite element analysis.

Finite element models, based on experimentally implanted components, simulated interference fits of 350 μm and 700 μm. Micromotions, gap dynamics, and bone deformation were assessed during gait and squat activities under both simplified and complex loading conditions.

Higher interference fits increased bone plastic deformation, limiting elastic energy accumulation, whereas lower interference fits exhibited a reduced effect. Micromotions and gaps were consistently larger in lower interference fit implants. Furthermore, simplified loading underestimated micromotions and gaps compared to the complex loading.

These findings help explain why higher interference fits provided limited improvements in primary stability during experimental tests, despite differing predictions from simulations. This study enhances our understanding of bone-implant interactions and suggests that increasing interference fit does not necessarily improve implant stability. It also highlights the importance of incorporating complex loading conditions for more accurate primary stability assessment.

Hydroxyapatite nanoparticles (HANPs) are becoming increasingly crucial in dental implant applications as they are highly compatible with biological systems, actively support biological processes, and closely resemble bone minerals. This review covers the latest progress in how HANPs are made, studied, and used in dentistry. It looks at critical methods for creating HANPs, such as sol-gel, microwave hydrothermal synthesis, and biomimetic approaches, and how they affect the particles' size, structure, and activity. The green synthesis method illustrated a new door to synthesize HAp for maintaining biocompatibilityand increasing antibacterial properties. The review also explores how HANPs improve the integration of implants with bone, support bone growth, and help treat sensitive teeth based on various laboratory and clinical studies. The usage of HAp in dentin and enamel shows higher potentiality through FTIR, XPS, XRD, EDS, etc., for mechanical stability and biological balance compared to natural teeth. Additionally, the use of HANPs in dental products like toothpaste and mouthwash is discussed, highlighting its potential to help rebuild tooth enamel and fight bacteria. There are some challenges for long-term usage against oral bacteria, but doping with inorganic materials, like Zn, has already solved this periodontal problem. Much more research is still essential to estimate the fabrication variation based on patient problems and characteristics. Still, it has favorable outcomes regarding its bioactive nature and antimicrobial properties. Due to their compatibility with biological tissues and ability to support bone growth, HANPs hold great promise for advancing dental materials and implant technology, potentially leading to better dental care and patient outcomes.

Here we report a novel strategy using bacterial extracellular polymeric substances (EPS) as decoys to enhance bacterial adhesion and contact-based antimicrobial activity. EPS extracted from Staphylococcus aureus and Bacillus subtilis was used to coat wafers as a conditioning layer to alter surface properties and facilitate bacterial aggregation. Results show that EPS downregulates quorum sensing-related genes (agr and atl in Staphylococcus aureus by 80.5 % and 86.6 %, respectively; fliC in Escherichia coli by ~58.3 %), suggesting that EPS facilitates energy-efficient adhesion independent of quorum sensing signals. Loading antibiotics (erythromycin, linezolid, levofloxacin) into the EPS layer further enhances adhesion and contact killing. Especially, the surfaces loaded with a levofloxacin concentration of 2 μg/mL exhibit a significant antimicrobial effect. For Staphylococcus aureus, the antimicrobial rate reaches 83.66 % after 4 h incubation but drops to 39.9 % after 8 h incubation. In contract, Escherichia coli exhibits greater sensitivity, with antibacterial activity increasing to 92.97 % after 8 h incubation. Laser confocal microscopy characterization further reveals that the antibiotic-loaded EPS surfaces possess remarkable contact bacteria-killing activity. Our results show the promising recruiting-killing efficacy of the antibiotics-loaded EPS against bacteria, which would give insight into exploring new antibacterial strategies for enhanced contact-antibacterial performances.

Corrosion is a significant issue affecting industrial metal surfaces, resulting in material degradation, economic losses, and safety concerns. This review comprehensively examines chitosan and its nano and bionanocomposite forms as sustainable, eco-friendly corrosion inhibitors, emphasizing key innovations in their development and application. The article highlights chitosan's ability to form protective films, which inhibit corrosion by creating a barrier on metal surfaces. A key advancement explored is the incorporation of chitosan nanoparticles, which significantly improve corrosion resistance due to their enhanced surface area, increased adhesion properties, and improved mechanical strength. Another innovative aspect is the synergistic effect of combining chitosan with other nanoparticles or inhibitors, resulting in superior corrosion protection and enhanced barrier properties. The review also addresses the chemical modifications of chitosan to overcome challenges such as poor solubility, mechanical weakness, and chemical instability in harsh environments. A novel contribution of this article is the focus on scalable, cost-effective production methods for chitosan-based bionanocomposites, facilitating their industrial application. This review provides a comprehensive summary of literature reports, offering valuable insights into the latest research advancements and highlights future prospects for chitosan-based materials as eco-friendly, high-performance corrosion inhibitors in diverse industrial settings.

Repair of infectious bone defects remains a serious problem in clinical practice owing to the high risk of infection and excessive reactive oxygen species (ROS) during the early stage, and the residual bacteria and delayed Osseo integrated interface in the later stage, which jointly creates a complex and dynamic microenvironment and leads to bone non-union. The melatonin carbon dots (MCDs) possess antibacterial and osteogenesis abilities, greatly simplifying the composition of a multifunctional material. Therefore, a multifunctional hydrogel containing MCDs (GH-MCD) is developed to meet the multi-stage and complex repair needs of infectious bone injury in this study. The GH-MCD can intelligently release MCDs responding to the acidic microenvironment to scavenge intracellular ROS and exhibit good antibacterial activity by inducing the production of ROS in bacteria and inhibiting the expression of secA2. Moreover, it has high osteogenesis and long-lasting antimicrobial activity during bone repair. RNA-seq results reveal that the hydrogels promote the repair of infected bone healing by enhancing cellular resistance to bacteria, balancing osteogenesis and osteoclastogenesis, and regulating the immune microenvironment. In conclusion, the GH-MCD can promote the repair of infectious bone defects through the programmed transformation of the microenvironment, providing a novel strategy for infectious bone defects.

•The success of cementless fixation in TJA depends on a multitude of factors including biological, mechanical, implant, surgical, and material properties.•Biologic fixation has become the primary mode of fixation for the majority of primary total hip arthroplasty (THA) surgeries done today in the United States (US) due to its low complication rate and superior longevity compared to cemented fixation.•Cementless fixation has yet to gain wider acceptance in total knee arthroplasty (TKA) and hip hemiarthroplasty due to several factors including host bone quality, implant design, and surgical technique.•Understanding a) the properties of the different biomaterials, b) the bone-implant interface characteristics of the different ingrowth and ongrowth surfaces, and c) the various factors that affect osseointegration can lead to:i)appropriate choice of implants for individual patients with consequent increase in revision-free survival, andii)the development of new techniques that can reduce the risk of aseptic loosening.

Hydroxyapatite (HAp)-coated bone implants are frequently used for orthopaedic or dental implants since they offer high biocompatibility and osteoconductivity. Yet, problems such as infections, e.g. periprosthetic joint infections, occur when implanting foreign material into the body. In this study, HAp coatings were produced via high-velocity suspension flame spraying (HVSFS). This method allows for the production of thin coatings. We investigated the effects of different gas parameters on the coating properties and on the biocompatibility, which was tested on the human osteosarcoma cell line MG63. Furthermore, Copper (Cu) was added to achieve antibacterial properties which were evaluated against standard microorganisms using the airborne assay. Three gas parameter groups (low, medium, and high) with different Cu additions (0 wt.%, 1 wt.% and 1.5 wt.%) were evaluated. Our findings show that porosity as well as hardness can be controlled through gas parameters. Furthermore, we showed that it is possible to add Cu through external injection. The Cu content in the coating as well as the release varies with different gas parameters. Both antibacterial efficacy as well as biocompatibility are affected by the Cu content. We could significantly reduce the amount of colony-forming units (CFU) in all coatings for E. coli, CFU for S. aureus was reduced by adding 1.5 wt.% of Cu to the coating. The biocompatibility testing showed a cytotoxicity threshold at a Cu-release of 14.3 mg/L in 120 hours. Based on our findings, we suggest medium gas parameters for HVSFS and the addition of 1 wt.% Cu to the coating. With these parameters, a reasonable antibacterial effect can be achieved while maintaining sufficient biocompatibility.

Chitosan is a promising natural polymer for coatings, it combines intrinsic antibacterial and pro-osteoblastic properties, but the literature still has a gap from the development to behavior of these coatings, so this systematic review aimed to answer, "What is the relationship between the physical and chemical properties of polymeric chitosan coatings on titanium implants on antibacterial activity and osteoblast viability?". PRISMA guidelines was followed, the search was applied into 4 databases and grey literature, without the restriction of time and language. The selection process occurred in 2 blinded steps by the authors. The criteria of eligibility were in vitro studies that evaluated the physical, chemical, microbiological, and biological properties of chitosan coatings on titanium surfaces. The risk of bias was analyzed by the specific tool. Of 734 potential articles 10 were included; all had low risk of bias. The coating was assessed according to the technique of fabrication, FT-IR, thickness, adhesion, roughness, wettability, antibacterial activity, and osteoblast viability. The analyzed coatings showed efficacy on antibacterial activity and cytocompatibility dependent on the class of material incorporated. Thus, this review motivates the development of time-dependent studies to optimize manufacturing and allow for an increase in patents and availability on the market.

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.

This study delves into the potential of amorphous titanium oxide (aTiO2) nano-coating to enhance various critical aspects of non-Ti-based metallic orthopedic implants. These implants, such as medical-grade stainless steel (SS), are widely used for orthopedic devices that demand high strength and durability. The aTiO2nano-coating, deposited via magnetron sputtering, is a unique attempt to improve the osteogenesis, the inflammatory response, and to reduce bacterial colonization on SS substrates. The study characterized the nanocoated surfaces (SS-a TiO2) in topography, roughness, wettability, and chemical composition. Comparative samples included uncoated SS and sandblasted/acid-etched Ti substrates (Ti). The biological effects were assessed using human mesenchymal stem cells (MSCs) and primary murine macrophages. Bacterial tests were carried out with two aerobic pathogens (S. aureusandS. epidermidis) and an anaerobic bacterial consortium representing an oral dental biofilm. Results from this study provide strong evidence of the positive effects of the aTiO2nano-coating on SS surfaces. The coating enhanced MSC osteoblastic differentiation and exhibited a response similar to that observed on Ti surfaces. Macrophages cultured on aTiO2nano-coating and Ti surfaces showed comparable anti-inflammatory phenotypes. Most significantly, a reduction in bacterial colonization across tested species was observed compared to uncoated SS substrates, further supporting the potential of aTiO2nano-coating in biomedical applications. The findings underscore the potential of magnetron-sputtering deposition of aTiO2nano-coating on non-Ti metallic surfaces such as medical-grade SS as a viable strategy to enhance osteoinductive factors and decrease pathogenic bacterial adhesion. This could significantly improve the performance of metallic-based biomedical devices beyond titanium.

Xenografts are commonly used for bone regeneration in dental and orthopaedic domains to repair bone voids and other defects. The first-generation xenografts were made through sintering, which deproteinizes them and alters their crystallinity, while later xenografts are produced using cold-temperature chemical treatments to maintain the structural collagen phase. However, the impact of collagen and the crystalline phase on physicochemical properties have not been elucidated. We hypothesized that understanding these factors could explain why the latter provides improved bone regeneration clinically. In this study, we compared two types of xenografts, one prepared through a low-temperature chemical process (Treated) and another subsequently sintered at 1100°C (Sintered) using advanced microscopy, spectroscopy, X-ray analysis and compressive testing. Our investigation showed that the Treated bone graft was free of residual blood, lipids or cell debris, mitigating the risk of pathogen transmission. Meanwhile, the sintering process removed collagen and the carbonate phase of the Sintered graft, leaving only calcium phosphate and increased mineral crystallinity. Microcomputed tomography revealed that the Treated graft exhibited an increased high porosity (81%) and pore size compared to untreated bone, whereas the Sintered graft exhibited shrinkage, which reduced the porosity (72%), pore size and strut size. Additionally, scanning electron microscopy displayed crack formation around the pores of the Sintered graft. The Treated graft displayed median mechanical properties comparable to native cancellous bone and clinically available solutions, with an apparent modulus of 166 MPa, yield stress of 5.5 MPa and yield strain of 4.9%. In contrast, the Sintered graft exhibited a lower median apparent modulus of 57 MPa. It failed in a brittle manner at a median stress of 1.7 MPa and strain level of 2.9%, demonstrating the structural importance of the collagen phase. This indicates why bone grafts prepared through cold-temperature processes are clinically favourable.

A challenge remains in the development of anti-infectious coatings for the inert surfaces of biomedical devices that are prone to bacterial colonization and biofilm formation. Here, a facile photocuring method to construct functionalized polymeric coatings on inert polydimethylsiloxane (PDMS) surfaces, is developed. Using atom transfer radical polymerization (ATRP) initiator bearing thymol group, hydrophilic DMAEMA and benzophenone (BP)-containing monomers are copolymerized to form polymers with end functional groups. An end-functionalized biocidal coating is then constructed on the inert PDMS surface in one step using a photocuring reaction. The functionalized PDMS surfaces show excellent antibacterial and antifouling properties, are capable of completely eradiating MRSA within ≈6 h, and effectively inhibit the growth of biofilms. In addition, they have good stability and long-lasting antibacterial activity in body fluid environments such as 0.9% saline and urine. According to bladder model experiments, the catheter's lifespan can be extended from ≈7 to 35 days by inhibiting the growth and migration of bacteria along its inner surface. The photocuring technique is therefore very promising in terms of surface functionalization of inert biomedical devices in order to minimize the spread of infection.

A wide variety of microorganisms have been closely linked to metal corrosion in the form of adherent surface biofilms. Biofilms allow the development and maintenance of locally corrosive environments and/or permit direct corrosion including pitting corrosion. The presence of numerous genetically distinct microorganisms in the oral environment poses a threat to the integrity and durability of the surface of metallic prostheses and implants used in routine dentistry. However, the association between oral microorganisms and specific corrosion mechanisms is not clear. It is of practical importance to understand how microbial corrosion occurs and the associated risks to metallic materials in the oral environment. This knowledge is also important for researchers and clinicians who are increasingly concerned about the biological activity of the released corrosion products. Accordingly, the main goal was to comprehensively review the current literature regarding oral microbiologically influenced corrosion (MIC) including characteristics of biofilms and of the oral environment, MIC mechanisms, corrosion behavior in the presence of oral microorganisms and potentially mitigating technologies. Findings included that oral MIC has been ascribed mostly to aggressive metabolites secreted during microbial metabolism (metabolite-mediated MIC). However, from a thermodynamic point of view, extracellular electron transfer mechanisms (EET-MIC) through pili or electron transfer compounds cannot be ruled out. Various MIC mitigating methods have been demonstrated to be effective in short term, but long term evaluations are necessary before clinical applications can be considered. Currently most in-vitro studies fail to simulate the complexity of intraoral physiological conditions which may either reduce or exacerbate corrosion risk, which must be addressed in future studies. STATEMENT OF SIGNIFICANCE: A thorough analysis on literature regarding oral MIC (microbiologically influenced corrosion) of biomedical metallic materials has been carried out, including characteristics of oral environment, MIC mechanisms, corrosion behaviors in the presence of typical oral microorganisms and potential mitigating methods (materials design and surface design). There is currently a lack of mechanistic understanding of oral MIC which is very important not only to corrosion researchers but also to dentists and clinicians. This paper discusses the significance of biofilms from a biocorrosion perspective and summarizes several aspects of MIC mechanisms which could be caused by oral microorganisms. Oral MIC has been closely associated with not only the materials research but also the dental/clinical research fields in this work.

Titanium (Ti) and its alloys are widely used biomaterials in bone repair. Although these biomaterials possess stable properties and good biocompatibility, the high elastic modulus and low surface activity of Ti implants have often been associated with infection, inflammation, and poor osteogenesis. Therefore, there is an urgent need to modify the surface of Ti implants, where changes in surface morphology or coatings loading can confer specific functions to help them adapt to the osseointegration formation phase and resist bacterial infection. This can further ensure a healthy microenvironment for bone regeneration as well as the promotion of immunomodulation, angiogenesis, and osteogenesis. Therefore, in this review, we evaluated various functional Ti implants after surface modification, both in terms of static modifications and dynamic response strategies, mainly focusing on the synergistic effects of antimicrobial activities and functionalized osteogenic. Finally, the current challenges and future perspectives are summarized to provide innovative and effective solutions for osseointegration and bone defect repair.

In order to reduce infections, porous NiTi alloys with 62% porosity were obtained by self-propagating high-temperature synthesis with the addition of 0.2 and 0.5 at. % silver nanoparticles. Silver significantly improved the alloys' antibacterial activity without compromising cytocompatibility. An alloy with 0.5 at. % Ag showed the best antibacterial ability against Staphylococcus epidermidis. All alloys exhibited good biocompatibility with no cellular toxicity against embryonic fibroblast 3T3 cells. Clinical evaluation of the results after implantation showed a complete absence of purulent-inflammatory complications in all animals. Even distribution of silver nanoparticles in the surface layer of the porous NiTi alloy provides a uniform antibacterial effect.

Prevention of cardiovascular implantable electronic devices (CIED) infection is crucial for successful outcomes. In this study, we report an adhesive and antibacterial hydrogel coating for CIED infection treatment, by immobilizing polyethylene glycol (PEG) and 2'-O-hydroxypropyl trimethyl ammonium chloride chitosan (HAC) on Ti surface. Initial alkali and APTES treatment caused the formation of -NH2 to enhance the adhesion of the hydrogel coating to Ti implants, followed by immobilizing a photo-cross-linkable PEG/2'-O-HTACCS hydrogel on Ti/OH/NH2 surface. Surface characterization of Ti/OH/NH2 sample and adhesion testing of hydrogel on Ti/OH/NH2 surface confirm successful immobilization of hydrogel onto the Ti/OH/NH2 surface. In vitro and in vivo antimicrobial results exhibited that the photo-cross-linkable PEG/HAC composite hydrogel has excellent antimicrobial capabilities against both Grampositive (S. aureus and S. epidermidis) and Gram-negative (P. aeruginosa and E. coli) bacteria. The outcome of this study demonstrates the photo-cross linked PEG/HAC coating hydrogels can be easily formed on the Ti implants, and has great potential in preventing CIED pocket infection.

Presently, millions worldwide suffer from degenerative and inflammatory bone and joint issues, comprising roughly half of chronic ailments in those over 50, leading to prolonged discomfort and physical limitations. These conditions become more prevalent with age and lifestyle factors, escalating due to the growing elderly populace. Addressing these challenges often entails surgical interventions utilizing implants or bone grafts, though these treatments may entail complications such as pain and tissue death at donor sites for grafts, along with immune rejection. To surmount these challenges, tissue engineering has emerged as a promising avenue for bone injury repair and reconstruction. It involves the use of different biomaterials and the development of three-dimensional porous matrices and scaffolds, alongside osteoprogenitor cells and growth factors to stimulate natural tissue regeneration. This review compiles methodologies that can be used to develop biomaterials that are important in bone tissue replacement and regeneration. Biomaterials for orthopedic implants, several scaffold types and production methods, as well as techniques to assess biomaterials' suitability for human use-both in laboratory settings and within living organisms-are discussed. Even though researchers have had some success, there is still room for improvements in their processing techniques, especially the ones that make scaffolds mechanically stronger without weakening their biological characteristics. Bone tissue engineering is therefore a promising area due to the rise in bone-related injuries.

Diamond-like carbon (DLC) layers are known for their high corrosion and wear resistance, low friction, and high biocompatibility. However, it is often necessary to dope DLC layers with additional chemical elements to strengthen their adhesion to the substrate. Ti-DLC layers (doped with 0.4, 2.1, 3.7, 6.6, and 12.8 at.% of Ti) were prepared by dual pulsed laser deposition, and pure DLC, glass, and polystyrene (PS) were used as controls. In vitro cell-material interactions were investigated with an emphasis on cell adhesion, proliferation, and osteogenic differentiation. We observed slightly increasing roughness and contact angle and decreasing surface free energy on Ti-DLC layers with increasing Ti content. Three-week biological experiments were performed using adipose tissue-derived stem cells (ADSCs) and bone marrow mesenchymal stem cells (bmMSCs) in vitro. The cell proliferation activity was similar or slightly higher on the Ti-doped materials than on glass and PS. Osteogenic cell differentiation on all materials was proved by collagen and osteocalcin production, ALP activity, and Ca deposition. The bmMSCs exhibited greater initial proliferation potential and an earlier onset of osteogenic differentiation than the ADSCs. The ADSCs showed a slightly higher formation of focal adhesions, higher metabolic activity, and Ca deposition with increasing Ti content.

Mineralized collagen (MC) is the fundamental unit of natural bone tissue and can induce bone regeneration. Unmodified MC has poor mechanical properties and a single component, making it unable to cope with complex physiological environment. In this study, we introduced sodium alginate (SA) and vascular endothelial growth factor (VEGF) into the MC material to construct functionalized mineralized collagen (FMC) with good mechanical strength and the ability to continuously release growth factors. The FMC is filled into the pores of 3D printed titanium alloy scaffold to form a new organic-inorganic bioactive interface. With the continuous degradation of FMC, bone marrow mesenchymal stem cells (BMSCs) and vascular endothelial cells (VECs) in the surrounding environment are recruited to the surface of the scaffold to promote bone and vascular regeneration. After implanting the scaffold into the distal femoral defect of rabbits, Micro CT, histological, push-out, as well as immunohistochemical analysis showed that the composite interface can significantly promote osseointegration. These findings provide a new strategy for the development and application of mineralized collagen materials.

Bacteria can swim upstream in a narrow tube and pose a clinical threat of urinary tract infection to patients implanted with catheters. Coatings and structured surfaces have been proposed to repel bacteria, but no such approach thoroughly addresses the contamination problem in catheters. Here, on the basis of the physical mechanism of upstream swimming, we propose a novel geometric design, optimized by an artificial intelligence model. Using Escherichia coli, we demonstrate the anti-infection mechanism in microfluidic experiments and evaluate the effectiveness of the design in three-dimensionally printed prototype catheters under clinical flow rates. Our catheter design shows that one to two orders of magnitude improved suppression of bacterial contamination at the upstream end, potentially prolonging the in-dwelling time for catheter use and reducing the overall risk of catheter-associated urinary tract infection.

Radiolucent lines occasionally develop around the proximal aspect of fully hydroxyapatite (HA)-coated tapered femoral stems after total hip arthroplasty (THA). It was hypothesised that distal wedging of stems may predispose to proximal radiolucent line formation, which may negatively impact clinical outcome.

All primary THA performed with a collarless fully HA-coated stem that had a minimum of 1 year of radiographic follow-up were identified in a surgical database (n = 244). Radiographic measures of proximal femoral morphology and femoral canal fill at the middle and distal thirds of the stem were analysed for association with the presence of proximal radiolucent lines. Linear regression was used to explore any association between radiolucent lines and patient reported outcome measures (PROMs), available in 61% of patients.

Proximal radiolucent lines developed in 31 cases (12.7%) at final follow-up. Dorr A femoral morphology and increased canal-fill at the distal ⅓ of the stem correlated with the development of radiolucent lines (p < 0.001). No correlation was observed between pain or PROMs and the presence of proximal radiolucent lines.

We observed an unexpectedly high incidence of proximal femoral radiolucent lines about collarless fully HA coated stems. Distal-only implant wedging in Dorr A bone may compromise proximal fixation. Although this finding did not correlate with short-term outcomes, the long-term clinical impact requires further study.

The failure of orthopedic implants is usually caused by inflammation, poor tissue integration, and infection, which can lead to pain, limited mobility, dysfunction of patients. This may require additional surgical interventions, such as removal, replacement, or repair of implants, as well as related treatment measures such as antibiotic therapy, physical therapy. Here, an injectable hydrogel carrier was developed for the steady release of inflammatory regulators to reduce the surface tissue inflammatory response of orthopedic implants and induce soft tissue regeneration, ultimately achieving the promotion of implants stability. The hydrogels carrier was prepared by hydroxyphenyl propionic acid-modified ε-Poly-l-lysine (EPA), hydrogen peroxide and horseradish peroxidase, which showed antibacterial bioactive and stable factor release ability. Due to the introduction of IL-4, EPA@IL-4 hydrogels showed good inflammatory regulation. EPA@IL-4 hydrogels regulated the differentiation of macrophages into M2 in inflammatory environment in vitro, and promoted endothelial cells to show a more obvious trend of tube formation. The composite hydrogels reduced the inflammation on the surface of the implants in vivo, induced local endothelial cell angiogenesis, and had more collagen deposition and new granulation tissue. Therefore, EPA hydrogels based on IL-4 release are promising candidates for promoting of implants surface anti-inflammatory, soft tissue regeneration, and anti-infection.

Regenerative medicine and tissue engineering have emerged as a multidisciplinary promising field in the quest to address the limitations of traditional medical approaches. One of the key aspects of these fields is the development of such types of biomaterials that can mimic the extracellular matrix and provide a conducive environment for tissue regeneration. In this regard, chitosan has played a vital role which is a naturally derived linear bi-poly-aminosaccharide, and has gained significant attention due to its biocompatibility and unique properties. Chitosan possesses many unique physicochemical properties, making it a significant polysaccharide for different applications such as agriculture, nutraceutical, biomedical, food, nutraceutical, packaging, etc. as well as significant material for developing next-generation hydrogel and bio-scaffolds for regenerative medicinal applications. Moreover, chitosan can be easily modified to incorporate desirable properties, such as improved mechanical strength, enhanced biodegradability, and controlled release of bioactive molecules. Blending chitosan with other polymers or incorporating nanoparticles into its matrix further expands its potential in tissue engineering applications. This review summarizes the most recent studies of the last 10 years based on chitosan, blends, and nanocomposites and their application in bone tissue engineering, hard tissue engineering, dental implants, dental tissue engineering, dental fillers, and cartilage tissue engineering.

Plasma, the fourth fundamental state of matter, comprises charged species and electrons, and it is a fascinating medium that is spread over the entire visible universe. In addition to that, plasma can be generated artificially under appropriate laboratory techniques. Artificially generated thermal or hot plasma has applications in heavy and electronic industries; however, the non-thermal (cold atmospheric or low temperature) plasma finds its applications mainly in biomedicals and therapeutics. One of the important characteristics of LTP is that the constituent particles in the plasma stream can often maintain an overall temperature of nearly room temperature, even though the thermal parameters of the free electrons go up to 1 to 10 keV. The presence of reactive chemical species at ambient temperature and atmospheric pressure makes LTP a bio-tolerant tool in biomedical applications with many advantages over conventional techniques. This review presents some of the important biomedical applications of cold-atmospheric plasma (CAP) or low-temperature plasma (LTP) in modern medicine, showcasing its effect in antimicrobial therapy, cancer treatment, drug/gene delivery, tissue engineering, implant modifications, interaction with biomolecules, etc., and overviews some present challenges in the field of plasma medicine.

Joint replacement is a common surgery and is predominantly utilized for treatment of osteoarthritis in the aging population. The longevity of many of these implants depends on bony ingrowth. Here, we provide an overview of current techniques in osteogenesis (inducing bone growth onto an implant), which is affected by aging and inflammation. In this review we cover the biologic underpinnings of these processes as well as the clinical applications. Overall, aging has a significant effect at the cellular and macroscopic level that impacts osteosynthesis at bone-metal interfaces after joint arthroplasty; potential solutions include targeting prolonged inflammation, preventing microbial adhesion, and enhancing osteoinductive and osteoconductive properties.

The application of orthopedic implants for bone tissue reconstruction and functional restoration is crucial for patients with severe bone fractures and defects. However, the abiotic nature of orthopedic implants allows bacterial adhesion and colonization, leading to the formation of bacterial biofilms on the implant surface. This can result in implant failure and severe complications such as osteomyelitis and septic arthritis. The emergence of antibiotic-resistant bacteria and the limited efficacy of drugs against biofilms have increased the risk of orthopedic implant-associated infections (OIAI), necessitating the development of alternative therapeutics. In this regard, antibacterial hydrogels based on bacteria repelling, contact killing, drug delivery, or external assistance strategies have been extensively investigated for coating orthopedic implants through surface modification, offering a promising approach to target biofilm formation and prevent OIAI. This review provides an overview of recent advancements in the application of antibacterial hydrogel coatings for preventing OIAI by targeting biofilm formation. The topics covered include: (1) the mechanisms underlying OIAI occurrence and the role of biofilms in exacerbating OIAI development; (2) current strategies to impart anti-biofilm properties to hydrogel coatings and the mechanisms involved in treating OIAI. This article aims to summarize the progress in antibacterial hydrogel coatings for OIAI prevention, providing valuable insights and facilitating the development of prognostic markers for the design of effective antibacterial orthopedic implants.

Biomaterials and coating techniques unlock major benefits for advanced medical therapies. Here, we explored layer-by-layer (LbL) deposition of silk fibroin (SF) by dip coating to deploy homogeneous films on different materials (titanium, magnesium, and polymers) frequently used for orthopedic and other bone-related implants. Titanium and magnesium specimens underwent preceding plasma electrolytic oxidation (PEO) to increase hydrophilicity. This was determined as surface properties were visualized by scanning electron microscopy and contact angle measurements as well as Fourier transform infrared spectroscopy (FTIR) analysis. Finally, biological in vitro evaluations of hemocompatibility, THP-1 cell culture, and TNF-α assays were conducted. A more hydrophilic surface could be achieved using the PEO surface, and the contact angle for magnesium and titanium showed a reduction from 73 to 18° and from 58 to 17°, respectively. Coating with SF proved successful on all three surfaces, and coating thicknesses of up to 5.14 μm (±SD 0.22 μm) were achieved. Using FTIR analysis, it was shown that the insolubility of the material was achieved by post-treatment with water vapor annealing, although the random coil peak (1640-1649 cm-1) and the α-helix peak (at 1650 cm-1) were still evident. SF did not change hemocompatibility, regardless of the substrate, whereas the PEO-coated materials showed improved hemocompatibility. THP-1 cell culture showed that cells adhered excellently to all of the tested material surfaces. Interestingly, SF coatings induced a significantly higher amount of TNF-α for all materials, indicating an inflammatory response, which plays an important role in a variety of physiological processes, including osteogenesis. LbL coatings of SF are shown to be promising candidates to modulate the body's immune response to implants manufactured from titanium, magnesium, and polymers. They may therefore facilitate future applications for bioactive implant coatings. However, further in vivo studies are needed to confirm the proposed effects on osteogenesis in a physiological environment.

A special generative manufacturing (AM) process was developed for the partial integration of active ingredients into open-porous matrix structures. A mixture of a silver-containing solution as an antibacterial material with an alginate hydrogel as a carrier system was produced as the active ingredient. The AM process developed was used to introduce the active ingredient solution into an open-porous niobium containing a β-titanium matrix structure, thus creating a reproducible active ingredient delivery system. The matrix structure had already been produced in a separate AM process by means of selective laser melting (SLM). The main advantage of this process is the ability to control porosity with high precision. To determine optimal surface conditions for the integration of active ingredients into the matrix structure, different surface conditions of the titanium substrate were tested for their impact on wetting behaviour of a silver-containing hydrogel solution. The solution-substrate contact angle was measured and evaluated to determine the most favourable surface condition. To develop the generative manufacturing process, an FDM printer underwent modifications that permitted partial application of the drug solution to the structure in accordance with the bioprinting principle. The modified process enabled flexible control and programming of both the position and volume of the applied drug. Furthermore, the process was able to fill up to 95% of the titanium matrix body pore volume used. The customised application of drug carriers onto implants as a drug delivery system can be achieved via the developed process, providing an alternative to established methods like dip coating that lack this capability.

Bacterial infection caused by biomaterials is a very serious problem in the clinical treatment of implants. The emergence of antibiotic resistance has prompted other antibacterial agents to replace traditional antibiotics. Silver is rapidly developing as an antibacterial candidate material to inhibit bone infections due to its significant advantages such as high antibacterial timeliness, high antibacterial efficiency, and less susceptibility to bacterial resistance. However, silver has strong cytotoxicity, which can cause inflammatory reactions and oxidative stress, thereby destroying tissue regeneration, making the application of silver-containing biomaterials extremely challenging. In this paper, the application of silver in biomaterials is reviewed, focusing on the following three issues: 1) how to ensure the excellent antibacterial properties of silver, and not easy to cause bacterial resistance; 2) how to choose the appropriate method to combine silver with biomaterials; 3) how to make silver-containing biomaterials in hard tissue implants have further research. Following a brief introduction, the discussion focuses on the application of silver-containing biomaterials, with an emphasis on the effects of silver on the physicochemical properties, structural properties, and biological properties of biomaterials. Finally, the review concludes with the authors' perspectives on the challenges and future directions of silver in commercialization and in-depth research.

The lack of osteoinductive, angiogenic and antimicrobial properties of hydroxyapatite coatings (HA) on titanium surfaces severely limits their use in orthopedic and dental implants. Therefore, we doped SiO2, Gd2O3 and CeO2 nanoparticles into HA to fabricate a HASiGdCe coating with a combination of decent antibacterial, angiogenic and osteogenic properties by the plasma spraying technique.

The HASiGdCe coating was analyzed by SEM (EDS), surface roughness tests, contact angle tests, XRD, FTIR spectroscopy, tensile tests and electrochemical dynamic polarization tests. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO-1) were used as representative bacteria to verify the antibacterial properties of the HASiGdCe coating. We evaluated the cytocompatibility and in vitro osteoinductivity of the HASiGdCe coating by investigating its effect on the cell viability and osteogenic differentiation of MC3T3-E1 cells. We assessed the in vitro angiogenic activity of the HASiGdCe coating by migration assay, tube formation assay, and RT‒PCR analysis of angiogenic genes in HUVECs. Finally, we used infected animal femur models to investigate the biosafety, antimicrobial and osteointegration properties of the HASiGdCe coating in vivo.

Through various characterization experiments, we demonstrated that the HASiGdCe coating has suitable microscopic morphology, physical phase characteristics, bonding strength and bioactivity to meet the coating criteria for orthopedic implants. The HASiGdCe coating can release Gd3+ and Ce4+, showing strong antibacterial properties against MRSA and PAO-1. The HASiGdCe coating has been shown to have superior osteogenic and angiogenic properties compared to the HA coating in in vitro cellular experiments. Animal implantation experiments have shown that the HASiGdCe coating also has excellent biosafety, antimicrobial and osteogenic properties in vivo.

The HASiGdCe coating confers excellent antibacterial, angiogenic and osteogenic properties on titanium implants, which can effectively enhance implant osseointegration and prevent bacterial infections, and it accordingly has promising applications in the treatment of bone defects related to orthopedic and dental sciences.

Titanium (Ti) and its alloys have been widely used as orthopedic implants, because of their favorable mechanical properties, corrosion resistance and biocompatibility. Despite their significant success in various clinical applications, the probability of failure, degradation and revision is undesirably high, especially for the patients with low bone density, insufficient quantity of bone or osteoporosis, which renders the studies on surface modification of Ti still active to further improve clinical results. It is discerned that surface physicochemical properties directly influence and even control the dynamic interaction that subsequently determines the success or rejection of orthopedic implants. Therefore, it is crucial to endow bulk materials with specific surface properties of high bioactivity that can be performed by surface modification to realize the osseointegration. This article first reviews surface characteristics of Ti materials and various conventional surface modification techniques involving mechanical, physical and chemical treatments based on the formation mechanism of the modified coatings. Such conventional methods are able to improve bioactivity of Ti implants, but the surfaces with static state cannot respond to the dynamic biological cascades from the living cells and tissues. Hence, beyond traditional static design, dynamic responsive avenues are then emerging. The dynamic stimuli sources for surface functionalization can originate from environmental triggers or physiological triggers. In short, this review surveys recent developments in the surface engineering of Ti materials, with a specific emphasis on advances in static to dynamic functionality, which provides perspectives for improving bioactivity and biocompatibility of Ti implants.

The American Musculoskeletal Society updated the diagnostic criteria for periprosthetic joint infection (PJI) in 2011 and 2018. However, the overall incidence of PJI since the introduction of these new standards has not been assessed. In order to fill this knowledge gap, a single-group meta-analysis was conducted using articles obtained from several databases, focusing on the incidence of PJI after primary total hip arthroplasty (THA). Our study revealed a significant difference in the incidence of PJI reported by different national or regional databases. Moreover, most cases of PJI were found to be underestimated. This highlights the crucial need for standardized diagnostic criteria and monitoring methods to accurately identify and track cases of PJI. Furthermore, a bibliometric analysis was conducted to provide a comprehensive overview of the current state of research on PJI after THA. This analysis explored the most productive countries, organizations, journals, and individuals in this research area. Additionally, it identified the research trends and hotspots of the last decade, highlighting the advancements and areas of focus in this field. By conducting these analyses, the study aims to contribute to the understanding of PJI after THA and provide valuable insights for clinicians, researchers, and policymakers involved in the management of this condition.

In the present work, we test four thin coatings for titanium implants, namely, bioglass, GB14, Beta-Tricalciumphosphate (β-TCP) and hydroxyapatite (HA) with and without incorporated copper ions for their osteointegrative capacity. A rabbit drill hole model for time intervals up to 24 weeks was used in this study. Implant fixation was evaluated by measuring shear strength of the implant/bone interface. Quantitative histological analysis was performed for the measurements of bone contact area. Implants with and without copper ions were compared after 24 weeks. Thin coatings of GB14, HA or TCP on titanium implants demonstrated high shear strength during the entire test period of up to 24 weeks. Results confirmed osteointegrative properties of the coatings and did not reveal any negative effect of copper ions on osteointegration. The integration of copper in degradable osteoconductive coatings with a thickness of approx. 20 μm represents a promising method of achieving antibacterial shielding during the entire period of bone healing while at the same time improving osteointegration of the implants.

With the aging of population and the rapid improvement of public health and medical level in recent years, people have had an increasing demand for orthopedic implants. However, premature implant failure and postoperative complications frequently occur due to implant-related infections, which not only increase the social and economic burden, but also greatly affect the patient's quality of life, finally restraining the clinical use of orthopedic implants. Antibacterial coatings, as an effective strategy to solve the above problems, have been extensively studied and motivated the development of novel strategies to optimize the implant. In this paper, a variety of antibacterial coatings recently developed for orthopedic implants were briefly reviewed, with the focus on the synergistic multi-mechanism antibacterial coatings, multi-functional antibacterial coatings, and smart antibacterial coatings that are more potential for clinical use, thereby providing theoretical references for further fabrication of novel and high-performance coatings satisfying the complex clinical needs.

The current standard for treating irreversibly damaged dental pulp is root canal therapy, which involves complete removal and debridement of the pulp space and filling with an inert biomaterial. A regenerative approach to treating diseased dental pulp may allow for complete healing of the native tooth structure and enhance the long-term outcome of once-necrotic teeth. The aim of this paper is, therefore, to highlight the current state of dental pulp tissue engineering and immunomodulatory biomaterials properties, identifying exciting opportunities for their synergy in developing next-generation biomaterials-driven technologies.

An overview of the inflammatory process focusing on immune responses of the dental pulp, followed by periapical and periodontal tissue inflammation are elaborated. Then, the most recent advances in treating infection-induced inflammatory oral diseases, focusing on biocompatible materials with immunomodulatory properties are discussed. Of note, we highlight some of the most used modifications in biomaterials' surface, or content/drug incorporation focused on immunomodulation based on an extensive literature search over the last decade.

We provide the readers with a critical summary of recent advances in immunomodulation related to pulpal, periapical, and periodontal diseases while bringing light to tissue engineering strategies focusing on healing and regenerating multiple tissue types.

Significant advances have been made in developing biomaterials that take advantage of the host's immune system to guide a specific regenerative outcome. Biomaterials that efficiently and predictably modulate cells in the dental pulp complex hold significant clinical promise for improving standards of care compared to endodontic root canal therapy.

Implant-associated infection (IAI) caused by pathogens colonizing on the implant surface is a serious issue in the trauma-orthopedic surgery, which often leads to implant failure. The complications of IAI bring a big threat to the clinical practice of implants, accompanied by significant economic cost and long hospitalization time. In this study, we propose an antibiotics-free strategy to address IAI-related challenges by using a biodegradable and cytocompatible hydrogel coating. To achieve this, a novel hydrogel system was developed to combine the synergistic effects of good cell affinity and antibacterial properties. The hydrogel material was prepared by modifying a photocross-linkable gelatin-based polymer (GelMA) with cationic quaternary ammonium salt (QAS) groups via a mild and simple synthesis procedure. By engineering the length of the hydrophobic carbon chain on the QAS group and the degree of functionalization, the resulting GelMA-octylQAS hydrogel exhibited an integration of good mechanical properties, biodegradability, excellent bactericidal activity against various types of bacteria, and high cytocompatibility with mammalian cells. When coated onto the implant via the in situ cross-linking procedure, our hydrogel demonstrated superior antimicrobial ability in the infective model of femoral fracture of rats. Our results suggest that the GelMA-octylQAS hydrogel might provide a promising platform for preventing and treating IAI.

A growing interest in creating advanced biomaterials with specific physical and chemical properties is currently being observed. These high-standard materials must be capable to integrate into biological environments such as the oral cavity or other anatomical regions in the human body. Given these requirements, ceramic biomaterials offer a feasible solution in terms of mechanical strength, biological functionality, and biocompatibility. In this review, the fundamental physical, chemical, and mechanical properties of the main ceramic biomaterials and ceramic nanocomposites are drawn, along with some primary related applications in biomedical fields, such as orthopedics, dentistry, and regenerative medicine. Furthermore, an in-depth focus on bone-tissue engineering and biomimetic ceramic scaffold design and fabrication is presented.