Organic materials contain synthetic organic polymer materials and natural organic materials. Among them, synthetic organic polymer materials include polymethyl methacrylate and polyglycolic acid, and natural organic materials include chitosan, alginate, and hyaluronic acid. They do not have antimicrobial properties per se, but function as carriers of drugs or antimicrobial materials.

Inorganic materials include calcium sulfate (CS), hydroxyapatite, and metals. Among them, CS and hydroxyapatite have no antimicrobial properties per se and are mainly used as carriers of antimicrobial units and bone fillers in the treatment of bone infections. Metals mainly function in the form of nanoparticles.

Due to their limitations, single organic or inorganic materials often do not reach the requirements of clinical applications, giving rise to composite materials. Composites are formed by two or more materials and make full use of their combined advantages, good biocompatibility, strength, and antibacterial properties. The structure of the material can also affect cell function, survival, and tissue formation (Chan and Mooney, 2008). Table 1 summarizes the research progress of various antimicrobial composites in the treatment of implant-associated infections in the past decade.

To improve the combination and advantages of a variety of materials, researchers and manufacturers use coatings, nanoparticles, hydrogels, and antibacterial bracket structures to achieve a better fit. For example, nanostructured composites in the form of coatings, which embed bioactive compounds in inorganic nanostructured matrixes, incorporate biopolymers and bioactive nanoceramics that mimic organic components of the bone extracellular matrix (such as collagen) to induce bone growth (Couto et al., 2009).

In one study, several sets of different ratios of methyl methacrylate (MMA), 3-(trimethoxy silyl)propyl methacrylate (KH570), borneol acrylate (BA), and hybrid silica sol were mixed in a solution to prepare organic-inorganic hybrid antimicrobial coatings (Figure 3A) (Cheng et al., 2019). The relative cell growth rate of the HS-MKB-8 (MMA/KH570/BA molar ratio of 8:1:8) coating was above 85% after 24 h of incubation, as detected by the standard MTT method, indicating the low in vitro cytotoxicity of the coating. The bacterial inhibition ratios of the coatings were obtained by agar plates, and the HS-MKB-0 (MMA/KH570 molar ratio of 8:1) coating adhered to a large number of bacteria, while the HS-MKB-8 coating was covered with few. A high-density distribution of E. coli and Streptococcus mutans (S. mutans) was clearly observed on the surface of the slides; however, almost no bacteria were found on the surface of the HS-MKB-8. A quantitative analysis of both bacteria showed significantly less adherence to HS-MKB-0 than HS-MKB-8 (p < 0.001) (Figures 3B, C). The HS-MKB-BA coating was found to significantly inhibit the growth of E. coli and S. mutans by OD test (Figures 3D, E). The organic–inorganic composite coating has high light transmission, excellent mechanical properties, and good antibacterial effects on Gram-negative and Gram-positive bacteria.

Nanostructured Ag has excellent antibacterial activity, and one of the main mechanisms of bactericidal activity is cytotoxicity caused by ROS (He et al., 2012). Wang et al. (2020a) combined graphene derivatives with antibacterial metal nanostructure formations of metal-graphene composites. This increased the number of ROS generated directly, and improved oxidative stress injury caused by Ag nanoparticles. This composite also improves the dispersion of metal nanoparticles and cell contact, achieving better bactericidal activity (Rojas-Andrade et al., 2017). Luo et al. (2020) created a 3D mesoporous bioactive glass (MBG) nano fiber scaffold by single tank template assisted sol-gel doping synthesized with copper (Cu). Studies have shown that the prepared scaffold has good biocompatibility, a large specific surface area, and is endowed with the antibacterial activity of Cu, which has excellent bactericidal activity against Gram-positive bacteria. Biodegradable composite hydrogels composed of carboxymethyl chitosan and clindamycin-loaded mesoporous silica nanoparticles possess multiple antibacterial activities and induce osteogenesis by modulating alkaline phosphatase activity (Sungkhaphan et al., 2021).

By adding a hydrogel matrix nanometer conductive filler, water can be manufactured into an injectable conductive gel. These hydrogels enhance antibacterial activity and reduce cytotoxicity by enhancing electrical signal transmission and simulated physiological environment within an organism (Makvandi et al., 2020). However, this composite is limited and is likely to remain a single material. For example, bone substitutes such as ceramics and porous metals do not have enough bone induction ability (González-Sánchez et al., 2015) and there is a need to constantly adjust the proportion of compounds of various materials. Therefore, the development of composite materials has great potential.

Biocompatible materials are defined as those that perform their desired functions in an organism without risking tissue damage, cytotoxicity, or rejection by the immune system, and without causing inappropriate local or systemic effects or reducing the ability of the host to respond and interact with living systems (Williams, 2008; Williams, 2017). Orthopedic biocompatibility and antibacterial materials now reduce the interference of bone and surrounding tissue homeostasis to reduce the release of any harmful products for the bone and surrounding tissue; optimize the biomechanics of bone deposition speed, quality, and environment; and improve the speed of bone adaptation and efficiency. Zhang et al. (2021), using a solvent and diethanolamine template method, prepared a corn lithium base with a typical structure of zeolitic imidazolate framework (ZIF)-8 antibacterial nanomaterials. The material has a larger specific surface area and smaller aperture, good biocompatibility and antibacterial properties, and significantly improves the antibacterial activity of E. coli and S. aureus. Antibacterial metal nanoparticles added to other materials is also a hotspot of current research, and antibacterial nano metal concentration significantly affects the surrounding tissue.

Nanoparticles, due to their small size and unique properties, are considered to have a high degree of mobility, a variety of proteins, and a strong nucleic acid structure formation in the biological environment, which may enhance or limit several cell functions (Liu et al., 2008). For example, (Liu et al., 2012) found that Ag nanoparticles added to a coating promoted osteoblast proliferation and maturation. Conversely, Zhao et al. (2011) and De Giglio et al. (2013) found that adding a coating of Ag nanoparticles increased the cytotoxicity of osteoblasts. A study using mercaptododecylphosphonic acid (MDPA) found that, after the occurrence of the AgNO₃ reaction, a MDPA/AgNO₃ nano coating forms, which prevents bacterial adhesion and biofilm formation on medical planted instruments without affecting biological compatibility (Tîlmaciu et al., 2015). Others studies used polylactic acid (PLA) and poly 3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) in the formation of a composite material by adding silver (Ag), and found that it does not significantly affect the mechanical properties and biodegradation rate, while increasing the protective barrier against bacteria, with excellent biocompatibility (Mazur et al., 2020).

Genipin (GP) is a biological crosslinking agent extracted from the fruit of Gardenia jasminoides that readily forms stable cross-networks and can provide good biocompatibility and low cytotoxicity. A novel nitrogen co-doped carbon dots (CDs)-genipin covalent coupling (N-CDs-GP) compound was synthesized by the hydrothermal method to couple quantum carbon nanomaterial CDs with GP to combine the features of excellent water solubility, high photostability, and low cytotoxicity (Chu et al., 2020). To verify the biocompatibility of N-CDs-GP, cells excited with CLSM488 and 543 nm laser pulses to an N-CD-GP aqueous solution exhibited bright green and red fluorescence, and the emission of multicolor fluorescence without any identifiable morphological defects, indicating that N-CDs-GP has reliable biocompatibility. Additionally, to verify its hemolytic activity, erythrocytes in phosphate-buffered saline were used as a negative control and erythrocytes in distilled water were used as a positive control. Compared with the negative control, erythrocytes in solution with a high concentration of N-CD exhibited a roughly normal biconcave shape, and erythrocytes in solution with N-CDs-GP exhibited a typical biconcave shape. The antibacterial effect was further demonstrated by the bacterial morphology observed by scanning electron microscopy. By comparing the S. aureus count and healing at the infection site in the mouse model, it was found that the infected site healed well after treatment and the amount of S. aureus in the infected tissue was much lower than that in the control group. A good combination of antimicrobial properties and biocompatibility of the material was obtained. Compared with traditional materials, this composite coating has good biocompatibility and antibacterial activity, and the superior features may be found in the development of potential orthopedic implants and antibacterial devices.

The fracture healing process is affected by the blood supply of the fracture, stability, and the healing site. The influence of nourishing blood vessels, once damaged, will seriously affect the healing of the fracture, and even cause infection (Claes et al., 2012). Although traditional orthopedic implants show effective bactericidal activity and are composed of antibacterial materials, they lack the ability to promote angiogenesis. Several attempts have been made to develop and promote angiogenesis of antibacterial materials to solve this problem. Recently, a study on the immobilization of vascular endothelial growth factor (VEGF) proved than repeated doses of soluble VEGF play a role in angiogenesis (Leslie-Barbick et al., 2009; Zhang et al., 2022). VEGF, used in the development of advanced bioactive scaffolds, not only promotes new bone formation and growth, but also induces angiogenesis (Kim et al., 2012; Wu et al., 2020).

Wu et al. (2013) prepared a load of ibuprofen copper-MBG (Cu-MBG) stents which, together with ion extract, stimulate human bone marrow stromal cells (hBMSCs) hypoxia inducing factor (HIF)-1 and the expression of VEGF to enhance angiogenesis and, through the relevant gene expression, improve bone stimulation of osteoblast. The sustained drug release load, and the presence of Cu₂₊, ensured good antibacterial properties (Borkow et al., 2008). Other studies have shown that cellulose nano fibrosis (NFC) and the formation of Cu-MBG composite aerogel materials enhance angiogenesis (Wang et al., 2016). A biomass chitosan hydrogel micro needle array (CSMNA) was recently developed with VEGF by temperature sensitive hydrogel coating in CSMNA pores. The intelligent release of drugs can be controlled by the temperature increase caused by the local inflammatory response, which can promote inflammation inhibition, collagen deposition, angiogenesis, and tissue regeneration in the process (Chi et al., 2020).

In original titanium implants, vulnerable to bacterial infection, the effective method to reduce implant failure is to modify the surface of the implant, making it suitable for bone forming cells with simultaneous anti-infective properties. Titanium is combined with the substrate surface by covalent grafting of dopamine, carboxymethyl chitosan (CMCS) or hyaluronic acid-catechins, and VEGF coupling for functional polysaccharide transplantation. CMCS and functional titanium promotes angiogenesis, strengthens the function of osteoblasts, and simultaneously reduces bacterial adhesion (Hu et al., 2010). Similarly, synthesis polymers can be easily coated on polydopamine modification of the titanium surface, and loaded with antibiotics for slow release (Zeng et al., 2018). These features of implantable medical devices provide a new function to prevent infections by the promotion of angiogenesis.

With the increase of orthopedic implant material use, we face the serious situation of bone infection treatment, and urgently need to improve the osteogenic and antimicrobial capabilities of implantable antimicrobial materials in the application of orthopedic implants, as biological complications such as insufficient bone mass and postoperative infection lead to treatment failure. The implantable material is in direct contact with the bone interface, and the promotion of osteogenesis is key for the antibacterial material to exert its physiological function. However, traditional implantable materials do not have this capability. Emerging antibacterial osteogenesis multifunctional materials are designed to compensate for these shortcomings, in both the osteogenesis phase and in the long-term support of the local structure.

Gallium doped materials enhance the osteogenesis effect in biologically active substances and improve antibacterial activity (Verron et al., 2012; Sanchez-Salcedo et al., 2018). Gallium added to biomaterials holds great potential to treat bone-related diseases, because it can be effectively transferred to the required area at a controlled rate. In addition, it can be used as a potential alternative to antibiotics, as well as in the initial and late stages of wound healing to inhibit infection (Keenan et al., 2017; Crunkhorn, 2018).

Chen et al. (2022) used alkali heat treatment of titanium on the implant surface layered with an Mg-Ga double oxide nano coating. The coating significantly promoted the autophagy activity of mesenchymal stem cells, induced osteogenetic differentiation, and suppressed the generation of osteoclasts. In addition, the researchers found that the zinc mixed with ZnO₂ delicately balanced the in antibacterial function and osteogenesis (Cheng et al., 2015). The titanium metal implant surface formed a nanostructure coating that stimulated macrophage elongation, promoted the production of proinflammatory cytokines, and induced macrophages to anti-inflammatory M2 phenotypes. This promote osteogenesis differentiation, such as cell adhesion, alkaline phosphatase activity, mineralization of the extracellular matrix, and raised the osteogenesis related gene expression (Chen et al., 2021; Jiang et al., 2022). Zhao et al. (2019) showed that the plasma electrolytic oxidation porous Mg-TiO₂ covered Ti surface not only promote osteoblast adhesion, proliferation, and differentiation, but also inhibited Staphylococcus engraftment and growth.

The hydrophilic nature of graphene can lead to enhanced expression of osteogenic genes. One study assembled titanium alloy nanomaterials by using graphitic diyne (GDY) and titanium combined to form titanium alloy nanomaterials. GDY enhances the osteogenic effect by promoting osteoblast adhesion to the nanomaterials, and UV irradiation (365 nm) leads to more ROS production for sterilization (Figure 4A) (Wang et al., 2020b). Bacterial colony plate counts were performed to detect colonies in an implanted femoral grinding solution of an infected model. It was found that the TiO₂/GDY + UV group had significantly less MRSA than the TiO₂ + UV group (Figures 4B, C). By SEM scanning of the implanted nanomaterials, the cells appeared to adhere firmly to the surface of the GDY-modified material. After observing the pathological tissue of femoral bone infection using HE staining, the investigators found that the TiO₂+UV group had obviously infected and necrotic areas in the bone defect area (orange dashed line), while the TiO₂/GDY + UV group had little inflammatory cell infiltration in the bone defect area. Multifunctional bone-promoting antibacterial materials have been intensively studied, and still have great potential.

Promotion of the blood-coagulation function of antibacterial material for trauma care is very important, as it prevents acute bleeding to save lives, and prevents bacterial proliferation in the early stage of open or acute tissue injury (Alam et al., 2012; Yang et al., 2021). To promote organism coagulation (Wang et al., 2019b), antibacterial hemostatic materials absorb moisture, enrich the blood components, initiate the endogenous or exogenous coagulation system, and induce rapid solidification, eventually forming a blood clot to limit bleeding (Yan et al., 2017; Krishnadoss et al., 2019).

Mesoporous silica is an emerging hemostatic material that absorbs water, promotes clotting factor activation, and assists in biodegradation (Dai et al., 2009). According to a study (Shen et al., 2020), cationic groups function to make use of the antibacterial properties of the polymer, with mesoporous silica coordination of superabsorbent hydrogel formation showing good potential utilization value. Cationic polymers absorb the negatively charged red blood cells, blood fibrinogen, and plasma protein, which constitute the hemostatic properties of cationic polymers (Qin et al., 2020). Structure modifications do not usually change the basic properties of the cationic polymer, but introduce a new function. For example, modified cationic chitosan has improved antibacterial ability and hemostatic properties (Sahariah and Másson, 2017). Lu et al. (2017) found that incorporation of Ag/ZnO further enhances the capacity of cationic chitosan blood coagulation, because Ag denatures the anticoagulant protein, thus affecting the organism coagulation pathway (Kapadia, 2005). The hemostatic activity of medical nanoscale antibacterial fibers has garnered wide attention because the characteristics and chemical properties of these fibers promote blood clotting (Fischer et al., 2008).

Blood clot formation is composed of platelet activation and aggregation and a multi-step coagulation cascade, which leads to the aggregation of fibrinogen and the formation of a crosslinked fibrin fiber network. The nano fiber structure of can be affected by rapid dehydration, as blood acts as a molecular sieve by producing a mechanical barrier, leading to blood clots. This process accelerates the coagulation cascade and promotes hemostasis (Giri Dev and Hemamalini, 2018). The excellent antiplatelet adhesion ability of polymers in the formation of nanofibers will trigger increased platelet adhesion and activation (Nakielski and Pierini, 2019). For example, when using chitosan nano powder (NCTS) in PLA, with the help of electrostatic spinning into nanofibers, the NCTS/PLA activated partial thrombin time is longer than in the PLA; more NCTS lead to a longer clotting time (Dong et al., 2018). In addition (Cheng et al., 2020), used electrostatic spinning to identify uniform distribution of silver nanoparticles (Ag-NPs) in PLA and gelatin (Gel) composite fibers forming inside the PLA/Gel/Ag composite. This showed the promotion between the proliferation and induction of osteogenesis of the mesenchymal stem cells, with good bone conductibility and hemostatic properties. Traditional hemostatic strategy depends on the use of blood components, such as fibrinogen and thrombin. These components come with a high cost and short shelf life. To overcome these limitations, the potent protease, thrombin, should be avoided. Qin et al. (2015b) photoconjugated thrombin-receptor-agonist-peptide-6 (TRAP6) onto cyto-compatible polyvinyl alcohol hydrogels via efficient thiol-norbornene photoconjugation, which preserve the platelet-activating activity, for safe hemostasis and infection prevention. Introducing antibacterial and procoagulant activities into nanofibers is a focus of current research regarding procoagulant antibacterial materials.

Recently, studies have used carboxymethyl-copper-carageen glue mixed with poly (vinyl alcohol) nanofibers (PVA-CMKC), to increase blood clotting and antibacterial activity, and promote platelet adhesion and activation (Madruga et al., 2021). Because the nanofibers of CMKC have rigid cell walls, neither Gram-positive nor Gram-negative bacteria readily adapt to the nanoscale features, which may kill bacteria on the nanostructured surface (Madruga et al., 2020).

Traditional antibacterial strategy is divided into two kinds: one is to kill adhering bacteria through the material’s natural bactericidal properties or fungicides (Xue et al., 2015; Pinho and Piedade, 2020); and the other bacteria-repellent material works through its properties that prevent bacterial adherence (Song et al., 2015; Moradi et al., 2016; Ramachandran et al., 2019). However, both types have limitations. The bactericidal properties or fungicide kill the bacteria, but the debris usually pile up at the local site, causing a lowering in germicidal efficacy. It is possible that this provide nutrients for subsequent bacterial adhesion and causes an immune response. In contrast, flooding the bacterial material without sterilization causes adhesion of the bacteria to the surface, which grows into a biofilm. Therefore, combining the functions of repellent and sterilization on one surface is the focus of current research. Bacterial killing and the release of specific functions may interfere with each other, and usually requires intelligent switching in function. These smart antibacterial surfaces kill the bacteria attached to the surface, and then switch to control the temperature, pH, humidity, or other external factors that stimulate the release of dead bacteria and its debris. This maintains kill efficiency (Wei et al., 2017).