Novel Bionic Topography with MiR-21 Coating for Improving Bone-Implant Integration through Regulating Cell Adhesion and Angiogenesis.

Implant loosening is still the major form of the failure of artificial joints. Herein, inspired by the operculum of the river snail, we prepared a novel bionic micro/nanoscale topography on a titanium surface. This bionic topography promoted early cell adhesion through up-regulating the expression of ITG α5ß1 and thus accelerated the following cell spreading, proliferation, and differentiation. Moreover, a miR-21 coating, which promoted the angiogenic differentiation of MSCs, was fabricated on the bionic topography. Benefiting from both bionic micro/nanoscale topography and miR-21, blood vessel growth and bone formation and mineralization around the implant, as well as bone-implant bonding strength, were significantly improved. Collectively, the present study highlights the combination of the bionic micro/nanoscale topography and miR-21 on promoting cell adhesion and angiogenic differentiation and improving in vivo angiogenesis and bone-implant osseointegration. This work provides a new train of thought propelling the development of implants for potential application in the orthopedics field.

Electrophoretic Deposited Stable Chitosan@MoS2 Coating with Rapid In Situ Bacteria-Killing Ability under Dual-Light Irradiation.

Developing in situ disinfection methods in vivo to avoid drug-resistant bacteria and tissue toxicity is an urgent need. Here, the photodynamic and photothermal properties of the chitosan-assisted MoS2 (CS@MoS2 ) hybrid coating are simultaneously inspired to endow metallic Ti implants with excellent surface self-antibacterial capabilities. This coating, irradiated by only 660 nm visible light (VL) for 10 min, exhibits an antibacterial efficacy of 91.58% and 92.52% against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively. The corresponding value is 64.67% and 57.44%, respectively, after irradiation by a single 808 nm near infrared light for the same amount of time. However, the combined irradiation using both lights can significantly enhance the efficiency up to 99.84% and 99.65% against E. coli and S. aureus, respectively, which can be ascribed to the synergistic effects of photodynamic and photothermal actions. The former produces single oxygen species under 660 nm VL while the latter induces a rise in temperature of implants, which can inhibit the growth of both E. coli and S. aureus. The introduction of CS can also promote the biocompatibility of implants, which provides a facile, rapid, and safe in situ bacteria-killing method in vivo without needing a second surgery.

In Situ Disinfection through Photoinspired Radical Oxygen Species Storage and Thermal-Triggered Release from Black Phosphorous with Strengthened Chemical Stability.

Photodynamic therapy (PDT) utilizing light-induced reactive oxygen species (ROS) is a promising alternative to combat antibiotic-resistant bacteria and biofilm. However, the photosensitizer (PS)-modified surface only exhibits antibacterial properties in the presence of light. It is known that extended photoirradiation may lead to phototoxicity and tissue hypoxia, which greatly limits PDT efficiency, while ambient pathogens also have the opportunity to attach to biorelevant surfaces in medical facilities without light. Here, an antimicrobial film composed of black phosphorus nanosheets (BPSs) and poly (4-pyridonemethylstyrene) endoperoxide (PPMS-EPO) to control the storage and release of ROS reversibly is introduced. BPS, as a biocompatible PS, can produce high singlet oxygen under the irradiation of visible light of 660 nm, which can be stably stored in PPMS-EPO. The ROS can be gradually thermally released in the dark. In vitro antibacterial studies demonstrate that the PPMS-EPO/BPS film exhibits a rapid disinfection ability with antibacterial rate of 99.3% against Escherichia coli and 99.2% against Staphylococcus aureus after 10 min of irradiation. Even without light, the corresponding antibacterial rate reaches 76.5% and 69.7%, respectively. In addition, incorporating PPMS significantly improves the chemical stability of the BPS.

A novel antibiotic: the antimicrobial effects of CFBSA and its application on electronspun wound dressing.

N-chloro-N-fluorobenzenesulfonylamide (CFBSA), was a novel chlorinating reagent, which exhibits potential antibacterial activities. In this study, CFBSA was confirmed as a wide-broad antimicrobial and bactericidal drug against different gram-negative bacteria, gram-positive bacteria and fungi, while it was found to have low cytotoxicity for eukaryotic cells. In addition, microorganism morphology assay and oxidative stress test was used to determine the antimicrobial mechanisms of CFBSA. According to the results, CFBSA probably had a target on cell membrane and killed microorganism by disrupting its cell membrane. Then, CFBSA was first combined with poly(L-lactide-co-caprolactone) (PLCL)/SF via electrospinning and applied in wound dressings. The characterization of different PLCL/SF of CFBSA-loaded nanofibrous mats was investigated by SEM, water contact angle, Fourier transform infrared spectroscopy, cell compatibility and antimicrobial test. CFBSA-loaded PLCL/SF nanofibrous mats showed excellent antimicrobial activities. In order to balance of the biocompatibility and antibacterial efficiency, SP-2.5 was selected as the ideal loading concentration for further application of CFBSA-loaded PLCL/SF. In conclusion, the electrospun CFBSA-loaded PLCL/SF nanofibrous mat with its broad-spectrum antimicrobial and bactericidal activity and good biocompatibility showed enormous potential for wound dressing.

Rapid and Highly Effective Noninvasive Disinfection by Hybrid Ag/CS@MnO2 Nanosheets Using Near-Infrared Light.

A bacterial infection on the surface of medical apparatus and instruments as well as artificial implants is threatening human health greatly. Antibiotics and traditional bacterial-killing agents, even silver nanoparticles, can induce bacterial resistance during long-term interaction with bacteria. Hence, rapid surface sterilization and prevention of bacterial infection in the long term are urgent for biomedical devices, especially for artificial implant materials. Herein, a hybridized chitosan (CS), silver nanoparticles (AgNPs), and MnO2 nanosheets coating was designed on the surface of titanium plates, which can ensure the implants a rapid and highly effective antibacterial efficacy of 99.00% against Staphylococcus aureus ( S. aureus) and 99.25% against Escherichia coli ( E. coli) within 20 min of 808 nm near-infrared light (NIR) irradiation. The exogenous NIR irradiation can trigger the MnO2 nanosheets to produce enough hyperthermia within 10 min, which can combine with a low concentration of prereleased Ag+ from the coating to achieve superior antimicrobial efficacy through synergistic effects. In contrast, either prereleased Ag ions or a photothermal effect alone can achieve much lower antibacterial efficiency under the same concentration, i.e., 24.00% and 30.01% for the former and 30.00% and 42.54% for the later toward S. aureus and E. coli, respectively. The possible cytotoxicity of coatings could be eliminated owing to the low concentration of AgNPs and chitosan encapsulation. Thus, the novel bifunctional coating Ag/CS@MnO2 can exhibit great potential in deep site disinfection of Ti implants through the synergy of prereleased Ag ions and a photothermal effect within a short time.

Enhancing the antibacterial efficacy of low-dose gentamicin with 5 minute assistance of photothermy at 50 °C.

Implant materials are prone to bacterial infections and cause serious consequences, while traditional antibiotic therapy has a long treatment cycle and even causes bacterial resistance. In this work, a photothermal therapy (PTT) assisted drug release system has been developed on the implant surface for in situ rapid disinfection under 808 nm light irradiation within a short time, in which gentamicin (Gent) is loaded by polyethylene glycol (PEG) modified molybdenum disulfide (MoS2) on Ti surface, and then encapsulated with chitosan (CS) (CS/Gent/PEG/MoS2-Ti). The hyperthermia produced by the coatings irradiated by 808 nm near-infrared (NIR) light can not only accelerate the local release of Gent, but also reduce the activity of bacteria, which makes it easy for these locally released drugs to enter the interior of the bacteria to inhibit the protein synthesis and destroy the cell membrane. When maintained at 50 °C for 5 min under NIR irradiation, this system can achieve an antibacterial efficacy of 99.93% and 99.19% against Escherichia coli and Staphylococcus aureus, respectively. By contrast, even after treatment for 120 min, only a 93.79% antibacterial ratio can be obtained for Gent alone. This is because hyperthermia produced from the coatings during irradiation can assist antibiotics in killing bacteria in a short time. Even under a low dose of 2 µg mL-1, the photothermal effect assisted gentamicin can achieve an antibacterial efficacy of 96.86% within 5 min. In vitro cell culture shows that the modified surface can facilitate cell adhesion, spreading and proliferation. The 7 day subcutaneous infection model confirms that the prepared surface system can exhibit a much faster sterilization and tissue reconstruction than the control group with light assistance. Compared with the traditional drug release system, this photothermy controlled drug-loaded implant surface system can not only provide rapid and high-efficiency in situ sterilization, but also offer long-term prevention of local bacterial infection.

"Imitative" click chemistry to form a sticking xerogel for the portable therapy of bacteria-infected wounds.

Xerogels usually possess a stable structure and have a low swelling rate due to their inferior dynamics. Herein, a xerogel was synthesized by "imitative" click chemistry based on lipoic acid for picking up bacteria from wound sites, and thus accelerating tissue repair. The cross-linking structure of disulfide and thioether inside the xerogel not only exhibited good ductility and intrinsic self-healing performance, but also showed superior biocompatibility. The xerogel captured more than 60% of the bacteria Staphylococcus aureus via strong electrostatic adsorption in the colonies with a bacteria count of 106. In addition, this xerogel can stick to the skin in the form of patches in the wounds during therapy for wound healing and can be easily stripped from the skin after treatment, which makes it appropriate for the portable therapy of bacteria-infected wounds in emergency circumstances.

Construction of perfluorohexane/IR780@liposome coating on Ti for rapid bacteria killing under permeable near infrared light.

Near infrared (NIR) light induced photodynamic antibacterial therapy (PDAT) is a promising antibacterial technique in rapid in situ disinfection of bacterially infected artificial implants due to its penetration ability into tissues. However, the lower oxygen content in vivo may restrict the yields of reactive oxygen species (ROS), thus reducing the antibacterial efficacy of PADT significantly. Herein, liposome encapsulated photosensitizers (PS), IR780 and perfluorohexane (PFH), have been constructed on the surface of Ti implants via a covalent linkage to overcome this issue. Thanks to the high oxygen capacity of PFH, more ROS can be generated during NIR irradiation regardless of the low content of oxygen in vivo. As a result, in vitro tests demonstrated that 15 minutes of 808 nm near-infrared irradiation could achieve a high antibacterial efficacy of 99.62% and 99.63% on the implant surface against Escherichia coli and Staphylococcus aureus, respectively. By contrast, the PDAT system without PFH modification shows a lower antibacterial efficacy (only 66.54% and 48.04%, respectively). In addition, this enhanced PDAT system also possesses great biocompatibility based on the in vitro and in vivo subcutaneous assays. This surface system makes it possible for rapid bacteria-killing in artificial implants that have been implanted in vivo under local conditions with lower oxygen content.

Controlled and sustained drug release performance of calcium sulfate cement porous TiO2 microsphere composites.

BACKGROUND: Calcium sulphate cement (CSC) is widely used as an osteoconductive biomaterial in bone repair and regeneration. PURPOSE: In this study, porous TiO2 microspheres were added to CSC to achieve a controlled and sustained drug (gentamicin) release. METHODS: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), and Brunauer-Emmett-Teller (BET) surface area analysis were conducted to analyse the morphology, phase composition, and surface area of the TiO2 micro-spheres and composite cements. In addition, the injection time, compressive strength, degradation behaviour, and antibacterial ability of the composite cements were examined during in vitro degradation. Gentamicin release profile was recorded using an ultraviolet spectrophotometer. RESULTS: The results revealed the excellent drug loading ability of the TiO2 microspheres. The addition of TiO2 microspheres improved the injectability and compressive strength of the composite cements, the maximum value of which was achieved at a TiO2 loading of 5 wt.%. When immersed in simulated body fluid (SBF), the composite cements doped with TiO2 microspheres were observed to release gentamicin in a stable and sustained manner, especially in the latter stages of in vitro degradation. During degradation, CSC doped with TiO2 microspheres exhibited a typical apatite-like behaviour. Further, antibacterial analysis showed that CSC doped with TiO2 microspheres exhibited long-term antibiotic activity. CONCLUSION: Thus, as an effective sustained-release formulation material, TiO2 microspheres show a great potential for application in bone cements.

Nano Ag/ZnO-Incorporated Hydroxyapatite Composite Coatings: Highly Effective Infection Prevention and Excellent Osteointegration.

Interfacial characteristics play an important role in infection prevention and osteointegration of artificial bone implants. In this work, both Ag nanoparticles (AgNPs) and ZnO NPs are incorporated into hydroxyapatite (HA) nanopowders and deposited onto Ti6Al4V (Ti6) implants by laser cladding. The composite coatings possess a hierarchical surface structure with homogeneous distributions of Ag and ZnO. The Ag and ZnO NPs that are immobilized by laser cladding ensure long-term and gradual release of Ag and Zn ions at low cumulative concentrations of 36.2 and 56.4 µg/L after immersion for 21 days. A large concentration of Ag released initially increases the cytotoxicity but the large initial ZnO content enhances the cell viability and osteogenetic ability. The nano Ag/ZnO-embedded HA coating (Ag/ZnO/HA = 7:3:90 wt %, namely Ag7ZnO3HA) exhibits optimal antibacterial efficacy and osteogenetic capability, as exemplified by the broad spectrum antibacterial efficacy of 96.5 and 85.8% against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively, together with enhanced osteoinductivity with higher alkaline phosphatase (ALP) activity of 134.60 U/g protein compared to 70.79 U/g protein for the untreated implants after culturing for 7 days. The rabbit femoral implant model further confirms that the optimized composite coating accelerates the formation of new bone tissues indicating 87.15% of the newly formed bone area and osteointegration showing 83.75% of the bone-implant contact area even in the presence of injected S. aureus. The laser-cladded Ag7ZnO3HA composite coatings are promising metallic implants with excellent intrinsic antibacterial activity and osteointegration ability.

Controlled-temperature photothermal and oxidative bacteria killing and acceleration of wound healing by polydopamine-assisted Au-hydroxyapatite nanorods.

Since skin wounds are subject to bacterial infection and tissue regeneration may be impeded, there is demand for biomaterials that possess rapid bactericidal and tissue repair capability. Herein we report in situ promotion of wound healing by a photothermal therapy (PTT) assisted nanocatalytic antibacterial system utilizing a polydopamine (PDA) coating on hydroxyapatite (HAp) incorporated with gold nanoparticles (Au-HAp). The PDA@Au-HAp NPs produce hydroxyl radicals (OH) via catalysis of a small concentration of H2O2 to render bacteria more vulnerable to the temperature change. The antibacterial efficacy against Escherichia coli and Staphylococcus aureus is 96.8% and 95.2%, respectively, at a controlled photo-induced temperature of 45 °C that causes no damage to normal tissues. By combining catalysis with near-infrared (NIR) photothermal therapy, the PDA@Au-HAp NPs provide safe, rapid, and effective antibacterial activity compared to OH or PTT alone. In addition, this system stimulates the tissue repairing-related gene expression to facilitate the formation of granulation tissues and collagen synthesis and thus accelerate wound healing. After the 10-day treatment of skin wounds in vivo, PDA@Au-HAp group exhibits quicker recovery than the control group and both sterilization and healing are completed after the 10-day treatment. STATEMENT OF SIGNIFICANCE: This study presents in situ promotion of wound healing by a low-temperature photothermal therapy (PTT) assisted nanocatalytic antibacterial system utilizing a polydopamine (PDA) coating on hydroxyapatite (HAp) incorporated with gold nanoparticles (Au-HAp). The PDA@Au-HAp NPs produce hydroxyl radicals (OH) via catalysis of a small concentration of H2O2 to render bacteria more vulnerable to temperature change. After irradiation by 808 nm laser, the antibacterial efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) is 96.8% and 95.2%, respectively, at a low photo-induced temperature of 45 °C which causes no damage to normal tissues. In addition, this system stimulates the tissue repairing-related gene expression to facilitate the formation of granulation tissues and collagen synthesis and accelerate wound healing.

Nanosized strontium substituted hydroxyapatite prepared from egg shell for enhanced biological properties.

The fabrication and application of bioactive hydroxyapatite has always been a research hot spot in the fields of orthopaedics. Now it is common to use calcium (Ca) salt as Ca2+ source to synthesise hydroxyapatite. And egg shell could be another promising raw material as Ca2+ source, which is not only economical but also biogenic. In this study, egg shell (ES)-hydroxyapatite was prepared by using egg shells via hydrothermal method. Furthermore, ES-Sr hydroxyapatite was synthesized by incorporation of bioactive element strontium (Sr2+) into ES-hydroxyapatite. The in vitro experiment showed that compared with hydroxyapatite, ES-hydroxyapatite showed better biological performances, which could be attributed to the trace elements in egg shell, such as magnesium (Mg). And the incorporation of Sr2+ could further enhance the bioactivity. These results indicated that apatite with high biological activity, which had great application prospects in orthopedics, could be produced by egg shells and the incorporation of Sr2+.

Rapid Biofilm Eradication on Bone Implants Using Red Phosphorus and Near-Infrared Light.

Bone-implant-associated infections are common after orthopedic surgery due to impaired host immune response around the implants. In particular, when a biofilm develops, the immune system and antibiotic treatment find it difficult to eradicate, which sometimes requires a second operation to replace the infected implants. Most strategies have been designed to prevent biofilms from forming on the surface of bone implants, but these strategies cannot eliminate the biofilm when it has been established in vivo. To address this issue, a nonsurgical, noninvasive treatment for biofilm infection must be developed. Herein, a red-phosphorus-IR780-arginine-glycine-aspartic-acid-cysteine coating on titanium bone implants is prepared. The red phosphorus has great biocompatibility and exhibits efficient photothermal ability. The temperature sensitivity of Staphylococcus aureus biofilm is enhanced in the presence of singlet oxygen (1 O2 ) produced by IR780. Without damaging the normal tissue, the biofilm can be eradicated through a safe near-infrared (808 nm) photothermal therapy at 50 °C in vitro and in vivo. This approach reaches an antibacterial efficiency of 96.2% in vivo with 10 min of irradiation at 50 °C. Meanwhile, arginine-glycine-aspartic-acid-cysteine decorated on the surface of the implant can improve the cell adhesion, proliferation, and osteogenic differentiation.

The synergistic effect of strontium-substituted hydroxyapatite and microRNA-21 on improving bone remodeling and osseointegration.

Surgical failure, mainly caused by loosening implants, causes great mental and physical trauma to patients. As the population ages, improving the physicochemical properties of implants to achieve favourable osseointegration will continue to be the focus of future research. Herein, we fabricated a titanium (Ti)-based SrHA/miR-21 composite coating that was generated by hydrothermal deposition of SrHA followed by miR-21 nanocapsule immobilisation. Both SrHA nanoparticles with good superhydrophilicity and miR-21 nanocapsules with uniform sizes were distributed evenly on the surface of Ti. In vitro experiments revealed that the composite coating was beneficial for osteoblast proliferation, differentiation and mineralization. In vivo evaluations demonstrated that this coating could not only promote the expression of the angiogenic factor CD31 but also enhance the expression of osteoblastic genes to facilitate angio-osteogenesis. In addition, the composite coating also showed a decreased RANKL expression compared with the miR-21 coating. As a result, the SrHA/miR-21 composite coating promoted new bone formation and mineralization and thus enhanced osseointegration and bone-implant bonding strength. Therefore, this method provides a new strategy for bone repair.

Construction of poly(lactic-co-glycolic acid)/ZnO nanorods/Ag nanoparticles hybrid coating on Ti implants for enhanced antibacterial activity and biocompatibility.

Poly(lactic-co-glycolic acid)/Ag/ZnO nanorods coating were successfully prepared on the surface of Ti metallic implants using a hydrothermal method and subsequent spin-coating of mixtures of poly(lactic-co-glycolic acid) and silver nanoparticles. The poly(lactic-co-glycolic acid)/Ag/ZnO nanorods coating exhibited excellent antibacterial efficacy of over 96% against both Staphylococcus aureus and Escherichia coli when the initial content of Ag nanoparticles was over 3wt%. In addition, the release of both silver and zinc could last for over a hundred days due to the enwrapping of poly(lactic-co-glycolic acid). Proliferation of mouse calvarial cells exhibited minimal cytotoxicity on the poly(lactic-co-glycolic acid)/Ag/ZnO coating with an initial content of Ag nanoparticles of 1wt% and 3wt%, while it inhibited cell proliferation once this value was increased to 6wt%. The results revealed that this poly(lactic-co-glycolic acid)/Ag/ZnO composite could provide a long-lasting antibacterial approach and good cytocompatibility, thus exhibiting considerable potential for biomedical application in orthopedic and dental implants with excellent self-antibacterial activity and good biocompatibility.

Atomic layer deposited ZrO2 nanofilm on Mg-Sr alloy for enhanced corrosion resistance and biocompatibility.

The biodegradability and good mechanical property of magnesium alloys make them potential biomedical materials. However, their rapid corrosion rate in the human body's environment impairs these advantages and limits their clinical use. In this work, a compact zirconia (ZrO2) nanofilm was fabricated on the surface of a magnesium-strontium (Mg-Sr) alloy by the atomic layer deposition (ALD) method, which can regulate the thickness of the film precisely and thus also control the corrosion rate. Corrosion tests reveal that the ZrO2 film can effectively reduce the corrosion rate of Mg-Sr alloys that is closely related to the thickness of the film. The cell culture test shows that this kind of ZrO2 film can also enhance the activity and adhesion of osteoblasts on the surfaces of Mg-Sr alloys. STATEMENT OF SIGNIFICANCE: The significance of the current work is to develop a zirconia nanofilm on biomedical MgSr alloy with controllable thickness precisely through atomic layer deposition technique. By adjusting the thickness of nanofilm, the corrosion rate of Mg-Sr alloy can be modulated, thereafter, the degradation rate of Mg-based alloys can be controlled precisely according to actual clinical requirement. In addition, this zirconia nanofilm modified Mg-Sr alloys show excellent biocompatibility than the bare samples. Hence, this work provides a new surface strategy to control the degradation rate while improving the biocompatibility of substrates.

The controlled drug release by pH-sensitive molecularly imprinted nanospheres for enhanced antibacterial activity.

In this study, we prepared pH-sensitive hybrid nanospheres through the implementation of a facile molecularly imprinted polymer (MIP) technique combined with a UV-initiated precipitation polymerization method using vancomycin (VA) for the templates. During the course of this investigation, both 2-hydroxyethyl methacrylate (HEMA) and 2-(diethylamino) ethyl methacrylate (DEAEMA) were utilized as the functional monomers, while ethylene glycol dimethacrylate (EGDMA) was used as a cross-linker. The obtained MIP nanospheres exhibited well-controlled particle size, with a drug loading capacity of about 17%, much higher than that of the non-imprinted polymer (NIP) nanospheres (5%). In addition, the VA loading quantity was closely correlated with the dosage of the cross-linking agent, and the MIP nanospheres exhibited a slower and more controlled VA release rate than the NIP nanospheres. Moreover, these MIP nanospheres were sensitive to pH values, and consequently showed an increasing release rate of VA as the pH level was decreased. The VA-loaded MIP nanospheres showed the higher antibacterial ratio of over 92% against Staphylococcus aureus (S. aureus) while the NIP nanospheres were friendly to S. aureus. These MIP nanospheres can be promising for targeting drug delivery system to achieve specific therapies such as preventing bacterial infections and killing cancer cells without damaging health cells and tissues.

The Incorporation of Strontium in a Sodium Alginate Coating on Titanium Surfaces for Improved Biological Properties.

Orthopedic implant failure is mainly attributed to the poor bonding of the implant to bone tissue. An effective approach to minimize the implant failure would be modifying the surface of the implant. Strontium (Sr) can stimulate the proliferation and differentiation of osteoblasts and reduce the activity of osteoclasts. In this study, a titanium (Ti) surface was successively functionalized by covalently grafting dopamine, sodium alginate (SA), and Sr2+ via the electrostatic immobilization method. The as-prepared coatings on the Ti surface were characterized by using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), and contact angle. The results indicated that the Sr-incorporated coatings were successfully prepared and that Sr distributed uniformly on the surface. A long-lasting and sustained Sr release had been observed in Sr2+ release studies. The Ti/DOPA/SA/Sr exhibited little cytotoxicity and a robust effect of Sr incorporation on the adhesion and spreading of MG63 cells. The proliferation and alkaline phosphatase (ALP) activity of MG63 cells were enhanced by immobilizing Sr2+ on the SA-grafted Ti. The Sr-containing coatings, which displayed excellent biocompatibility and osteogenic activity, may provide a promising solution for promoting the tissue integration of implants.

Balancing Bacteria-Osteoblast Competition through Selective Physical Puncture and Biofunctionalization of ZnO/Polydopamine/Arginine-Glycine-Aspartic Acid-Cysteine Nanorods.

Bacterial infection and lack of bone tissue integration are two major concerns of orthopedic implants. In addition, osteoinductivity often decreases and toxicity may arise when antibacterial agents are introduced to increase the antibacterial ability. Here hybrid ZnO/polydopamine (PDA)/arginine-glycine-aspartic acid-cysteine (RGDC) nanorod (NR) arrays are designed and prepared on titanium (Ti) implants to not only enhance the osteoinductivity but also effectively kill bacteria simultaneously, which are ascribed to the selective physical puncture and the biofunctionalization of ZnO/PDA/RGDC nanorods during the competition between bacteria and osteoblasts. That is, owing to the much larger size of osteoblasts than bacteria, the hybrid NRs can puncture bacteria but not damage osteoblasts. Meanwhile, the cytocompatibility can be enhanced through the suppression of both reactive oxygen species and higher Zn2+ concentration by the covering of PDA and RGDC. The in vitro results confirm the selective puncture of the bacterial membrane and the better osteoinductivity. In vivo tests also show much higher antibacterial efficacy of the hybrid NRs with far less amounts of lobulated neutrophils and adherent bacteria in the surrounding tissues. In addition, the hybrid NRs also accelerate formation of new bone tissues (20.1% higher than pure Ti) and osteointegration between implants and newly formed tissues (32.0% higher than pure Ti) even in the presence of injected bacteria. This work provides a surface strategy for designing implants with desirable ability of osseointegration and infection prevention simultaneously, which will exhibit tremendous clinical potential in orthopedic and dental applications.

Incorporation of silver and strontium in hydroxyapatite coating on titanium surface for enhanced antibacterial and biological properties.

Implant-related infection in primary total joint prostheses has attracted considerable research attention. As a measure to improve the antimicrobial properties of implant materials, silver (Ag) was incorporated into calcium phosphate (CaP) coatings on Titanium (Ti) via a hydrothermal method. Further, strontium (Sr) was added as a binary dopant to reduce the cytotoxicity of Ag in the coatings. Results showed that the CaP coatings were uniformly deposited on Ti with enhanced hydrophilicity and nanoscale surface roughness. Moreover, cell adhesion, proliferation, and differentiation were improved after the CaP coating deposition. The antibacterial properties of the coatings were distinctly improved by the incorporation of Ag, but the cell proliferation and differentiation were significantly decreased. Owing to the incorporation of Sr, the Ag-CaP coatings were able to effectively counteract the negative effects of Ag while maintaining good antibacterial properties. In summary, hydrothermally deposited CaP coatings doped with Ag and Sr exhibit excellent biocompatibility and antimicrobial activity. Thus, such co-doped CaP coatings have considerable potential for orthopaedic implant modification.