Near-Infrared Emissive Cascaded Artificial Light-Harvesting System with Enhanced Antibacterial Efficiency.

Combination of platinum(II) metallacycles and photodynamic inactivation presents a promising antibacterial strategy. Herein, a cascaded artificial light-capturing system is developed in which an aggregation-induced emission-active platinum(II) metallacycle (PtTPEM) is utilized as the antenna, sulforhodamine 101 (SR101) as a key conveyor, and the near-infrared emissive photosensitizer Chlorin-e6 (Ce6) as the final energy acceptor. The well-dispersed Ce6 in the proximity of energy donors not only avoids self-quenching in the physiological environment but also contributes to energy transfer from donor to acceptor, thereby significantly improving the 1 O2 generation ability of the light-harvesting system under white light irradiation. By integrating the platinum(II) metallacycle and 1 O2 , a more efficient synergistic antibacterial effect is achieved at low concentrations, along with a significant decrease in dark toxicity caused by PtTPEM.

Redox Homeostasis Strategy for Inflammatory Macrophage Reprogramming in Rheumatoid Arthritis Based on Ceria Oxide Nanozyme-Complexed Biopolymeric Micelles.

The synovial tissues under rheumatoid arthritis conditions are usually infiltrated by inflammatory cells, particularly M1 macrophages with aberrant redox homeostasis, which causes rapid deterioration of articular structure and function. Herein, we created an ROS-responsive micelle (HA@RH-CeOX) through the in situ host-guest complexation between ceria oxide nanozymes and hyaluronic acid biopolymers, which precisely delivered nanozyme and clinically approved rheumatoid arthritis drug Rhein (RH) to proinflammatory M1 macrophage populations in inflamed synovial tissues. The abundant cellular ROS could cleave the thioketal linker to trigger the release of RH and Ce. Specifically, the Ce3+/Ce4+ redox pair could present SOD-like enzymatic activity to rapidly decompose ROS and alleviate the oxidative stress in M1 macrophages, while RH could inhibit the TLR4 signaling in M1 macrophages, both of which could act in a concerted manner to induce their repolarization into anti-inflammatory M2 phenotype to ameliorate local inflammation and promote cartilage repair. Notably, rats bearing rheumatoid arthritis showed a drastic increase in the M1-to-M2 macrophage ratio from 1:0.48 to 1:1.91 in the inflamed tissue and significantly reduced inflammatory cytokine levels including TNF-α and IL-6 following the intra-articular injection of HA@RH-CeOX, accompanied by efficient cartilage regeneration and restored articular function. Overall, this study revealed an approach to in situ modulate the redox homeostasis in inflammatory macrophages and reprogram their polarization states through micelle-complexed biomimetic enzymes, which offers alternative opportunities for the treatment of rheumatoid arthritis.

ROS-activatable biomimetic interface mediates in-situ bioenergetic remodeling of osteogenic cells for osteoporotic bone repair.

Bioenergy (ATP) is essentially required for supporting the osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs). However, factors such as high ROS levels and decreased glucose metabolism severely limit the bioenergy production in osteoporotic MSCs. We have prepared CaCO3-Quercetin- chromium (CaCO3-Qu-Cr) nanoparticles via ion coordination and packaged them into ROS-responsive gelatin/chitosan coating on titanium surface (Ti/Gel/CaCO3-Qu-Cr), aiming to improve the ATP production and cell mineralization by ameliorating ROS levels via Qu-mediated antioxidative effect and the promotional effect of Qu-Cr combination on glucose metabolism. Characterization results confirmed that Ti/Gel/CaCO3-Qu-Cr could be degraded in an ROS-responsive manner to release CaCO3-Qu-Cr nanoparticles continuously and eliminate excessive ROS in both the MSCs and microenvironment. Meanwhile, Ti/Gel/CaCO3-Qu-Cr significantly increased the glucose uptake and metabolism in osteoporotic MSCs and boosted their ATP and citrate production. This study laid the foundation for the development of functional titanium-based implants for the improvement of osteoporotic osseointegration.

Promoting osseointegration by in situ biosynthesis of metal ion-loaded bacterial cellulose coating on titanium surface.

The biologically inert and excessive elastic modulus of Ti implant surface, as well as the excessive gap between implant and host, will lead to poor bone integration even implant failure. To solve the above problems, in this study, a method for functional Ti implant is reported, in which metal ions-containing bacterial cellulose (BC) coating is introduced in situ on the surface of Ti with complex shapes. Magnesium and strontium ions can be loaded into BC by in situ biosynthesis, which have great effects on the growth of bacteria and the structure of cellulose. In addition, both in vitro and in vivo experiments confirmed that the in situ preparation of functional BC coating on the Ti surface can integrate the operative crevices and promote osteogenesis. This simple and novel method for functional Ti implants has potential application value in clinical bone tissue repair and regeneration.

Nanocatalytic Biofunctional MOF Coating on Titanium Implants Promotes Osteoporotic Bone Regeneration through Cooperative Pro-osteoblastogenesis MSC Reprogramming.

An elevated bone microenvironmental reactive oxygen species (ROS) level is a hallmark of osteoporosis that often leads to the dysfunction of bone-related mesenchymal stem cells (MSCs), which would induce MSC senescence and severely undermine their osteoblastic potential. Herein, we report the in situ construction of bone microenvironment-responsive biofunctional metal-organic framework (bio-MOF) coating on the titanium surface through the coordination between p-xylylenebisphosphonate (PXBP) and Ce/Sr ions by a hydrothermal method. Taking advantage of the anchored Ce and Sr ions, the AHT-Ce/SrMOF implants demonstrate on-demand superoxide dismutase and catalase-like catalytic activities to decompose ROS in MSCs and restore their mitochondrial functions. In vitro analysis showed that the AHT-Ce/SrMOF implants substantially activated the AMP-activated protein kinase (AMPK) signaling pathway in MSCs and reduced the ROS levels. Meanwhile, MSCs grown on AHT-Ce/SrMOF implants displayed significantly higher expressions of the mitochondrial fission marker (DRP1), mitochondrial fusion marker (MFN2 and OPA1), and mitophagy marker (PINK1 and LC3) than those of the AHT-CeMOF and AHT-SrMOF groups, which indicated that the bio-MOF could amend mitochondrial function in MSCs to reverse senescence. In vivo evaluations showed that the bio-MOF-coated Ti implants could restore MSC function in the implant site and promote new bone formation, leading to improved osteointegration in osteoporotic rat. This study may improve implant-mediated fracture healing in the clinics.

Construction of Wogonin Nanoparticle-Containing Strontium-Doped Nanoporous Structure on Titanium Surface to Promote Osteoporosis Fracture Repair.

M2 polarization of macrophage is an important immunomodulatory event that attenuates inflammation. To regulate the immune microenvironment in osteoporotic conditions for enhancing bone healing, strontium-doped nano-structure is fabricated on the surface of titanium implant via microarc oxidation and electrochemical deposition technology, followed by the addition of multiplayer coatings embedded with silk fibroin-based wogonin nanoparticles (Ti-MAO/Sr/LBLWNP ) by layer-by-layer self-assembly technique (LBL). It is found that Ti-MAO/Sr/LBLWNP can release wogonin and Sr2+ in a sustainable manner for more than 7 and 21 days. In vitro studies show that Ti-MAO/Sr/LBLWNP significantly upregulates the expression of CD206 while reducing the expression of CD86. Meanwhile, Ti-MAO/Sr/LBLWNP can promote the expression level of M2 macrophage anti-inflammatory factor (TGF-ß1, Arg-1), which improves the proliferation and osteogenic differentiation of osteoblasts through paracrine signaling. Compared to bare titanium, Ti-MAO/Sr/LBLWNP significantly inhibits the expression of inflammatory factors around the implant and effectively promotes new bone formation at pre-implant interface after implantation for 4 weeks. This study provides a simple and effective method to develop functional titanium alloy materials for osteoporotic fracture repair.

Constructions of ROS-responsive titanium-hydroxyapatite implant for mesenchymal stem cell recruitment in peri-implant space and bone formation in osteoporosis microenvironment.

To solve the issue of unsatisfactory recruitment of mesenchymal stem cells (MSCs) around implant in osteoporotic fractures, we fabricated a ROS-responsive system on titanium surface through hydroxyapatite coating and biomolecule grafting. The porous hydroxyapatite and phosphorylated osteogenic growth peptides (p-OGP) were introduced onto titanium surface to synergistically improve osteogenic differentiation of MSCs. After the p-OGP-promoted expression of osteogenic related proteins, the calcium and phosphate ions were released through the degradation of hydroxyapatite and integrated into bone tissues to boost the mineralization of bone matrix. The ROS-triggered release of DNA aptamer (Apt) 19S in the osteoporotic microenvironment guides MSC migration to implant site due to its high affinity with alkaline phosphatase on the membrane of MSCs. Once MSCs reached the implant interface, their osteogenic differentiation potential was enhanced by p-OGP and hydroxyapatite to promote bone regeneration. The study here provided a simple and novel strategy to prepare functional titanium implants for osteoporotic bone fracture repair.

Enhanced biocompatibility and osteogenic differentiation of mesenchymal stem cells of titanium by Sr-Ga clavate double hydroxides.

To improve in vivo osseointegration of pure titanium implant, Sr-Ga clavate double hydroxide (CDH) coating was grown in situ on a titanium (Ti) substrate with simple hydrothermal and calcination treatments at 500 °C. The obtained coating on the Ti substrate (Ti-CDH and Ti-CDH500) was researched by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive spectroscopy (EDS). Ti-CDH exhibited a sustained release profile of metal ions and maintained a slightly alkaline environment. The CDH coating was beneficial for osteogenic differentiation of mesenchymal stem cells (MSCs), which were reflected by the results of cellular assays, including alkaline phosphatase activity (ALP), cell mineralization capability (ARS), and osteogenesis-related gene expression. Besides, Ti-CDH could effectively improve the autophagic levels in MSCs, which further promoted osteogenic differentiation of MSCs. Hence, the Ti surface with Sr-Ga CDH modification supplied a simple and effective strategy to design biomaterials for bone generation.

Enzymatically-degradable hydrogel coatings on titanium for bacterial infection inhibition and enhanced soft tissue compatibility via a self-adaptive strategy.

Ideal percutaneous titanium implants request both antibacterial ability and soft tissue compatibility. ZnO structure constructed on titanium has been widely proved to be helpful to combat pathogen contamination, but the biosafety of ZnO is always questioned. How to maintain the remarkable antibacterial ability of ZnO and efficiently reduce the corresponding toxicity is still challenging. Herein, a hybrid hydrogel coating was constructed on the fabricated ZnO structure of titanium, and the coating was proved to be enzymatically-degradable when bacteria exist. Then the antibacterial activity of ZnO was presented. When under the normal condition (no bacteria), the hydrogel coating was stable and tightly adhered to titanium. The toxicity of ZnO was reduced, and the viability of fibroblasts was largely improved. More importantly, the hydrogel coating provided a good buffer zone for cell ingrowth and soft tissue integration. The curbed Zn ion release was also proved to be useful to regulate fibroblast responses such as the expression of CTGF and COL-I. These results were also validated by in vivo studies. Therefore, this study proposed a valid self-adaptive strategy for ZnO improvement. Under different conditions, the sample could present different functions, and both the antibacterial ability and soft tissue compatibility were finely preserved.

Osteogenesis regulation of mesenchymal stem cells via autophagy induced by silica-titanium composite surfaces with different mechanical moduli.

The high surface elastic modulus of the titanium (Ti) implant is one of the critical factors causing poor osteointegration between the implant surface and surrounding bone tissue. To address this challenge, spherical silica nanoparticles (SSNs) and spherical titania nanoparticles (STNs) with different sizes were synthesized and embedded into Ti surfaces via a micro-arc oxidation (MAO) technique. There were no significant changes in the surface roughness and protein adsorption behaviors before and after the embedding of spherical silica nanoparticles and titania nanoparticles into the Ti implant. However, the surface elastic modulus of Ti-SSNs decreased from 93 GPa to 6.7 GPa, while there was still no change in surface elastic modulus between Ti and Ti-STN groups. In vitro experiments showed that Ti-SSNs, especially Ti-SSN3, significantly stimulated the expression level and nuclear localization of the transcription factor YAP. YAP/TAZ could further inhibit the phosphorylation of AKT and mTOR proteins in MSCs, leading to higher LC3-II protein expression and osteogenic differentiation of MSCs. Ti-SSNs also showed a higher level of autophagosome formation, ALP activity and mineralization capability compared to the other groups. Our results showed that the surface elasticity modulus of an implant plays an important role in the regulation of MSC behaviors. Therefore, designing an implant with an optimal elastic modulus at the surface might have great clinical potential in the bone repair field.

A facile and novel design of multifunctional electronic skin based on polydimethylsiloxane with micropillars for signal monitoring.

Electronic skins (e-skins) with monitoring capabilities have attracted extensive attention and are being widely employed in wearable devices for medical diagnosis. In particular, e-skins based on strain sensors have been reported extensively due to their simple structure and efficient performance in collecting human physiological information. Flexible sensors with high sensitivity, simplified fabrication, and low-cost are highly desired for human signal monitoring; this work provides a novel strain-sensing e-skin with micro-structures, which is simply made of modified polydimethylsiloxane (PDMS) and silver nanowires (AgNWs). The fabricated e-skin has great sensitivity towards strain changes, and its mechanical properties and sensitivity could be regulated by varying the micro-structures. Furthermore, the e-skin demonstrated significant capacity for monitoring human body movements, temperature changes, and spatial resolution, highlighting its great potential in personalized medicine.

Functionalization of Ti substrate with pH-responsive naringin-ZnO nanoparticles for the reconstruction of large bony after osteosarcoma resection.

After bone tumor resection, the large bony deficits are commonly reconstructed with Ti-based metallic endoprosthesis, which provide immediate stable fixation and allow early ambulation and weight bearing. However, when used in osteosarcoma resection, Ti implant-relative infection and tumor recurrence were recognized as the two critical factors for implantation failure. Hence, in this work, a novel zinc oxide nanoparticle decorating with naringin was prepared and immobilized onto Ti substrate. The drugs delivery profiles proved that in the bacterial infection and Warburg effect of osteosarcoma-induced acidic condition, naringin and Zn2+ can be released easily from the functional Ti substrate. The anti-osteosarcoma and antibacterial assay showed the delivered naringin and Zn2+ can induce a remarkable increase of oxidative stress in bacteria (Escherichia coli and Staphylococcus aureus) and osteosarcoma (Saos-2 cells) by producing reactive oxygen species (ROS). Accumulation of ROS results in damage of bacterial biofilm and bacterial membrane, leading to the leakage of bacterial RNA and DNA. Meanwhile, the increase of ROS induces osteosarcoma cell apoptosis by activating ROS/extracellular signal-regulated kinase signaling pathway. Furthermore, in vitro cellular experiments, including cell viability, alkaline phosphatase activity, collagen secretion, extracellular matrix mineralization level, indicated that the functional Ti substrate exhibited great potential for osteoblasts proliferation and differentiation. Hence, this study provides a simple and promising strategy of developing multifunctional Ti-based implants for the reconstruction of large bony after osteosarcoma resection.

Osteogenic differentiation of mesenchymal stem cells by silica/calcium micro-galvanic effects on the titanium surface.

Based on the sensitivity to the extracellular H+ concentration of proton-sensing receptors, we immobilized Si/CaCO3 nanoparticles on a titanium surface (TiMNPs) by using micro-arc oxidation (MAO) to produce micro-galvanic effects by Schottky contact, aiming to regulate the hydrogen evolution reaction of micro-galvanic couples and osteogenic response of mesenchymal stem cells (MSCs). The surface zeta potential measurement and dynamic potential polarization test confirmed that micro-galvanic effects were successfully produced on the titanium surface after the treatment of Si/CaCO3 nanoparticles. The Ti substrate with a Si/CaCO3 nanoparticle loading concentration of 100 mg mL-1 (TiMNPs 100) could lead to the highest level of hydrogen evolution reaction. In vitro experiments showed that TiMNPs 100 were significantly superior in their ability to down-regulate the expression level of proton-sensing receptors and key proteins in the PLC/Ca2+ signal pathway, which in turn promoted MSC osteogenesis differentiation. A higher level of ALP activity, mineralization capacity and collagen secretion on TiMNPs 100 was confirmed as compared to those of other groups. This study provides a new insight into designing novel biomaterials for bone generation.

Programmable prodrug micelle with size-shrinkage and charge-reversal for chemotherapy-improved IDO immunotherapy.

IDO blockade-based immunotherapy has been impeded by the activation of antitumor immune response and low delivery efficiency of immunotherapeutic, resulting from natural biological barriers and immune resistance. Herein, a programmable drug delivery nanosystem with enhanced tumor penetration and endocytosis is constructed for chemotherapy-enhanced immunotherapy by loading immune checkpoint IDO inhibitor NLG919 in pH/redox cascade-responsive prodrug micelle. The nanosystem shrinked micelles sizes and converted charge from negative to positive for enhanced tumor penetration and endocytosis in responding to the weakly acidic tumor microenvironment. The endocytosed nanosystem dramatically disassembled and released curcumin and NLG919 in redox-rich cytoplasm. In vitro and in vivo studies demonstrate that the nanosystem not only effectively overcame biological barriers, but also significantly boosted antitumor immune response and reduced immune resistance. It was realized by the combined effects of chemotherapy-enhanced immunogenicity, and NLG919-induced IDO-blockade immunotherapy, consequently inhibiting tumor growth, metastasis and recurrence with high efficiency in vivo. The study offers a nanoplatform with deep tumor penetration, high cellular uptake and effective antitumor immune response for the advance of chemo-immunotherapy.

Near-Infrared Light-Triggered Nitric-Oxide-Enhanced Photodynamic Therapy and Low-Temperature Photothermal Therapy for Biofilm Elimination.

Photothermal treatment (PTT) involving a combination of therapeutic modalities recently emerged as an efficient alternative for combating biofilm. However, PTT-related local high temperature may destroy the surrounding healthy tissues. Herein, we present an all-in-one phototherapeutic nanoplatform consisting of l-arginine (l-Arg), indocyanine green (ICG), and mesoporous polydopamine (MPDA), namely, AI-MPDA, to eliminate the already-formed biofilm. The fabrication process included surface modification of MPDA with l-Arg and further adsorption of ICG via π-π stacking. Under near-infrared (NIR) exposure, AI-MPDA not only generated heat but also produced reactive oxygen species, causing a cascade catalysis of l-Arg to release nitric oxide (NO). Under NIR irradiation, biofilm elimination was attributed to the NO-enhanced photodynamic therapy and low-temperature PTT (≤45 °C). Notably, the NIR-triggered all-in-one strategy resulted in severe destruction of bacterial membranes. The phototherapeutic AI-MPDA also displayed good cytocompatibility. NIR-irradiated AI-MPDA nanoparticles not only prevented bacterial colonization but also realized a rapid recovery of infected wounds. More importantly, the all-in-one phototherapeutic platform displayed effective biofilm elimination with an efficiency of around 100% in a abscess formation model. Overall, this low-temperature phototherapeutic platform provides a reliable tool for combating already-formed biofilms in clinical applications.

A dual-functional implant with an enzyme-responsive effect for bacterial infection therapy and tissue regeneration.

Biomaterial-associated bacterial infection is one of the major causes of implant failure. The treatment of such an implant infection typically requires the elimination of bacteria and acceleration of tissue regeneration around implants simultaneously. To address this issue, an ideal implanted material should have the dual functions of bacterial infection therapy and tissue regeneration at the same time. Herein, an enzyme-responsive nanoplatform was fabricated in order to treat implant-associated bacterial infection and accelerate tissue regeneration in vivo. Firstly, Ag nanoparticles were pre-encapsulated in mesoporous silica nanoparticles (MSNs) by a one-pot method. Then, poly-l-glutamic acid (PG) and polyallylamine hydrochloride (PAH) were assembled by the layer-by-layer (LBL) assembly technique on MSN-Ag to form LBL@MSN-Ag nanoparticles. Furthermore, the LBL@MSN-Ag nanoparticles were deposited on the surface of polydopamine-modified Ti substrates. PG is a homogeneous polyamide composed of an amide linkage, which can be degraded by glutamyl endonuclease secreted by Staphylococcus aureus. Inductively coupled plasma spectroscopy (ICP) results proved that the LBL@MSN-Ag particles show a significant enzyme responsive release of Ag ions. Furthermore, results of antibacterial experiments in vitro showed that the Ti substrates modified with an LBL@MSN-Ag nanocoating presented an excellent antibacterial effect. As for an animal experiment in vivo, in a bacterium infected femur-defect rat model, the modified Ti implants effectively treated bacterial infection. More importantly, the results of micro-CT, haematoxylin-eosin staining and Masson's trichrome staining demonstrated that the modified Ti implants significantly promoted the formation of new bone tissue after implantation for 4 weeks. The present system paves the way for developing the next generation of implants with the functions of treating bacterial infection and promoting tissue regeneration.

Substance P-embedded multilayer on titanium substrates promotes local osseointegration via MSC recruitment.

In this study, the chemokine substance P (SP) was inserted into multilayered systems on titanium (Ti)-based substrates for endogenous mesenchymal stem cell (MSC) recruitment to facilitate bone healing. The multilayer was constructed with cationic chitosan (Chi), SP and anionic gelatin (Gel) via a spin-coater-assisted layer-by-layer (LBL) approach. The characterization results demonstrated that the multilayer system was successfully constructed and was capable of continuously releasing SP for almost 2 weeks. We further confirmed that MSCs grown on SP-modified Ti-based substrates showed improved migration capabilities as well as enhanced secretion of matrix metalloproteinases (MMP2, MMP9), rather than enhanced MSC proliferation and differentiation in vitro. In the CD29+/CD90+ double immunofluorescence assay, the Ti/LBL-SP group showed the highest number of MSCs migrating to the peri-implant area after implantation. Consistently, the Ti/LBL-SP implants also significantly enhanced new bone formation according to the results of micro-CT scanning analysis, H&E staining, Masson's trichrome staining and immunohistochemical staining. The obtained results reveal that SP-modified Ti-based substrates were beneficial for bone formation via recruiting endogenous MSCs.

Regulation of MSC and macrophage functions in bone healing by peptide LL-37-loaded silk fibroin nanoparticles on a titanium surface.

Titanium-based materials have been long regarded as effective bone implants for clinical use, yet the corresponding osteointegration ability needs to be optimized. This challenge can be overcome by fabricating titanium (Ti) materials with physiological functions. In this study, peptide LL-37-loaded silk fibroin nanoparticles (SFNPs) were immobilized on a titanium surface to facilitate osteointegration by regulating the physiological functions of mesenchymal stem cells (MSCs) and macrophages. According to our results, the cell viability, recruitment and paracrine responses of MSCs and macrophages were improved by the modified Ti samples. MSC differentiation was promoted by the macrophages incubated on the modified Ti samples, and the phenotype switch of macrophages was also modulated by the MSCs incubated on the modified Ti samples. In vivo studies proved that the modified Ti implant induced MSC and macrophage recruitments to injury sites and the inflammatory response was positively regulated. Moreover, better bone formation was achieved around the modified Ti implant 28 days after surgery. This suggested that the immobilization of peptide LL-37-loaded SFNPs on a titanium surface improves osteointegration via the regulation of physiological functions of MSCs and macrophages.

Zn-incorporation with graphene oxide on Ti substrates surface to improve osteogenic activity and inhibit bacterial adhesion.

The poor osseointegration and postoperative bacterial infection are prominently responsible for the failure of titanium (Ti)-based implant in clinic. To address above issues, methacryloyl modified graphene oxide (GOMA) as zinc ions (Zn2+ ) reservoir and release platform was fabricated on the Ti substrates with cathode electrophoresis deposition (EPD). Afterward, phenylboronic acid (PBA) functionalization methacryloyl-gelatin (GelMA-PBA) was reacting with GOMA through in situ free-radical polymerization to prepare GO-Zn/GelMA-PBA coating. The obtained coating was confirmed by scanning electron microscopy, X-ray photoelectron spectroscopy, and Zn ions release property, respectively. in vitro cellular experiments including cell activity, alkaline phosphatase, collagen secretion, extracellular matrix (ECM) mineralization, osteogenic genes and proteins, revealed that GO-Zn/GelMA-PBA coating was beneficial for enhancing the adhesion, proliferation, and differentiation of osteoblasts. The positive results were related to the existence of gelatin, formation of boronic ester between PBA groups, and carbohydrates of osteoblasts surface. Meanwhile, antibacterial assay against Staphylococcus aureus and Pseudomonas aeruginosa confirmed that GO-Zn/GelMA-PBA coating on Ti substrates had superior antibacterial capacity, availably inhibited the bacterial adhesion, and prevented formation of biofilm. Hence, the study provides a promising strategy for designing pro-osteogenesis and antibacterial coating on Ti substrates for orthopedic applications.

BMP2-loaded titania nanotubes coating with pH-responsive multilayers for bacterial infections inhibition and osteogenic activity improvement.

Bacterial infection and surface biointertness are two main causes for titanium (Ti)-based orthopedic implants failure. To improve the antibacterial ability and enhance poor osteogenic property of Ti substrates, in this work, we employed titania nanotubes (TNTs) as Bone Morphogenetic Protein 2 (BMP2) carrier, and a pH-responsive multilayer film composed of alginate dialdehyde-gentamicin (ADA-Gen) and chitosan (Chi) was constructed onto BMP2-loaded TNTs substrates through layer-by-layer (LBL) assembly technique, resulting in TNT-BMP2-LBLg samples. The release experiments revealed that acidic environment could trigger the release of Gen from the multilayer films and in turn accelerate the release of BMP2 from TNTs. Moreover, antibacterial assay against E. coli and S. aureus confirmed that the TNT-BMP2-LBLg had excellent antibacterial capacity both in early (6 h) and in long-term (72 h). Meanwhile, in vitro cellular tests demonstrated that TNT-BMP2-LBLg had good cytocompatibility toward osteoblasts even co-cultured with S. aureus. Importantly, the obtained TNT-BMP2-LBLg promoted differentiation of osteoblasts, including enhanced alkaline phosphatase activity, improved mineralization capability and stimulated osteogenic-relative gene expression. This study thus provides a promising strategy to develop pH-responsive antibacterial and enhance bone integrative Ti-based implants for potential orthopedic application.