Fabrication of enzyme-responsive composite coating for the design of antibacterial surface.

In this study, a type of bacteria enzyme-triggered antibacterial surface with a controlled release of Ag ions was developed. Firstly, chitosan-silver nanocomposites (Chi@Ag NPs) were in situ synthesized via using ascorbic acid as reducing agent. Chi@Ag NPs were characterized by transmission electron microscopy, ultraviolet-visible spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Subsequently, Chi@Ag NPs and hyaluronic acid (HA) were used to fabricate antibacterial composite coating via Layer-by-Layer (LBL) self-assembly method. The successful construction of Chi@Ag NPs/HA composite coating was confirmed by scanning electron microscopy, energy dispersive spectroscopy and contact angle measurements, respectively. Then, the amount of released Ag ion was analyzed by inductively coupled plasma atomic emission spectrometry, which demonstrated that the release of Ag ions from the surface could be triggered by enzyme (e.g. hyaluronidase). A series of antibacterial tests in vitro, including zone of inhibition test, bacterial viability assay, antibacterial rate measurement and bacteria adhesion observation, demonstrated that the enzyme-responsive surface could inhibit the growth of bacteria. On the whole, this study provides an alternative approach for the fabrication of antibacterial surfaces on synthetic materials in various fields with the minimal side effects on surrounding environment and human body.

Repeated CT-guided percutaneous radiofrequency thermocoagulation for recurrent trigeminal neuralgia.

AIMS: To investigate the long-term outcomes of repeated percutaneous radiofrequency thermocoagulation (PRT) for recurrent trigeminal neuralgia (TN) patients. METHODS: Between 2002 and 2012, 33 patients with recurrent TN following an initial PRT procedure were retrospectively studied and underwent 43 repeated PRT procedures. RESULTS: The mean length of follow-up after repeated PRT was 34 months. Pain relief was immediate in 30 patients (90.9%), and no pain relief occurred in 3 patients (9.1%) following a second PRT procedure. The percentage of patients who remained in an 'excellent' and 'good' pain relief condition (pain intensity ≤BIN grade III) after the second PRT procedure was 75% at 1 year, 68% at 2 years and 68% at 5 years, and 22 of these patients (54.5%) remained satisfied with their pain relief during the follow-up period. Nine patients underwent PRT three times and 1 patient four times. The total number of patients who benefited from repeated PRT was 28 (84.8%). Postprocedure complications including masseter weakness were present in 3 patients and limited mouth opening affected 1 patient. No mortalities were observed during or after repeated PRT procedures. CONCLUSION: Repeated PRT provides long-term pain relief benefits to patients with recurrent TN and should be considered as an alternative treatment for recurrent TN.

Long-term outcome of computed tomography-guided percutaneous radiofrequency thermocoagulation for classic trigeminal neuralgia patients older than 70 years.

The incidence of trigeminal neuralgia (TN) in elderly patients is higher. However, for those with poor fitness, the optimal surgical treatment for those refractory to medical treatment is controversial. The aim of current study was to investigate the long-term outcome of computed tomography (CT)-guided percutaneous radiofrequency thermocoagulation (PRT) for 304 TN patients 70 years or older. We conducted a retrospective study of 304 elderly patients with TN who were treated with CT-guided PRT between 2002 and 2012. Follow-up was censored at the time of last contact, additional surgery, or death. Sixty-seven patients (22.1%) were of more than American Society of Anesthesiologists classification system physical status II. Excellent pain relief was 100% at discharge, 85% at 1 year, 75% at 3 years, 71% at 5 years, and 49% at 10 years. Pain relief outcomes were correlated with facial numbness. Lower temperature group (≤75°C) can attain the same long-term pain relief as higher temperature group (≥80°C); however, the incidence of painful dysesthesia rate of higher temperature group was higher than lower temperature group. Postoperative morbidity included facial numbness, masseter weakness, corneitis, hearing loss, dropping eyelid, and limited mouth opening. There were no mortalities observed during or after PRT. Our result showed CT-guided PRT is safe and effective for classic TN patients 70 years or older, including poor-fitness patients (American Society of Anesthesiologists classification system physical status >II). Lower temperature (≤75°C) is recommended for PRT in the treatment of TN.

Infection Microenvironment-Responsive Coating on Titanium Surfaces for On-Demand Release of Therapeutic Gas and Antibiotic.

Aseptic loosening and bacterial infection pose significant challenges in the clinical application of titanium (Ti) orthopedic implants, which are primarily caused by insufficient osseointegration and bacterial contamination. To address these issues, a responsive coating on Ti surface is constructed, which achieves enhanced osseointegration and infection elimination by on-demand release of therapeutic gas hydrogen sulfide (H2S) and antibiotic. TiO2 nanotubes (TNT) are anodized on the Ti surface to enhance its bioactivity and serve as reservoirs for the antibiotic. An infection microenvironment-responsive macromolecular H2S donor layer is coated on top of TNT to inhibit premature leakage of antibiotic. This layer exhibits a sustained release of low-dosage H2S, which is capable of promoting the osteogenic differentiation and migration of cells. Moreover, the compactness of the macromolecular H2S donor layer could be broken by bacterial invasion, leading to rapid antibiotic release thus preventing infection. In vitro antibacterial experiments validates significant antibacterial activity of the coating against both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Crucially, this coating effectively suppresses implant-associated infection with 98.7% antibacterial efficiency in a rat femoral bone defect model, mitigates inflammation at the defect site and promotes osseointegration of the Ti orthopedic implant.

Abscess formation in vertebral canal and presacral area following penetrating injury of rectum and sacral vertebra by a steel rod.

Penetrating injury to the rectum, vertebral body and spinal cord by a steel rod is a rare condition. Treatment of this kind of injury is very challenging. Rectal injury requires repair and fecal diversion, while debridement of the spine is difficult, especially when the injury site is very long. Here we report a case of penetrating injury of rectum and sacral vertebra by a steel rod after falling onto the ground from 1 m height. The abscess cavity was irrigated with 3% hydrogen peroxide and physio-logical saline repeatedly. The bony canal was carefully debrided, curetted and bony fragments were removed. Spinal irrigation and drainage lasted for 2 months and sensitive antibiotic (amikacin sulfate) was given 7 days after surgery, but abscess was still formed in the vertebral canal. At 6-month follow-up, the patient was paralyzed without any neurological improvement, and the pain in low back and lower limb still continued.

Positively-charged microcrystalline cellulose microparticles: Rapid killing effect on bacteria, trapping behavior and excellent elimination efficiency of biofilm matrix from water environment.

Pathogen and biofilm contamination in aqueous systems leave millions of people at risk of waterborne diseases. Herein, to address this issue, a green and highly efficient strategy is developed to concurrently trap and kill bacteria, eliminate the debris and the existing biofilm matrix in water environment via magnetic microparticles. The particles (TPFPs) were prepared from the in-situ deposition of Fe3O4 nanoparticles onto the surface of antibacterial functionalized microcrystalline cellulose (MCC). Noticeably, TPFPs can completely inactivate both S. aureus and E. coli once contacting for 30 min by disrupting the bacterial membrane. Meanwhile, the MCC-based magnetic particles retained 100% biocidal efficiency against E. coli (5 * 104E. coli/mg particles) during ten recycling procedures without any treatment. More importantly, according to the results of trapping behavior and antibiofilm assays, not only bacteria could be captured by the particles (trapping rate was over 85%), but also the residual debris from dead bacteria and fragmented biofilm was together removed based on the special structure and functions of the antibacterial particles (~ 80%), including extremely rough surfaces, surficial positive charge and magneto-responsive property. This study presents an efficient approach for microorganism management in water system which can be expectantly applied to improve the water safety.

Efficacy of polyethylene glycol 4000 on constipation of posttraumatic bedridden patients.

OBJECTIVE: To investigate the efficacy and safety of polyethylene glycol 4000 on adult patients with functional constipation due to posttraumatic confinement to bed. METHODS: A total of 201 posttraumatic bedridden patients were studied in this prospective, open-labeled, single-group study. Polyethylene glycol 4000 was administered orally for 14 days and the dosage was adjusted according to the Bristol stool types. Demographic characteristics, disease status, treatment period and factors affecting clinical outcome, especially the concomitant medications, were recorded. RESULTS: After administration of polyethylene glycol 4000, 194 cases (96.52%) showed remission of constipation, including 153 (76.12%) persistent remission. The average defecation frequency increased significantly after treatment and the percentage of patients with stools of normal types (Bristol types 3-5) increased as well. Genders, ages and concomitant medications showed no significant influence on the persistent remission rate. After consecutive treatment for two weeks, patients with slight movement showed a significantly higher remission rate than those without movement (95% vs 80%). At the end of treatment, most accompanying symptoms were relieved obviously. Patients with a medical history of constipation or ever taking laxatives showed a lower remission rate. Sixty cases (29.85%) developed diarrhea during the observational period, among whom 6 (10%) withdrew from the clinical observation voluntarily at the first onset of diarrhea. Two cases suffered from abdominal pain. CONCLUSIONS: Polyethylene glycol 4000 has efficacy on functional constipation in posttraumatic bedridden patients. Furthermore, patients with milder symptoms, more movement in bed, and longer duration of treatment but without accompanying symptoms can achieve a higher remission rate.

Fabrication of strontium-incorporated protein supramolecular nanofilm on titanium substrates for promoting osteogenesis.

The inherent biological inertness of Ti substrates is a general challenge in orthopedic and dental clinical application. In this study, the strontium-containing phase change lysozyme coating was prepared on titanium via a supramolecular self-assembly method for accelerating osseointegration. Successful preparation of the Sr-incorporated lysozyme nanofilm onto the Ti substrate (Ti-Ly-Sr) was proved by tests of scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and Contact angle (CA). Furthermore, the results of cell morphology observation, cell viability assay, alkaline phosphatase staining and quantitative analysis showed that Ti-Ly-Sr substrate enhanced early adhesion, proliferation and osteogenic differentiation of bone marrow stromal cells (BMSCs). The quantitative real-time polymerase chain reaction (qRT-PCR) assays confirmed that Ti-Ly-Sr enhanced the expression of osteogenic related genes (BMP2, OPG, Runx2 and COL-1) of BMSCs at the molecular level. Moreover, Micro-CT and histological analysis proved that the strontium-incorporated lysozyme nanofilm modified Ti implants had significant capability of new bone formation in vivo after implantation for 4 weeks. We anticipate that the present system would provide a facile and effective means for surface modification of Ti-based implants. Relevant ideas and techniques in this study will contribute to the development of new implant devices.

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.

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.

Remote eradication of biofilm on titanium implant via near-infrared light triggered photothermal/photodynamic therapy strategy.

Biofilm formation is a main challenge in treatment of bone-implant-associated infections, resulting in tolerance to immune system and antibiotics. However, smart non-surgical or non-invasive treatment methods of combating established biofilm on an implant have been less reported. Herein, a therapeutic system consisting of mesoporous polydopamine nanoparticles (MPDA) to combat biofilm is reported for the first time. We develop a synergistic photothermal/photodynamic therapy (PTT/PDT) strategy aiming for biofilms eradication on titanium (Ti) implant, which is integrated with MPDA loading with photosensitizer Indocyanine Green (ICG) by π-π stacking. Specifically, MPDA is functionalized with RGD peptide to endow the modified Ti sample (Ti-M/I/RGD) with good cytocompatibility. More importantly, Ti-M/I/RGD implant remarkably kills Staphylococcus aureus (S. aureus) biofilm with an efficiency of 95.4% in vivo upon near infrared (NIR). After biofilm eradication, implant still displays great performance regarding osteogenesis and osseointegration. Overall, this study provides a PTT/PDT strtategy for the development of antibacterial Ti implants for potential orthpediac application.

Biocompatible MoS2/PDA-RGD coating on titanium implant with antibacterial property via intrinsic ROS-independent oxidative stress and NIR irradiation.

To inhibit bacterial infection in situ and improve osseointegration are essentially important for long-term survival of an orthopedic implant, in particular for infection-associating revision surgery. Herein, we fabricate a functional molybdenum disulfide (MoS2)/polydopamine (PDA)-arginine-glycine-aspartic acid (RGD) coating on titanium (Ti) implant to address above concerns simultaneously. The coating not only improved the osteogenesis of mesenchymal stem cells (MSCs), but also endowed Ti substrates with effective antibacterial ability when exposing to near-infrared (NIR) irradiation. It accelerated glutathione (GSH) oxidation via photothermal energy and induced intrinsic ROS-independent oxidative stress damage deriving from MoS2 nanosheets. The results displayed that RGD-decorated MoS2 nanosheets significantly increased the cellular osteogenic behaviors of MSCs via up-regulating osteogenesis-related genes (ALP, Runx2, Col I and OCN) in vitro. Moreover, the functionalized Ti substrates demonstrated great antibacterial efficiency of over 92.6% inhibition for S. aureus and E. coli under NIR-irradiation. Hyperthermia induced by photothermal effect accelerated the GSH consumption and ROS-independent oxidative stress destroyed the integrity of bacteria membranes, which synergistically led to protein leakage and ATP decrease. Furthermore, co-culture experiment showed that S. aureus contamination was efficiently cleaned from MoS2/PDA-RGD surface after NIR photothermal treatment, while MSCs adhered and proliferated on the MoS2/PDA-RGD surface. In an S. aureus infection model in vivo, MoS2/PDA-RGD modified Ti rods killed bacteria with an efficiency of 94.6% under NIR irradiation, without causing damage to normal tissue. More importantly, the MoS2/PDA-RGD modified Ti implants accelerated new bone formation in comparison with TNT implants in vivo.

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.

Construction of Ag-incorporated coating on Ti substrates for inhibited bacterial growth and enhanced osteoblast response.

In orthopedic fields, effective anti-infection property and promotive biocompatibility on surface of titanium implants are two crucial factors for long-term successful implants. Herein, Ag nanoparticles (NPs) loaded TiO2 nanotubes (TNT) arrays were fabricated on Ti substrates with assistance of ultraviolet irradiation. Then, bioactive multilayer films of chitosan (CHI) and dialdehyde alginate (ADA) pair were deposited onto the Ag-loaded TNT arrays via a layer-by-layer (LBL) self-assembly technique, which could effectively achieve the impactful antibacterial ability of titanium and endow the substrates with favorable biocompatibility. The driving force of the assembling of multilayer films came from two sources, electrostatic interaction and covalent interaction of Schiff-bonds between CHI and ADA. The surface topography and wettability of different samples were characterized by field emission scanning electron microscopy, transmission electron microscopy and contact angle measurements, respectively. In addition, Ag ions release from TNT-Ag and LBL substrate was measured via inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results of a series of biological behaviors of osteoblasts on different substrates in vitro, including lactate dehydrogenase activity assay, cytoskeleton observation and cell viability measurement, confirmed that LBL substrates coated with (ADA-CHI)10 multilayer films have negligible cytotoxicity and promote osteoblast growth compared with TNT-Ag substrates, which could ascribe to the slow-release of Ag ions and the biocompatibility of (ADA-CHI)10 multilayer. More importantly, owing to the release of Ag ions, the LBL samples still exhibited a prominent antibacterial activity for S.aureus and E.coli. Characteristics of bacterial adhesion and viability measurement proved that the fabricated Ag-incorporated platform was capable of obviously inhibiting the adhesion and growth of bacteria. Therefore, this approach of surface modification for Ti substrates presented here may provide an alternative strategy to simultaneously meet the desirable osteoblast growth and reduce bacterial infection for implants in clinical application.

The fabrication and in vitro properties of antibacterial polydopamine-LL-37-POPC coatings on micro-arc oxidized titanium.

Bacterial infection commonly occurs in clinical settings when the procedure involves a medical implant. Thus, the fabrication of antimicrobial medical materials has attracted much attention in recent years. To improve the antibacterial properties of titanium (Ti)-based biomedical materials, surface microporous structures, with antimicrobial peptide coatings, were employed in this study. Native Ti substrates were endowed with a certain level of antibacterial activity after treatment with the micro-arc oxidation (MAO). A multilayer consisting of polydopamine, cationic antimicrobial peptides LL-37, and phospholipid (POPC) was coated onto MAO substrates, leading to antibacterial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria. The combination of polydopamine-LL-37-POPC was found to alleviate the burst release of LL-37 in the initial phase. This multilayer coated onto microporous Ti substrates also showed favorable cytocompatibility to both mesenchymal stem cells (MSCs) and osteoblasts. These findings illustrate a novel strategy for the development of antibacterial Ti-based implants.

Surface engineering of titanium implants with enzyme-triggered antibacterial properties and enhanced osseointegration in vivo.

Preventing bacterial infection and improving the osseointegration of titanium (Ti) and its alloys are both highly crucial factors for their long-term successful implantation in clinical applications. However, the straightforward applications of antibacterial surfaces on Ti-based materials remain limited due to their side effects on cytocompatibility. Herein, catechol-functionalized multilayer films composed of dopamine-modified hyaluronic acid (HA-c) and 3,4-dihydroxyhydrocinnamic acid-modified chitosan (Chi-c) were developed on Ti substrates modified with TiO2 nanotube arrays loaded with an antibacterial drug. The treated Ti substrate showed strong hydrophilicity, with a water contact angle of about 20°, and obviously inhibited early-stage bacterial adhesion. Moreover, this system displayed an enzyme-responsive release of antibacterial drug triggered by the hyaluronidase degradation of HA-c, which exhibited effective antibacterial ability and eliminated side effects caused by burst release of antibiotics. Meanwhile, the modified Ti substrates significantly promoted initial osteoblast adhesion through up-regulating the expression of adhesion-related genes, including integrin αv and ß3. More importantly, this prepared coating with bacterial self-responsiveness improved osseointegration and prevented bacterial infection of Ti implants in vivo. Overall, our developed catechol-functionalized and bacterial self-responsive coating on Ti substrate has great significance in clinical applications of orthopedic and dental implants.

N-halamine-based multilayers on titanium substrates for antibacterial application.

Bacterial infection is one of the most severe postoperative complications leading to clinical orthopedic implants failure. To improve the antibacterial property of titanium (Ti) substrates, a bioactive coating composed of chitosan-1-(hydroxymethyl)- 5,5-dimethylhydantoin (Chi-HDH-Cl) and gelatin (Gel) was fabricated via layer-by-layer (LBL) assembly technique. The results of Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1HNMR) and X-ray photoelectron spectroscopy (XPS) showed that Chi-HHD-Cl conjugate was successfully synthesized. Scanning electron microscopy (SEM), atomic force microscope (AFM) and water contact angle measurements were employed to monitor the morphology, roughness changes and surface wettability of Ti substrates, which proved the multilayers coating formation. Antibacterial assay against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) revealed that the Gel/Chi-HDH-Cl modified Ti substrates most efficiently inhibited the adhesion and growth of bacteria. Meanwhile, in vitro cellular tests confirmed that Gel/Chi-HDH-Cl multilayers had no obvious cytotoxicity to osteoblasts. The study thus provides a promising method to fabricate antibacterial Ti-based substrates for potential orthopedic application.

Peptide LL-37 coating on micro-structured titanium implants to facilitate bone formation in vivo via mesenchymal stem cell recruitment.

Titanium (Ti) and Ti-alloys were widely used in clinic orthopedics, however, the insufficient bone formation surrounding Ti-based implants still limited their biological performances. Surface modification of Ti substrates is essential to improve their interactions with bone-forming cells and bone tissue. In this study, we modified Ti substrates by coating peptide LL-37 onto micro-structured Ti substrates and aimed to (i) induce mesenchymal stem cells (MSCs) migration both in vitro and in vivo, (ii) facilitate osteogenic differentiation of MSCs and new bone formation. The surface micro-structured Ti substrates with hydroxyapatite deposition were fabricated by a two-step method including micro-arc oxidation (MAO) and hydrothermal treatment. LL-37 was loaded on micro-structured Ti substrates with the assistance of polydopamine coating. We confirmed that surface-modified Ti substrates benefited viability, adhesion, migration and osteogenic differentiation of MSCs in vitro. In a femur-defect rat model, the surface-modified Ti implants effectively induced CD29+/CD90+ positive cells migration in one week after implantation. According to the results of H&E, Masson's trichrome staining and immunohistochemical staining of OCN, OPN and collagen I, the targeted Ti implants exhibited significant new bone formation after implantation for 4 weeks. These results indicate that the surface modification of Ti samples facilitated bone formation through MSCs recruitment. STATEMENT OF SIGNIFICANCE: The inherent surface bioinertness of titanium (Ti) and Ti-alloys still limits their biological performances in clinical applications. Recently, the strategy of mesenchymal stem cells (MSCs) recruitment has been proposed to improve the osteointegration of bone implants. Herein, we reports the surface modification of Ti implants from the point of MSCs recruitment. Peptide LL-37 was coated on micro-structured Ti substrates to (i) recruit MSCs, (ii) regulate bio-physiological performance of MSCs, and (iii) facilitate bone formation in vivo. Our results improve the understanding of the interaction between Ti implants and MSCs, and provide a promising strategy of MSCs recruitment in the design of bone repair related biomaterials.

Surface functionalization of titanium implants with chitosan-catechol conjugate for suppression of ROS-induced cells damage and improvement of osteogenesis.

Oxidative stress induced by reactive oxygen species (ROS) overproduction would hinder bone healing process at the interface of bone/implant, yet underlying mechanism remains to be explored. To endow titanium (Ti) substrates with antioxidant activity for enhanced bone formation, multilayered structure composing of chitosan-catechol (Chi-C), gelatin (Gel) and hydroxyapatite (HA) nanofibers was constructed on Ti substrates. Surface wettability and topography of multilayer coated Ti substrates were characterized by water contact angle measurement, scanning electron microscopy and atomic force microscopy, respectively. Chi-C containing multilayer on Ti surface effectively protected osteoblasts from ROS damage, which was revealed by high level of intracellular ROS scavenging activity and reduced oxidative damage on cellular level by regulating the expression of cell adhesion related genes (integrin αv, ß3, CDH11 and CDH2). Moreover, it regulated the production of cell adhesive and anti-apoptotic related proteins (p-MYPT1, p-FAK, p-Akt and Bcl-2) and pro-apoptotic critical executioners (Bax and cleaved caspase 3). Beside, the composite multilayer of Chi-C/Gel/HA nanofibers on Ti substrates promoted osteoblasts differentiation, which was evidenced by high expression levels of alkaline phosphatase activity, collagen secretion, ECM mineralization and osteogenesis-related genes expression in vitro. The in vivo experiments of µ-CT analysis, push out test and histochemistry staining further confirmed that Chi-C multilayered implant had great potential for improved early bone healing. Overall, the study offers an effective strategy for the exploration of high quality Ti implants for orthopedic applications.

The Long-Term Effective Rate of Different Branches of Idiopathic Trigeminal Neuralgia After Single Radiofrequency Thermocoagulation: A Cohort Study.

To evaluate the efficacy of computed tomography (CT) guided single radiofrequency thermocoagualtion (RFT) in 1137 patients with idiopathic trigeminal neuralgia after a follow-up period of 11 years, specially focused on duration of pain relief in different branches of trigeminal nerve, side effect, and complications. Retrospective study of patients with idiopathic trigeminal neuralgia treated with a single CT guided RFT procedure between January 2002 and December 2013. The mean follow-up time was 46.14 ±â€Š30.91 months. Immediate postprocedure pain relief was 98.4%. V2 division obtained the best pain relief rate: 91%, 89%, 80%, 72%, 60%, and 54% at 1, 3, 5, 7, 9, and 11 years, respectively. No statistical difference pairwise comparison was in other groups. The complications included masseter muscle weakness, corneitis, diplopia, ptosis, hearing loss, limited mouth opening, and low pressure headache. Masticatory weakness mostly occurred in patients with V3 branch involvement, while Corneitis and Diplopia all in patients with V1 branch involvement. No mortalities observed during or after RFT. All different branches division of trigeminal neuralgia achieved comparable satisfactory curative effect; V2 obtained the best excellent pain relief, after RFT procedure. Facial numbness is inevitable after RFT, which patients who have pain in all 3 trigeminal divisions and patients who desire no facial numbness should be cautious. Masticatory weakness is mainly related with V3 injured, while Corneitis and Diplopia in patients with V1 injured by RFT.