Search

Drug-coated balloon therapy is a minimally invasive endovascular approach to treat obstructive arterial disease, with increasing utilization in the peripheral circulation due to improved outcomes as compared to alternative interventional modalities. Broader clinical use of drug-coated balloons is limited by an incomplete understanding of device- and patient-specific determinants of treatment efficacy, including late outcomes that are mediated by postinterventional maladaptive inward arterial remodeling. To address this knowledge gap, we propose a predictive mathematical model of pressure-mediated femoral artery remodeling following drug-coated balloon deployment, with account of drug-based modulation of resident vascular cell phenotype and common patient comorbidities, namely, hypertension and endothelial cell dysfunction. Our results elucidate how postinterventional arterial remodeling outcomes are altered by the delivery of a traditional anti-proliferative drug, as well as by codelivery with an anti-contractile drug. Our findings suggest that codelivery of anti-proliferative and anti-contractile drugs could improve patient outcomes following drug-coated balloon therapy, motivating further consideration of novel payloads in next-generation devices., (Copyright © 2023 by ASME.)

Aim: The aim of the study was to evaluate the osteogenic potential of Cissus quadrangularis (CQ) hydrogel in enhancing the osseointegration of titanium to the bone in an experimental rabbit model., Materials and Methods: Six adult male New Zealand white rabbits were used in this study. A total of 24 implants (12 coated test implants and 12 uncoated control implants) were placed in these 6 rabbits. A polyethylene glycol (PEG) hydrogel was prepared with the C. quadrangularis hydrogel in which the test implants were coated. Each rabbit was operated on both hind legs and one implant, each, was placed in the femur and tibia. Hence, one rabbit received four implants [two test implants (HG coated) and two control implants (uncoated)]. The animals were sacrificed after 4 weeks, and the specimens were histomorphometrically analyzed. The bone-to-implant contact (BIC) and the bone area fraction occupancy (BAFO) were calculated using Image J analysis., Results: The statistically analyzed values which were obtained by paired t -test, revealed that the average mean values were higher in the test implants (coated) than the control implants (uncoated). The BIC values of the test implants were not significantly different from the control implants in the case of both femur and tibia ( p >0.05). The test implants showed significantly increased BAFO values in femur ( p <0.05). However, the BAFO values of test implants in tibia did not vary significantly from the control implants., Conclusion: Based on the findings of the study, the authors conclude that the coating of C. quadrangularis hydrogel enhances the osseointegration of titanium implants to bone. The further studies need to be designed to check the osseointegrative potential of C. quadrangularis ., Clinical Significance: The findings of this study suggest that the C. quadrangularis hydrogel is a potent osteogenic material that can reduce the osseointegration period and thus enhance the patient compliance toward implant treatment.

The prevention of surgical site infections is directly related to the minimization of surgical invasiveness, and is in line with the concept of minimally invasive spine therapy (MIST). In recent years, the incidence of postoperative infections has been increasing due to the increased use of spinal implant surgery in patients at high risk of infection, including the elderly and easily infected hosts, the limitations of poor bone marrow transfer of antibiotics, and the potential for contamination of surgical gloves and instruments. Thus, the development of antimicrobial implants in orthopedic and spinal surgery is becoming more and more popular, and implants with proven antimicrobial, safety, and osteoconductive properties (i.e., silver, iodine, antibiotics) in vitro, in vivo, and in clinical trials have become available for clinical use. We have developed silver-containing hydroxyapatite (Ag-HA)-coated implants to prevent post-operative infection, and increase bone fusion capacity, and have successfully commercialized antibacterial implants for hip prostheses and spinal interbody cages. This narrative review overviews the present status of available surface coating technologies and materials; describes how the antimicrobial, safety, and biocompatibility (osteoconductivity) of Ag-HA-coated implants have been demonstrated for commercialization; and reviews the clinical use of antimicrobial implants in orthopedic and spinal surgery, including Ag-HA-coated implants that we have developed.

The rapid development of multidrug-resistant (MDR) bacteria and biofilm-related infections (BRIs) has urgently called for new strategies to combat severe orthopaedic device-related infections (ODRIs). Antimicrobial coating has emerged as a promising strategy in halting the incidence of ODRIs and treating ODRIs in long term. With the advancement of material science and biotechnology, numerous antimicrobial coatings have been reported in literature, showing superior antimicrobial and osteogenic functions. This review has specifically discussed the currently developed antimicrobial coatings in the perspective of drug release from the coating system, focusing on their realization of controlled and on demand antimicrobial agents release, as well as multi-functionality. Acknowledging the multidisciplinary nature of antimicrobial coating, the conceptual design, the deposition method and the therapeutic effect of the antimicrobial coatings have been described in detail and discussed critically. Particularly, the challenges and opportunities on the way toward the clinical translation of antimicrobial coatings have been highlighted., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Silk sutures with antibacterial and anti-inflammatory functions were developed for sustained dual-drug delivery to prevent surgical site infections (SSIs). The silk sutures were prepared with core-shell structures braided from degummed silk filaments and then coated with a silk fibroin (SF) layer loaded with berberine (BB) and artemisinin (ART). Both the rapid release of drugs to prevent initial biofilm formation and the following sustained release to maintain effective concentrations for more than 42 days were demonstrated. In vitro assays using human fibroblasts (Hs 865.Sk) demonstrated cell proliferation on the materials, and hemolysis was 2.4 ± 0.8%, lower than that required by ISO 10993-4 standard. The sutures inhibited platelet adhesion and promoted collagen deposition and blood vessel formation. In vivo assessments using Sprague-Dawley (SD) rats indicated that the coating reduced the expression of pro-inflammatory cytokines interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α), shortening the inflammatory period and promoting angiogenesis. The results demonstrated that these new sutures exhibited stable structures, favorable biocompatibility, and sustainable antibacterial and anti-inflammatory functions with potential for surgical applications.

Background: Although percutaneous transluminal angioplasty and stenting (PTAS) was an effective and safe alternative treatment for severe intracranial atherosclerosis disease (ICAD), the high rate of restenosis remained a major issue for this endovascular procedure. Recently, the application of drug-coated balloons (DCB) in ICAD was developed to reduce restenosis. This systematic review aimed to evaluate the efficacy and safety of DCB angioplasty for ICAD., Methods: We searched relevant databases for eligible studies enrolling ICAD patients treated with DCB. The event rates of restenosis and periprocedural complications in the follow-up period were pooled with random-/fixed-effect models using Freeman-Tukey double arcsine transformation. Heterogeneity tests and publication bias tests were performed., Results: Two hundred and twenty-four ICAD patients treated with DCB from 9 eligible studies were included. Rate of stenosis in the DCB arm before treatment was ranged from 62% to 90% and reported median follow-up was ranged from 3 to 10.7 months. The pooled incidence of restenosis were 5.7% (95% confidence interval [CI] 2.6%-9.7%; I 2 = 0%, p = 0.516) and 5.9% for periprocedural complications (95% CI: 2.5-10.3%; I 2 = 0%, p = 0.649) in follow-up term., Conclusion: With the limitation of the low quality of the available evidence, angioplasty with DCB appears to be effective and safe in severe ICAD. Further larger randomized trials are needed to provide more definitive evidence and to address the ideal clinical context for their application., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are life-threatening conditions best approached with multidisciplinary burn-equivalent care. There is a lack of consensus on wound management, in particular, whether to debride detached epidermis. Our center instituted "antishear" wound therapy 35 years ago, where detached skin is left in situ as a biologic dressing and a standardized protocol avoids shear forces to prevent further desquamation. Our center's initial results showed outcomes comparable to SCORTEN predictions, but advancements in burn critical care necessitate a reevaluation of the antishear approach. A retrospective chart review was conducted for all patients admitted between June 2004 and May 2020 with a dermatologist-confirmed diagnosis of SJS/TEN (N = 51). All patients were treated with burn-equivalent critical care and antishear wound therapy. Standardized mortality ratios were calculated using the established SCORTEN, and newly developed ABCD-10, prediction models. Mean SCORTEN, ABCD-10, and %TBSA were 2.6, 2.0, and 28%. Overall mortality was 22%; SCORTEN score (P < .001), ABCD-10 score (P < .01), %TBSA involved (P = .02), and development of multisystem organ failure (P < .001) correlated with increased mortality. Cohort-wide standardized mortality based on ABCD-10 was 1.18 (P = .79). Standardized mortality based on SCORTEN was 0.62 (P = .20) and 0.77 (P = .15) for patients with scores ≤3 and >3; across the cohort it was 0.71 (P = .11), representing a 29% mortality reduction. Incorporating the antishear approach as part of burn-equivalent care for SJS/TENs led to outcomes comparable to those predicted for surgical debridement via SCORTEN. However, the antishear approach has the advantage of avoiding painful dressing changes, sedation, and general anesthesia required for surgical debridement., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Biofilms formed from the pathogenic bacteria that attach to the surfaces of biomedical devices and implantable materials result in various persistent and chronic bacterial infections, posing serious threats to human health. Compared to the elimination of matured biofilms, prevention of the formation of biofilms is expected to be a more effective way for the treatment of biofilm-associated infections. Herein, we develop a facile method for endowing diverse substrates with long-term antibiofilm property by deposition of a hybrid film composed of tannic acid/Cu ion (TA/Cu) complex and poly(ethylene glycol) (PEG). In this system, the TA/Cu complex acts as a multifunctional building block with three different roles: (i) as a versatile "glue" with universal adherent property for substrate modification, (ii) as a photothermal biocidal agent for bacterial elimination under irradiation of near-infrared (NIR) laser, and (iii) as a potent linker for immobilization of PEG with inherent antifouling property to inhibit adhesion and accumulation of bacteria. The resulted hybrid film shows negligible cytotoxicity and good histocompatibility and could prevent biofilm formation for at least 15 days in vitro and suppress bacterial infection in vivo , showing great potential for practical applications to solve the biofilm-associated problems of biomedical materials and devices.

Purpose: The causes and pathogenetic mechanisms underlying abdominal aortic aneurysms (AAAs) and pseudoaneurysms are not fully understood. We hypothesized that inhibiting programmed death-1 (PD-1) can decrease AAA and pseudoaneurysm formation in mouse and rat models., Methods: Human AAA samples were examined in conjunction with an adventitial calcium chloride (CaCl 2 ) application mouse model and an aortic patch angioplasty rat model. Single-dose PD-1 antibody (4 mg/kg) or BMS-1 (PD-1 inhibitor-1) (1 mg/kg) was administered by intraperitoneal (IP) or intraluminal injection. In the intramural injection group, PD-1 antibody was injected after CaCl 2 incubation. The rats were divided into three groups: (1) the control group was only decellularized without other special treatment, (2) the PD-1 antibody-coated patch group, and (3) the BMS-1 coated patch group. Patches implanted in the rat abdominal aorta were harvested on day 14 after implantation and analyzed., Results: Immunohistochemical analysis showed PD-1-positive cells, PD-1 and CD3, PD-1 and CD68, and PD-1 and α-actin co-expressed in the human AAA samples. Intraperitoneal (IP) injection or intraluminal injection of PD-1antibody/BMS-1 significantly inhibited AAA progression. PD-1 antibody and BMS-1 were each successfully conjugated to decellularized rat thoracic artery patches, respectively, by hyaluronic acid. Patches coated with either humanized PD-1 antibody or BMS-1 can also inhibit pseudoaneurysm progression and inflammatory cell infiltration., Conclusion: PD-1 pathway inhibition may be a promising therapeutic strategy for inhibiting AAA and pseudoaneurysm progression., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This prospective, randomized controlled trial study compared the effects of four dressings for adult partial thickness burns, focusing on re-epithelialization time and cost effectiveness. Adults with partial thickness burns meeting inclusion criteria were randomized to either Biobrane™, Acticoat™, Mepilex® Ag, or Aquacel® Ag. Primary endpoint for analysis was >95% re-epithelialization. Incremental cost-effectiveness ratios were calculated based on dressing costs. Dominance probabilities between treatment arms were calculated from bootstrap resampling trial data. One hunderd thirty-one partial thickness burn wounds in 119 patients were randomized. Adjusting for sex, age, smoking status, burn mechanism, TBSA, and first aid adequacy, Mepilex® Ag had a reduced time to re-epithelialization compared to Biobrane™ (IRR: 1.26; 95% CI: 1.07-1.48, P < .01). Economic analysis showed that there was a 99%, 71%, and 53% probability that Mepilex® Ag dominated (cheaper and more effective) Biobrane™, Acticoat™, and Aquacel® Ag, respectively. Mepilex® Ag achieved faster re-epithelialization and better cost effectiveness. Patient satisfaction and comfort seems better with Biobrane™ although not reflected within the end outcome of the healed wound. It is the patients' (after extensive education) and clinicians' choice, level of experience, and availability of products in praxis that will guide the decision as to which the product is used individually on which patient., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cardiovascular disease (CVD) poses serious health concerns worldwide. The lack of transplantable vascular grafts is an unmet clinical need in the surgical treatment of CVD. Although expanded polytetrafluoroethylene (ePTFE) vascular grafts have been used in clinical practice, a low long-term patency rate in small-diameter transplantation application is still the biggest challenge. Thus, surface modification of ePTFE is sought after. In this study, polydopamine (PDA) was used to improve the hydrophilia and provide immobilization sites in ePTFE. Bivalirudin (BVLD), a direct thrombin inhibitor, was used to enhance the anti-thrombotic activity of ePTFE. The peptides derived from extracellular matrix proteins were used to elevate the bioactivity of ePTFE. The morphology, chemical composition, peptide modified strength, wettability, and hemocompatibility of modified ePTFE vascular grafts were investigated. Then, an endothelial cell proliferation assay was used to evaluate the best co-modification strategy of the ePTFE vascular graft in vitro . Since a large animal could relatively better mimic human physiology, we chose a porcine carotid artery replacement model in the current study. The results showed that the BVLD/REDV co-modified ePTFE vascular grafts had a satisfactory patency rate (66.7%) and a higher endothelial cell coverage ratio (70%) at 12 weeks after implantation. This may offer an opportunity to produce a multi-biofunctional ePTFE vascular graft, thereby yielding a potent product to meet the clinical needs.

Over the last decade, upconversion nanoparticles (UCNP) have been widely investigated in nanomedicine due to their high potential as imaging agents in the near-infrared (NIR) optical window of biological tissues. Here, we successfully develop active targeted UCNP as potential probes for dual NIR-NIR fluorescence and radioactive-guided surgery of prostate-specific membrane antigen (PSMA)(+) prostate cancers. We designed a one-pot thermolysis synthesis method to obtain oleic acid-coated spherical NaYF 4 :Yb,Tm@NaYF 4 core/shell UCNP with narrow particle size distribution (30.0 ± 0.1 nm, as estimated by SAXS analysis) and efficient upconversion luminescence. Polyethylene glycol (PEG) ligands bearing different anchoring groups (phosphate, bis- and tetra-phosphonate-based) were synthesized and used to hydrophilize the UCNP. DLS studies led to the selection of a tetra-phosphonate PEG (2000) ligand affording water-dispersible UCNP with sustained colloidal stability in several aqueous media. PSMA-targeting ligands ( i.e. , glutamate-urea-lysine derivatives called KuEs) and fluorescent or radiolabelled prosthetic groups were grafted onto the UCNP surface by strain-promoted azide-alkyne cycloaddition (SPAAC). These UCNP, coated with 10 or 100% surface density of KuE ligands, did not induce cytotoxicity over 24 h incubation in LNCaP-Luc or PC3-Luc prostate cancer cell lines or in human fibroblasts for any of the concentrations evaluated. Competitive binding assays and flow cytometry demonstrated the excellent affinity of UCNP@KuE for PSMA-positive LNCaP-Luc cells compared with non-targeted UCNP@CO 2 H. Furthermore, the binding of UCNP@KuE to prostate tumour cells was positively correlated with the surface density of PSMA-targeting ligands and maintained after 125 I-radiolabelling. Finally, a preliminary biodistribution study in LNCaP-Luc-bearing mice demonstrated the radiochemical stability of non-targeted [ 125 I]UCNP paving the way for future in vivo assessments.

Within this study, new materials were synthesized and characterized based on polysiloxane modified with different ratios of N -acetyl-l-cysteine (NAC) and crosslinked via UV-assisted thiol-ene addition, in order to obtain efficient membranes able to resist bacterial adherence and biofilm formation. These membranes were subjected to in vitro testing for microbial adherence against S. pneumoniae using standardized tests. WISTAR rats were implanted for 4 weeks with crosslinked siloxane samples without and with NAC. A set of physical characterization methods was employed to assess the chemical structure and morphological aspects of the new synthetized materials before and after contact with the microbiological medium.

Titanium (Ti) and titanium alloys have been widely used in the field of biomedicine. However, the unmatched biomechanics and poor bioactivities of conventional Ti implants usually lead to insufficient osseointegration. To tackle these challenges, it is critical to develop a novel Ti implant that meets the bioadaptive requirements for load-bearing critical bone defects. Notably, three-dimensional (3D)-printed Ti implants mimic the microstructure and mechanical properties of natural bones. Additionally, eco-friendly techniques based on inorganic-binding peptides have been applied to modify Ti surfaces. Herein, in our study, Ti surfaces were modified to reinforce osseointegration using chimeric peptides constructed by connecting W9, RP1P, and minTBP-1 directly or via (GP) 4 , respectively. PR1P is derived from the extracellular VEGF-binding domain of prominin-1, which increases the expression of VEGF and promotes the binding of VEGF to endothelial cells, thereby accelerating angiogenesis. W9 induces osteoblast differentiation in bone marrow mesenchymal stem cells and human mesenchymal stem cells to promote bone formation. Overall, chimeric peptides promote osseointegration by promoting angiogenesis and osteogenesis. Additionally, chimeric peptides with P3&4 were more effective than those with P1&2 in improving osseointegration, which might be ascribed to the capacity of P3&4 to provide a greater range for chimeric peptides to express their activity. This work successfully used chimeric peptides to modify 3D-Ti implant surfaces to improve osseointegration on the implant-bone surface.

Glycosylated pH-sensitive mesoporous silica nanoparticles (MSNs) of capecitabine (CAP) were developed for targeting colorectal cancer. The MSNs possessed an average pore diameter of 8.12 ± 0.43 nm, pore volume of 0.73 ± 0.21 cm 3 /g, and particle size of 245.24 ± 5.75 nm. A high loading of 180.51 ± 5.23 mg/g attributed to the larger pore volume was observed. The surface of the drug-loaded MSNs were capped with chitosan-glucuronic acid (CHS-GCA) conjugate to combine two strategies viz. pH-sensitive, and lectin receptor mediated uptake. In vitro studies demonstrated a pH-sensitive and controlled release of CAP which was further enhanced in the presence of rat caecal content. Higher uptake of the (CAP-MSN)CHS-GCA was observed in HCT 116 cell lines. The glycosylated nanoparticles revealed reduction in the tumors, aberrant crypt foci, dysplasia and inflammation, and alleviation in the toxic features. This illustrated that the nanoparticles showed promising antitumor efficacy with reduced toxicity and may be used as a effective carrier against cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: The present study aimed to investigate the short- and long-term clinical outcomes of self-made polyurethane-covered stents (PU-CS) in patients for the management of coronary artery perforation (CAP) during percutaneous coronary intervention (PCI)., Background: Coronary artery perforation is reckoned as a serious complication in PCI and associated with considerable morbidity and mortality. Covered stents have been used for treating the life-threatening CAP during PCI. But in some catheterization laboratories, no commercial CS is immediately available when there is an urgent need for CS to rescue the coronary rupture site., Methods: We retrospectively identified 24 patients who underwent 31 self-made PU-CS implantations due to CAP in Zhongshan Hospital, Fudan University, from June 2015 to January 2020., Results: The total procedural success rate of CS to seal the perforation was 79.2%. Nine patients (37.5%) developed cardiac tamponade, of which 8 patients (33.3%) underwent pericardiocentesis and 4 patients (16.7%) underwent cardiac surgeries. Except for 4 cardiac death cases (16.7%), none of myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis (ST) was reported during hospital stay. Data from 22 patients (91.7%) were available at 610.4 ± 420.9 days of follow-up. Major adverse cardiac events (MACE) occurred in 6 patients (27.3%), including 5 cases of cardiac death and one TLR case., Conclusions: Self-made PU-CS demonstrates high rates of successful delivery and sealing of severe CAP during PCI. Although the in-hospital mortality remains high after PU-CS implantation, the long-term follow-up shows favorable clinical outcomes, indicating the feasibility of PU-CS in treating CAP., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Xiaoyue Song et al.)

Phacoemulsification with implantation of intraocular lens (IOLs) has been widely applied as a standard treatment for cataract, which is the leading cause of vision impairment. However, it still remains a critical challenge to prevent posterior capsule opacification (PCO) in terms of postoperative visual quality. Herein, we report IOLs with mussel-inspired coatings for inhibiting lens epithelial cells and then preventing PCO through photothermal conversion effect. The mussel-inspired coatings are deposited on the nonoptical surface areas of IOLs, endowing the modified IOLs with efficient photothermal conversion property. The temperature can be facilely raised to 50-60 °C for the photothermal IOLs (PT-IOLs) by near-infrared (NIR) laser irradiation at a safe intensity of 0.3 W/cm 2 . These PT-IOLs display high capability of inhibiting lens epithelial cells (LECs) in vitro . Therefore, under routine NIR laser irradiation, New Zealand white rabbits implanted with the PT-IOLs demonstrate significantly lower evaluation of PCO (EPCO) scores than the control groups. The overall results indicate that our PT-IOLs provide a promising choice for the clinical prevention of PCO, thus opening a way to maintain the postoperative visual qualities for cataract patients.

Purpose: To analyze the first results of calcium-phosphate-coated porous tibia cones., Methods: Patients treated with TrabecuLink ® -CaP Cones were retrospectively recruited from January 2016 to December 2017. These custom-made cones were produced using titanium alloy Ti-6Al-4 V (Tilastan ® ) and using additive manufacturing with a special calcium-phosphate coating (HX ® -coating). Clinical outcome was evaluated using Oxford Knee Score. For radiological evaluation of the implants, patients sent us outpatient taken radiographs. A minimum follow-up of one year was required. Lastly, we analyzed postoperative complications and revision rates., Results: 52 patients with revision knee arthroplasty (RKA) were recruited for final analysis, of whom, we had 17 septic RKAs (33%) and 35 aseptic cases of RKA (67%). The bone defects were grouped into 17 AORI Type 2A (32.7%), 14 Type 2B (26.9%) and 21 Type 3 (40.4%). After a mean follow-up of 22 months (13.2-34.8; SD = ± 10), we had 4 surgical revisions (7.7%), 2 septic and 2 aseptic cases. The mean Oxford Knee Score was 28.6 points (8-47; SD = ± 10). 22 of 28 radiographs (78.6%) showed regular positioning of the cones and TKAs at a mean follow-up of 16.8 months (13.2-34.8; SD = ± 6). Three patients (10.7%) showed slight radiolucencies in the bone-cement interfaces and 3 patients (10.7%) had beginning heterotopic ossifications., Conclusions: This study shows the initial clinical results of calcium-phosphate-coated tibia cones showing a good functional outcome. Further research should focus on long-term clinical and radiological follow-up.

Purpose: Improvement of biomechanical properties of cobalt-chromium-molybdenum (CoCrMo) implant surface and reduction of adhesive wear is achieved by titanium-nitride (TiN) coating in vitro. Less pain, higher postoperative outcome scores and a lower revision rate after TKA with a TiN-coated CoCrMo TKA compared with uncoated CoCrMo TKA after 10-year follow-up was hypothesized., Methods: In a double-blinded RCT, 101 patients received a cementless mobile-bearing CoCrMo TKA, either TiN-coated or uncoated. The primary outcome measure was the visual analogue scale (VAS) score for pain and secondary outcome measures were the Knee Society Score (KSS), Oxford Knee Score (OKS), revision rate and adverse events. Patients were assessed at 6 weeks, 6 months, 1 year, 5 years and 10 years, postoperatively., Results: 68 patients (67%) were available for 10-year follow-up. No difference was found in any of the assessed outcome measures with a mean decrease in VAS score (31.6 ± 22.9) and a mean increase in OKS (10.9 ± 8.4), KSS (29.3 ± 31.4), KSSK (26.4 ± 18.2) and KSSF (4.1 ± 22.9). Overall revision rate was 7% (coated 6% vs uncoated 8%) without additional revision procedures between 5 and 10-year follow-up., Conclusions: The in vitro potential benefits of TiN coating did not result in better clinical outcome when compared to an uncoated cementless TKA. Pain, functional outcome and revision rates were comparable after 10-year follow-up. TiN-coated cementless TKA provides comparable good long-term results, similar to uncoated cementless CoCrMo TKA., Level of Evidence: Level 1, Therapeutic Study NETHERLANDS TRIAL REGISTER: NL2887/NTR3033.

Peri-implantitis is a typical pathological condition characterized by the destructive inflammation in the soft tissue and the progressive loss of supporting bones. As the current effective treatments and preventive measures are inconsistent and unpredictable, the use of biomaterials as carriers of bioactive ion coatings is a promising approach. However, the translation from lab to large-scale production and clinical applications is difficult due to a technology barrier. Determining the effective dosage of each ion to achieve an in vivo application of the in vitro screening is challenging. Here, we selected zinc and strontium ions to provide multiple effects on antibacterial activity and osteogenesis. The optimal coating with effective release concentrations of the two ions was obtained after the two-step screening from in vitro testing. The results showed that this type of in vivo bioactive ion usage leads to an enhanced osseointegration during the immediate implantation in a periodontitis-affected environment and prevents soft tissue inflammation and bone resorption in an inflammatory environment. The new biologically active ion screening method could verify the effectiveness of this clinical translation and its potential for large-scale production and could determine the effective dosage of each ion for a specific application.

Hydroxyapatite (HA) coatings directly deposited by hydrothermal electrochemical technology (HET) onto carbon/carbon (C/C) composites exhibited a catastrophic failure occurring at the interface of the HA and C/C. To overcome this problem, a polyvinyl alcohol (PVA)/graphene oxide (GO) interlayer (P/G interlayer) was applied on the (NH 4 ) 2 S 2 O 8 -pretreated C/C substrate (named P/G-C/C) by using a dipping method. Subsequently, a calcium phosphate coating was deposited on P/G-C/C, shortened as M-P/G-C/C, by HET, and then converted into HA coating (abbreviated as HA-P/G-C/C) through posthydrothermal treatment. For comparison, HA coating was prepared onto C/C without a P/G interlayer through the same process, which was denoted as HA-C/C. The composition, microstructure, and morphology of the samples were characterized by X-ray diffractometry (XRD), energy-dispersive spectroscopy (EDS), scanning electron microscopy (SEM), Raman spectra, Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS). The adhesive performance of the coatings on C/C was measured by a scratch test. Finally, an in vitro bioactivity of the coatings was evaluated in a simulated body fluid solution at 37 °C. Results showed no apparent differences in the morphology and phase of the posttreated coatings, both of which are composed of a dense structure containing needle-like HA crystals. However, the HA-P/G-C/C sample possessed a higher Ca/P ratio and denser interface, thereby exhibiting higher adhesive performance and better bioactivity. The adhesive strength of the HA-P/G coating was observed at a critical load of 41.04 N, which increased by 29.3% relative to the HA coating. Moreover, the failure site was on the HA-P/G coating rather than at the interface. The enhanced adhesive performance was ascribed to the PVA/GO-repairing pits on C/C and PVA and GO toughening effects on the HA coating. In vitro and in vivo tests revealed no statistical significance for the two HA-coated C/C samples, although the HA-P/G coating exhibited better bioactivity, inducing the growth of bonelike apatite than the HA coating.

Preventing bacterial colonization on scaffolds while supporting tissue formation is highly desirable in tissue engineering as bacterial infection remains a clinically significant risk to any implanted biomaterials. Elemental selenium (Se 0 ) nanoparticles have emerged as a promising antimicrobial biomaterial without tissue cell toxicity, yet it remains unknown if their biological properties are from soluble Se ions or from direct cell-nanoparticle interactions. To answer this question, in this study, we developed a layered coating consisting of a Se nanoparticle layer underneath a micrometer-thick, biomimetic calcium phosphate (CaP) layer. We showed, for the first time, that the release of soluble HSe - ions from the Se nanoparticles strongly inhibited planktonic growth and biofilm formation of key bacteria, Staphylococcus aureus . The Se-CaP coating was found to support higher bone formation than the CaP-only coating in critical-size calvarial defects in rats; this finding could be directly attributed to the released soluble Se ions as the CaP layers in both groups had no detectable differences in the porous morphology, chemistry, and release of Ca or P. The Se-CaP coating was highly versatile and applicable to various surface chemistries as it formed through simple precipitation from aqueous solutions at room temperature and therefore could be promising in bone regeneration scaffolds or orthopedic implant applications.

Natural animal collagen and its recombinant collagen are favourable replacements in human tissue engineering due to their remarkable biomedical property. However, this exploitation is largely restricted due to the potential of immunogenicity and virus contamination. Exploring new ways to produce human collagen is fundamental to its biomedical and clinical application. All human fibrillar collagen molecules have three polypeptide chains constructed from a repeating Gly-Xaa-Yaa triplet, where Xaa and Yaa represent one random amino acid. Using cDNA techniques to modify several repeat sequences of the cDNA fragment, a novel human collagen, named recombinant human-like collagen (rHLC), with low immunogenicity and little risk from hidden virus can be engineered and notably tailored to specific applications. Human-like collagen (HLC) was initially used as a coating to modify the tissue engineering scaffold, and then used as the scaffold after cross-link agents were added to increase its mechanical strength. Due to its good biocompatibility, low immunogenicity, stabilised property, and the ability of mass production, HLC has been widely used in skin injury treatments, vascular scaffolds engineering, cartilage, bone defect repair, skincare, haemostatic sponge, and drug delivery, including coating with medical nanoparticles. In this review, we symmetrically reviewed the development, recent advances in design and application of HLC, and other recombinant human collagen-based biomedicine potentials. At the end, future improvements are also discussed.

Device-related problems of drug-eluting stents, including stent thrombosis related to antiproliferative drugs and polymers, can cause adverse events such as inflammation and neointimal hyperplasia. Stent surface modification, wherein the drug and polymer are not required, may overcome these problems. We developed hydrophilic polyethylene glycol (PEG)-coating and hydrophobic octadecylthiol (ODT)-coating stents without a drug and polymer and evaluated their histopathologic response in a porcine coronary restenosis model. PEG-coating stents (n = 12), bare-metal stents (BMS) (n = 12), and ODT-coating stents (n = 10) were implanted with oversizing in 34 porcine coronary arteries. Four weeks later, the histopathologic response, arterial injury, inflammation, and fibrin scores were analyzed. A p value < 0.05 was considered statistically significant. There were significant differences in the internal elastic lamina area, lumen area, neointimal area, percent area of stenosis, arterial injury score, inflammation score, and fibrin score among the groups. Compared to the BMS or ODT-coating stent group, the PEG-coating stent group had significantly increased internal elastic lamina and lumen area (all p < 0.001) and decreased neointimal area and percent area of stenosis (BMS: p = 0.03 and p < 0.001, respectively; ODT-coating: p = 0.013 and p < 0.001, respectively). Similarly, the PEG-coating group showed significantly lower inflammation and fibrin scores than the BMS or ODT-coating groups (BMS: p = 0.013 and p = 0.007, respectively; ODT-coating: p = 0.014 and p = 0.008, respectively). In conclusion, hydrophilic PEG-coating stent implantation was associated with lower inflammatory response, decreased fibrin deposition, and reduced neointimal hyperplasia than BMS or hydrophobic ODT-coating stent implantation in the porcine coronary restenosis model.

Recent years have seen a marked rise in implantation into the body of a great variety of devices: hip, knee, and shoulder replacements, pacemakers, meshes, glucose sensors, and many others. Cochlear and retinal implants are being developed to restore hearing and sight. After surgery to implant a device, adjacent cells interact with the implant and release molecular signals that result in attraction, infiltration of the tissue, and attachment to the implant of various cell types including monocytes, macrophages, and platelets. These cells release additional signaling molecules (chemokines and cytokines) that recruit tissue repair cells to the device site. Some implants fail and require additional revision surgery that is traumatic for the patient and expensive for the payer. This review examines the literature for evidence to support the possibility that fibronectins and BMPs could be coated on the implants as part of the manufacturing process so that the proteins could be released into the tissue surrounding the implant and improve the rate of successful implantation.

Background: The funnel has been used in esthetic breast surgery that requires a small incision. Recent advances in minimally invasive surgical techniques have led to more cases of nipple-sparing mastectomy (NSM) through periareolar incision. However, prepectoral implant placement and complete coverage with acellular dermal matrix (ADM) is almost impossible with the periareolar approach. Funnels can also be useful for direct-to-implant breast reconstruction., Methods: NSM with periareolar incision and direct-to-implant breast reconstruction were performed with prepectoral implant placement between January 2017 and July 2019. The ADM full-wrapped anatomic textured implant was inserted using a funnel without additional incisions during surgery., Results: A total of 21 patients were enrolled, including 2 who received bilateral breast reconstruction. All operations were successfully performed using funnels with minimal periareolar incisions. Anatomic textured implants (mean: 251.7 cc, range: 90-450 cc) wrapped in ADM can be effectively inserted in the prepectoral plane using a funnel. Two patients experienced delayed wound healing of the areola that was treated by conservative wound management. Patients also experienced less pain overall, and the cosmetic result was very good. Patient satisfaction scores were also very high., Conclusions: While the periareolar incision is esthetically pleasing, additional resection is often necessary. However, the use of funnels ensured that no additional incision was needed even in large implants. This subsequently led to better results in terms of pain and scarring. Prepectoral breast reconstruction involving complete implant coverage with ADM using a funnel through the periareolar approach represents a good alternative to the traditional dual plane subpectoral method. This method provides good patient satisfaction without adverse outcomes., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Airway stenting is an efficacious approach in management of malignant airway disease (MAD) with improvement in survival outcome., Objective: To determine the indications and long-term clinical outcomes of tracheobronchial stenting in patients with MAD., Methods: A cross-sectional review of 51 patients who underwent airway stenting from June 2011 to June 2019 was done. Paired t-test was used to compare mean difference of clinical characteristics between pre- and post-airway stenting. Kaplan-Meier curves were used to assess overall survival., Results: A total of 51 patients had stent insertion with mean age 46.63±17.10years including 27(52.9%) females. Mainly 37(72.5%) patients had esophageal and 06(11.8%) had lung cancer. The main indications were bronchial stenosis 18(35.3%), tracheal stenosis 11(21.6%) and Tracheo-esophageal/bronchial fistula 13(25.5%). Obstruction was intrinsic, extrinsic and mixed in 20(39.2%), 13(25.5%) and 5(9.8%) patients, respectively. There was statistically significant mean difference in pre- and post-procedure oxygen saturation (mean (M)=89.8, standard deviation (SD)=6.70 vs M =95.5,SD=2.54.p =0.001) and performance status (M =3.65,SD =0.6 vs M =2.59, SD=0.83.p =0.001). Overall median survival was 16±3.44 weeks, highest amongst patients with intrinsic obstruction (27±6.51 weeks)., Conclusion: Airway stenting is an effective endoscopic procedure to re-establish airway patency in MAD with minimal complications..

Background: Surgical-site infection after implant-based breast reconstruction remains a leading cause of morbidity. Doxycycline is an antibiotic used to treat soft-tissue infections. The authors hypothesize that doxycycline-coated breast implants will significantly reduce biofilm formation, surgical-site infection, and inflammation after bacterial infection., Methods: Pieces of silicone breast implants were coated in doxycycline. In vitro studies to characterize the coating include Fourier transmission infrared spectroscopy, elution data, and toxicity assays (n = 4). To evaluate antimicrobial properties, coated implants were studied after methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa inoculation in vitro and in a mouse model at 3 and 7 days (n = 8). Studies included bacterial quantification, cytokine profiles, and histology., Results: Coated silicone breast implants demonstrated a color change, increased mass, and Fourier transmission infrared spectroscopy consistent with a doxycycline coating. Coated implants were nontoxic to fibroblasts and inhibited biofilm formation and bacterial adherence after MRSA and P. aeruginosa incubation in vitro, and measurable doxycycline concentrations at 24 hours were seen. In a mouse model, a significant reduction of MRSA and P. aeruginosa bacterial colonization after 3 and 7 days in the doxycycline-coated implant mice was demonstrated when compared to the control mice, control mice treated with intraperitoneal doxycycline, and control mice treated with a gentamicin/cefazolin/bacitracin wash. Decreased inflammatory cytokines and inflammatory cell infiltration were demonstrated in the doxycycline-coated mice., Conclusions: A method to coat silicone implants with doxycycline was developed. The authors' doxycycline-coated silicone implants significantly reduced biofilm formation, surgical-site infections, and inflammation. Further studies are needed to evaluate the long-term implications.

Background: Conventional stent-based angioplasty was challenged for the high incidence of perioperative complications and follow-up in-stent restenosis (ISR) in treating intracranial atherosclerotic disease (ICAD). Currently, the drug-coated balloon (DCB) has shown promise in preventing and treating ISR., Objective: To compare the efficacy and safety of DCB dilation (with or without stenting) with conventionally only stenting angioplasty for symptomatic ICAD in routine clinical practice., Methods: From January 2016 to January 2019, consecutive patients treated with endovascular therapy for symptomatic ICAD were identified and dichotomized by whether DCB was used. The efficacy and safety endpoints, including periprocedural complications, clinical, and imaging follow-up outcomes between the 2 groups, were compared by propensity score matching., Results: A total of 42 patients in the DCB group and 73 patients in the non-DCB group were enrolled. Propensity score matching analysis selected 76 matched patients. Angiographic follow-up was completed at 185 ± 33 d. The median stenosis degree (0 [0%-20.0%] vs 15.0 [0%-62.5%], P = .005) and total restenosis incidence (5.3% [2/38] vs 34.2% [13/38], P = .003) in the DCB group were significantly lower than those in the non-DCB group. The periprocedural complications (2.6% vs 10.5%, P = .375), recurrent ischemic events (2.6% vs 13.2%, P = .219), and symptomatic restenosis (2.6% vs 10.5%, P = .375) were not statistically different between the 2 groups., Conclusion: Compared with conventionally only stenting angioplasty, DCB dilation can effectively lower restenosis degree and total restenosis risk, with no superiority in symptomatic restenosis at 6-mo follow-up., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Introduction: This study aimed to evaluate the safety and efficacy of paclitaxel-coated balloon compared with conventional plain balloon for the treatment of failing native dialysis access., Materials and Methods: This prospective study included 60 patients presenting to the Kasr Alainy Hospitals and Aseer Central Hospital in the period from September 2015 to December 2017 with failing native vascular access. Dilatation with a plain balloon was done in 30 patients (group I) and with a paclitaxel-coated balloon in 30 patients (group II) with either stenosis or occlusion. The majority were outflow lesions, with 20 (66.7 %) patients in group I and 21 (70%) patients in group II. Mean balloon diameter was 7.1mm (± 1.5mm) compared with 6.5mm (± 1.2mm) and length 66mm (± 19.1mm) compared with 54.6mm (± 15.7mm), respectively. Safety endpoint was reported as 30 day's freedom from procedure-related major complications and mortality. Procedural technical success was defined as a residual diameter 30% or less for treated lesions. Target lesion primary patency, circuit primary patency and secondary patency were reported at 3, 6 and 12 months., Results: There were no 30-day procedure-related major complications or mortality in either group. Procedural technical success of 100% was achieved in both groups. Target lesion primary patency, circuit primary patency and secondary patency in group II were better than in group I, especially at 12 months (90% vs 66.7%, 83.3% vs 60% and 96.7% vs 93.3%, respectively). There was a statistically significant difference in target lesion primary patency ( p = 0.029) in patients who were treated with paclitaxel-coated balloon angioplasties., Conclusion: The paclitaxel-coated balloon proved to be safe and effective, and improved the patency of failing vascular access. Results are comparable with previous studies.

Background: Grilling has become increasingly common in Germany. Although grilling is considered a non-negligible household burn hazard, few reports have assessed this type of injury. This study aimed to determine the patterns and characteristics of grill-related burn injuries and to compare these with other types of burn injuries., Methods: This retrospective observational study included all grill-related burn injuries admitted to Cologne Merheim Burn Center during 1989-2017. The collected data were analyzed descriptively and compared statistically with other fire injuries., Results: Of 1706 cases admitted with fire injuries during the study period, 160 (∼10%) involved grill-related injuries. Most cases (85%) involved men, with an average age of 34 years. Moreover, 48% and 38% of cases occurred in summer and spring, respectively. The most common mechanism of injury was ignition via fluid accelerant. The upper limb was the most commonly affected body part, followed by the head. Statistical analyses revealed that grill-related injuries were associated with a lower mean age and total body surface area, shorter in-hospital stay, and fewer complications than the other fire injury group., Conclusion: Grill-related injuries are a relatively common cause of admission to the Cologne Burn Center. Although grill-related injuries underwent a less aggressive approach than the other investigated fire injuries, the former represent a public health concern because they mainly affect the upper body, with both psychologic and aesthetic consequences. We recommend a German nationwide multi-centric study of the patterns and characteristics of burn injury., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

In situ regeneration of the enamel-like structure of hydroxyapatite (HAp) crystals under oral conditions is significant for dental caries treatment. However, it is still a challenge for dentists to duplicate the elegant and well-aligned apatite structure bonding to the surface of demineralized enamel. A biocompatible amelogenin-inspired matrix, a phase-transited lysozyme (PTL) film mimicking an N-terminal amelogenin with central domain (N-Ame) combined with synthetic peptide (C-AMG) based on the functional domains of C-terminal telopeptide (C-Ame) is shown here, which is formed by amyloid-like lysozyme aggregation at the enamel interface through a rapid one-step aqueous coating process. In the PTL/C-AMG matrix, C-AMG facilitated the oriented arrangement of amorphous calcium phosphate (ACP) nanoparticles and their transformation to ordered enamel-like HAp crystals, while PTL served as a strong interfacial anchor to immobilize the C-AMG peptide and PTL/C-AMG matrix on versatile substrate surfaces. PTL/C-AMG film-coated enamel induced both of the in vivo and in vitro synthesis of HAp crystals, facilitated epitaxial growth of HAp crystals and recovered the highly oriented structure and mechanical properties to levels nearly identical to those of natural enamel. This work underlines the importance of amyloid-like protein aggregates in the biomineralization of enamel, providing a promising strategy for treating dental caries., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The stability of plasma-sprayed hydroxyapatite (HA) coatings on metallic implants in vivo remains a significant challenge for load-bearing orthopedic implants despite their excellent mechanical and osteoconductive properties. This study focuses on oxide layer formation on the surface of Ti6Al4V samples through furnace heating at 600, 700, and 800 °C for 10 min for optimization of the most effective oxide layer to increase plasma coating crystallinity and improve plasma coating bond strength with the metal surface. The 800 °C heat treatment shows an effective oxide layer which increases coating crystallinity from 64 to 75% and coating adhesive bond strength from 25.9 ± 2.3 to 30.7 ± 1.1 MPa, while simultaneously reducing the dissolution rate of HA coatings. The addition of biologically relevant dopants, MgO and SiO 2 , show negligible effects on crystallinity and adhesive bond strength on plasma-sprayed HA coatings and additionally show an enhancement effect on osteoblast proliferation and differentiation. Moreover, the inclusion of these additivess shows an increase in osteogenesis in a rat distal femur model after 6 and 10 weeks of implantation. Overall, this study provides a direct solution to improve the crystallinity, adhesive bond strength, and osteogenic properties of plasma-sprayed HA coatings on orthopedic implants that is more manufacturable and translational from research to an industrial scale.

In 2020, the world is being ravaged by the coronavirus, SARS-CoV-2, which causes a severe respiratory disease, Covid-19. Hundreds of thousands of people have succumbed to the disease. Efforts at curing the disease are aimed at finding a vaccine and/or developing antiviral drugs. Despite these efforts, the WHO warned that the virus might never be eradicated. Countries around the world have instated non-pharmaceutical interventions such as social distancing and wearing of masks in public to curb the spreading of the disease. Antiviral polysaccharides provide the ideal opportunity to combat the pathogen via pharmacotherapeutic applications. However, a layer-by-layer nanocoating approach is also envisioned to coat surfaces to which humans are exposed that could harbor pathogenic coronaviruses. By coating masks, clothing, and work surfaces in wet markets among others, these antiviral polysaccharides can ensure passive prevention of the spreading of the virus. It poses a so-called "eradicate-in-place" measure against the virus. Antiviral polysaccharides also provide a green chemistry pathway to virus eradication since these molecules are primarily of biological origin and can be modified by minimal synthetic approaches. They are biocompatible as well as biodegradable. This surface passivation approach could provide a powerful measure against the spreading of coronaviruses., Competing Interests: The authors declare no conflict of interest.

Atherosclerosis can lead to thrombosis, blood supply disorders, and even serious consequences such as lumen occlusion or wall rupture and bleeding, so it is urgent to develop an effective comprehensive therapy. Here, a novel kind of drug-coated balloon, where drug-loaded porous nanomotors with autonomous motion ability are used as the coating of the balloon, is reported. The drug-loaded porous nanomotors based on Janus aminated mesoporous silica (JAMS) that was obtained by asymmetric modification of platinum (Pt) nanoparticles are prepared and characterized. The platelet membrane is used to wrap the nanomotors to reduce the leakage of drugs before reaching the plaque. The motion ability of the nanomotor under the irradiation of near-infrared light, the sustained release behavior and effect of the loaded drugs (anti-proliferative drug paclitaxel and the anti-vascular cell adhesion molecule-1 antibody) are investigated in detail. The biomimetic effect and encapsulation effect on drug loading of the platelet membrane, and the elimination of inflammatory macrophages under the photothermal effect produced by Pt are also characterized. The results indicate that the drug-loaded porous nanomotors proposed for drug balloon coating in this work can penetrate into the plaque and enhance the drug retention efficiency, realizing short-term photothermal elimination of inflammatory macrophages and long-term anti-proliferation effect of the drug, providing a possible choice for drug balloon coating with high efficiency in the treatment of atherosclerosis.

Purpose: The post-hoc multivariable analysis of EffPac study data aimed to identify explanatory variables for efficacy of femoropopliteal artery angioplasty., Methods: In the prospective, randomized, controlled EffPac study, patients were allocated to either DCB or plain old balloon angioplasty. Multivariable regression including interaction analysis was conducted to assess the impact of selected variables on the outcome measures of late lumen loss (LLL) at 6 months, and on binary restenosis, target lesion revascularization (TLR), clinical improvement, and hemodynamic improvement at 12 months., Results: A total of 171 patients (69 ± 8 years, 111 men) were treated at 11 German centers. Hypertension increased, and advanced age decreased LLL (B coefficient [B]: 0.7 [95% CI - 0.04 to 1.3], p = 0.06 and - 0.3 per 10 years [95% CI - 0.5 to 0.01], p = 0.06, respectively). DCB angioplasty decreased odds of 12-month TLR and binary restenosis (OR 0.4 [95% CI 0.2 to 0.8], p = 0.01 and OR 0.1 [95% CI 0.01 to 0.6], p = 0.02, respectively). Lesion length and severe calcification decreased clinical improvement (B: - 0.1 per 10 mm [95% CI - 0.1 to - 0.03], p = 0.001 and - 0.1 [95% CI - 1.7 to - 0.1], p = 0.03, respectively). DCB angioplasty in former smokers improved ABI (0.2 [95% CI 0.01 to 0.5], p = 0.04)., Conclusion: DCB angioplasty decreased the incidence of 12-month restenosis and TLR. Increasing lesion length and severe calcification reduced clinical improvement. Hypertension is suspected to facilitate, and advanced age to mitigate LLL. DCB improved ABI most in former smokers.

Soft tissue management and fracture fixation including initial external fixation in Gustilo-Anderson type II and type III open fractures are cornerstones in the treatment but details on timing and type of wound closure, irrigation and debridement, systemic and local antibiotics, antimicrobial-coated implants and the use of Bone Morphogenetic Protein-2 remain controversial. This article looks at current clinical evidence of these items for the management of open fractures. Timing of debridement and wound closure remains critical. Early debridement by an experienced team within 24 h seems adequate while gross contamination, a devascularized limb, a multi-injured patient and compartment syndrome require immediate surgical intervention. Wound closure during the first surgery was shown to result in reduced rates for infections and nonunion. If soft-tissue reconstruction is needed, it should be performed within the first 7 days. Regarding types of irrigation fluid, antiseptic and antibacterial solutions did not prove to be superior to saline. High pressure irrigation has not been demonstrated to be beneficial whereas antibiotic administration as soon as possible has been proven to be favorable. Administration of more than 72 h was not superior to shorter systemic antibiotic intervals. For Gustilo-Anderson type I and II, broad spectrum antibiotic therapy is reasonable. Additional aminoglycosides for broader coverage are recommended in Gustilo-Anderson type III fractures. There is newer literature on the beneficial effects of the use of local antibiotics, e.g. by antibiotic beads. Coating of internal fixation devices is a modern approach to improve infection prophylaxis and gentamicin-coated implants have been demonstrated to be safe in clinical application. Vacuum assisted closure (VAC) could not evidence negative pressure wound therapy to reduce infection risk, improve self-rated disability or quality of life in open fractures, however, enhance treatment costs. Recombinant human bone morphogenetic proteins (rhBMP)-2 showed promising data in Gustilo-Anderson type III open tibial shaft fractures with lower rates of invasive secondary procedures. In conclusion, there is evidence for thorough debridement and irrigation with saline, early soft tissue coverage and the use of systemic and local antibiotics. Except for a short-term soft tissue coverage VAC seems not to be beneficial and rhBMP-2 is an additional tool in Gustilo-Anderson type III open fractures., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Titanium-based endosseous implants with high antibacterial and osseointegration activities are extremely required in clinics. To achieve this line, herein the doped coatings with three kinds of Zn doses were micro-arc oxidized (MAOed) on Ti. They were examined to reveal a bilayered structure, in which the outer layer consisted completely of the amorphism comprising elements of Ti, O and Zn with Zn doped in the form of weaken Zn-O bonds, and the underlying layer was partially crystallized with nanocrystalline TiO 2 and Zn 2 TiO 4 to embed an amorphous matrix. While the Zn doped doses of the surface amorphous layers increased with elevating the MAOed voltages, the weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn 2+ controllable release and the generator of reactive oxide species (ROS) on the coatings. The enhanced HO• and O 2 - • formation on the elevated voltage MAOed coatings caused serious break of the cell walls and plasma membranes of S. aureus. In parallel, the enhanced Zn 2+ release and extracellular H 2 O 2 formation led to the enhanced intracellular ROS level of S. aureus, further aggravating the damage of plasma membrane, resulting in bacteria death. On contrary to the overdose of Zn doped coating, the moderate doses of Zn doped coatings did not induce additional intracellular ROS and attenuate viability and proliferation of osteoblasts in vitro, and promoted osseointegration in both S. aureus-uninfected and infected rat tibias, which ascribed to the strong antibacterial activity and un-attenuated cell function of the coatings in the infected case. STATEMENT OF SIGNIFICANCE: (1) The Zn-doped coatings revealed a bilayered structure of the surface layer comprising the Ti, O and Zn constructed amorphism with Zn in the form of weaken Zn-O bonds, and the underlying layer comprising nanocrystalline TiO 2 and Zn 2 TiO 4 to embed amorphous matrix. (2) The weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn 2+ controllable release and the generator of ROS on the coatings. (3) The enhanced Zn 2+ release and ROS formation on the coatings killed S. aureus by inducing serious break of their cell walls and plasma membranes. This effect in combination of un-attenuated osteoblast proliferation endowed the moderate Zn doped coatings with enhanced osseointegration in S. aureus-infected rat tibias., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Restenosis remains a significant problem in endovascular therapy for hemodialysis vascular access. Drug-coated balloon (DCB) angioplasty decreases restenosis in peripheral and coronary artery diseases. The aim of this systematic review and meta-analysis is to assess the patency outcomes following DCB angioplasty, as compared to conventional balloon (CB) angioplasty for the stenosis of hemodialysis vascular access., Methods: A comprehensive search in the MEDLINE, EMBASE, and CENTRAL databases was conducted in order to identify eligible randomized controlled trials evaluating DCB angioplasty for hemodialysis vascular access dysfunction. The primary endpoint was the 6-month target lesion primary patency and the secondary endpoints were 12-month target lesion primary patency and procedure-related complications. Risk ratios (RR) were pooled and relevant subgroups were analyzed separately., Results: Eleven randomized controlled trials comprised of 487 patients treated with DCB angioplasty and 489 patients treated with CB angioplasty were included. There were no significant differences in the target lesion primary patency at 6 months [RR, 0.75; 95% confidence interval (CI), 0.56, 1.01; p = 0.06] and at 12 months (RR 0.89; 95% CI, 0.79, 1.00; p = 0.06). The absence of benefit for the DCB group remained, even in the arteriovenous fistula subgroup or the subgroup of studies excluding central vein stenosis. The risk of procedure-related complication did not differ between the two groups (RR 1.00; 95% CI 0.98, 1.02; p = 0.95)., Conclusion: DCB angioplasty did not demonstrate significant patency benefit for the treatment of hemodialysis vascular access dysfunction. Wide variations in patency outcomes across studies were noted. Further studies focusing on specific types of access or lesions are warranted to clarify the value of DCB for hemodialysis vascular access. (PROSPERO Number CRD42019119938)., Competing Interests: The authors have declared that no competing interests exist.

In the treatment of coronary artery disease (CAD), the use of stent implantation often leads to clinical complications such as restenosis, delayed endothelial healing, and thrombosis. Here, we develop a double drug sustained-release coating for the stent surface by grafting heparin/NONOate nanoparticles (Hep/NONOates). The Hep/NONOates and surface modification of the stent were characterized by X-ray photoelectron spectroscopy, attenuated total reflection Fourier-transform infrared spectroscopy, static water contact angle, and scanning electron microscopy (SEM), and the release behaviors of the anticoagulant, heparin (Hep) and the bioactive molecule, nitric oxide (NO) were studied. Furthermore, the blood compatibility and cytotoxicity of the modified stent were evaluated by whole blood adhesion and platelet adhesion tests, hemolysis assay, morphological changes of red blood cells, plasma recalcification time assay, in vitro coagulation time tests, and MTT assay. Finally, the results of a rabbit carotid artery stent implantation experiment showed that the double drug sustained-release coating for the stent can accelerate regeneration of endothelial cells and keep good anticoagulant activity. This study can provide new design ideas based on nanotechnology for improving the safety and effectiveness of drug-eluting stents.

In this review article, we are going to present an overview on possible applications of light-addressable electrodes (LAE) as actuator/manipulation devices besides classical electrode structures. For LAEs, the electrode material consists of a semiconductor. Illumination with a light source with the appropiate wavelength leads to the generation of electron-hole pairs which can be utilized for further photoelectrochemical reaction. Due to recent progress in light-projection technologies, highly dynamic and flexible illumination patterns can be generated, opening new possibilities for light-addressable electrodes. A short introduction on semiconductor-electrolyte interfaces with light stimulation is given together with electrode-design approaches. Towards applications, the stimulation of cells with different electrode materials and fabrication designs is explained, followed by analyte-manipulation strategies and spatially resolved photoelectrochemical deposition of different material types.

Oral administration of actives is the most desired form of delivery, but the formulations need to overcome a variety of barriers including the intestinal mucus. This feature article summarizes the developments from the past 2-3 years in this context focusing on polymer-based formulations. The progress in assembling mucopenetrating nanoparticles is outlined considering coatings using noninteracting polymers as well as virus-like particles and charge-shifting particles. Next, polymers and their modification to enhance mucoadhesion are discussed, followed by providing examples of double-encapsulation systems that aim to combine mucopenetration with mucoadhesion in the same formulation. Finally, a short outlook is provided highlighting a few of the most pressing challenges to address., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This review focuses on the biomedical applications and toxicity of spinel ferrite nanoparticles (SFNPs) with more emphasis on the recently published work. A critical review is provided on recent advances of SFNPs applications in biomedical areas. The novelty of SFNPs in addressing the bottleneck problems encountered in the areas of health; in particular, for diagnosis and treatment of tumour cells are well reviewed. Furthermore, research gaps, toxicity of SFNPs and areas which still need more attention are highlighted. Based on the result of this review, the SFNPs have unlimited capacity in cancer treatment, disease diagnosis, magnetic resonance imaging, drug delivery and release. Overall, stepping out of the conventional way of treatment is difficult but also essential in bringing long lasting solution for cancer and other diseases treatment. In fact, the toxicity study and commercialisation of the SFNPs based cancer treatment options are the main challenges and need further study, in order to reduce unforeseen consequences., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the last 5 years, a wide variety of surface modification strategies are explored to improve the integration of poly(etheretherketone) (PEEK) implants with bone. Since PEEK does not support bone on-growth, its surface properties need to be tailored to promote osteogenesis at the bone-implant interface. Surface modifications applied to achieve this response range from simple surface morphology changes to the deposition of osteoconductive coatings. Of the many methods, titanium and/or hydroxyapatite coatings, extrusion to create surface pores, and an accelerated neutral atom beam treatment have been approved by the U.S. Food and Drug Administration to improve the integration of PEEK spinal cages. The success of these surface modifications brings hope for the clinical translation of other techniques in the future, but there are several limitations that may be preventing other treatments from reaching the clinic. This review describes numerous strategies that have been applied to PEEK-based implants for improving their osseointegration and enhancing their antibacterial properties. The review concludes with a discussion about future directions for the field and provides suggestions for advancing clinical translation of surface-modified PEEK implants to improve the lives of patients in need of these implants., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Titanium (Ti) implants are commonly regarded as well accepted by the body. However, metal ion release is still a cause for concern. A small decrease in pH, which can be caused by inflammation, may produce a large increase in the corrosion rate of Ti implants. Coating the alloy with a buffer layer could have a significant protective effect. In this study, a calcium carbonate coating was developed on commercially pure Ti and a Ti-6Al-4V alloy through a hydrothermal treatment of previously NaOH-treated surfaces in calcium-citric acid chelate complexes. The results showed that a superstructured calcite coating layer formed on the Ti substrate after treatment at 170°C for 3 hr. The coating was approx. 1 μm thick and covered the substrate surface uniformly. When prolonging the hydrothermal treatment from 5 hr to 24 hr, the rhombohedral structure of calcite was observed in addition to the superstructure of calcite. Dissolution test results showed no significant differences in solution pH between the coated- and un-coated samples. However, the CaCO 3 coating reduced by approx. 2-5 times the Ti and V ion release from the substrate as compared to the uncoated material, at pH 4. CaCO 3 and hydroxyapatite (HA) coatings gave nonsignificant effects at neutral pH although the HA coating showed a trend for better results at the longer time points. The reduction in metal ion release from the substrate and the buffering ability of the CaCO 3 coating encourage further studies on this coating for clinical applications., (© 2019 Wiley Periodicals, Inc.)

The use of red blood cell (RBC) membrane coatings has recently been found to be a biomimetic strategy to confer inner core nanomaterials with improved pharmacokinetic profiles by utilizing the intrinsic long blood circulation time of RBCs. Here, we envelope superparamagnetic nanoclusters (MNCs) with RBC membrane ghosts to obtain MNC@RBCs with significantly improved physiological stability compared to that of bare MNCs. After being loaded with near-infrared (NIR) cypate molecules, the as-prepared Cyp-MNC@RBCs show remarkably increased NIR absorbance and resultant efficient photothermal conversion efficacy. By tracking the NIR fluorescence of cypate in an in vivo fluorescence imaging system, we uncover that such Cyp-MNC@RBCs upon intravenous injection show significantly improved tumor-homing capacity as compared to bare cypate-loaded MNCs. A similar result is further evidenced by recording the T 2 -weighted magnetic resonance imaging (MRI) signal of MNCs. Furthermore, upon exposure to 808 nm laser irradiation, the tumors grown on the mice with the intravenous injection of Cyp-MNC@RBCs show a higher temperature increase than the tumors grown on the mice injected with plain MNC@RBCs and thus are significantly suppressed via photothermal ablation. This study presents the preparation of biomimetic Cyp-MNC@RBCs with greatly improved tumor-homing capacity as multifunctional nanotheranostic agents for fluorescence and MRI bimodal imaging-guided cancer photothermal therapy.

Objective: To investigate whether covered stents show a higher efficacy than uncovered stents in percutaneous treatment of malignant hilar biliary obstruction., Methods: Patients with obstructive jaundice caused by an unresectable hilar malignancy were included after failed endoscopic intervention in a prospective randomized trial comparing expanded polytetrafluoroethylene and fluorinated ethylene propylene (ePTFE-FEP)-covered nitinol stents with uncovered nitinol stents. Exclusion criteria were as follows: primary tumors existing more than 3 months, a biliodigestive anastomosis, previous stenting, and a Karnofsky score of less than 50. Safety, clinical success, and adjuvant chemotherapy were compared as well as occlusion rate, patency, and survival., Results: A total of 120 patients were included. One patient was post hoc excluded. Fourteen patients who died within 7 days and one patient without patency data were excluded from patency analysis. Serious adverse events (p = 0.4), 30-day mortality (p = 0.5), and clinical success (p = 0.8) were equivalent for both stent groups. Twenty-one out of 61 (34%) patients in the covered and 24/58 (41%) in the uncovered stent groups received adjuvant chemotherapy (p = 0.5). Occlusion rate was 54% (27/50) in the covered stent group and 57% (31/54) in the uncovered stent group (p = 0.8). Median patency was 229 days (95% CI 113-345) for covered stents and 130 days (95% CI 75-185) for uncovered stents (p = 0.1). Median survival in patients with covered stents was 79 days (95% CI 52-106) and with uncovered stents 92 days (95% CI 60-124) (p = 0.3)., Conclusion: In malignant hilar biliary obstruction, there is no evidence that ePTFE-FEP-covered stents are superior to uncovered stents in terms of safety, clinical success, adjuvant chemotherapy, patency, or survival., Key Points: • Percutaneous palliation of hilar biliary obstruction is feasible with both uncovered and covered stents. • Clinical success in terms of bilirubin decrease and adjuvant chemotherapy is achievable with both stents. • Thirty-day mortality is considerable when stenting is also offered to patients with a low performance status.

Prevention of bacterial infection and promotion of osseointegration are two important issues for titanium (Ti) implants in medical research. In addition, after a biofilm is formed on the surface of implants, the immune system and antibiotic therapy may fail. In this work, bio-functionalized titanium dioxide (TiO 2 )/molybdenum disulfide (MoS 2 )/polydopamine (PDA)/arginine-glycine-aspartic acid (RGD) nanorod arrays (NAs) are prepared on Ti implants to not only kill bacteria noninvasively upon co-irradiation of 660 nm visible light (VL) and 808 nm near infrared (NIR) light, but also promote the osteogenic activity simultaneously. Dual light irradiation triggers the TiO 2 /MoS 2 NA to generate hyperthermia and reactive oxygen species (ROS) in 10 min. The synergistic effects of the generated hyperthermia and ROS increase the bacterial membrane permeability and bacteria are killed rapidly and efficiently in vitro and in vivo. The biofilm is also eradicated and RGD on the nanorods improves cell adhesion, proliferation, and osteogenic differentiation. The strategy described here for the design of bio-functionalized coatings on Ti implants has great clinical potential in orthopedics, dentistry, and other medical fields.

Despite many early accomplishments in nanomaterial design and synthesis, there remains a significant requirement for novel inorganic and organic nanohybrids with the potential to act as efficacious molecular imaging agents and theranostic vectors. The functionalization of surfactant-coated inorganic nanoparticles with polymer shells represents one of the most suitable and popular methods to synthesize polymer/inorganic nanohybrids for theranostic applications. Key requirements for effective imaging agent design include water dispersibility, biocompatibility and functionality to enable enhanced contrast magnetic resonance imaging (MRI), positron-emission tomography (PET), computed tomography (CT), or ultrasound modalities. In this Perspective, we highlight recent advances in the fabrication of organic/inorganic nanohybrids exploiting functionalized polymers prepared using reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymer shells can imbue favorable traits to the nanoparticles such as stealth, image enhancement, storage (and release) of therapeutics, and sensitivity to biological stimuli. In this Perspective, we discuss the design and synthesis of hybrid nanoparticles and discuss current trends and future opportunities.

Modification of titanium (Ti) bone implant materials with hybrid organic-inorganic coatings is a novel promising approach to improve the osteoconductivity and osteointegration of implants and prevent their failure after implantation. However, in these coatings, which are mostly hydrophilic, chemically active moieties capable of releasing oxidizing ions can have a significant influence on the corrosion resistance of Ti, which is critical for the Ti implant osteointegration behavior. In this research, in order to study the dependence of the change of the corrosion behavior of Ti on the composition of the coating, Ti surfaces were modified with various coatings: organic (alginate hydrogel crosslinked with Ca 2+ ions (Alg), and dextran sulfate (DS)), inorganic (porous calcium carbonate CaCO 3 ), and composite organic-inorganic (Alg-CaCO 3 , DS-CaCO 3 ). The morphology and composition of these materials before and after the corrosion experiment, performed in simulated body fluid (SBF), were followed by extensive characterization. Electrochemical impedance spectroscopy (EIS) was performed to study the corrosion behavior of the prepared materials in SBF. The characteristics obtained during the EIS measurements revealed the dependence of the variation of the corrosion resistance level on the composition of the coating. The bare Ti surface had the higher value of the total impedance compared with the modified surfaces, while the Ti surfaces modified with organic coatings demonstrated the best charge transfer resistance in comparison with the coatings containing the inorganic CaCO 3 component and uncoated Ti.