BackgroundSelective laser melting (SLM) titanium is an ideal option to manufacture customized implants with suitable surface modification to improve its bioactivity. The peri-implant soft tissues form a protective tissue barrier for the underlying osseointegration. Therefore, original microrough SLM surfaces should be treated for favorable attachment of surrounding soft tissues.Material and methodsIn this study, anodic oxidation (AO) was applied on the microrough SLM titanium substrate to form TiO2 nanotube arrays. After that, calcium phosphate (CaP) nanoparticles were embedded into the nanotubes or the interval of nanotubes by electrochemical deposition (AOC). These two samples were compared to untreated (SLM) samples and accepted mechanically polished (MP) SLM titanium samples. Scanning electron microscopy, energy dispersive spectrometry, X-ray diffraction, surface roughness, and water contact angle measurements were used for surface characterization. The primary human gingival epithelial cells (HGECs) and human gingival fibroblasts (HGFs) were cultured for cell assays to determine adhesion, proliferation, and adhesion-related gene expressions.ResultsFor HGECs, AOC samples showed significantly higher adhesion, proliferation, and adhesion-related gene expressions than AO and SLM samples (P<0.05) and similar exceptional ability in above aspects to MP samples. At the same time, AOC samples showed the highest adhesion, proliferation, and adhesion-related gene expressions for HGFs (P<0.05).ConclusionBy comparison between each sample, we could confirm that both anodic oxidation and CaP nanoparticles had improved bioactivity, and their combined utilization may likely be superior to mechanical polishing, which is most commonly used and widely accepted. Our results indicated that creating appropriate micro-/nano-topographies can be an effective method to affect cell behavior and increase the stability of the peri-implant mucosal barrier on SLM titanium surfaces, which contributes to its application in dental and other biomedical implants.

High aggressiveness and recurrence of melanoma tumors require multiple systemic drug administrations, causing discomfort and severe side effects to the patients. Topical treatment strategies that provide repetitively controllable and precise drug administrations will greatly improve treatment effects. Methods: In this study, a spatiotemporally controlled pulsatile release system, which combined dissolving microneedles (DMNs) and thermal-sensitive solid lipid nanoparticles (SLNs), was constructed to realize multiple doses of dual-modal chemo-photothermal therapy in a single administration. Paclitaxel (PTX) and photothermal agent IR-780 were encapsulated into SLNs and were concentrated in the tips of DMNs (PTX/IR-780 SLNs @DMNs). Equipped with several needles, the DMN patch could be directly inserted into the tumor site and provide a stable “Zone accumulation” to constrain the PTX/IR-780 SLNs at the tumor site with uniform distribution. Results: In vitro experiments showed that after irradiation with near-infrared light, the PTX/IR-780 SLNs gradually underwent phase transition, thereby accelerating the release of PTX. When irradiation was switched off, the PTX/IR-780 SLNs cooled to re-solidify with limited drug release. Compared with intravenous and intratumoral injections, very few SLNs from PTX/IR-780 SLNs @DMNs were distributed into other organs, resulting in enhanced bioavailability at the tumor site and good safety. In vivo analysis revealed that PTX/IR-780 SLNs @DMNs exhibited significant anti-tumor efficacy. In particular, the primary tumor was completely eradicated with a curable rate of 100% in 30 days and the highest survival rate of 66.67% after 100 days of treatment. Conclusion: Herein, we developed a DMN system with a unique spatiotemporally controlled pulsatile release feature that provides a user-friendly and low-toxicity treatment route for patients who need long-term and repeat treatments.

Objective— Myocardial injury during cardiac surgery is a major cause of perioperative morbidity and mortality. We determined whether perioperative statin therapy is cardioprotective in patients undergoing noncoronary artery cardiac surgery and the potential mechanisms. Methods and Results— One hundred fifty-one patients undergoing noncoronary artery cardiac surgery were randomly assigned to either a statin group (n=77) or a control group (n=74). Simvastatin (20 mg) was administered preoperatively and postoperatively. Plasma were analyzed for troponin T, isoenzyme of creatine kinase, C-reaction protein, interleukin-6, interleukin-8, creatinine, and blood urea nitrogen. Cardiac echocardiography was performed. Endothelial nitric oxide synthase (eNOS), Akt, p38, heat shock protein 90, caveolin-1, and nitric oxide (NO) in the heart were detected. Simvastatin significantly reduced plasma troponin T, isoenzyme of creatine kinase, C-reaction protein, blood urea nitrogen , creatinine, interleukin-6, interleukin-8, and the requirement of inotropic postoperatively. Simvastatin increased NO production, the expression of eNOS and phosphorylation at serine1177, phosphorylation of Akt, expression of heat shock protein 90, heat shock protein 90 association with eNOS and decreased eNOS phosphorylation at threonine 495, phosphorylation of p38, and expression of caveolin-1. Simvastatin also improved cardiac function postoperatively. Conclusion— Perioperative statin therapy can improve cardiac function and renal function by reducing myocardial injury and inflammatory response through activating Akt-eNOS and attenuating p38 signaling pathways in patients undergoing noncoronary artery cardiac surgery. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01178710.

Our data demonstrate that MPs generated from VHD patients before and after cardiac surgery contributed to endothelial dysfunction, by uncoupling and inhibiting eNOS. Circulating MPs are potential therapeutic targets for the maintenance of vascular function postoperatively.

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