Novel Therapeutic Platform of Micelles and Nanogels from Dopa-Functionalized Triblock Copolymers.

Multi-drug delivery systems constructed from a basic polymeric scaffold, and which have the ability to target a variety of biomedical applications, can streamline the development of nanomedicine to provide both environmental and economical relief. Herein, amphiphilic ABA-triblock copolymers are synthesized and assembled sequentially into micelles and nanogels as drug delivery systems following a thorough evaluation on advanced in vitro models to explore their potential for the treatment of cancer and bacterial infections. Short blocks of 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) are oligomerized from PEG6k and thereafter functionalized with dihydroxyphenylalanine (dopa)-functional thiols using thiol-ene coupling (TEC) click chemistry. The copolymers self-assemble into well-defined micelles in aqueous solution and are further formulated into nanogels via UV-induced TEC. The resulting spherical micelles and nanogels are stable nanoparticles, with sizes ranging between 100 and 200 nm. The nanogels are found to be non-toxic to a panel of cell lines and mask the toxicity of the potent drugs until their release. The nanogels would be superior to micelles for the elimination of cancer cells supported by both 2D cell culture and a 3D spheroid model. The opposite conclusion could be drawn for bacteria inhibition.

Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections.

Antimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK-060, a human kininogen-derived AMP. Once embedded into the poloxamer gel, DPK-060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time-kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti-infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK-060 at the wound site, all formulations display superior efficacy compared to DPK-060 in solution.

Constructing a Dual-Function Surface by Microcasting and Nanospraying for Efficient Drag Reduction and Potential Antifouling Capabilities.

To improve the drag-reducing and antifouling performance of marine equipment, it is indispensable to learn from structures and materials that are found in nature. This is due to their excellent properties, such as intelligence, microminiaturization, hierarchical assembly, and adaptability. Considerable interest has arisen in fabricating surfaces with various types of biomimetic structures, which exhibit promising and synergistic performances similar to living organisms. In this study, a dual bio-inspired shark-skin and lotus-structure (BSLS) surface was developed for fabrication on commercial polyurethane (PU) polymer. Firstly, the shark-skin pattern was transferred on the PU by microcasting. Secondly, hierarchical micro- and nanostructures were introduced by spraying mesoporous silica nanospheres (MSNs). The dual biomimetic substrates were characterized by scanning electron microscopy, water contact angle characterization, antifouling, self-cleaning, and water flow impacting experiments. The results revealed that the BSLS surface exhibited dual biomimetic features. The micro- and nano-lotus-like structures were localized on a replicated shark dermal denticle. A contact angle of 147° was observed on the dual-treated surface and the contact angle hysteresis was decreased by 20% compared with that of the nontreated surface. Fluid drag was determined with shear stress measurements and a drag reduction of 36.7% was found for the biomimetic surface. With continuous impacting of high-speed water for up to 10 h, the biomimetic surface stayed superhydrophobic. Material properties such as inhibition of protein adsorption, mechanical robustness, and self-cleaning performances were evaluated, and the data indicated these behaviors were significantly improved. The mechanisms of drag reduction and self-cleaning are discussed. Our results indicate that this method is a potential strategy for efficient drag reduction and antifouling capabilities.

Fabricating hierarchical micro and nano structures on implantable Co-Cr-Mo alloy for tissue engineering by one-step laser ablation.

Surface texturing is one of the effective strategies to improve bioactivity of implantable materials. In this study, hierarchical micro and nano structure (HMN) were fabricated on Co-Cr-Mo alloy substrate by a movable picosecond laser irradiation. Respectively, microgrooves with nano ripples and islands were produced on Co-Cr-Mo alloy by low and high laser power density. X-ray diffraction apparatus (XRD) phase analysis illustrated that substrate was in the phase of γ- face-centered cubic structure (FCC) before laser treatment, while it was in ε-hexagonal closest packing structure (HCP) phase dominant after laser treatment. Cell adhesion and proliferation studies showed that the HMN surface exhibits enhanced adhesion of MC3TC-E1 osteoblast and promoted cell activity. Analyzing of the morphology of osteoblast cells indicated cells were in high ratio of elongation on the HMN surface, while they mainly kept in round shape on the polished surface. Results indicated the formation of hierarchical structure on Co-Cr-Mo alloy was able to improve biological performances, suggesting the potential application in cobalt based orthopedic implants.

Preparation and bioactive properties of chitosan and casein phosphopeptides composite coatings for orthopedic implants.

Using the layer-by-layer deposition method, functional chitosan/casein phospopeptides (CS/CPP) composite coatings were produced on Co-Cr-Mo alloy. The CS/CPP composite coatings had the dendritic topography, and were quite hydrophilic. Zeta potential measurements showed the composite coatings were negative charged at neural pH. XPS results indicated that the CS/CPP composite coatings were covalently bond to the substrate. When MC3T3-E1 cells were seeded on the CS/CPP composite coatings, no cytotoxicity was observed. The bone morphogenetic protein-2 (BMP-2) mRNA expression was significantly up-regulated in MC3T3-E1 cells cultured on the composite coatings and it was twice as much as that of cells cultured on the bare substrate. The expression of osteoprotegerin (OPG) mRNA and the ratio of OPG/receptor activator of nuclear factor-κB ligand (RNAKL) mRNA were increased 5-fold and 55-fold, respectively. These results suggested the CS/CPP composite coatings may have potential application in cobalt matrix orthopaedic implants.

In vivo synthesis of calcium oxalate whiskers on CoCrMo alloy surfaces via biomineralization.

Surface treatments using bio-technology are valuable and fascinating in the sense that such treatments are natural and yield good biocompatibility. Calcium oxalate whiskers for biomedical applications were successfully synthesized on the CoCrMo alloy surfaces implanted in Aloe leaves which consist of many active bio-chemical elements. The effect of surface wettability and surface morphology on the formation of whiskers was investigated using four differently treated CoCrMo surfaces: (i) smoothly polished surface, (ii) electrochemical etched surface, (ii) textured surface with dimples, and (iv) parallel orientated-grooved surface. Results showed that the formed whiskers had a length ranging between 100 µm and 600 µm, and a diameter in the range of 2 µm to 5 µm. Electrochemically etched surfaces had better wettability and were favorably for growing whiskers. Surface morphology with (i) dimple textures or (ii) parallel grooves facilitated the effective control of the size and amount of the grown whiskers.