Bio-mimicking nano and micro-structured surface fabrication for antibacterial properties in medical implants.

Orthopaedic and dental implants have become a staple of the medical industry and with an ageing population and growing culture for active lifestyles, this trend is forecast to continue. In accordance with the increased demand for implants, failure rates, particularly those caused by bacterial infection, need to be reduced. The past two decades have led to developments in antibiotics and antibacterial coatings to reduce revision surgery and death rates caused by infection. The limited effectiveness of these approaches has spurred research into nano-textured surfaces, designed to mimic the bactericidal properties of some animal, plant and insect species, and their topographical features. This review discusses the surface structures of cicada, dragonfly and butterfly wings, shark skin, gecko feet, taro and lotus leaves, emphasising the relationship between nano-structures and high surface contact angles on self-cleaning and bactericidal properties. Comparison of these surfaces shows large variations in structure dimension and configuration, indicating that there is no one particular surface structure that exhibits bactericidal behaviour against all types of microorganisms. Recent bio-mimicking fabrication methods are explored, finding hydrothermal synthesis to be the most commonly used technique, due to its environmentally friendly nature and relative simplicity compared to other methods. In addition, current proposed bactericidal mechanisms between bacteria cells and nano-textured surfaces are presented and discussed. These models could be improved by including additional parameters such as biological cell membrane properties, adhesion forces, bacteria dynamics and nano-structure mechanical properties. This paper lastly reviews the mechanical stability and cytotoxicity of micro and nano-structures and materials. While the future of nano-biomaterials is promising, long-term effects of micro and nano-structures in the body must be established before nano-textures can be used on orthopaedic implant surfaces as way of inhibiting bacterial adhesion.

Symptom Cluster Experiences of Patients Operated for Oral Cancer: A Mixed Methods Study.

OBJECTIVE: This convergent mixed methods study aimed to obtain a comprehensive understanding of symptom cluster experiences in patients with oral cancer. Survey and phenomenological interviews were conducted in parallel to identify distinct patient subgroups based on symptom cluster experiences along with their predictors and explore experiences of living with symptom clusters, respectively. DATA SOURCES: A convenience sample of 300 patients with oral cancer who had completed surgery provided the quantitative data, and a maximum variation purposive subsample of 20 participants, drawn from the survey sample, provided the qualitative data. Agglomerative hierarchical cluster analysis was used to identify subgroups, multivariate analyses were done to identify predictors, and thematic analysis was used for patient narratives. CONCLUSION: Almost 94% of the survey participants had two or more co-occurring symptoms. The four most severe and prevalent symptoms were dysphagia, problems with teeth or gums, speech difficulty, and dry mouth. A distinct subgroup consisting of 61% of patients reported severe dysphagia and teeth problems, which was associated with age, oral cancer stage and site. Interviews revealed the causes and the context influencing the perception and response to these symptoms. Thus, the quantitative data provided information on severity and patient subgroups based on symptom cluster experiences, while the qualitative data validated these conclusions and additionally provided in-depth details and meaningful insight on perceived causes and contextual influences of their experiences. This comprehensive picture of symptom cluster experiences can aid in the development of patient-centered interventions for people with oral cancer. IMPLICATIONS FOR NURSING PRACTICE: An interdisciplinary approach to targeting concurrent symptoms incorporating psychological and physical interventions is necessary. Older patients treated for Stage IV cancers and for buccal mucosa tumors are at high-risk of having severe dysphagia postoperatively, and these patients should be targeted for dysphagia interventions. The contextual factors play an important role in developing patient-centered interventions.

Distinct Dysphagia Profiles in Patients With Oral Cancer After Surgery.

OBJECTIVES: To determine distinct profiles based on symptom severity in patients undergoing surgery for oral cancer and examine whether these profiles differ by participant characteristics. SAMPLE & SETTING: 300 patients who underwent surgery for oral cancer at two outpatient clinics between June and December 2021. METHODS & VARIABLES: Symptoms were assessed using the MD Anderson Symptom Inventory-Head and Neck Cancer Module. Sociodemographic and clinical characteristics were collected. Latent profile analysis was performed. RESULTS: Five distinct dysphagia profiles were identified, which qualitatively differed regarding co-occurrence patterns of dysphagia, mucus-related symptoms, speech disturbances, and psychoneurologic symptoms. Significant differences were reported in interference to function, number of co-occurring symptoms, time since diagnosis and treatment completion, use of symptom management medications, oral cancer stage and site, and treatment completed. IMPLICATIONS FOR NURSING: Identifying distinct dysphagia profiles can improve patient outcomes and help in planning specific nursing interventions to influence nutritional and functional status in oral cancer survivors. Dysphagia and dry mouth can persist beyond one year post-treatment, so follow-up dysphagia assessments are needed.

Control of bacterial attachment by fracture topography.

In the biomedical arena, bacterial fouling is a precursor to complications such as implant infection and nosocomial infection. These complications are further compounded by biochemical mechanisms of resistance that threaten the action of traditional antibacterial strategies. Accordingly, antibacterial property by physical, not biochemical, mechanisms of action is becoming increasingly popular and promising. The present work falls in line with this paradigm shift. Here, microtextured Ti-6Al-4V surfaces were manufactured by destructive tension at three different cross-head speeds, probed with scanning electron microscopy (SEM) and multifocus optical microscopy, and treated with Staphylococcus aureus to study bacterial attachment. The fractographic study revealed the presence of dual-mode fracture, typical of Ti-6Al-4V, comprising  regions of both ductile, microvoid coalescence and brittle, cleavage faceting. Based on load-extension curves, quantitative roughness data, and qualitative SEM visualisation, it was evident that cross-head speed modulated fracture behaviour such that increased speed produced more brittle fracture whilst lower speeds produced more ductile fracture. The topography associated with ductile fracture was found to possess notable antibiofouling property due to geometric constrains imposed by the coalesced microvoids. Accordingly, fracture at low cross-head speeds (1 mm/min and 10 mm/min) yielded significant reduction in bacterial attachment, whilst fracture at high cross-head speeds (100 mm/min) did not. The greatest reduction (~72%) was achieved at a cross-head speed of 1 mm/min. These findings suggest that antibiofouling property can be elicited by fracture and further 'tuned' by fracture speed. Discovery of this novel, albeit simple, avenue for topography-mediated antibacterial property calls for further research into alternate techniques for the manufacture of 'physical antibacterial surfaces'.

Antimicrobial and Immunomodulatory Surface-Functionalized Electrospun Membranes for Bone Regeneration.

Guided bone regeneration (GBR) is a surgical procedure utilizing occlusive membranes for providing space maintenance and enabling selective repopulation of the damaged area. While this technique is effective in regenerating bone, bacterial infiltration occurs frequently and can compromise the regenerative outcome. In this study, the authors describe the development and characterization of a GBR membrane made of medical grade polycaprolactone (mPCL) electrospun fibers with antibacterial and immunomodulatory properties. This is achieved by the immobilization of the antibiotic azithromycin into the membrane via a solvent evaporation technique leading to a sustained release of the drug over 14 d. In vitro testing shows that this controlled release of azithromycin is proficient at inhibiting the growth of Staphylococcus aureus for 14 d. Implantation of azithromycin loaded mPCL membrane in a rodent calvarial defect induces macrophage polarization toward the M2 phenotype after one week and results in significantly more bone regeneration eight weeks post-surgery. The results suggest that this antibacterial membrane should be effective at preventing infection and also impacts on the macrophage polarization enhancing bone regeneration. The drug loading technique developed in this study is simple, effective with a strong potential for clinical translation and can be applied to different types of scaffolds and implants for applications in craniofacial and orthopedics applications.

An ex-vivo multiple sclerosis model of inflammatory demyelination using hyperbranched polymer.

Multiple sclerosis (MS) is characterized by the presence of inflammatory demyelinating foci throughout the brain and spinal cord, accompanied by axonal and neuronal damage. Although inflammatory processes are thought to underlie the pathological changes, the individual mediators of this damage are unclear. In order to study the role of pro-inflammatory cytokines in demyelination in the central nervous system, we have utilized a hyperbranched poly(2-dimethyl-aminoethylmethacrylate) based non-viral gene transfection system to establish an inflammatory demyelinating model of MS in an ex-vivo environment. The synthesized non-viral gene transfection system was optimized for efficient transfection with minimal cytotoxicity. Organotypic brain slices were then successfully transfected with the TNF or IFNγ genes. TNF and IFNγ expression and release in cerebellar slices via non-viral gene delivery approach resulted in inflammation mediated myelin loss, thus making it a promising ex-vivo approach for studying the underlying mechanisms of demyelination in myelin-related diseases such as MS.

Hyperbranched PEGmethacrylate linear pDMAEMA block copolymer as an efficient non-viral gene delivery vector.

A unique hyperbranched polymeric system with a linear poly-2-dimethylaminoethyl methacrylate (pDMAEMA) block and a hyperbranched polyethylene glycol methyl ether methacrylate (PEGMEMA) and ethylene dimethacrylate (EGDMA) block was designed and synthesized via deactivation enhanced atom transfer radical polymerisation (DE-ATRP) for efficient gene delivery. Using this unique structure, with a linear pDMAEMA block, which efficiently binds to plasmid DNA (pDNA) and hyperbranched polyethylene glycol (PEG) based block as a protective shell, we were able to maintain high transfection levels without sacrificing cellular viability even at high doses. The transfection capability and cytotoxicity of the polymers over a range of pDNA concentration were analysed and the results were compared to commercially available transfection vectors such as polyethylene imine (branched PEI, 25 kDa), partially degraded poly(amido amine)dendrimer (dPAMAM; commercial name: SuperFect(®)) in fibroblasts and adipose tissue derived stem cells (ADSCs).

Transfection of macrophages by collagen hollow spheres loaded with polyplexes: a step towards modulating inflammation.

Macrophages are key orchestrators of inflammation as they secrete proteases and inflammatory cytokines. To date, therapies aimed at modulating macrophage phenotype have failed due to the short half-life of biomolecules in the body. Therefore, inhibition of inflammation by gene therapy constitutes a new hope. In the present study, we have assessed collagen hollow spheres as a reservoir system for polyplexes in order to transfect human macrophages while preserving cell viability. Polyplexes were formed by complexing G-Luc plasmid with a poly(2-dimethylaminoethyl methacrylate) poly(ethylene glycol) based hyperbranched polymer. Several ratios of polymer/pDNA (5:1, 8:1, 10:1w/w) complexes in two different sphere sizes (1.24 and 4.5µm) were tested. Collagen hollow spheres were loaded with polyplexes up to 80µg of pDNA per mg of microspheres. The release of polyplexes from the spheres was delayed and prolonged i.e. 20% of the initial amount released in 5days. Following incubation with polyplex-loaded microspheres, macrophages were transfected (polyplex pDNA:polymer ratio 1:10w/w). In addition, collagen hollow spheres maintained cell viability as more than 80% of cells were viable after 4days in culture. In contrast, when used alone, polyplexes were seen to be toxic, while there was no transfection detected. Taken together, these results show that collagen hollow spheres may be used as a reservoir for controlled gene delivery to macrophages. Unlike existing gene delivery systems, this system allows for macrophage transfection with minimal toxicity. Hence, this system has a potential for the delivery of a therapeutic gene in order to modulate inflammation.

Tunable elastin-like polypeptide hollow sphere as a high payload and controlled delivery gene depot.

Self-assembly driven processes can be utilized to produce a variety of nanostructures useful for various in vitro and in vivo applications. Characteristics such as size, stability, biocompatibility, high therapeutic loading and controlled delivery of these nanostructures are particularly crucial in relation to in vivo applications. In this study, we report the fabrication of tunable monodispersed elastin-like polypeptide (ELP) hollow spheres of 100, 300, 500 and 1000 nm by exploiting the self-assembly property and net positive charge of ELP. The microbial transglutaminase (mTGase) cross-linking provided robustness and stability to the hollow spheres while maintaining surface functional groups for further modifications. The resulting hollow spheres showed a higher loading efficiency of plasmid DNA (pDNA) by using polyplex (~70 µg pDNA/mg of hollow sphere) than that of self-assembled ELP particles and demonstrated controlled release triggered by protease and elastase. Moreover, polyplex-loaded hollow spheres showed better cell viability than polyplex alone and yielded higher luciferase expression by providing protection against endosomal degradation. Overall, the monodispersed, tunable hollow spheres with a capability of post-functionalization can provide an exciting new opportunity for use in a range of therapeutic and diagnostic applications.

Preparation of chitosan/polyglutamic acid spheres based on the use of polystyrene template as a nonviral gene carrier.

The major difficulty in designing carrier system for gene delivery is finding a good compromise between structure, stability, and efficiency. Current carrier systems are limited in terms of release kinetics, toxicity, and overall capacity to carry biomolecules. The objectives of this study were to develop a process of producing biodegradable polymer-based hollow spheres and to characterize their potential use as carriers of plasmid DNA (pDNA) for gene delivery. The method developed involves coating a template with a polymer layer. After the removal of the template, a hollow core is obtained. Specifically, the production process begins with chitosan coating and is followed by polyglutamic acid cross-linking. The advantage of this production process is that it could be applied to a variety of polymeric systems. Because the hollow polymer structures can encapsulate a large variety of guest molecules, these spheres have significant potential for delivery. After physical characterization, the ability of the spheres to encapsulate and retain pDNA was investigated. The chitosan/polyglutamic acid spheres were used to encapsulate pDNA with up to 90% efficiency, and the encapsulated pDNA was retained for 3 days without degradation in 10% fetal bovine serum (FBS)-complemented media and released up to 30% after 3 days in the presence of the lysozyme, suggesting that these spheres represent an attractive method for gene delivery.