ABSTRACT
This paper presents a novel approach for designing a freeform bending-resistant structure from the combination of explicit discrete component-based topology optimization (TO) and the porcupine quill-inspired features. To embed the porcupine quill's features into the TO formulations, the method involves constructing discrete components at various scales to imitate features including solid shell, stochastically distributed pores, and graded stiffeners. The components are iteratively updated, and the optimization process allows for the grading of quill-inspired features while achieving optimal structural compliance under bending loads. The proposed approach is demonstrated to be effective through the resolution of Messershmitt-Bolkow-Blohm (MBB) beam designs, parameterized studies of geometric parameters, and numerical validation of long-span and short-span quill-inspired beam designs. By examining the von Mises stress distribution, the study highlights the mitigation of material yielding at the shell region brought by the geometric features of porcupine quills, leading to the potential theory support for the bending resistance. The optimized MBB beams are manufactured using the material extrusion technique, and three-point bending tests are conducted to explore the failure mitigation capability of the quill-inspired beam under large deformation. Consequently, the study concludes that the proposed quill-inspired component-based TO approach can design a structure with excellent bending resistance according to the improved energy absorption as well as increased deformation after reaching 75% peak load.
Subject(s)
Porcupines , Porosity , Porcupines/physiology , Porcupines/anatomy & histology , Animals , Stress, Mechanical , Biomimetic Materials/chemistry , Biomimetics/methods , Computer SimulationABSTRACT
This study demonstrates the control of neuronal survival and development using nitrogen-doped ultrananocrystalline diamond (N-UNCD). We highlight the role of N-UNCD in regulating neuronal activity via near-infrared illumination, demonstrating the generation of stable photocurrents that enhance neuronal survival and neurite outgrowth and foster a more active, synchronized neuronal network. Whole transcriptome RNA sequencing reveals that diamond substrates improve cellular-substrate interaction by upregulating extracellular matrix and gap junction-related genes. Our findings underscore the potential of conductive diamond as a robust and biocompatible platform for noninvasive and effective neural tissue engineering.
Subject(s)
Diamond , Tissue Engineering , Diamond/pharmacology , Diamond/chemistry , Electric Conductivity , Neurons/physiology , Cell SurvivalABSTRACT
Pelvic floor disorders, including pelvic organ prolapse (POP) and stress urinary incontinence (SUI), are serious and very common. Surgery is commonly undertaken to restore the strength of the vaginal wall using transvaginal surgical mesh (TVM). However, up to 15% of TVM implants result in long-term complications, including pain, recurrent symptoms, and infection.Clinical Relevance- In this study, a new bioengineered TVM has been developed to address these issues. The TVM is visible using noninvasive imaging techniques such as computed tomography (CT); it has a highly similar structural profile to human tissue and potential to reduce pain and inflammation. These combined technological advances have the potential to revolutionize women's health.
Subject(s)
Pelvic Organ Prolapse , Urinary Incontinence, Stress , Female , Humans , Pelvic Organ Prolapse/diagnostic imaging , Pelvic Organ Prolapse/surgery , Pelvic Organ Prolapse/complications , Urinary Incontinence, Stress/diagnostic imaging , Urinary Incontinence, Stress/surgery , Urinary Incontinence, Stress/complications , Vagina/diagnostic imaging , Surgical Mesh/adverse effects , Tomography/adverse effectsABSTRACT
PURPOSE: Bone tumours must be surgically excised in one piece with a margin of healthy tissue. The unique nature of each bone tumour case is well suited to the use of patient-specific implants, with additive manufacturing allowing production of highly complex geometries. This work represents the first assessment of the combination of surgical robotics and patient-specific additively manufactured implants. METHODS: The development and evaluation of a robotic system for bone tumour excision, capable of milling complex osteotomy paths, is described. The developed system was evaluated as part of an animal trial on 24 adult male sheep, in which robotic bone excision of the distal femur was followed by placement of patient-specific implants with operative time evaluated. Assessment of implant placement accuracy was completed based on post-operative CT scans. RESULTS: A mean overall implant position error of 1.05 ± 0.53 mm was achieved, in combination with a mean orientation error of 2.38 ± 0.98°. A mean procedure time (from access to implantation, excluding opening and closing) of 89.3 ± 25.25 min was observed, with recorded surgical time between 58 and 133 min, with this approximately evenly divided between robotic (43.9 ± 15.32) and implant-based (45.4 ± 18.97) tasks. CONCLUSIONS: This work demonstrates the ability for robotics to achieve repeatable and precise removal of complex bone volumes of the type that would allow en bloc removal of a bone tumour. These robotically created volumes can be precisely filled with additively manufactured patient-specific implants, with minimal gap between cut surface and implant interface.
Subject(s)
Dental Implants , Orthopedics , Robotics , Surgery, Computer-Assisted , Male , Animals , Sheep , Surgery, Computer-Assisted/methods , Tomography, X-Ray Computed , Femur/diagnostic imaging , Femur/surgeryABSTRACT
Phosphorylcholine (ChoP) can be found in all life forms. Although this molecule was first thought to be uncommon in bacteria, it is now appreciated that many bacteria express ChoP on their surface. ChoP is usually attached to a glycan structure, but in some cases, it is added as a post-translational modification to proteins. Recent findings have demonstrated the role of ChoP modification and phase variation (ON/OFF switching) in bacterial pathogenesis. However, the mechanisms of ChoP synthesis are still unclear in some bacteria. Here, we review the literature and examine the recent developments in ChoP-modified proteins and glycolipids and of ChoP biosynthetic pathways. We discuss how the well-studied Lic1 pathway exclusively mediates ChoP attachment to glycans but not to proteins. Finally, we provide a review of the role of ChoP in bacterial pathobiology and the role of ChoP in modulating the immune response.
Subject(s)
Bacteria , Phosphorylcholine , Phosphorylcholine/metabolism , Bacteria/metabolism , PolysaccharidesABSTRACT
BACKGROUND: Perioperative nutrition support is recommended for patients undergoing upper gastrointestinal (UGI) cancer surgery; however, limited evidence exists regarding implementation of a nutrition care pathway in clinical practice. The aims of this pilot study were to determine whether implementation of a standardised perioperative nutrition pathway for patients undergoing UGI cancer surgery improves access to dietetics care, as well as to evaluate study feasibility, fidelity, resource requirements and effect on clinical outcomes. METHODS: Patients with newly diagnosed UGI cancer from four major metropolitan hospitals in Melbourne, planned for curative intent surgery, were included in the prospective pilot study (n = 35), with historical controls (n = 35) as standard care. Outcomes were dietetics care (dietetics contacts) nutritional status, hand grip strength, weight change, preoperative hospital admissions, complications and length of stay, recruitment feasibility, fidelity and adherence, and resource requirements. Continuous data were analysed using independent samples t test accounting for unequal variances or a Mann-Whitney U test. Dichotomous data were analysed using Fisher's exact test. RESULTS: The percentage of participants receiving preoperative dietetic intervention increased from 55% to 100% (p < 0.001). Mean ± SD dietetics contacts increased from 2.2 ± 3.7 to 5.9 ± 3.9 (p < 0.001). Non-statistically significant decreases in preoperative nutrition-related hospital admissions, and surgical complications were demonstrated in patients who underwent neoadjuvant therapy. Recruitment rate was 81%, and adherence to the nutrition pathway was high (> 70% for all stages of the pathway). The mean ± SD estimated resource requirement for the preoperative period was 3.7 ± 2.8 h per patient. CONCLUSIONS: Implementation of this standardised nutrition pathway resulted in improved access to dietetics care. Recruitment feasibility and high fidelity to the intervention suggest that a larger study would be viable.
Subject(s)
Gastrointestinal Neoplasms , Nutritional Status , Humans , Pilot Projects , Critical Pathways , Prospective Studies , Hand Strength , Length of StayABSTRACT
BACKGROUND: Implementation studies of complex interventions such as nutrition care pathways are important to health services research, as they support translation of research into practice. There is limited research regarding implementation of a nutrition care pathway in an upper gastrointestinal (UGI) cancer population. The aim of this study was to comprehensively evaluate the implementation process of a perioperative nutrition care pathway in UGI cancer surgery using The Consolidated Framework for Implementation Research (CFIR). METHODS: This was a mixed methods implementation study conducted during a pilot study of a standardised nutrition care pathway across four major hospitals between September 2018 to August 2019. Outcome measures included five focus groups among study dietitians (n = 4-8 per group), and quantitative satisfaction surveys from multi-disciplinary team (MDT) members (n = 14) and patients (n = 18). Focus group responses were analysed thematically using the CFIR constructs, which were used as a priori codes. Survey responses were summarised using means and standard deviations. A convergent parallel mixed methods approach according to CFIR domains and constructs was used to integrate qualitative and quantitative data. RESULTS: Qualitative data demonstrated that dietitian perceptions primarily aligned with five CFIR constructs (networks and communications, structural characteristics, adaptability, compatibility and patient needs/resources), indicating a complex clinical and implementation environment. Challenges to implementation mostly related to adapting the pathway, and the compatibility of nutrition coordination to existing aspects of care within each setting. Identified benefits from dietitian qualitative data and MDT survey responses included increased engagement between the dietitian and MDT, and a more proactive approach to nutrition care. Patients were highly satisfied with the service, with the majority of survey items being rated highly (≥4 of a possible 5 points). CONCLUSIONS: The nutrition care pathway was perceived to be beneficial by key stakeholders. Based on the findings, sustainability and compliance to this model of care may be achieved with improved systems level coordination and communication.
Subject(s)
Neoplasms , Nutrition Therapy , Critical Pathways , Focus Groups , Humans , Pilot ProjectsABSTRACT
BACKGROUND & AIMS: Functional gastrointestinal disorders are common and costly to the healthcare system. In the Multidisciplinary Treatment of Functional Gastrointestinal Disorders study, we demonstrated that multidisciplinary care resulted in superior clinical and cost outcomes, when compared with standard gastroenterologist-only care at end of treatment. In this study we evaluate the longer-term outcomes. METHODS: In a single-center, pragmatic trial patients with Rome IV criteria-defined functional gastrointestinal disorders were randomized 1:2 to a gastroenterologist-only standard care vs a multidisciplinary clinic comprising gastroenterologists, dietitians, gut hypnotherapists, psychiatrists, and biofeedback physiotherapists. Outcomes in this study were assessed 12 months after the end of treatment. Global symptom improvement was assessed by using a 5-point Likert scale. Symptoms, specific disorder status, psychological state, quality of life, and cost were additional outcomes. A modified intention-to-treat analysis was performed. RESULTS: Of 188 randomized patients, 143 (46 standard care, 97 multidisciplinary) formed the longer-term modified intention-to-treat analysis. Sixty-two percent of multidisciplinary clinic patients saw allied clinicians. Sixty-five percent (30/46) standard care versus 76% (74/97) multidisciplinary clinic patients achieved global symptom improvement 12 months after end of treatment (P = .17), whereas 20% (9/46) versus 37% (36/97) rated their symptoms as "5/5 much better" (P = .04). A ≥50-point reduction in Irritable Bowel Syndrome Severity Scoring System occurred in 38% versus 66% (P = .02), respectively, for irritable bowel syndrome patients. Anxiety and depression were greater in the standard care than multidisciplinary clinic (12 vs 10, P = .19), and quality of life was lower in standard care than the multidisciplinary clinic (0.75 vs 0.77, P =·.03). An incremental cost-effectivness ratio found that for every additional 3555AUD spent in the multidisciplinary clinic, a further quality-adjusted life year was gained. CONCLUSIONS: Twelve months after the completion of treatment, integrated multidisciplinary clinical care achieved a greater proportion of patients with improvement of symptoms, psychological state, quality of life, and cost, compared with gastroenterologist-only care. CLINICAL TRIALS: gov: number NCT03078634.
Subject(s)
Gastroenterologists , Gastrointestinal Diseases , Irritable Bowel Syndrome , Delivery of Health Care , Humans , Quality of LifeABSTRACT
Gallium and its alloys, such as eutectic gallium indium alloy (EGaIn), a form of liquid metal, have recently attracted the attention of researchers due to their low toxicity and electrical and thermal conductivity for biomedical application. However, further research is required to harness EGaIn-composites advantages and address their application as a biomedical scaffold. In this research, EGaIn-polylactic acid/polycaprolactone composites with and without a second conductive filler, MXene, were prepared and characterized. The addition of MXene, into the EGaIn-composite, can improve the composite's electrochemical properties by connecting the liquid metal droplets resulting in electrically conductive continuous pathways within the polymeric matrix. The results showed that the composite with 50% EGaIn and 4% MXene, displayed optimal electrochemical properties and enhanced mechanical and radiopacity properties. Furthermore, the composite showed good biocompatibility, examined through interactions with fibroblast cells, and antibacterial properties against methicillin-resistant Staphylococcus aureus. Therefore, the liquid metal (EGaIn) polymer composite with MXene provides a first proof-of-concept engineering scaffold strategy with low toxicity, functional electrochemical properties, and promising antimicrobial properties.
Subject(s)
Gallium , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Gallium/chemistry , Gallium/pharmacology , Indium/chemistry , Polymers/pharmacologyABSTRACT
Recently, there has been an increasing interest on the sustainability advantage of 3D concrete printing (3DCP), where the original cement-based mixtures used for printing could be replaced or incorporated with environmental-friendly materials. The development in digital modeling and design tools also creates a new realm of form-finding architecture for 3DCP, which is based on topological optimization of volumetric mass and physical performance. This review provides a perspective of using different green cementitious materials, applications of structural optimization, and modularization methods for realizing sustainable construction with additive manufacturing. The fresh and hardened mechanical properties of various sustainable materials for extrusion-based 3D printing are presented, followed by discussions on different topology optimization techniques. The current state of global research and industrial applications in 3DCP, along with the development of sustainable construction materials, is also summarized. Finally, research and practical gaps identified in this review lead to several recommendations on material developments, digital design tool's prospects for 3DCP to achieve the sustainability goal.
ABSTRACT
Titanium-based implants are the leading material for orthopaedic surgery, due to their strength, versatility, fabrication via additive manufacturing and invoked biological response. However, the interface between the implant and the host tissue requires improvement to better integrate the implant material and mitigate foreign body response. The interface can be manipulated by changing the surface energy, chemistry, and topography of the Titanium-based implant. Recently, polycrystalline diamond (PCD) has emerged as an exciting coating material for 3D printed titanium scaffolds showing enhanced mammalian cell functions while inhibiting bacterial attachment in vitro. In this study, we performed in-depth characterisation of PCD coatings investigating the surface topography, thickness, surface energy, and compared its foreign body response in vivo with uncoated titanium scaffold. Coating PCD onto titanium scaffolds resulted in a similar microscale surface roughness (RMS(PCD-coated) = 24 µm; RMS(SLM-Ti) = 28 µm), increased nanoscale roughness (RMS(PCD-coated) = 35 nm; RMS(SLM-Ti) = 66 nm) and a considerable decrease in surface free energy (E(PCD-coated) = 4 mN m-1; E(SLM-Ti) = 16 mN m-1). These surface property changes were supported by X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy as corresponding to observed surface chemistry changes induced by the coating. The underlying mechanism of how the diamond coatings chemical and physical properties changes the wettability of implants was examined. In vivo, the coated scaffolds induced similar level of fibrous encapsulation with uncoated scaffolds. This study thus provides further insight into the physicochemical characteristics of PCD coatings, adding evidence to the promising potential of PCD-coatings of medical implants.
Subject(s)
Foreign Bodies , Titanium , Animals , Coated Materials, Biocompatible/pharmacology , Diamond , Printing, Three-Dimensional , Surface PropertiesABSTRACT
The ability of an orthopedic implant to integrate successfully with the surrounding bone tissue is imperative for optimal patient outcomes. Here, the recent advances and future prospects for diamond-based coatings of conventional osteo-implant materials (primarily titanium) are explored. The ability of these diamond coatings to enhance integration into existing bone, improved implant mechanical properties, facilitate surface chemical functionalization, and provide anti-microbial properties are discussed in context of orthopedic implants. These diamond-based materials may have the additional benefit of providing an osteo-inductive effect, enabling better integration into existing bone via stem cell recruitment and bone regeneration. Current and timely research is highlighted to support the discussion and suggestions in further improving implant integration via an osseoinductive effect from the diamond composite materials.
Subject(s)
Bone-Implant Interface , Diamond , Coated Materials, Biocompatible , Humans , Surface Properties , TitaniumABSTRACT
Owing to several key attributes, diamond is an attractive candidate material for neural interfacing electrodes. The emergence of additive-manufacturing (AM) of diamond-based materials has addressed multiple challenges associated with the fabrication of diamond electrodes using the conventional chemical vapor deposition (CVD) approach. Unlike the CVD approach, AM methods have enabled the deposition of three-dimensional diamond-based material at room temperature. This work demonstrates the feasibility of using laser metal deposition to fabricate diamond-titanium hybrid electrodes for neuronal interfacing. In addition to exhibiting a high electrochemical capacitance of 1.1 mF cm-2 and a low electrochemical impedance of 1 kΩ cm2 at 1 kHz in physiological saline, these electrodes exhibit a high degree of biocompatibility assessed in vitro using cortical neurons. Furthermore, surface characterization methods show the presence of an oxygen-rich mixed-phase diamond-titanium surface along the grain boundaries. Overall, we demonstrated that our unique approach facilitates printing biocompatible titanium-diamond site-specific coating-free conductive hybrid surfaces using AM, which paves the way to printing customized electrodes and interfacing implantable medical devices.
Subject(s)
Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Brain/cytology , Diamond/chemistry , Neurons/drug effects , Printing, Three-Dimensional , Titanium/chemistry , Animals , Electric Impedance , Neurons/cytology , Oxygen/chemistry , Surface PropertiesABSTRACT
IMPORTANCE: Current guidelines for postmenopausal recurrent urinary tract infection (rUTI) prevention recommend the use of vaginal topical estrogen products but not systemic estrogens. Studies show that vaginal estrogen decreases the risk of rUTI, but evidence against use of systemic estrogen is less convincing. OBJECTIVE: We performed a comprehensive literature review to evaluate the effect of systemic estrogen on UTI occurrence among postmenopausal women. EVIDENCE REVIEW: MEDLINE (PubMed), EMBASE, and CINAHL were searched for manuscripts published in English between January 1990 and July 2020. The search terms were "urinary tract infection" and "estrogen." Inclusion criteria were studies of postmenopausal women who received systemic estrogen therapy (any regimen) that reported UTI frequency during any follow-up period. Case studies, commentaries, and reviews were excluded. A priori specifications of seven study criteria were set representing the ideal study for assessing efficacy of systemic estrogen for rUTI prevention and were used to evaluate each included study. FINDINGS: Searches identified 281 results, and after deduplication and review, 8 studies met inclusion criteria: 4 randomized controlled trials, 1 secondary analysis of a randomized controlled trial, 1 prospective cohort study, 1 case-control study, and 1 cross-sectional study. Of the eight included studies, only two enrolled postmenopausal women with a rUTI diagnosis, four had sufficient sample size to detect a clinically meaningful difference between systemic estrogen versus placebo, two used dosage regimens anticipated to achieve a therapeutic effect, and three assessed UTI rates for an adequate duration of 6âmonths or more (the standard minimum duration of time needed to make a diagnosis of rUTI). Overall, none of the studies met all predefined criteria for the ideal study to assess the efficacy of systemic estrogen for rUTI prevention. CONCLUSIONS AND RELEVANCE: UTIs will continue to be a significant cause of morbidity and hospitalizations in postmenopausal women unless more research is done to better understand the role of estrogen on UTI rates. The evidence arguing use (or abandonment) of systemic estrogen for the prevention of rUTI is based on few studies with substantial methodologic limitations; there is significant room for improvement.
Subject(s)
Postmenopause , Urinary Tract Infections , Case-Control Studies , Cross-Sectional Studies , Estrogens , Female , Humans , Prospective Studies , Urinary Tract Infections/prevention & controlABSTRACT
Dissociative experiences have been associated with diachronic disunity. Yet, this work is in its infancy. Dissociative identity disorder (DID) is characterized by different identity states reporting their own relatively continuous sense of self. The degree to which patients in dissociative identity states experience diachronic unity (i.e., sense of self over time) has not been empirically explored. This study examined the degree to which patients in dissociative identity states experienced diachronic unity. Participants were DID adults (n=14) assessed in adult and child identity states, adults with a psychotic illness (n=19), adults from the general population (n=55), children from the general population (n=26) and adults imagining themselves as children (n=23). They completed the Diachronic Disunity Scale (DDS), the Dissociative Experiences Scale (DES), and the Self-Concept Clarity Scale (SCCS). Diachronic disunity was not limited to psychiatric groups, but evident to some degree in all adult and child samples. The DID adult sample experienced more dissociation and self-confusion than the psychosis and adult comparison groups, but did not differ on the diachronic measure. DID patients in their child identity states and child comparisons showed disunity and were significantly different from child simulators, who showed relatively more unity. Results suggest that DID patients in either adult or child dissociative identity states, like those in other samples, do not universally experience themselves as having a consistent sense of self over time.
ABSTRACT
The next-generation sutures should provide in situ monitoring of wound condition such as temperature while reducing surgical site infection during wound closure. In this study, functionalized nanodiamond (FND) and reduced graphene oxide (rGO) into biodegradable polycaprolactone (PCL) are incorporated to develop a new multifunctional suture with such capabilities. Incorporation of FND and rGO into PCL enhances its tensile strength by about 43% and toughness by 35%. The sutures show temperature sensing capability in the range of 25-40 °C based on the shift in zero-splitting frequency of the nitrogen-vacancy (NV- ) centers in FND via optically detected magnetic resonance, paving the way for potential detection of infection or excessive inflammation in healing wounds. The suture surface readily coats with antibiotics to reduce bacterial infection risk to the wounds. The new suture thus is promising in monitoring and supporting wound closure.
Subject(s)
Surgical Wound Infection/prevention & control , Sutures , Temperature , Animals , Anti-Bacterial Agents/pharmacology , Cell Line , Electric Impedance , Humans , Mice , Microbial Sensitivity Tests , Nanocomposites/chemistry , Nanocomposites/ultrastructure , Optics and Photonics , Staphylococcus aureus/drug effects , Vancomycin/pharmacologyABSTRACT
Additive manufacturing of metals using selective laser melting can create customized parts with various degrees of complexity and geometry for medical implants. However, challenges remain in accepting orthopedic implants due to the bio-inert surface of metal scaffolds, resulting in a lack of osseointegration. Here, we show that polycrystalline diamond (PCD) coatings on selective laser melted titanium (SLM-Ti) scaffolds can improve the cell-to-material interaction of osteoblasts. The results show that by controlling the uniformity of the diamond coatings, we can mediate the biological response of osteoblasts, such as cell adhesion, proliferation, and spreading. The osteoblasts show favorable cell adhesion and spreading on non-planar PCD-coated scaffolds compared to the un-coated SLM-Ti scaffold. This study plays an important role in understanding the key physicochemical behavior of bone cell growth on customized orthopedic implant materials.
Subject(s)
Diamond , Osteoblasts , Diamond/metabolism , Osseointegration , Osteoblasts/metabolism , Surface Properties , Titanium/pharmacologyABSTRACT
Additive manufacturing (AM) of orthopedic implants is growing in popularity as it offers almost complete design flexibility and freedom, meaning complex geometries mimicking specific body parts can be easily produced. Novel composite materials with optimized functionalities present opportunities for 3D printing osteoconductive implants with desirable mechanical properties. Standard metals for bone implants, such as titanium and its alloys, are durable and nontoxic but lack bioactivity. Bioactive glasses promote strong bone formation but are susceptible to brittle failure. Metal-bioactive glass composites, however, may combine the mechanical reliability of metals with the bone-bonding ability of bioactive glasses, potentially reducing the incidence of implant failure. Processing such composites by AM paves the way for producing unprecedented bespoke parts with highly porous lattices, whose stiffness can be tailored to meet the mechanical properties of natural bone tissue. This Perspective focuses on titanium-bioactive glass composites, critically discussing their processability by AM and highlighting their potential as a next-generation implantable biomaterial.
Subject(s)
Ceramics/chemistry , Titanium/chemistry , Alloys/chemistry , Alloys/metabolism , Biocompatible Materials/chemistry , Bone-Implant Interface , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Porosity , Surface Properties , Tissue Scaffolds/chemistryABSTRACT
Bacterial biofilms are involved in most device-associated infections and remain a challenge for modern medicine. One major approach to addressing this problem is to prevent the formation of biofilms using novel antimicrobial materials, device surface modification or local drug delivery; however, successful preventive measures are still extremely limited. The other approach is concerned with treating biofilms that have already formed on the devices; this approach is the focus of our manuscript. Treating biofilms associated with medical devices has unique challenges due to the biofilm's extracellular polymer substance (EPS) and the biofilm bacteria's resistance to most conventional antimicrobial agents. The treatment is further complicated by the fact that the treatment must be suitable for applying on devices surrounded by host tissue in many cases. Nanomaterials have been extensively investigated for preventing biofilm formation on medical devices, yet their applications in treating bacterial biofilm remains to be further investigated due to the fact that treating the biofilm bacteria and destroying the EPS are much more challenging than preventing adhesion of planktonic bacteria or inhibiting their surface colonization. In this highly focused review, we examined only studies that demonstrated successful EPS destruction and biofilm bacteria killing and provided in-depth description of the nanomaterials and the biofilm eradication efficacy, followed by discussion of key issues in this topic and suggestion for future development.
ABSTRACT
Fatigue is a difficult multi-scale modelling problem nucleating from localised plasticity at the scale of dislocations and microstructure with significant engineering safety implications. Cold dwell fatigue is a phenomenon in titanium where stress holds at moderate temperatures lead to substantial reductions in cyclic life, and has been implicated in service failures. Using discrete dislocation plasticity modelling complemented by transmission electron microscopy, we successfully predict lifetimes for 'worst case' microstructures representative of jet engine spin tests. Fatigue loading above a threshold stress is found to produce slip in soft grains, leading to strong dislocation pile-ups at boundaries with hard grains. Pile-up stresses generated are high enough to nucleate hard grain basal dislocations, as observed experimentally. Reduction of applied cyclic load alongside a temperature excursion during the cycle lead to much lower densities of prism dislocations in soft grains and, sometimes, the elimination of basal dislocations in hard grains altogether.