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Kidney transplantation is the current optimal treatment for suitable patients with end-stage renal disease. The second warm ischemic time (SWIT) is known to negatively impact delayed graft function, and long-term graft survival, and methods are required to ameliorate the impacts of SWIT on transplantation outcomes.This study primarily focused on determining the effect of a novel thermally insulating jacket on the thermal profile of the human kidney and quantifying the reduction in thermal energy experienced using this device (KPJ™). An ex vivo simulated transplantation model was developed to determine the thermal profiles of non-utilized human kidneys with and without KPJ™ (n = 5). Control kidney temperature profiles were validated against the temperature profiles of n = 10 kidneys during clinical kidney transplantation.Using the ex-vivo water bath model, the thermally insulated human kidney reached the 15°C metabolic threshold temperature at 44.5 ± 1.9 min (vs control: 17.3 ± 1.8 min (p = 0.00172)) and remained within the 18°C threshold until 53.3 ± 1.3 min (vs control: 20.9 ± 2.0 min (p = 0.002)). The specific heat capacity of KPJ™ protected kidney was four-fold compared to the control kidney. The clinical temperature audit, closely correlated with the water bath model, hence validating this ex-vivo human kidney transplant model.Intraoperative thermal protection is a simple and viable method of reducing the thermal injury that occurs during the SWIT and increasing the specific heat capacity of the system. Such technology could easily be translated into clinical kidney transplant practice.

Electrospinning is a versatile method with a broad range of applications, including in biomaterials. In this study, an electrospinning apparatus was built to fabricate polycaprolactone (PCL) fibrous biomaterials for future use as a fibrocartilage tissue engineering scaffold. The properties of the resultant fibers were determined by many factors, thus understanding the effects of the factors was required for optimizing the process. For screening the important factors and studying the relationship between these factors and fiber output, an experiment using factorial design was carried out. The investigation was focused on the processing parameters tunable from the apparatus setup, including flow rate, collector distance, and collector rotation speed. Optimization was carried out to estimate the best combination of processing parameters to achieve the optimal fiber characteristics, specifically fiber diameter and elastic modulus. All three parameters under study showed a significant effect on fiber properties, either as single or interacting variables. The optimized setup produced fibrous structures with an average fiber diameter of 1.7 µm and an elastic modulus of 25 MPa. This study demonstrated that factorial design could be advantageous for optimizing electrospinning apparatus, thereby providing a basis for further development and optimization of electrospinning technologies for the fabrication of fibrous scaffolds. An electrospinning tool was constructed to fabricate fiber-based biomaterials for future use as fibrocartilage tissue engineering scaffolds. The characteristics of the electrospun fiber depend on many factors; hence, a factorial experiment was conducted to study the relationship between processing factors and the fiber output, followed by an optimization procedure. The outcome of the optimized setup was a fibrous membrane with fiber properties potentially suitable for tissue engineering applications. This study also showed that the electrospinning process, a complex multivariate system, could be optimized using factorial design, hence laying a basis for further development of other electrospinning technologies.

Background To clinically evaluate 3D print-formed implant process, using cranioplasty as a proof of concept, to examine its effectiveness and utility as a method of intraoperative implant fabrication. Methods Twelve patients had a 3D print-formed template created for patient-specific implant manufacture. Of these patients, 10 received intraoperatively formed polymethylmethacrylate cranioplasty implants between 2013 and 2019. The 3D print-formed implant templates produced to manufacture these patient-specific implants were generated using patient computed tomography scans and 3D printed using fused deposition modelling technology. Cosmetic and functional results were determined by participating surgeons, in conjunction with a patient questionnaire. Results The functional results and stability of the implants were deemed to be favourable by participating surgeons. Three of the 10 patients completed a post-cranioplasty survey, all of whom judged their cosmetic results as good or excellent. At time of writing, the rate of surgical revision was zero and without clinically adverse outcomes. Conclusions 3D print-formed implants are an effective method of patient-specific implant formation.

Piezoelectric materials are intensively investigated for usage in biomedical applications ranging from in vivo sensors and energy harvesters to implants for bone and neural cell stimulation. Besides the high requirements for reliability and low cytotoxicity, implantable materials must be sterilizable without losing their functionality. In this study, we investigate the impact of low temperature plasma sterilization and the associated cleaning routines on the piezoelectric properties of PZT, BCZT and KNN bulk ceramics. The stability of the piezoelectric response strongly depends on the material system, with BCZT ceramics showing the strongest decline in properties. Several factors were identified to contribute to this reduction of the piezoelectric coefficient, the most important being mechanical stress due to sample handling as well as chemical reactions during cleaning, disinfection and sterilization. The study highlights the importance of evaluating the impact of all influencing factors along the pre-implantation handling chain in the material selection process.

Kidney transplantation is the optimum treatment for kidney failure in carefully selected patients. Technical surgical complications and second warm ischemic time (SWIT) increase the risk of delayed graft function (DGF) and subsequent short- and long-term graft outcomes including the need for post-transplant dialysis and graft failure. Intraoperative organ thermal regulation could reduce SWIT, minimizing surgical complications due to time pressure, and limiting graft ischemia-reperfusion injury.A novel ischemic-injury thermal protection jacket (iiPJ) was designed and fabricated in silicone composite and polyurethane (PU) elastomer prototypes. Both were compared with no thermal insulation as controls. Time to reach ischemic threshold (15°C) and thermal energy transfer were compared. A water bath model was used to examine the thermal protective properties of porcine kidneys, as a feasibility study prior to in vivo translation.In both iterations of the iiPJ, the time taken to reach the warm ischemia threshold was 35.2 ± 1.4 minutes (silicone) and 38.4 ± 3.1 minutes (PU), compared with 17.2 ± 1.5 minutes for controls (n = 5, P .001 for both comparisons). Thermal energy transfer was also found to be significantly less for both iiPJ variants compared with controls. There was no significant difference between the thermal performance of the 2 iiPJ variants.Protection from SWIT by using a protective insulation jacket is feasible. With clinical translation, this novel strategy could facilitate more optimal surgical performance and reduce transplanted organ ischemia-reperfusion injury, in particular the SWIT, potentially affecting delayed graft function and long-term outcomes.

ObjectiveThe structural and functional complexity of the respiratory system present significant challenges to capturing conditions vital for maintaining phenotypic cellular functions in vitro. Here we report a unique tissue engineering system that enables respiratory constructs to be cultured under physiological loading at an air-liquid interface (ALI).MethodsThe system consists of a porous poly-e-caprolactone scaffold mounted in a well insert, which articulates via magnetic coupling with a linear actuator device to strain attached scaffolds through a sterile barrier. For proof of concept, NCI-H460 human carcinoma cells were seeded on scaffold inserts which were subjected to 5-15% cyclic tensile strain at 0.2Hz within a six well plate. The dynamic constructs were cultured at an ALI in a standard incubator for up to 10 days along with unstimulated (static) ALI and static submerged control groups.ResultsHigh (near-100%) cell seeding efficiency was achieved within the scaffold-strain device. Both dynamic and static ALI groups yielded higher cell densities compared to the submerged control for all time points. Distinctly different patterns in cellular growth and behaviour between dynamic air-liquid interface and conventional static submerged culture groups were revealed by nuclei staining, where the actuated group displayed more uniform cellular distribution throughout the construct compared to both static controls.ConclusionAir-liquid interface culture and physiological strain are important for engineering respiratory tissue models.SignificanceThe system described allows scalable and replicable culture of 3-D tissue engineered respiratory models under biologically-relevant conditions.

The selection of biomaterials as biomedical implants is a significant challenge. Ultra-high molecular weight polyethylene (UHMWPE) and composites of such kind have been extensively used in medical implants, notably in the bearings of the hip, knee, and other joint prostheses, owing to its biocompatibility and high wear resistance. For the Anterior Cruciate Ligament (ACL) graft, synthetic UHMWPE is an ideal candidate due to its biocompatibility and extremely high tensile strength. However, significant problems are observed in UHMWPE based implants, such as wear debris and oxidative degradation. To resolve the issue of wear and to enhance the life of UHMWPE as an implant, in recent years, this field has witnessed numerous innovative methodologies such as biofunctionalization or high temperature melting of UHMWPE to enhance its toughness and strength. The surface functionalization/modification/treatment of UHMWPE is very challenging as it requires optimizing many variables, such as surface tension and wettability, active functional groups on the surface, irradiation, and protein immobilization to successfully improve the mechanical properties of UHMWPE and reduce or eliminate the wear or osteolysis of the UHMWPE implant. Despite these difficulties, several surface roughening, functionalization, and irradiation processing technologies have been developed and applied in the recent past. The basic research and direct industrial applications of such material improvement technology are very significant, as evidenced by the significant number of published papers and patents. However, the available literature on research methodology and techniques related to material property enhancement and protection from wear of UHMWPE is disseminated, and there is a lack of a comprehensive source for the research community to access information on the subject matter. Here we provide an overview of recent developments and core challenges in the surface modification/functionalization/irradiation of UHMWPE and apply these findings to the case study of UHMWPE for ACL repair.

This paper will report the fabrication process and microstructure analysis of fibrous composite incorporating ultra-high molecular weight polyethylene (UHMWPE) fabric, electrospun polycaprolactone (PCL), and bioglass particles. Briefly, electrospinning was performed to form PCL fibre lamination in the surface of UHMWPE fabric. This UHMWPE/PCL material was then bioglass-coated. Sequentially, microstructure of the UHMWPE fabric, UHMWPE/PCL, and UHMWPE/PCL/bioglass was imaged and analysed. The composite showed aligned ultrafine PCL fibres and distribution of bioglass particles in the layer of electrospun PCL. The results of this study provide groundwork for more advanced investigation, as well as development of implant prototype.

A variety of assessment tools are currently available to help clinicians assess Sports Related Concussion (SRC). Currently, the most widely available tools are neither objective nor portable, and are therefore not ideal for assessment at the site and time of a suspected injury. A portable system was developed to deliver a measurement of the steady-state visual-evoked potential (SSVEP). This system involved a smartphone housed in a Google Cardboard frame, which delivered a 15-Hz flicker visual stimulus while an electroencephalography (EEG) headset recorded EEG signals. Sixty-five rugby union players were tested during their regular season and were stratified into healthy, concussed, and recovered groups based on clinical examination. Their SSVEP response was quantified into a signal-to-noise ratio (SNR). The SNRs of players in each study group were summarized. Additionally, the SNRs of individual players who had baseline, post-injury, and post-recovery readings were analyzed. Sixty-five participants completed a baseline evaluation to measure their SSVEP. Twelve of these participants sustained a medically diagnosed concussion and completed SSVEP re-testing within 72 h. Eight concussed players received follow-up SSVEP testing after recovery. Concussed participants had a lower SNR [2.20 (2.04–2.38)] when compared to their baseline [4.54 (3.79–5.10)]. When clinically recovered, participant SNR was not significantly different to their baseline [4.82 (4.13–5.18)]. The baseline SNRs of the players who experienced a concussion during the season were not different to those of players who did not experience a concussion [4.80 (4.07–5.68)]. This is the first study to identify differences in SSVEP responses in male amateur rugby union players with and without concussion. It is also the first SSVEP demonstration for concussion evaluation at point-of-care. SSVEPs are significantly attenuated in the presence of concussion in these male athletes. Individuals returned to their baseline SSVEP following clinical recovery from the concussive injury. The use of SSVEPs has the potential to be a supplemental aid for the assessment and management of concussion.

The clinical use of photodynamic therapy (PDT) with rose bengal (RB) is emerging as an effective t reatment for a range of applications given its non-invasive and localised mode of delivery. In particular, rose bengal PDT has shown promising antifungal action in vitro. While focus has largely been on the physical and chemical impacts of PDT on the cell, an understanding of the role of genetics underpinning the cellular response is still limited. We have, therefore, reported a screen of the entire non-essential gene library of the model organism, Saccharomyces cerevisiae, using rose bengal PDT to ascertain the key genetic pathways affecting fungal tolerance to PDT. We also investigated the dosage of PDT required to eradicate Trichophyton rubrum spores, the main causative organism of onychomycosis infection. Following this, we conducted a pilot patient study of six patients (seven toenails) for the treatment of onychomycosis using rose bengal PDT (140 μM RB and ~763 J/cm2 green light), where the clinical treatment protocol was developed on the basis of the in vitro outcomes. The key biochemical pathways identified by the genetic screen as having altered tolerance to PDT included ergosterol biosynthesis, vacuolar acidification, and purine/S-adenosyl-L-methionine biosynthesis. The subsequent pilot patient study saw the complete cure of onychomycosis for all patients within three to five treatment sessions in the absence of pain or other local side effects. The outcome of the genetic screen for tolerance may thus inform the development of efficient clinical treatments using rose bengal PDT.

Every year more and more medical devices are being implanted in the human body. Sutures are currently the gold standard for attachment of these devices, but they have associated issues such as needle trauma, unsuitability for certain tissues, such as eye or lung, and require skilled surgeons. A variety of sutureless methods have been developed to overcome some of these issues. Sutureless methods developed include fibrin glue, cyanoacrylates, scaffolds and bio-inspired adhesives. A sutureless method that is receiving increasing attention is Photochemical Tissue Bonding (PTB). This method involves using photoactive dyes and light-activation to initiate a chemical reaction that forms cross-links with collagen. In this review, we describe the current status of PTB. A variety of dyes have been identified and the literature analysed to identify the most promising photoactive dyes for PTB. Rose Bengal appears to be the most promising of the dyes identified as it produces the strongest bonding of all the dyes and its use is associated with minimal thermal damage. Development of applications for Rose Bengal is an area of active research with multiple articles published in the last 5 years. The outlook is promising for PTB and Rose Bengal to provide clinically viable solutions for tissue adhesion.

Aim A two-body wear test experiment was performed on human enamel, in simulated chewing motion, against non-veneered zirconia ceramic. Aim-1 was to ascertain the effect of zirconia roughness on enamel wear. Aim-2 was to ascertain the relative enamel wear between enamel-zirconia wear pair and enamel-enamel control pair. Materials Six molar and premolar human enamel cusps per group were used for a dental wear test against laboratory polished (LP) zirconia and laboratory polished and clinically adjusted (LP + CA) zirconia. Enamel antagonists were tested against incisor teeth as a control group to demonstrate laboratory enamel wear. Methodology Two-body wear tests were conducted in a dual-axis biomimetic dental wear simulator. 49N loading force was used for 120,000 cycles with 1 mm lateral movement of the test specimen at 1.6Hz frequency, under constant ambient temperature water flow. Surface roughness before testing was determined using 3D profilometry. Loss of enamel height and volume i.e. vertical wear and volumetric wear respectively, were measured by superimposition of before and after testing scans by 3D laser scanning. Scanning electron microscopy was used for surface morphology assessment. One-way ANOVA and Post Hoc Multiple Comparisons with Bonferroni corrections were used at the 5% significance level to determine whether surface finish affected volumetric and vertical enamel loss. The relationship between volumetric and vertical loss of enamel was assessed using Pearson's correlation test. Results No significant difference was found between LP and LP + CA zirconia in vertical and volumetric enamel wear results. Control enamel had significantly higher vertical and volumetric enamel wear than LP and LP + CA zirconia. Pearson correlation revealed a strong relationship between vertical wear and volumetric wear of enamel. Conclusion Within the constraints of the test method in this experiment, zirconia irrespective of surface preparation, was found to cause less vertical and volumetric enamel wear compared to control enamel. No statistically significant difference was seen between LP zirconia and LP + CA zirconia.

Electrospun fibres have gained broad interest in biomedical applications, including tissue engineering scaffolds, due to their potential in mimicking extracellular matrix and producing structures favourable for cell and tissue growth. The development of scaffolds often involves multivariate production parameters and multiple output characteristics to define product quality. In this study on electrospinning of polycaprolactone (PCL), response surface methodology (RSM) was applied to investigate the determining parameters and find optimal settings to achieve the desired properties of fibrous scaffold for acetabular labrum implant. The results showed that solution concentration influenced fibre diameter, while elastic modulus was determined by solution concentration, flow rate, temperature, collector rotation speed, and interaction between concentration and temperature. Relationships between these variables and outputs were modelled, followed by an optimization procedure. Using the optimized setting (solution concentration of 10% w/v, flow rate of 4.5 mL/h, temperature of 45 °C, and collector rotation speed of 1500 RPM), a target elastic modulus of 25 MPa could be achieved at a minimum possible fibre diameter (1.39 ± 0.20 µm). This work demonstrated that multivariate factors of production parameters and multiple responses can be investigated, modelled, and optimized using RSM.

Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that binds to partners to mediate responses to environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with lysozyme M-Cre recombinase animals to generate lysozyme M-ARNT (LAR) mice with reduced ARNT expression. Myeloid cells of LAR mice had altered mRNA expression and delayed wound healing. Interestingly, when the animals were rendered diabetic, the difference in wound healing between the LAR mice and their littermate controls was no longer present, suggesting that decreased myeloid cell ARNT function may be an important factor in impaired wound healing in diabetes. Deferoxamine (DFO) improves wound healing by increasing hypoxia-inducible factors, which require ARNT for function. DFO was not effective in wounds of LAR mice, again suggesting that myeloid cells are important for normal wound healing and for the full benefit of DFO. These findings suggest that myeloid ARNT is important for immune function and wound healing. Increasing ARNT and, more specifically, myeloid ARNT may be a therapeutic strategy to improve wound healing.

Nanocrystalline α-Fe2O3 with particle sizes in the range 10–24 nm were produced by mechanical milling of micron-sized α-Fe2O3 particles. Microstructures of sintered pellets of cold compacted powder were investigated by electron microscopy. Nanoindentation studies showed the creep strain rates had values of the order of 10−4 s−1 at room temperature with creep increasing to higher values with increase of particle diameter. This was attributed to grain boundary sliding enhancement due to a piezomagnetic-type effect in the particles. Compressive tests at room temperature carried out on bulk samples with nanosized crystallites also showed large creep strain rate behaviour. The result will be helpful in designing ceramic systems with plastic behaviour at room temperature.

In this study, a fibrous composite was developed as synthetic graft for labral reconstruction treatment, comprised of ultra-high molecular weight polyethylene (UHMWPE) fabric, ultrafine fibre of polycaprolactone (PCL), and 45S5 Bioglass&reg, This experiment aimed to examine the mechanical performance and cytocompatibility of the composite. Electrospinning and a slurry dipping technique were applied for composite fabrication. To assess the mechanical performance of UHMWPE, tensile cyclic loading test was carried out. Meanwhile, cytocompatibility of the composite on fibroblastic cells was examined through a viability assay, as well as SEM images to observe cell attachment and proliferation. The mechanical test showed that the UHMWPE fabric had a mean displacement of 1.038 mm after 600 cycles, approximately 4.5 times greater resistance compared to that of natural labrum, based on data obtained from literature. A viability assay demonstrated the predominant occupation of live cells on the material surface, suggesting that the composite was able to provide a viable environment for cell growth. Meanwhile, SEM images exhibited cell adhesion and the formation of cell colonies on the material surface. These results indicated that the UHMWPE/PCL/Bioglass&reg, composite could be a promising material for labrum implants.

Knee meniscal injuries account for the greatest number of surgical procedures performed by orthopaedic surgeons worldwide. Each year in excess of 400,000 operations are performed in Europe and over one million in the United States and yet no suitable replacement for the meniscus is available. Fibrocartilage tissue engineering holds great potential in the regeneration of meniscal tissue however current developments have been limited. Difficulties in imitating the anisotropic nature of the meniscus, patient specific geometry, attaining sterility assurance requirements remain as developmental challenges for meniscal scaffold devices. A novel approach was developed to rapidly form terminally sterilized pre-packaged scaffold templates into anatomically matched regenerative meniscal implants. Formed meniscal implants exhibited the structural and functional architecture of the native meniscus. Meniscal implants fabricated using this method displayed mechanical properties approaching to that of the native meniscus and imparted rotational stability. Fixation techniques influenced the biomechanical response of implants and 45S5 bioactive glass modification was found to enhance radio-opacity of the scaffold. Biocompatibility of the implant was confirmed using a fibroblast cell culture model.

Thick Section 3D Bioresorbable Scaffolds Are Proposed as a Potential Alternative to Biologic Skin Grafts and Supportive Fillers for Non-Healing Chronic Wound Ulcers. Synthetic Bioresorbable Scaffolds Avoid Human and Animal Derived Contamination Risks, Provide Feasible Shelf Life, Availability and Cost, and Act as a Consistent Platform for Localized Drug Elution. A Bioresorbable Polyester-Based Scaffold (Infilon™) Was Investigated as a Drug Delivery Vehicle for Chloramphenicol Antibiotic (CAP) Combined with a Bioactive Envelope. the Effect of Varying Envelope Protocols on Antibiotic Elution Profile and Antimicrobial Potency on Scaffolds Were Analysed. the Maximum Antibiotic Loading Efficiency of the Scaffold Was 10.18% W/w. the Antibiotic Elution Profile Showed that the Burst Phase Lasted One Hour Subsequent to a Sustained Phase Approaching near Asymptotic Release. Envelope Permutations of Bulk Metallic Glass (BMG) and Bioglass 45S5 Reduced the Total Amount of Antibiotic Released by 1 to 1.8 Mg while the Polyethylene Oxide Envelope Extended the Burst Phase to 2 Hours. CAP Loaded Scaffolds Demonstrated Antimicrobial Effectiveness for 24 Hours. Results Show Potential for the Infilon™ Scaffold to Be Used as a Platform for Localized Antibiotic Delivery. Delivery Profiles Can Be Enhanced with Additional BMG or Bioglass Envelopes. this Approach Has Opportunity to Provide a Synergistic Coupling of Antimicrobial Action and the Harbouring of Granular Tissue Subsequent to Final Wound Healing.

A Novel Six-Chamber Biomimetic Dental Wear System with Multi-Axis Mechanical, Thermal, Chemical, and Biologic Control Capabilities Was Developed for in Vitro Dental Wear Testing. User and Mechanical Requirements Were Ascertained from the Ivoclar Wear Method as a Part of Review of Existing Dental Wear Systems. A Thermocyling Irrigation System with Water Medium Was Incorporated to Mimic the Physiologic Temperature Variation of the Oral Environment. Configuration Details of the Design Were Explained. the Outcome of the Development Was Specified and Application Potentials Were Discussed.

This in vitro study compared the effects of nucleotomy alone, with nucleotomy then implantation with a novel nucleus replacement device (D3 device) in a single segment kangaroo spine model. This study utilised dynamic biaxial biomechanical testing of intact, nucleotomy and nucleus replacement implant conditions to evaluate the kinematic behaviour of the single segment kangaroo lumbar spine. Studies have examined the biomechanical efficacy of invasive treatments such as Total Disc Replacement and Intervertebral Fusion for the treatment of chronic low back pain, however no studies to date have investigated the biomechanical effects of a novel elastomeric compressive load sharing nucleus replacement device. Kangaroo lumbar spine motion segments with all musculature, ligamentous tissue and posterior elements removed, were tested in intact state prior to undergoing nucleotomy or nucleotomy then nucleus implantation using the D3 device. All specimens were tested in flexion-extension and lateral-bending; Range of motion (ROM), Neutral Zone (NZ), Hysteresis (H), and Elastic Stiffness (ES) were evaluated. Nucleotomised motion segments demonstrated a 30% to 90% increase in ROM, NZ, H, but not ES for all Flexion-Extension testing conditions and in Lateral Bending test conditions when compared to intact state. Implantation of the nucleus replacement device demonstrated no significant difference when compared to intact state except for H during Lateral Bending testing conditions when compared to the intact state. Therefore, there was a significant increase in ROM, NZ, and H after Nucleotomy during Flexion-Extension motions and an increase in ROM alone during lateral bending motions in the single segment kangaroo spine model. These changes return to that of the intact state with the placement of a novel nucleus replacement device. Our data suggest that the D3 device tested can restore the kinematic changes of a degenerated disc represented by the nucleotomised single motion segment.

Intramedullary (IM) nails are routinely used to stabilize long bone fractures. They can however lead to stress shielding, pain, migration, obstruct hematopoietic tissue, become a loci for infection, and require subsequent surgical retrieval. Novel intra-osseous scaffold (IOS™) prototypes for fracture healing have been developed to function as a regenerative scaffold to enhance callous formation under mechanically stabilized conditions then resorb. Prototype fixation pins and rod systems were formed from glass-reinforced-glass. Flexion, torsion and shear tests were performed to evaluate the composite pins and rods. A modular rod design was successfully deployed and dilated while in a deformable state. When fitted and gripping the intramedullary canal then set in a rigid state. An obliquely sectioned ovine femur was used as a long bone fracture model for deployment and mechanical verification. Flexural support provided by the intramedullary scaffold was superior to multiple k-wire fixation, while the k-wire approach was more stabilizing under torsional loads. Glass reinforced glass samples were mechanically tested after soaking for up to 4 weeks in saline. Strength and modulus of the composite was reduced to approximately 25% of initial values after 2 weeks.

Tissue engineering will play an increasingly vital role in cancer research. Provision of biomimetic microenvironment systems for in vitro cancer models can be addressed in part by utilizing thick 3D scaffolds with high interconnective porosity . This approach gives rise to new analytical challenges and opportunities. In this preliminary study, Variotis™ synthetic scaffolds of high interconnected porosity and hierarchical structure were used. An effective macroscopic porosity of 94.3 ±1.74 vol% was attained by using microCT and finite element methods. The actual porosity was determined to be 94.6±0.29 vol%. Scaffolds were compressed in a customized jig to thicknesses of 99.5 mm, 74.6 mm, 46.3 mm (±0.5% tolerance) and then annealed to set respective porosities of 94.3 vol%, 93.2 vol%, 89.5 vol% (±1.5% tolerance). Scaffolds were then sectioned to 2mm thickness. DLD-1 colon cancer cells were grown on 3D scaffolds of three specified porosities for varying periods of time then imaged using confocal and scanning electron microscopy methods. Hoechst staining resulted with minimal scaffold autofluoresence while autofluoresence exceeded useful limits when used in conjunction with Alexa488-phalloidin under argon laser excitation in confocal microscopy. Using Hoechst staining, DLD-1 cells (nuclei) were observed to readily attach and proliferate on Variotis™ scaffolds. Normal DLD-1 cell morphologies were evident using scanning electron microscopy. The high interconnected porosity of the scaffolds allowed cells to be observed deep within scaffolds. Scaffolds remained structurally stable and unified throughout all culture experiments and provided ease of handling during cell culture and microscopy.

An elastomeric spinal disk prosthesis design (BioFI™) with vertebral interlocking anchors has been modified using an embedded TiNi wire array. Bioinert styrenic block copolymer (Kraton®) and polycarbonate urethane (Bionate®) thermoplastic elastomer (TPE) matrices were utilized. Fatigue resistant NiTi wire was pretreated to induce superelastic martensitic microstructure. Stent-like helical structures were produced for incorporation within homogenous TPE matrix. Composite prototypes were fabricated in a vacuum hot press using transfer moulding techniques. Implant prototypes were subject to axial compression using a BOSE ® ELF3400. The NiTi reinforced implants exhibited reduction in axial strain, compliance, and creep compared to TPE controls. The axial properties of the NiTi reinforced Bionate® BioFI™ implant best approximated those of a spinal disk followed by Kraton®-NiTi, Bionate® and Kraton® prototypes. An ovine lumbar segment biomechanical model was used to characterize the disk prosthesis prototypes. Specimens were subject to 7.5Nm pure moments in axial rotation, flexion-extension and lateral bending with a custom jig mounted on an Instron® 8874. The motion preserving ligamentous nature of this arthroplasty prototype was not inhibited by NiTi reinforcement. Joint stiffness for all prototypes was significantly less than the intact and discectomy controls. This was due to lack of vertebral anchor rigidity rather than BioFI™ motion segment matrix type or reinforcement. Implant stress profiles for axial compression and axial torsion conditions were obtained using finite element methods. The biomechanical testing and finite element modelling both support existing BioFI™ design specifications for higher modulus vertebral anchors, endplates and motion segment periphery with gradation to a low modulus core within the motion segment. This closer approximation of the native spinal disk form translates to improvements in prosthesis biomechanical fidelity and longevity. Axial compressive strain induced within a TiNi reinforced Kraton® BioFI™ was found to be linearly proportional to the NiTi helical coil electrical resistance. This neural network capability delivers opportunities to monitor and telemeterize in situ multiaxis joint structural performance and in vivo spine biomechanics.

Composite films of poly(vinyl alcohol) (PVA) and chemically modified fly ash (MFA) by sodium hydroxide were prepared by aqueous cast method with 5, 10, 15, 20 and 25 wt% MFA treated with 1 wt% cross-linking agent (glutaraldehyde, GLA). The tensile strengths of the composite films were found to increase proportionally with MFA and the maximum strength attained was 414% higher in the case of 20 wt% MFA than that in neat PVA film. The percentage of strain at break exponentially decreased with addition of MFA. The modulus of the composites was determined to increase proportionally up to a maximum 685% at 20 wt% MFA compared to that of neat PVA film. Interfacial networking between the MFA and PVA was evident from scanning electron microscopy (SEM) images of tensile-fractured surfaces, which was not observed for the unmodified fly ash (FA) system. Atomic force microscopy (AFM) analysis showed that the mean square surface roughness of the composite films of PVA–MFA was 53% smoother than the films with FA.

Review of current Anterior Cruciate Ligament (ACL) anchor technologies indicates that many devices facilitate osteointegration but not soft tissue in-growth. The design and preliminary testing of a novel biomimetic in-situ dilating bioabsorbable ACL anchor for simultaneous soft and hard tissue attachment is the subject of this study. The anchor method for this concept has been developed to mimic the mechanical-key configuration observed in a hair root. Reviewed anchor devices are typically interference screw-based. Screw anchors can lead to unnecessary ligament pre-stress, tearing during deployment and poor graft-bone contact. This work demonstrates a new fixation concept specifically developed for use with devices consisting of temperature-sensitive glass-reinforced-glass (GRG) soft tissue conductive biomaterial. Ligament anchorage is accomplished by dilation of the device into the base of a hair-root shaped osteotomy where a ligament with a collar and self tightening knot is inserted beforehand. This method facilitates full ligament-to-bone contact at the osteotomy zone where critical physiological ligament anchorage develops. Ligament pull-out loads equivalent to published results for conventional anchors were achieved using graft analogue. Testing with porcine ligaments resulted in a substantial reduction in ligament pull-out loads. Tibia bone sample constraints combined with the unraveling of the ligament knot were identified as primary factors for low pull-out loads for the porcine ligament tests. Subsequent design iterations will employ a reduction in prototype dimensions in addition to the use of a suture to lock the ligament knot. The hair-root shaped osteotomy and ligament anchor knot elements of this approach may be translated to other fixation systems and methods. By improving macro-mechanical-key interaction between the anchor, bone and ligament, further increase in pull-out forces may be achieved without unnecessary ligament pre-stress and tear damage caused by conventional interference screw threads.

The nucleus of a spinal disc is seamlessly connective and protectively supportive of the joint within which it is enveloped. A range of nucleus prosthesis configurations have been proposed and applied with some success. Those that have demonstrated clinical efficacy have approximated physiological form and function using established biomaterials while preserving key anatomical structures. The minimally invasive biostable, biomimetic Columna Disc Device (CDD) partial spinal disc replacement has been developed to clinical trial stage. It mimics the geometry and response of the nucleus that it replaces. While the implant configuration and materials have been set, the geometry and interfacial properties of this prosthesis may be modulated to account for versatility in surgical deployment, implant stiffness, and subsequent long-term tissue remodelling response. FEA models were developed to study effects of implant jacket geometry and surface properties on implant deployment and biomechanics. Studded and dimpled textures provide a method for increasing surface area to diffuse jacket-filler interfacial stress and similar for the implant-tissue junction. Surface texture design elements observed in nature can protect against delamination and interlayer slippage. This is the case with adherent outer layers of human skin. A textured implant design is also proposed to guard against third body wear by housing debris remote of wear sites and by reducing sliding. The periodically varying strain fields provided by the textured jacket may also help mitigate for tears by diverting and arresting micro-fissures. Increasing friction at the implant-tissue interface to the point of tissue-attachment was shown to increase the stiffness of the implant in axial-loading. In contrast, increasing bulk surface area is expected to contribute to a decrease in implant stiffness. This is, however, dependent on the intimacy and properties of interfacing tissues.

Chronic non-healing wounds are a common complication of diabetes. Prolonged inflammation and decreased matrix accumulation may contribute. Connective tissue growth factor (CTGF) is induced during normal wound healing, but its regulation in diabetic wounds is unknown. We developed a primate model for the study of in vivo wound healing in baboons with long diabetes duration.Drum implants were placed subcutaneously into thighs of diabetic and non-diabetic control baboons. After 2 and 4 weeks the skin incision sites were removed for measurement of breaking strength and epithelial thickness. Drum implants were removed for analysis of granulation tissue and inflammatory cells, CTGF and tissue inhibitor of matrix metalloproteinase (TIMP-1). Degradation of added CTGF by wound fluid was also examined.Healed incision site skin was stiffer (less elastic) in diabetic baboons and epithelial remodelling was slower compared with controls. Granulation tissue from diabetic baboons was reduced at 2 and 4 weeks, with increased vessel lumen areas at 4 weeks. Macrophages were reduced while neutrophils persisted in diabetic tissue. In diabetic wound tissue at 4 weeks there was less CTGF induced, as shown by immunohistochemistry, compared with controls. In contrast, immunoreactive fragments of CTGF were significantly increased in whole tissue lysate in diabetic baboons, suggesting that CTGF is redistributed in diabetes from granulation tissue into wound fluid. When recombinant human CTGF was co-incubated with wound fluid, increased CTGF degradation products were observed in both control and diabetic samples.This baboon model of wound healing reflects the abnormal microenvironment seen in human diabetic wounds and provides insights into the dysregulation of CTGF in diabetic wounds.

Porous calcium silicates (CaSiO3, WT) are regarded as a potential bioactive material for bone tissue engineering. However, their insufficient mechanical strength and high dissolution (degradation) limit their biological applications. The aim of this study is to surface modify WT scaffolds with poly(d,l-lactic acid) (PDLLA) to improve their mechanical and biological properties. The phase composition, microstructure, porosity and interconnectivity of WT and PDLLA-modified WT (WTPL) scaffolds were analyzed by X-ray diffraction, scanning electron microscopy and micro-computerized tomography. The WTPL scaffolds maintained a more uniform and continuous inner network, compared to that of the WT scaffolds, while maintaining the pore size, porosity and interconnectivity of the original materials. The compressive strength, compressive modulus and percentage strain of the WT and WTPL scaffolds were assessed in air and phosphate-buffered saline. PDLLA modification significantly improved the compressive strength and decreased the brittleness of the WT scaffolds. The weight loss and apatite-forming ability of the two scaffolds were evaluated by soaking them in simulated body fluid (SBF) for 1, 3, 7, 14 and 28days. PDLLA modification decreased the dissolution of the WT scaffolds while maintaining their apatite-forming ability in SBF. In addition, PDLLA modification improved the spreading and viability of human bone-derived cells. Our results indicate that PDLLA-modified CaSiO3 scaffolds possess improved mechanical and biological properties, suggesting their potential application for bone tissue regeneration.

The most common methods for attaching a device to the internal tissues of the human body are via sutures, clips or staples. These attachment techniques require penetration and manipulation of the tissue. Tears and leaks can often be a complication post-attachment, and scarring usually occurs around the attachment sites. To resolve these issues, it is proposed to develop a soft tissue scaffold impregnated with Rose Bengal/Chitosan solution (RBC-scaffold, 0.01% w/v Rose Bengal, 1.7% w/v Medium Molecular Weight Chitosan). This scaffold will initially attach to the tissue via a light activation method. The light activates the dye in the scaffold which causes cross-links to form between the scaffold and tissue, thus adhering them together. This is done without mechanically manipulating the surrounding tissue, thus avoiding the issues associated with current techniques. Eventually, the scaffold will be resorbed and tissue will integrate for long-term attachment. A variety of tests were performed to characterise the RBC-scaffold. Porosity, interconnectivity, and mechanical strength were measured. Light activation was performed with a broad spectrum (380-780nm) 10W LED lamp exposed to various time lengths (2-15min, Fluence range 0.4-3J/cm(2) ). Adhesive strength of the light-activated bond was measured with lap-shear tests performed on porcine stomach tissue. Cell culture viability was also assessed to confirm tissue integration potential. These properties were compared to Variotis™, an aliphatic polyester soft tissue scaffold which has proven to be viable for soft tissue regeneration. The RBC-scaffolds were found to have high porosity (86.46±2.95%) and connectivity, showing rapid fluid movement. The elastic modulus of the RBC-scaffolds (3.55±1.28MPa) was found to be significantly higher than the controls (0.15±0.058MPa, p

Tissue engineering scaffolds are biomimetic structures with carefully controlled chemical and physical properties. Scaffolds are implanted medical devices and as such are required to meet stringent sterility regulations to ensure patient safety. Common sterilization methods involve harsh conditions that are required to inactivate tough microscopic pathogens. Unfortunately, these conditions will commonly alter the susceptible scaffold biomaterials being sterilized, causing a multitude of chemical, morphological, and mechanical changes that ultimately affect the function of the tissue-engineering device. Because of this phenomenon, tissue engineers need to consider the terminal sterilization method in the initial design process of tissue scaffolds. Recently, tissue engineers have been realizing the elegant solutions in which sterilization methods can be applied to simultaneously provide favorable changes to scaffolds. Scaffolds designed in this way may overcome the high cost shortfalls of current tissue scaffolds.

Nail fungal infections are notoriously persistent and difficult to treat which can lead to severe health impacts, particularly in the immunocompromized. Current antifungal treatments, including systemic and topical drugs, are prolonged and do not effectively provide a complete cure. Severe side effects are also associated with systemic antifungals, such as hepatotoxicity. Light treatments of onychomycosis are an emerging therapy that has localized photodynamic, photothermal or photoablative action. These treatments have shown to be an effective alternative to traditional antifungal remedies with comparable or better cure rates achieved in shorter times and without systemic side effects. This report reviews significant clinical and experimental studies in the field, highlighting mechanisms of action and major effects related to light therapy; in particular, the impact of light on fungal genetics.

Aims/Hypothesis. Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken.Methods. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid.Results. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Woundα-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r=0.406;P<0.001).Conclusions/Interpretation. These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers.

Electrospinning is a technique that can produce fibres in the nanoscale range. This process is useful for many applications, including fabrication of fibrous scaffolds for fibrocartilage tissue engineering. For this application, cell attachment and tissue development is influenced by fibre morphology and mechanical properties. This electrospinning study investigated the influence of rotating collector design on morphology and mechanical properties of electrospun polycaprolactone fibre. The experiment employed 4 mandrel designs: 1) full surface of aluminium; 2) with gap feature; 3) with gap feature and teflon support; 4) with gap feature and tape support. The highest elastic modulus was obtained from mandrel with gap and tape support, which was 24.6 MPa and significantly higher compared to fibres acquired from other collector designs. Fibre diameter attained was identical across the different collectors, ranging from 0.5 - 2 µm. Gap introduction showed enhanced alignment in the resultant fibre. It can be concluded that fibre alignment and tensile properties can be improved by simply modifying the collector design. This improved fibre mat can be developed as a biomaterial for fibrocartilage tissue engineering scaffolds

Nanodimensional metallic silver was grown by electrodeposion technique in a semi solid polymer matrix of polyacrylamide. The whole structure looks like dendronic. The average particle diameter of the as grown metallic silver is 13 nm. Nanoindentation study of these nanoparticles shows modulus and hardness value as 103.93 GPa and 3.12 GPa respectively.

Naturally occurring gradients have been identified in the natural spinal disk joint. Emulating these gradients within a total joint arthroplasty may allow the motion-moderating function of the disk to be more closely replicated. Biomimetic functionally gradient materials have been developed for providing rigid bone-engaging caudal and coronal bioactive surfaces that transition to a flexible fibrocartilage-like portion. Methods are detailed for forming thermoplastic elastomers, bioactive reinforcement, radially aligned anisotropic composites and functionally graded materials with axial and radial gradients. Employing these methods to the vertebral-interlocking spinal disk design provides a biomimetic approach to reduce risk of hypermobility, stress concentration and implant migration.

Background. Human cancer is a three-dimensional (3D) structure consisting of neighboring cells, extracellular matrix, and blood vessels. It is therefore critical to mimic the cancer cells and their surrounding environment duringin vitrostudy. Our aim was to establish a 3D cancer model using a synthetic composite scaffold.Methods. High-density low-volume seeding was used to promote attachment of a non-small-cell lung cancer cell line (NCI-H460) to scaffolds. Growth patterns in 3D culture were compared with those of monolayers. Immunohistochemistry was conducted to compare the expression of Ki67, CD44, and carbonic anhydrase IX.Results. NCI-H460 readily attached to the scaffold without surface pretreatment at a rate of 35% from a load of 1.5 × 106cells. Most cells grew vertically to form clumps along the surface of the scaffold, and cell morphology resembled tissue origin; 2D cultures exhibited characteristics of adherent epithelial cancer cell lines. Expression patterns of Ki67, CD44, and CA IX varied markedly between 3D and monolayer cultures.Conclusions. The behavior of cancer cells in our 3D model is similar to tumor growthin vivo. This model will provide the basis for future study using 3D cancer culture.

Nanoindentation of CuO-lithia silica nanoglass (CuO-NG) composite was studied and compared with only CuO nanoparticles (CuO). Young's Modulus (E) and hardness (H) of the composite was found to be greater in comparison with CuO nanoparticles. Creep measurements showed that Creep strain rate (CSR) is lower for composite material than only CuO. This is due to decrease of copper diffusion through nanoglass phase in composite sample.

Hydrogels are currently applied in the treatment of numerous degenerative diseases because of their three dimensional (3D) nature, high water content and wide range of polymers that can be used for their fabrication. Hydrogels have been investigated and commercialized, for example, as soft contact lens-based ophthalmic drug delivery systems. These novel devices improved the bioavailability of ophthalmic drugs and their residence time. Hydrogels are also being investigated to facilitate and augment targeted delivery of chemotherapeutic agents. This approach minimizes significantly the side effects associated with conventional administration of anti-cancer therapeutics. The application of hydrogels as 3D scaffold has recently gained momentum because they can mimic key features of the extracellular matrix. For this reason, hydrogels are representing a viable alternative to traditional tumor xenograft in cancer biology studies. This review highlights recent advances in the development of hydrogels that are applied in degenerative diseases such as ocular, cancer, spine and cartilage degenerative pathologies.

We prepared biodegradable composite films of poly(vinyl alcohol) (PVA) and fly ash (FA) spanning 5, 10, 15, 20, and 25 wt % concentrations by casting aqueous solutions. The tensile strengths of the composite films were increased proportionally via the addition of FA. The strength of the film was enhanced by 193% with 20% FA compared to the neat PVA control. Further addition of FA deviated from the linear trend. The moduli of the composites also increased proportionally with FA addition to 212% at 20 wt % FA addition compared to the control. The percentage strain at break exponentially decreased with the addition of FA. In the dynamic mechanical behavior, the storage and loss moduli both increased with FA content. The tan δ peaks corresponding to the glass-transition temperature shifted 5–10°C higher above the control sample (73°C). This shift was attributed to a reduction in the mobility of PVA segments because they were anchored by the FA surface. The reductions in mobility manifested in strong interfacial interactions were indicative of hydrogen bonding. Broadening and reduction in the intensities of the stretching and bending peaks of OH, CH and CO of PVA in the Fourier transform infrared spectra were observed. This suggested that hydrogen bonding was active between the functional groups in the FA and PVA chains. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010