Insulating jackets thermally protect kidneys in an ex vivo model of second warm ischemia.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Reduction of ARNT in myeloid cells causes immune suppression and delayed wound healing.

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.

Continuous non-invasive estimates of cerebral blood flow using electrocardiography signals: a feasibility study.

This paper describes a potential method to detect changes in cerebral blood flow (CBF) using electrocardiography (ECG) signals, measured across scalp electrodes with reference to the same signal across the chest-a metric we term the Electrocardiography Brain Perfusion index (EBPi). We investigated the feasibility of EBPi to monitor CBF changes in response to specific tasks. Twenty healthy volunteers wore a head-mounted device to monitor EBPi and electroencephalography (EEG) during tasks known to alter CBF. Transcranial Doppler (TCD) ultrasound measurements provided ground-truth estimates of CBF. Statistical analyses were applied to EBPi, TCD right middle cerebral artery blood flow velocity (rMCAv) and EEG relative Alpha (rAlpha) data to detect significant task-induced changes and correlations. Breath-holding and aerobic exercise induced highly significant increases in EBPi and TCD rMCAv (p < 0.01). Verbal fluency also increased both measures, however the increase was only significant for EBPi (p < 0.05). Hyperventilation induced a highly significant decrease in TCD rMCAv (p < 0.01) but EBPi was unchanged. Combining all tasks, EBPi exhibited a highly significant, weak positive correlation with TCD rMCAv (r = 0.27, p < 0.01) and the Pearson coefficient between EBPi and rAlpha was r = - 0.09 (p = 0.05). EBPi appears to be responsive to dynamic changes in CBF and, can enable practical, continuous monitoring. CBF is a key parameter of brain health and function but is not easily measured in a practical, continuous, non-invasive fashion. EBPi may have important clinical implications in this context for stroke monitoring and management. Additional studies are required to support this claim. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00265-z.

Functional Ultra-High Molecular Weight Polyethylene Composites for Ligament Reconstructions and Their Targeted Applications in the Restoration of the Anterior Cruciate Ligament.

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.

Clinical evaluation of rapid 3D print-formed implants for surgical reconstruction of large cranial defects.

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.

Protection From the Second Warm Ischemic Injury in Kidney Transplantation Using an Ex Vivo Porcine Model and Thermally Insulating Jackets.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Two-body wear test of enamel against laboratory polished and clinically adjusted zirconia.

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.

Corrigendum: Steady-State Visual-Evoked Potentials as a Biomarker for Concussion: A Pilot Study.

[This corrects the article DOI: 10.3389/fnins.2020.00171.].

Steady-State Visual-Evoked Potentials as a Biomarker for Concussion: A Pilot Study.

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.

Mechanical and Cytocompatibility Evaluation of UHMWPE/PCL/Bioglass® Fibrous Composite for Acetabular Labrum Implant.

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®. 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® composite could be a promising material for labrum implants.

Improvement of mechanical and biological properties of porous CaSiO3 scaffolds by poly(D,L-lactic acid) modification.

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.

Modelling and Optimization of Polycaprolactone Ultrafine-Fibres Electrospinning Process Using Response Surface Methodology.

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.

A method for investigating the cellular response to cyclic tension or compression in three-dimensional culture.

We have an interest in the cellular response to mechanical stimuli, and here describe an in-vitro method to examine the response of cells cultured in a three-dimensional matrix to mechanical compressive and tensile stress. Synthetic aliphatic polyester scaffolds coated with 45S5 bioactive glass were seeded with human dental follicular cells (HDFC), and attached to well inserts and magnetic endplates in six well palates. Scaffolds were subjected to either cyclic 10% tensile deformation, or 8% compression, at 1 Hz and 2 Hz respectively for 6, 24 or 48 h, by uniaxial motion of magnetically-coupled endplates. It was possible to isolate high quality mRNA from cells in these scaffolds, as demonstrated by high RNA integrity numbers scores, and ability to perform meaningful cRNA microarray analysis, in which 669 and 727 genes were consistently upregulated, and 662 and 518 genes down regulated at all times studied under tensile and compressive loading conditions respectively. MetaCore analysis revealed the most regulated gene ontogenies under both loading conditions to be for: cytoskeletal remodelling; cell adhesion-chemokines and adhesion; cytoskeleton remodelling-TGF WNT and cytoskeletal remodelling pathways. We believe the method here described will be of value for analysis of the cellular response to cyclic loading.

Light treatments of nail fungal infections.

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.

Characterisation of a novel light activated adhesive scaffold: Potential for device attachment.

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<0.01) and approached reported values for human gastrointestinal tissue (2.3MPa). The maximum adhesion strength achieved of the RBC-scaffolds was 8.61±2.81kPa after 15min of light activation, this is comparable to the adhesion strength of fibrin glue on scaffolds. Cell attachment was seen to be similar to the controls, but cells appeared to have better cell survivability. In conclusion, the RBC-scaffolds show promise for use as a novel light activated attachment device with potential applications in attaching an anti-reflux valve in the lower oesophagus and also in wound healing applications for stomach ulcers.

A dynamic perfusion bioreactor approach for engineering respiratory tissues in-vitro.

In vitro culture of respiratory tissues poses many challenges due to the intrinsic complexity of the respiratory system. Multiple cellular phenotypes comprise the respiratory epithelium and operate under dynamic, gas-interchanging conditions that should be replicated for near-physiologic cultivation of functional tissues in vitro. A novel biomimetic perfusion bioreactor system has been proposed to reconstitute key functional conditions of the human lung. This portable system consists of several biologically-inspired components: (i) a 3-dimensional (3-D) elastomeric soft tissue scaffold construct, (ii) a mechanical actuator, (iii) a perfusion system and (iv) gaseous exchange capabilities. These integrated components operate synergistically to create a unique, dynamic air-liquid interface (ALI) environment that allows controlled application of physiological and pathological strain while complementing standard cell culture techniques. This system holds potential for engineering 3-D tissues to meet growing demand for a range of applications, from more ethical and efficient pharmaceutical screening to clinical graft transplants.

A novel method for single sample multi-axial nanoindentation of hydrated heterogeneous tissues based on testing great white shark jaws.

Nanomechanical testing methods that are suitable for a range of hydrated tissues are crucial for understanding biological systems. Nanoindentation of tissues can provide valuable insights into biology, tissue engineering and biomimetic design. However, testing hydrated biological samples still remains a significant challenge. Shark jaw cartilage is an ideal substrate for developing a method to test hydrated tissues because it is a unique heterogeneous composite of both mineralized (hard) and non-mineralized (soft) layers and possesses a jaw geometry that is challenging to test mechanically. The aim of this study is to develop a novel method for obtaining multidirectional nanomechanical properties for both layers of jaw cartilage from a single sample, taken from the great white shark (Carcharodon carcharias). A method for obtaining multidirectional data from a single sample is necessary for examining tissue mechanics in this shark because it is a protected species and hence samples may be difficult to obtain. Results show that this method maintains hydration of samples that would otherwise rapidly dehydrate. Our study is the first analysis of nanomechanical properties of great white shark jaw cartilage. Variation in nanomechanical properties were detected in different orthogonal directions for both layers of jaw cartilage in this species. The data further suggest that the mineralized layer of shark jaw cartilage is less stiff than previously posited. Our method allows multidirectional nanomechanical properties to be obtained from a single, small, hydrated heterogeneous sample. Our technique is therefore suitable for use when specimens are rare, valuable or limited in quantity, such as samples obtained from endangered species or pathological tissues. We also outline a method for tip-to-optic calibration that facilitates nanoindentation of soft biological tissues. Our technique may help address the critical need for a nanomechanical testing method that is applicable to a variety of hydrated biological materials whether soft or hard.

Quantitative in vitro assessment of Mg65 Zn30 Ca5 degradation and its effect on cell viability.

A bulk metallic glass (BMG) of composition Mg(65) Zn(30) Ca(5) was cast directly from the melt and explored as a potential bioresorbable metallic material. The in vitro degradation behavior of the amorphous alloy and its associated effects on cellular activities were assessed against pure crystalline magnesium. Biocorrosion tests using potentiodynamic polarization showed that the amorphous alloy corroded at a much slower rate than the crystalline Mg. Analysis of the exchanged media using inductively coupled plasma optical emission spectrometry revealed that the dissolution rate of Mg ions in the BMG was 446 µg/cm(2)/day, approximately half the rate of crystalline Mg (859 µg/cm(2)/day). A cytotoxicity study, using L929 murine fibroblasts, revealed that both the BMG and pure Mg are capable of supporting cellular activities. However, direct contact with the samples created regions of minimal cell growth around both amorphous and crystalline samples, and no cell attachment was observed.

The use of porous scaffold as a tumor model.

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 during in vitro study. 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 × 10(6) cells. 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 growth in vivo. This model will provide the basis for future study using 3D cancer culture.

Advances in hydrogels applied to degenerative diseases.

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.