Philip Boughton

Restoration of compressive loading properties of lumbar discs with a nucleus implant-a finite element analysis study.

BACKGROUND CONTEXT Discectomy is a common procedure for treating sciatica. However, both the operation and preceding herniated disc alter the biomechanical properties of the spinal segment. The disc mechanics are also altered in patients with chronic contained herniation. The biomechanical properties of the disc can potentially be restored with an elastomeric nucleus replacement implanted via minimally invasive surgery. PURPOSE The purpose of this study was to determine whether the compressive characteristics of the intervertebral disc after a nucleotomy can be restored with an elastomeric nucleus replacement. STUDY DESIGN A finite element model of the L4-L5 intervertebral disc was created to investigate the effect of the implantation of an elastomeric nucleus replacement on the biomechanical properties of the disc under axial loading. METHOD A L4-L5 physiologic intervertebral disc model was constructed and then modified to contain a range by volume of nucleotomies and nucleus replacements. The material properties of the nucleus replacement were based on experimental data for an elastomeric implant. The compressive stiffness, radial annular bulge, and stress distribution of the nucleotomy and nucleus replacement models were investigated under displacement-controlled loading. RESULTS Removal of nucleus pulposus from the physiologic disc reduced the force necessary to compress the disc 2 mm by 50%, altered the von Mises stress distribution, and reduced the outward radial annular bulge. Replacing the natural nucleus pulposus of the physiologic disc with an artificial nucleus reduced the force required to compress the disc 2 mm by 10%, indicating a restoration of disc compressive stiffness. The von Mises stress distribution and annular bulge observed in the disc with an artificial nucleus were similar to that observed in the physiologic disc. CONCLUSION This study demonstrates that despite having different material properties, a nucleus replacement implant can restore the axial compressive mechanical properties of a disc after a discectomy. The implant carries compressive load and transfers the load into annular hoop stress.

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.

Quantitative in vitro assessment of Mg65Zn30Ca5 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 × 106 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.

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.

A Kangaroo Spine Lumbar Motion Segment Model: Biomechanical Analysis of a Novel In Situ Curing Nucleus Replacement Device

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.

Nanoindentation studies on silver nanoparticles

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.

Growth of DLD-1 Colon Cancer Cells on Variotis™ Scaffolds of Controlled Porosity: A Preliminary Study

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.

Methods for Achieving Soft Tissue Scaffold Sterility

The manufacturing process for in vitro tissue culture products and medical devices relies on a validated sterilization route for ensuring product sterility, safety and performance. Two key aspects that contribute toward final sterilization validation are (1) the reliable estimation of product bioburden and (2) the development of a proficient sterile packaging system. Bioabsorbable composite systems and architecture of tissue scaffolds can lead to numerous challenges for bioburden testing and packaging design. This study is concerned with the development of bioburden assessment methods and packaging systems for Variotis™; a soft tissue engineering scaffold. A bioburden test method relying on mechanical agitation was established. Bioburden assessment was achieved by recovering Geobacillus stearothermophilus spore inoculant for analysis. A packaging system was developed which provides adequate protection for Variotis™ scaffolds while meeting other user/sterilization requirements for research grade product. The guidelines and design approaches included in this study are generally applicable to other tissue engineering scaffold and medical devices.

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.