Biomedical subjects

Mairead A Wood

Publications and source records attributed to Mairead A Wood.

5 recordsLinked to original sources

PubMed2006

Using dihydropyridine-release strategies to enhance load effects in engineered human bone constructs.

We report on the development of a novel biodegradable scaffold capable of enhancing mechanical signals for tissue-engineering applications. It has been shown that mechanotransduction enhances bone formation in vitro and in vivo; in tissue-engineering applications, this phenomenon is exploited through the use of mechanical bioreactors to generate bone tissue. The dihydropyridine agonist Bay K8644 (Bay) acts to increase the opening time of mechanosensitive voltage-operated calcium channels (VOCCs), specifi- cally L-type VOCCs, which are known to play a fundamental role in the early mediation of mechanotransduction. We have produced porous 3-dimensional, Bay-encapsulated biodegradable poly(L-lactide) acid scaffolds using a solvent-casting and salt-leaching technique. The effects of the released Bay on osteoid production and mineralization in human bone cell-seeded constructs following incubation in a perfusion-compression bioreactor in vitro was investigated using Western blotting techniques and a calcium assay protocol developed in our lab. Our newly developed scaffolds act by slowly releasing the calcium channel agonist Bay K8644 as observed using ultraviolet spectroscopy, maintaining the open state of mechanosensitive VOCCs responding to load, which augments the load signal at sites of strain across the scaffold. Our results demonstrate that, in the presence of physiological loading regimes in vitro, release of Bay enhances collagen I protein production and osteoid calcification more than non-Bay control constructs do. Osteopontin and alpha2delta1 VOCC subunit protein levels were also higher as a result of perfusion-compression conditioning. These results indicate that Bay-encapsulated scaffolds can be used in the presence of load to enhance the production of load-bearing engineered tissue.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2006

The effects of colloidal nanotopography on initial fibroblast adhesion and morphology.

Colloidal lithography offers a simple, inexpensive method of producing irregular nanotopographies, a pattern not easily attainable utilizing conventional serial writing processes. Colloids with 20- or 50-nm diameter were utilized to produce such an irregular topography and were characterized by calculating the percentage area coverage of particles. Interparticle and nearest neighbor spacing were also assessed for the individual colloids in the pattern. Two-way analysis of variance (ANOVA) indicated significant differences between the number of fibroblasts adhering to planar, 20-, and 50-nm-diameter colloidal topographies, the number of fibroblasts adhering to the substrates at the time intervals studied, namely 20 min, 1 h, and 3 h and significant interaction between time and topography on fibroblast adhesion (P < 0.01). Tukey tests were utilized for sensitive identification of the differences between the sample means and compounded ANOVA results. Cytoskeletal and general cell morphology were investigated on planar and colloidal substrates, and indicated cells in contact with irregular nanotopographies exhibit many peripheral protrusions while such protrusions are absent in cells on planar control surfaces. These protrusions are rich in microtubules on 20-nm-diameter colloidal surfaces while microfilaments are prevalent on 50-nm-diameter surfaces. Moreover, by 3 h, cells on the colloidal substrates initiate cell-cell adhesions, also absent in controls.

Cell Adhesion↗

PubMed2005

Human fibroblast reactions to standard and electropolished titanium and Ti-6Al-7Nb, and electropolished stainless steel.

Stainless steel (SS), titanium (cpTi), and Ti-6Al-7Nb (TAN) are frequently used metals in orthopedic internal fracture fixation. Although reactivity to SS and cpTi are noted in reference, the soft tissue compatibility of TAN has not been comprehensively studied. This study focuses on the in vitro soft tissue compatibility of TAN in comparison to SS and cpTi using a human fibroblast model. The industrial standard surface finishes of these three materials vary considerably in view of their use in similar applications. To distinguish between material parameters of topography and chemistry, we have included electropolished (e.p) counterparts of the standard preparations of cpTi and TAN in the study (standard SS is e.p). All materials were characterized using atomic force microscopy, profilometry, and scanning electron microscopy. Our findings demonstrate that cell morphology and growth rate was similar for SS, and e.p. cpTi and TAN, with cells well spread and forming a confluent monolayer by 10 days. Cell growth on standard cpTi was similar to the electropolished samples; however, they showed a less spread morphology with more filopodia and surface ruffling present. Cell morphology on standard TAN was rounded or elongated and proliferation was inhibited at all time points, with possible cell necrosis by day 10. We found evidence of endocytosis of beta-phase particles originating from the standard TAN surface. We believe that the particle uptake coupled with the characteristic surface topography contribute to the noncytocompatibility of fibroblasts on standard TAN.

Biocompatible Materials↗

PubMed2005

Controlling cell biomechanics in orthopaedic tissue engineering and repair.

Tissue engineering offers an alternative approach with great potential for the treatment or replacement of damaged tissues or organs. In contrast to current treatments, a small sample of cells can be collected from the patient and cultured in vitro, greatly increasing the number of cells available for engineering tissue implants. As a result, engineered tissue implants limit the problems associated with patient trauma and undesirable immune response currently observed in surgical treatments practised in tissue and organ replacement. Mechano-transduction is known to play an essential role in bone tissue remodelling and repair. At physiological magnitudes, the effects of secondary messenger pathways, their components and local mediators generated as a direct result of mechanical load are known to result in an elevation of specific matrix protein mRNAs. Up-regulation of matrix protein production is paramount to tissue formation. Thus, mechano-transduction offers a method of producing bone tissue in vitro. However, successful transduction of mechanical stimuli from a substrate to cells is reliant upon a number of factors including cell-substrate adhesion, scaffold material mechanics and the activation of membrane channels, for example voltage-operated calcium channels (VOCC). Our research focuses on the optimisation of mechano-transduction pathways for successful bone tissue engineering. In this paper, we focus on the effects of cell-substrate adhesion, attenuation of VOCC activation states and biological conditioning of cell-scaffold constructs utilising bioreactors in relation to mechano-transduction-induced bone tissue production. The effects of these factors on successful bone tissue formation observed in increased matrix protein synthesis due to the optimisation of mechano-transduction pathways is discussed.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2002

Steps toward a model nanotopography.

A natural lithography technique is employed to create an irregular, submonolayer colloidal topography. Epitenon cells were cultured on these colloidal surfaces, and cell morphology investigations using scanning electron microscropy were conducted. Preliminary experiments brought into question the stability of the colloidal nanotopography, and it was unsure if the surface was presented to cells as a static structure. Investigations using secondary electron and backscattered electron imaging, and also X-ray microanalysis, indicated that the colloidal structure was in fact stable, and cells were capable of direct interactions at the peripheral membrane with the colloids.

Biocompatible Materials↗