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Biomedical subjects

Andre M Gobin

Publications and source records attributed to Andre M Gobin.

4 recordsLinked to original sources

Overexpression of lysyl oxidase to increase matrix crosslinking and improve tissue strength in dermal wound healing.

In this study, we aimed to increase crosslinking in collagen and elastin in the extracellular matrix through overexpression of lysyl oxidase (LO) in order to improve mechanical strength in dermal wounds during healing. We had used a gene activated matrix (GAM) approach to locally deliver plasmid DNA (pDNA) complexed with polyethylenimine (PEI) in collagen gels at the wound site for localized and sustained transfection of cells involved in the healing process. We first demonstrated in vitro that PEI-pDNA complexes in collagen gels could be taken up and expressed by cultured fibroblasts for at least 20 days. In vitro studies showed that fibroblast-seeded GAMs with the LO transgene exhibited over a 3-fold increase in mechanical strength as compared with a green fluorescent protein (GFP)-transgene control. Addition of an inhibitor of LO abolished this increase. We applied this system in a rat dermal wound healing model and showed that treatment with LO-producing GAMs led to significantly enhanced mechanical strength of the wound site.

Animals↗

Metal nanoshells.

Metal nanoshells are a new class of nanoparticles with highly tunable optical properties. Metal nanoshells consist of a dielectric core nanoparticle such as silica surrounded by an ultrathin metal shell, often composed of gold for biomedical applications. Depending on the size and composition of each layer of the nanoshell, particles can be designed to either absorb or scatter light over much of the visible and infrared regions of the electromagnetic spectrum, including the near infrared region where penetration of light through tissue is maximal. These particles are also effective substrates for surface-enhanced Raman scattering (SERS) and are easily conjugated to antibodies and other biomolecules. One can envision a myriad of potential applications of such tunable particles. Several potential biomedical applications are under development, including immunoassays, modulated drug delivery, photothermal cancer therapy, and imaging contrast agents.

Animals↗

Near infrared laser-tissue welding using nanoshells as an exogenous absorber.

BACKGROUND AND OBJECTIVE: Gold nanoshells are a new class of nanoparticles that can be designed to strongly absorb light in the near infrared (NIR). These particles provide much larger absorption cross-sections and efficiency than can be achieved with currently used chemical chromophores without photobleaching. In these studies, we have investigated the use of gold nanoshells as exogenous NIR absorbers to facilitate NIR laser-tissue welding. STUDY DESIGN/MATERIALS AND METHODS: Gold nanoshells with peak extinction matching the NIR wavelength of the laser being used were manufactured and suspended in an albumin solder. Optimization work was performed on ex vivo muscle samples and then translated into testing in an in vivo rat skin wound-healing model. Mechanical testing of the muscle samples was immediately performed and compared to intact tissue mechanical properties. In the in vivo study, full thickness incisions in the dorsal skin of rats were welded, and samples of skin were excised at 0, 5, 10, 21, and 32 days for analysis of strength and wound healing response. RESULTS: Mechanical testing of nanoshell-solder welds in muscle revealed successful fusion of tissues with tensile strengths of the weld site equal to the uncut tissue. No welding was accomplished with this light source when using solder formulations without nanoshells. Mechanical testing of the skin wounds showed sufficient strength for closure and strength increased over time. Histological examination showed good wound-healing response in the soldered skin. CONCLUSIONS: The use of nanoshells as an exogenous absorber allows the usage of light sources that are minimally absorbed by tissue components, thereby, minimizing damage to surrounding tissue and allowing welding of thicker tissues.

Animals↗

Nano-C60 cytotoxicity is due to lipid peroxidation.

This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C60, a fullerene aggregate that readily forms when pristine C60 is added to water. Nano-C60 was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses>or= 50 ppb (LC50=2-50 ppb, depending on cell type) after 48 h exposure. This water-soluble nano-C60 colloidal suspension disrupts normal cellular function through lipid peroxidation; reactive oxygen species are responsible for the membrane damage. Cellular viability was determined through live/dead staining and LDH release. DNA concentration and mitochondrial activity were not affected by the nano-C60 inoculations to cells in culture. The integrity of cellular membrane was examined by monitoring the peroxy-radicals on the lipid bilayer. Subsequently, glutathione production was measured to assess the cell's reaction to membrane oxidation. The damage to cell membranes was observed both with chemical assays, and confirmed physically by visualizing membrane permeability with high molecular weight dyes. With the addition of an antioxidant, L-ascorbic acid, the oxidative damage and resultant toxicity of nano-C60 was completely prevented.

Antioxidants↗