Medical device regulation: what a practicing dermatologist should know.

The practicing dermatologist uses many medical devices during his or her day-to-day practice. The authors present a broad overview of how such medical devices are reviewed for safety and reasonable assurance of effectiveness, and evaluated for classification prior to marketing in the United States by the Food and Drug Administration. The specific example of dermal fillers as a class III medical device is discussed together with its regulatory ramifications. This article is written by staff currently employed at the Center for Devices and Radiological Health and should provide information useful to the practicing dermatologist.

Dynamics of smooth muscle cell deadhesion from thermosensitive hydroxybutyl chitosan.

Thermoresponsive polymer (TRP) enables the enzyme-free harvesting of cells through an acute increase in surface hydrophilicity of TRP across its lower critical solution temperature (LCST), rendering feasible the generation of polymer-free cell sheets for regenerative medicine applications. To date, the intricate mechanisms of cell deadhesion/detachment on TRP surface remain obscure. Elucidation of such biophysical responses would be valuable for the cell sheet technology. In this study, integrative biophysical techniques are applied to probe the thermal-induced deadhesion kinetics of smooth muscle cell (SMC) on thermoresponsive hydroxybutyl chitosan (HBC29) against different periods of pre-culture time at 37 degrees C. Atomic force microscopy demonstrates that both the surface topography and mechanical property of HBC29 film in water are acutely modulated across its LCST. Firstly, cells show negligible changes in adhesion contact area during low-temperature incubation on unmodified tissue culture polystyrene (TCPS). Secondly, the recession of adhesion contact and retraction of cell body for cells with different pre-culture times are triggered by HBC29 coating on TCPS. Interestingly, the initial rate of reduction in the normalized adhesion contact area of SMC is negatively correlated with the pre-culture time. Thirdly, the degree of cell deformation and average adhesion energy are reducing functions of time only for SMCs with the lowest pre-culture time. In contrast, adhesion energy per cell is a reducing function of time irrespective of the change of pre-culture time. Lastly, the temporal dynamics of cytoskeleton organization and beta-actin/smoothelin-B mRNA expression for SMCs is strongly dependent on the pre-culture time. Overall, this study demonstrates that the thermal-induced deadhesion of SMC on TRP is characterized by the evolution of its contractile phenotypes.

Natural polymers for gene delivery and tissue engineering.

Although the field of gene delivery is dominated by viral vectors and synthetic polymeric or lipid gene carriers, natural polymers offer distinct advantages and may help advance the field of non-viral gene therapy. Natural polymers, such as chitosan, have been successful in oral and nasal delivery due to their mucoadhesive properties. Collagen has broad utility as gene activated matrices, capable of delivering large quantities of DNA in a direct, localized manner. Most natural polymers contain reactive sites amenable for ligand conjugation, cross-linking, and other modifications that can render the polymer tailored for a range of clinical applications. Natural polymers also often possess good cytocompatibility, making them popular choices for tissue engineering scaffolding applications. The marriage of gene therapy and tissue engineering exploits the power of genetic cell engineering to provide the biochemical signals to influence proliferation or differentiation of cells. Natural polymers with their ability to serve as gene carriers and tissue engineering scaffolds are poised to play an important role in the field of regenerative medicine. This review highlights the past and present research on various applications of natural polymers as particulate and matrix delivery vehicles for gene delivery.

Temperature-responsive hydroxybutyl chitosan for the culture of mesenchymal stem cells and intervertebral disk cells.

Temperature-responsive polymers are attractive candidates for applications related to injectable delivery of biologically active therapeutics, such as stem cells. In this study, we evaluate the potential of thermosensitive hydroxybutyl chitosan (HBC) as a biomaterial for the culture of human mesenchymal stem cells (hMSC) and cells derived from the intervertebral disk, with the eventual goal of using the HBC polymer as an injectable matrix/cell therapeutic. Conjugation of hydroxybutyl groups to chitosan renders the polymer water soluble and thermally responsive. Below its lower critical solution temperature, a solution of HBC can be maintained indefinitely in its solvated state. Upon exposure to a 37 degrees C environment, within 60 s, a 3.8 wt% HBC solution rapidly forms a gel that can be maneuvered with forceps. Upon cooling, the gel once again is able to revert to its solvated state. The gel exhibits a dramatic increase in both G' and G'' with increasing temperature, signifying a temperature-dependent enhancement of gel mechanical properties. Although a solid structure upon gelation, due to its physical nature of polymer interaction and gel formation, the gel exhibits a fluid-like viscoelastic behavior when exposed to shear stresses of up to 10% strain, with both G' and G'' approaching zero with increasing shear stress. Formulations of HBC gels presented in this study have gelation temperatures ranging from 13.0 to 34.6 degrees C and water contents of 67-95%. Minimal cytotoxicity in MSC and disk cell cultures was observed with these polymers up to a concentration of 5 wt%. Detection of metabolic activity, genetic analysis of synthesized mRNA, and histological staining of MSC and disk cell cultures in these gels collectively indicate cell proliferation without a loss in metabolic activity and extracellular matrix production. This study suggests the potential of HBC gel as an injectable carrier for future applications of delivering therapeutics to encourage a biologically relevant reconstruction of the degenerated disk.

Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration.

Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i) neuraminidase treatment of the neurons; (ii) blocking neuronal ganglioside biosynthesis; (iii) genetically modifying the terminal structures of nerve cell surface gangliosides; and (iv) adding highly specific IgG-class antiganglioside mAbs. Furthermore, neurite outgrowth inhibition is mimicked by highly multivalent clustering of GD1a or GT1b by using precomplexed antiganglioside Abs. These data implicate the nerve cell surface gangliosides GD1a and GT1b as functional MAG ligands and suggest that the first step in MAG inhibition is multivalent ganglioside clustering.