Biomedical subjects

Christina J Lee

Publications and source records attributed to Christina J Lee.

5 recordsLinked to original sources

PubMed2006

Thin collagen film scaffolds for retinal epithelial cell culture.

Collagen films have been used in biological implantation and surgical grafts. The development of thin collagen films on the order of 10 microm thick that ensure a planar distribution of implanted cells is a necessary step towards surgical grafts for treatment of age-related macular degeneration (AMD). Here, collagen films were manufactured on a Teflon support to a thickness of 2.4+/-0.2 microm, comparable to that of native Bruch's membrane. Because one important function of Bruch's membrane is allowing the flow of nutrients and waste to and from the retinal pigment epithelium the diffusion properties of the collagen films were studied using blind-well chambers. The diffusion coefficient of the collagen film was determined to be 4.1 x 10(-10)cm(2)/s for 71,200 Da dextran molecules. Viability studies utilizing the blind-well chambers also confirmed that nutrient transport through the films was sufficient to sustain retinal pigment epithelial (RPE) cells. The films were bioassayed in a RPE cell culture model to confirm cell attachment and viability. RPE cells were shown to form an epithelial phenotype and were able to phagocytize photoreceptor outer segments.

Biocompatible Materials↗

PubMed2005

Determination of human lens capsule permeability and its feasibility as a replacement for Bruch's membrane.

We have investigated human anterior lens capsule as a potential replacement for Bruch's membrane as a treatment for age-related macular degeneration. Any substrate to replace Bruch's membrane should possess certain characteristics to maintain proper function of the overlying retina. One of the important properties of Bruch's membrane is allowing the flow of nutrients and waste between the retinal pigment epithelium and the choriocapillaris. Here, we measured the permeability of the lens capsule by studying the diffusion of various molecular weight FITC-dextran molecules. Expressions for extraction of diffusion coefficients from concentration vs. time data from a blind-well chamber apparatus were derived for both a single and double membrane experiments. The diffusion coefficients in the lens capsule were found to be in the range of 10(-6) to 10(-10)cm2/s. We demonstrated a power law relationship, with the diffusion coefficient possessing a -0.6 order dependence on molecular weight. The molecular weight exclusion limit was determined to be 150+/-40 kDa. We have compared this value with reported values of Bruch's membrane molecular weight exclusion limit and find that the lens capsule has the potential to act as a substitute Bruch's membrane.

Bruch Membrane↗

PubMed2004

Controlling cell adhesion on human tissue by soft lithography.

Soft lithographic techniques are widely used for fundamental biological applications. This study investigates the extension of soft lithography for use on human tissue to create a biological implant by systematically studying the effect of pattern size on cellular morphology. We focus on mimicking a key layer of the physiological retina with an organized monolayer of epithelial cells to act as a new treatment for age-related macular degeneration. We show that epithelial cells can be confined to cytophilic islands defined on lens capsule by the inhibitory polymer poly(vinyl alcohol). In addition, as the size of the cytophilic islands grows, both the fraction of islands with cells attached and the number of cells adhered to each island increase. High densities of cell adhesion and single cell attachment per island were achieved with a 25 microm pattern size. Over time, the cells spread over the 5 microm wide barriers to form a confluent monolayer that may eventually serve as a functional retinal implant. With the ability to apply soft lithography to tissue samples, human tissue may become a universal membrane substrate for other ocular diseases or in tissue engineering applications elsewhere in the body.

Biocompatible Materials↗

PubMed2003

The Artificial Synapse Chip: a flexible retinal interface based on directed retinal cell growth and neurotransmitter stimulation.

The Artificial Synapse Chip is an evolving design for a flexible retinal interface that aims to improve visual resolution of an electronic retinal prosthesis by addressing cells individually and mimicking the physiological stimulation achieved in synaptic transmission. We describe three novel approaches employed in the development of the Artificial Synapse Chip: (i) micropatterned substrates to direct retinal cell neurite growth to individual stimulation sites; (ii) a prototype retinal interface based on localized neurotransmitter delivery; and (iii) the use of soft materials to fabricate these devices. By patterning the growth of cells to individual stimulation sites, we can improve the selectivity of stimulation and decrease the associated power requirements. Moreover, we have microfabricated a neurotransmitter delivery system based on a 5- micro m aperture in a 500-nm-thick silicon nitride membrane overlying a microfluidic channel. This device can release neurotransmitter volumes as small as 2 pL, demonstrating the possibility of chemical-based prostheses. Finally, we have fabricated and implanted an equivalent device using soft flexible materials that conform to the retinal tissue more effectively. As many of the current retinal prosthesis devices use hard materials and electrical excitation at a lower resolution, our approach may provide more physiologic retinal stimulation.

Animals↗

PubMed2002

Microcontact printing on human tissue for retinal cell transplantation.

OBJECTIVES: To demonstrate that microcontact printing, a modern materials fabrication technique, can be used to engineer the surface of human tissue and to show that inhibitory molecules can be used to pattern the growth of retinal pigment epithelial cells or iris pigment epithelial cells on human lens capsule for transplantation. METHODS: Photolithographic techniques were used to fabricate photoresist-coated silicon substrates into molds. Poly(dimethylsiloxane)stamps for microcontact printing were made from these molds. The poly(dimethylsiloxane) stamps were then used to "wet-transfer" growth inhibitory molecules to the surface of prepared human lens capsules that were obtained during cataract surgery. Human retinal pigment epithelial and rabbit iris pigment epithelial cells were grown on a lens capsule substrate in the presence and absence of a patterned array of inhibitory factors. RESULTS: We found that human lens capsule could be microprinted with a precision similar to that obtained on glass or synthetic polymers. Retinal pigment epithelial cells and iris pigment epithelial cells cultured onto an untreated lens capsule showed spreading and formed into fusiform-appearing cells. In contrast, cells cultured on a lens capsule with a hexagonal micropattern of growth inhibitory molecules retained an epithelioid form within the inhibitory hexagons. CONCLUSION: Inhibitory growth molecules can be micropatterned onto human lens capsule, and these micropatterns can control the organization of retinal pigment epithelial cells or iris pigment epithelial cells cultured onto the lens capsule surface. CLINICAL RELEVANCE: Microprinting on autologous human tissue may facilitate efforts to effectively organize cell cultures and transplantations for the replacement of vital ocular tissues such as the retinal pigment epithelium in age-related macular degeneration.

Animals↗