Pharmaceuticals & Vitamin D : Organ & tissue transplants

Pharmaceuticals & Vitamin D Portfolios


Bioengineered Vocal Fold Mucosa for Voice Restoration

UW–Madison researchers have engineered vocal fold mucosae from isolated and purified human VF fibroblasts and epithelial cells, co-cultured under organotypic conditions. When grafted into larynges ex vivo, the engineered VF mucosae generate vibratory behavior and acoustic output indistinguishable from native VF tissue, thus demonstrating that they have the biomechanical properties essential for use as an implant in treating voice impairment due to tissue damage, loss or disease.

In addition, when grafted into humanized mice in vivo (a transgenic mouse model supporting a functional human adaptive immune system) the mucosae survive and are well tolerated by the human adaptive immune system. This indicates that implanting the engineered mucosa into the larynx of a human patient would likely not trigger rejection or immune system attack against the implant.

Portable Carbon Monoxide Source for Therapy and Organ Delivery

UW–Madison researchers have developed a portable carbon monoxide generator for medical use that creates precise, therapeutically relevant, concentrations of medical grade CO out of the surrounding air in real time. The device is inherently safe, as it produces only the amount of CO needed for therapy. The device is incapable of producing enough CO to pose a safety hazard.

The heart of the generator is a reaction chamber holding a small cartridge of purified carbon. The CO is produced by heating the carbon in the presence of air that is fed continuously into the reaction chamber. The carbon can be heated by any controllable energy source, such as an electrical filament or laser.

The amount of CO in the output stream is monitored by a sensor. Using feedback on both the gas flow rate and the heat source, the amount of CO generated is controlled to match the prescribed, adjustable value.

Method and System for Delivering Nucleic Acid into a Target Cell

UW-Madison researchers have developed a DNA delivery method that uses a sequestering approach to enable spatial and temporal control over the transfection of stem cells. Oligonucleotide “handles” are covalently attached to a supporting substrate, which may be a solid surface or a two- or three-dimensional semi-solid structure, such as a hydrogel network. The oligonucleotides sequester complementary nucleic acid molecules, such as DNA, in pre-determined locations. The length of the oligonucleotides handles can be varied to control the availability of the sequestered DNA. Recipient cells are adhered to the substrate, and the nucleic acid molecules are exposed to the cells under conditions that support transfection. The culture conditions can be controlled to modulate the timing with which the DNA is made available to the cells.

Multilayer Tissue Regeneration System

A UW-Madison researcher has developed an approach for regenerating natural skeletal tissues that more closely mimics in vivo conditions by localizing and temporally controlling the activity of multiple growth factors. This method for growing tissue is based on a matrix of minerals and growth factors. Engineered protein growth factors are incorporated into the layers of the inorganic matrix. Each layer is designed to dissolve at a separate rate. As the matrix material gradually breaks down, the growth factors are delivered sequentially, enabling the growth of new bone tissue. Alternatively, the growth factors can be engineered to bind to the surface of the inorganic matrix.

Spatial Control of Signal Transduction

UW-Madison researchers have developed a novel approach for the delivery of growth factors and other biologically active signaling molecules that allows for spatial control of signal transduction. Molecular handles (e.g., peptides or oligonucleotides) with an affinity for growth factors or other signaling molecules are attached to specific locations on a surface or within a matrix. The surface or matrix includes a translucent, biologically inert polymer backbone. Signaling molecules are drawn to the precisely desired location of the substrate or matrix by associating specifically, reversibly and non-covalently with the handles. The affinity of the molecular handle for the signaling molecule is tailored so that it selectively attracts the growth factor but does not bind so tightly that it blocks interaction of the growth factor with percursor cells. The signaling molecules can then be presented to precursor cells in locally high concentrations, mimicking complex developmental processes like organogenesis, which is particularly important in stem cell-based approaches to tissue regeneration.