Tissue Bioreactor Research Articles

Chemical sensing and control in cell & tissue bioreactors.

To meet needs in cell and tissue engineering bioreactors are evolving to allow cells and tissues to be cultured under precisely defined physical and chemical conditions. Many cell-tissue types are now being cultured, and considered in this work are chondrocytes, vascular endothelial cells, and smooth muscle cells. The culture processes are dynamic and optimisation requires monitoring of key process variables. The chemical sensing in cell and tissue bioreactors described here has the long term aim of achieving automatic optimal control. Invasive and non-invasive electrochemical and optical systems are described for a wide range of target analytes (gases, ions, metabolites, hormones and proteins), but emphasis is on O2, pH, CO2and glucose. The sensing is performed with: (a) interrogation via the bioreactor wall; (b) probes placed within the cell culture chamber; (c) analysis within a shunt/sampling chamber. Analysis of culture medium is used for measurement of glucose and for proteins that are markers of cell biosynthetic behaviour. Optical absorbance and scatter of cells and tissues are also investigated for both chemical and structural analysis.

Optical measurement of three-dimensional collagen gel constructs by elastic scattering spectroscopy.

Analysis of the formation and organization of new connective tissue formed in tissue-engineered constructs is a major requirement for tissue bioreactor technology. We have analyzed early-stage responses in collagen lattices, using elastic scattering spectroscopy to assess its potential to monitor tissue structural changes in structures up to 3 mm thick, under normal culture conditions. The method is based on an optical system in which an optical fiber delivers white light onto the tissue and the back-scattered light is collected for spectroscopy by another optical fiber. Results show correlation between changes in the spectral signatures with changes in the collagen gel contraction or internal organization in all three models of collagen construct analyzed. Therefore elastic scattering spectroscopy is a promising tool to monitor tissue-engineered constructs or early repair in collagenous tissues.

In Vivo Cartilage Formation From Growth Factor Modulated Articular Chondrocytes

Recent procedures for autologous repair of cartilage defects may be difficult in elderly patients because of the loss of stem cells and chondrocytes that occurs with age and the slow in vitro proliferation of chondrocytes from aged cartilage. In this study secondary chondroprogenitor cells were obtained by modulating the phenotype of articular chondrocytes with growth factors and stimulating the proliferation of these cells in culture. Chondrocytes isolated from the articular cartilage of mature New Zealand White rabbits were exposed to a combination of transforming growth factor beta and basic fibroblast growth factor treatment. These cells ceased the production of Collagen II (a marker for the chondrocyte phenotype) and underwent a 136-fold increase in cell number. Next, the cells were placed in high density culture and reexpressed the chondrocyte phenotype in vitro and formed hyaline cartilage in an in vivo assay. Primary chondrocytes obtained from articular cartilage of elderly humans could be manipulated in a similar fashion in vitro. These human secondary chondroprogenitor cells formed only cartilage tissue when assayed in vivo and in tissue bioreactors. This approach may be essential for autologous repair of degenerated articular cartilage in elderly patients with osteoarthritis.

Tissue bioreactor for eliminating interferences in flow analysis.

Tissue bioreactor for eliminating interferences in flow analysis.