Bioreactor non-invasively monitors changes in tissue

Tissue created this way might some day be used to replace damaged or diseased cartilage in the knee and hip, according to researchers at the US National Institute of Standards and Technology (NIST) and project partners from the University of Colorado Boulder (CU).

According to a statement from NIST, conventional methods for evaluating the development and properties of engineered tissue are time consuming and destructive and need to be repeated many times.

By using ultrasound to monitor tissue during processing without destroying it, the novel bioreactor — a device for culturing cells to create engineered tissue — could be a faster and less expensive alternative.

‘Most bioreactors don’t do any type of non-destructive evaluation,’ said NIST postdoctoral researcher Jenni Popp, first author of a new paper about the instrument. ‘Having some sort of ongoing evaluation of the developing tissue is definitely novel.’

Cartilage is smooth connective tissue that supports joint motion and natural cartilage is created by specialised cells that generate large amounts of structural proteins to weave a tough support material called extracellular matrix.

Lacking blood vessels, cartilage has limited capability to heal from arthritis, sports injuries or other defects. Damage can be treated with drugs or joint replacement, but results can be imperfect.

Engineered tissue is used in some medical treatments but is not yet a routine alternative to metal or plastic joint replacements. The NIST bioreactor is said to give researchers a non-invasive way to monitor important structural changes in developing tissue.

The NIST/CU bioreactor can fit inside a standard incubator, which controls temperature and acidity in the growth environment.

The bioreactor applies force to stimulate five small cubes of cartilage cells embedded in water-based gels. The mechanical force mimics the natural stimuli needed for the cells to create matrix proteins and to develop the structure and properties of real cartilage. Ultrasound techniques monitor tissue changes over time, while a digital video microscope takes images.

Preliminary studies indicate that the bioreactor stimulates and monitors development of cells, matrix content and scaffolds to make three-dimensional engineered cartilage.

The cell-laden gels were stimulated twice daily for an hour. Sulphated glycosaminoglycan (sGAG) — which combines with fibrous proteins to form the extracellular matrix — increased significantly after seven days. This structural change was detected by a significant decrease in ultrasound signals after seven days.

The research described in the new paper was performed at, and led by, NIST. The bioreactor is a collaborative project with several co-authors from the CU Department of Chemical and Biological Engineering.

NIST and CU researchers continue to develop ultrasonic measurement methods and plan to conduct longer experiments.