Technical Strategies to Improve Tissue Engineering of Cartilage-Carrier-Constructs

Abstract

Technical aspects play an important role in tissue engineering. Especially an improved design of bioreactors is crucial for cultivation of artificial three-dimensional tissues in vitro. Here formation of cartilage-carrier-constructs is used to demonstrate that the quality of the tissue can be significantly improved by using optimized culture conditions (oxygen concentration, growth factor combination) as well as special bioreactor techniques to induce fluid-dynamic, hydrostatic or mechanical load during generation of cartilage.

Ultrasonic Bioreactor as a Platform for Studying Cellular Response

“…3,4 Central to a successful tissue engineering strategy to grow functional tissue equivalents is the establishment of a bioreactor or a bioprocessing unit that maintains cells seeded on biodegradable polymeric scaffolds and provides essential gas and nutrient transport between the cells and the culture media, as well as the mechanical stimuli which are necessary to promote extracellular matrix (ECM) synthesis. [5][6][7] Bioreactors offer several advantages compared with simple tissue-flask and Petri-dish culture systems, notably the ability to provide mechanical forces influencing tissue development and to achieve better control over culture conditions. 8,9 Designs of bioreactors that are currently commercially available for the cultivation of tissue-engineered constructs are mainly based on the following driving forces: hydrostatic pressure, that is, dynamic compression, hydrodynamic stress at low shear rates, that is, perfusion systems, rotating bioreactors, wavy-wall bioreactors, and conventional spinning flasks.…”

Joint Cartilage Tissue Engineering and Pre-Clinical Safety and Efficacy Testing

“…It has been suggested that mechanical loading may increase extracellular matrix (ECM) synthesis during cartilage engineering (Portner et al, 2009). The hypothesis that mechanical stimulation enhances cartilage formation is based on studies of developmental biology where restriction of joint loading after birth leads to poor post-natal cartilage adaptation (Williamson et al, 2003a;Williamson et al, 2001;Williamson et al, 2003b;Mikic et al, 2004;Mikic et al, 2000).…”

“…The hypothesis that mechanical stimulation enhances cartilage formation is based on studies of developmental biology where restriction of joint loading after birth leads to poor post-natal cartilage adaptation (Williamson et al, 2003a;Williamson et al, 2001;Williamson et al, 2003b;Mikic et al, 2004;Mikic et al, 2000). Overall, mechanical stimulation leads to increased cell expansion as well as increased extracellular matrix proteins production compared to regular static cultures (Portner et al, 2009). A bioreactor is defined as any device in which a biological/biochemical process is performed under controlled conditions.…”

“…When compared to static cultures, bioreactors offer a number of advantages such as uniformed distribution and increased mass transfer, control of pH, temperature, gas supply (O 2 and CO 2 ), nutrients, waste product removal, and the opportunity to incorporate mechanical stimuli. Detailed reviews on the general concepts of bioreactors for tissue engineering and the application of bioreactors for the purpose of cartilage engineering are available (Godara et al, 2008;Chen et al, 2006;Chung and Burdick, 2008;Portner et al, 2009;Haasper et al, 2008;Huang et al, 2010b;Schulz and Bader, 2007;Concaro et al, 2009;Grad et al, 2011). Selected physical outcome parameters used in cartilage engineering in defined and described in Text Box 1.…”

“…Multiaxial compression and shearing stimulation represent more closely in vivo conditions and are associated with broader chondrogenic gene expression profiles compared to uniaxial compressive loading (Grad et al, 2011). Another trend is the ability of bioreactors to simultaneously provide mechanical stimuli and evaluate the physical properties of the developing tissue (Portner et al, 2009). The ability to monitor the construct as it develops allows for a reduction in sample size since temporal changes can be assessed on the same sample.…”