Artificial chondrons in cartilage tissue engineering; A preliminary study;

Introduction Articular cartilage is an important mechanical entity covering the joint surfaces. Damaged cartilage often results in progressive osteoarthritis, because cartilage has a very low self-repairing or self-regenerating capacity [40]. In order to treat osteoarthritis, joint resurfacing, autograft transplants , prosthesis and complete joint replacement have been evaluated [27][47]. Unfortunately, these methods are all limited in their repair capabilities and usability. When tissue engineering came up in the late nineties, tissue engineering of cartilage was from scratch one of the main topics. It is advantageous to work with cartilage, since it is a relative simple tissue consisting only of chondrocytes and their extracellular matrix (ECM). Furthermore cartilage is avascular, so chondrocytes stay viable in a non-vascularized environment and it has a low immunogenicity. Various approaches of cartilage tissue engineering have been tested throughout the years. Cells have been cultured in monolayers, micromasses or scaffolds [13][22][46]. Scaffolds show the most promising results, so many different types of scaffolds have been developed and tested: • hydrogels, such as alginate, agarose and fibrin [10][34][43] • natural polymers, such as collagen and chitosan [21][31] • biodegradable materials such as polyurethane, polylactides, hydroxyapatite and polyglycol-ide [6][16][45][50] To enhance cartilage matrix synthesis, continuous or periodic loading [8][29][49], different types of bioreactors [47] and different oxygen-tensions [41][51] have been evaluated. Until today none of these methods has created a cartilage-like structure with the exact same composition, appearance and mechanical properties as normal cartilage. Chondrocytes cultured in a scaffold do not show a homogenous matrix production throughout the scaffold. Matrix production is mostly observed around the edges of the scaffolds [19][28][42]. The cells at the boundaries of the construct use all available nutrients, so less nutrients enter the scaffold. Nutrient availability is required for matrix synthesis. Hence, nutrient deficiency in the center causes an even less homogenous matrix distribution and eventually cell-dead in the center. v vi The maximal nutrition diffusion-depth determines the maximal dimensions of a construct during cartilage tissue engineering [7][12]. This maximal diffusion-depth is basically an equilibrium between nutrient diffusion according to Fick's law and the nutrition consumption of the cells. The nutrient concentration in the center of a construct rises when cells consume smaller amounts of nutrients. A difference in nutrient consumption between a single cell and a chondron (cell surrounded by its pericellular matrix (PCM)) is expected, because cells need to generate a PCM and a ECM, while chondrons only need to generate …