15502-m-pleumeekers

The idea of a prefabricated framework was further elaborated via novel biological engineering techniques first introduced by Vacanti and Langer [22] named tissue engineering . Tissue engineering has the potential to overcome limitations of current treatments, reestablishing unique biological and functional properties of the tissue. It endeavors to develop functional living cartilage by using cells, inductive signals and a prefabricated scaffold or framework. In short, cartilage tissue engineering starts with a small tissue biopsy, from which the residing cells are isolated. Thereafter, cells are proliferated in vitro under controlled conditions, seeded into a prefabricated scaffold and implanted subcutaneously. (Figure 2) Tissue engineering is a promising solution for restoring missing or damaged cartilage in the head and neck area, as it translates complex biological science into a living prefabricated cartilaginous framework. Future surgical techniques are thereby simplified, improving surgical outcomes. Besides, tissue engineering aims to circumvent the resulting donor-site morbidity by engineering rather than harvesting cartilage tissue. Therefore, in this work, I aim to develop a cell-based cartilaginous framework for the surgical repair of cartilage defects in the head and neck area by using a tissue engineering strategy. Cartilage form and function Cartilage plays an important role in the form and function of the face as it provides flexibility and mechanical support to soft tissues. However, mechanical properties of facial cartilage are sparsely investigated, and limited data are available on human ear [23, 24] and nasal cartilages [25-30]. Cartilage rigidity and elasticity are due primarily to the properties of its complex extracellular matrix (ECM). It constitutes by a complex network of various macromolecules. The most abundant ECM macromolecule is collagen, making up 60-80% of the dry weight of cartilage, followed by approximately 20-30% of proteoglycans (PGs). Collagen, mostly collagen type 2, form a highly organized fiber network defining form and tensile strength. [31] Within this collagen network, PGs are intertwined, of which aggrecan is most common. Their negatively charged glycosaminoglycan (GAG) side chains are responsible for compressive strength by attracting large amounts of water to the cartilage ECM. Basically, 60-80% of the wet weight of cartilage is water. [32] Finally, elastin, the main component of elastic fibers, is variably found in the cartilage ECM and provides elastic recoil and resilience to the tissue. [31] Other matrix constituents, only form a small fraction of the total dry weight of cartilage and are not further discussed. Depending on the exact composition and organization of the ECM, three major cartilage subtypes can be distinguished with variable flexibility and mechanobiology: hyaline, elastic and fibrous cartilage. (Figure 3) The most prevalent cartilage subtype is hyaline cartilage. It is characterized by a homogeneous ECM that mainly consists of collagen type 2 fibers, PGs and water. In the head and neck area, hyaline cartilage is located in the nasal septum, trachea and larynx. Outside this area, hyaline cartilage is mainly found at the articular surfaces of joints and on the ventral ends of ribs. Besides, it is also transitorily involved in skeletal development through the process of endochondral ossification. Elastic cartilage also consists of a refined network of collagen type 2 fibers, PGs and water. It additionally contains insoluble elastin fibers. Elastic cartilage is found in the pinna of the ear, Eustachian tube and 1 GENERAL INTRODUCTION 15

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