15502-m-pleumeekers

INTRODUCTION Ear cartilage defects - either caused by congenital malformation, trauma or tumor destruction - are a commonly encountered problem in reconstructive surgery, since cartilage has a limited capacity for self-regeneration once damaged. Therefore, ear cartilage defects can ultimately lead to physical and aesthetic impairment. Despite the great demand for treating ear cartilage defects, current treatments using autologous cartilage are challenging. Not only because they require a high degree of surgical expertise, but also because they are associated with limited availability of autologous cartilage and can cause severe donor site morbidity. For successful cartilage reconstruction, the properties of the three-dimensional (3D) matrix is of major importance, in: (1) providing temporary or permanent support while maintaining size and shape; and (2) providing specific structural, mechanical and biological cues to cells, which guide tissue remodeling. [82, 284] Ideally, the best scaffold for cartilage reconstruction should mimic the extracellular matrix (ECM) of the targeted tissue itself. As a result, several 3D scaffolds, including both natural and synthetic materials, have been developed and investigated for their use in cartilage reconstruction. [23, 83, 285] A frequently used alternative to autologous cartilage implants are synthetic materials such as porous polyethylene [286, 287]. Although this material is advantageous to work with it is prone to induce a foreign body reaction, the ensuing extrusion [124] in most cases resulting in removal of the entire implant. [288] Additionally, the biomechanical mismatch of the implants compared to normal ear cartilage can result in eventual collapse of the framework. [289]. So far, no ideal scaffold has emerged since the complex 3D composition and architecture of native ECM makes it extremely difficult to precisely mimic. Recently, natural acellular ECM scaffolds have become increasingly popular. These acellular ECM scaffolds are acquired by a process called decellularization: a method that requires chemical, physical and/or enzymatic treatments. [93] Decellularized ECM scaffolds provide a 3D ECM structure with immediate functional support without evoking an adaptive immune response upon implantation due to absence of donor cellular antigens. [94] To date, various cartilaginous structures have already been decellularized including tracheal cartilage [94-99], articular cartilage [100-103], nasal cartilage [106, 110], intervertebral discs [104, 105] and meniscal cartilage [106-109]. Currently, no method to specifically decellularize full thickness ear cartilage that belongs to the elastic cartilage type, has been described in literature. In contrast to hyaline and fibrous cartilage, elastic cartilage contains additional thick elastic fibers, making it denser and therefore more challenging to decellularize. Furthermore, the ability to prepare scaffolds from whole cartilage tissue rather than scaffolds that are derived from ECM [290, 291], provides the opportunity to decellularize large tissues and structures that hold complex native shapes such as ears. Therefore, the goal of this study was to prepare decellularized ear cartilage scaffolds and extensively characterize their biochemical and biomechanical properties, as well as investigate their cytocompatibility. Furthermore, by preparing human ear cartilage scaffolds with desirable size and shape, we show the potential of decellularized cartilage to improve human cartilage reconstruction. 131 DECELLULARIZED CARTILAGE: AN ECM-DERIVED SCAFFOLD 7