Novel and Unique Matrix Design for Osteochondral Tissue Engineering
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Novel and Unique Matrix Design for Osteochondral Tissue Engineering Deborah L. Dorcemus1,2, Syam P. Nukavarapu1,2,3,4 1 Institute for Regenerative Engineering, University of Connecticut Health Center Farmington, CT 06030, U.S.A 2 Biomedical Eng., 3Materials Science & Eng. University of Connecticut Storrs, CT 06269, U.S.A 4 Department of Orthopedic Surgery University of Connecticut Health Center Farmington, CT 06030, U.S.A ABSTRACT Osteochondral (OC) tissue is comprised of articular cartilage, the subchondral bone and the central cartilage-bone interface. To facilitate proper regeneration, an equally complex and multiphasic matrix must be used. Although mono-phasic and bi-phasic matrices were previously applied, they failed to establish the OC interface upon regeneration. In this study, we designed and developed a novel matrix with increasing pore volume from one end to other, along the matrix length. For this matrix polylactide-co-glycolide (PLGA) 85:15 microspheres were combined with a water-soluble porogen in a layer-by-layer fashion and thermally sintered. The resulting matrix was then porogen-leached to form a gradiently-porous structured matrix. The formation of this gradient pore structure was established using Micro-Computed Tomography (μCT) scanning. A biodegradable hydrogel was infiltrated into the structure to form a unique OC matrix where the microsphere and hydrogel phases co-exist with opposing gradients. When the individual phases are associated with osteogenic and chondrogenic growth factors, the structureinduced factor delivery might provide the spatially controlled factor delivery necessary to regenerate osteochondral tissue structure. Overall, we designed a gradient matrix system that is expected to support osteochondral tissue engineering while forming a seamless interface between the cartilage and the bone matrix. INTRODUCTION Osteochondral defect repair has been a significant challenge in orthopedic surgery [1,2]. Fresh or frozen allografts are commonly used as osteochondral plugs, however shortcomings associated with the allograft transplantation, such as disease transmission and lack of integration with the host tissue warrant the development of modern methods for OC defect repair and regeneration [1,3]. Tissue engineering offers several possibilities and a number of TE strategies have been recently developed for this purpose [1,4]. In the past both monophasic and biphasic matrices have been studied for OC tissue engineering [5,6,7,8]. Although, these structures somewhat supported cartilage and bone regeneration in their specified layers, they failed to establish an interface similar to that of native OC tissue [9,10]. Since OC tissue is uniquely structured, with a subchondral layer followed by three well-organized articular cartilage zones from the bottom to top of the structure, OC tissue engineering requires the development of unique matrices, which not only support regeneration of the zonal structure but also helps to establish a proper cartilage-bone interface [1,11,12]. The authors have
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