Clinical treatment options for articular cartilage repair are progressing with the incorporation of synthetic matrices alongside current autologous chondrocyte implantation techniques. This work explores mechanical and mass transport design of potential matrices. Solid freeform fabrication (SFF) is used to create highly reproducible scaffolds with precise structural features in order to explore the mechanical potential of 3D designed poly(ε-caprolactone) (PCL) and poly(glycerol sebacate) (PGS) scaffolds, and to examine the effects of a designed physical property, permeability, for cartilage regeneration.
Our first aim explores the potential of PCL and PGS scaffolds to provide temporary mechanical function within a tissue defect. We find that PCL mimics the viscoelastic nature of cartilage; however its stiffness properties cannot be changed through alterations in molecular weight or melting temperature. Fabricated into the architectures explored, it has aggregate modulus (H A ) values within the correct magnitude, but higher than native cartilage. Furthermore, we demonstrate the importance of mechanically testing PCL scaffolds at physiological temperatures and we quantify their contraction in polar environments.
Poly(glycerol sebacate) has never been used for cartilage tissue engineering. We characterize how variations in the molar ratios of glycerol to sebacic acid (during pre- polymer synthesis) or variations in curing time can be used to change the stiffness of PGS, enabling fabrication of scaffolds with a wide range of architectures (designed for optimal tissue regeneration) that all support in vivo loads. Chondrocytes seeded onto PGS produce cartilaginous matrix and express cartilage specific genes similar to or better than cells cultured on PCL, showing the biocompatibility of PGS for cartilage applications for the first time.
Our second aim looks at enhancing cartilage regeneration by optimizing scaffold permeability. We show that chondrocytes prefer a lower permeable scaffold that mimics the natural environment of native tissue, producing significantly more matrix and increased expression of cartilage specific markers. Bone marrow stromal cells (BMSCs) display the opposite trend, favoring a higher permeable environment for chondrogenic differentiation, as displayed through collagen 2 to collagen 1 expression, suggesting that increased access to chondrogenic induction factors in media is more important to these cells than mimicking the low permeable environment of native tissue.
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