Additive manufacturing of an elastic poly(ester)urethane for cartilage tissue engineering

Abstract

Although a growing knowledge on the field of tissue engineering of articular cartilage exists, reconstruction or in-vitro growth of functional hyaline tissue still represents an unmet challenge. Despite the simplicity of the tissue in terms of cell population and absence of innervation and vascularization, the outstanding mechanical properties of articular cartilage, which are the result of the specificity of its extra cellular matrix (ECM), are difficult to mimic. Most importantly, controlling the differentiation state or phenotype of chondrocytes, which are responsible of the deposition of this specialized ECM, represents a milestone in the regeneration of native articular cartilage. In this study, we fabricated fused deposition modelled (FDM) scaffolds with different pore sizes and architectures from an elastic and biodegradable poly(ester)urethane (PEU) with mechanical properties that can be modulated by design, and that ranged the elasticity of articular cartilage. Cell culture in additive manufactured 3D scaffolds exceeded the chondrogenic potential of the gold-standard pellet culture. In-vitro cell culture studies demonstrated the intrinsic potential of elastic (PEU) to drive the re-differentiation of de-differentiated chondrocytes when cultured in-vitro, in differentiation or basal media, better than pellet cultures. The formation of neo-tissue was assessed as a high deposition of GAGs and fibrillar collagen II, and a high expression of typical chondrogenic markers. Moreover, the collagen II / collagen I ratio commonly used to evaluate the differentiation state of chondrocytes (ratio > 1 being chondrocytes and, ratio < 0 being de-differentiated chondrocytes) was higher than 5. STATEMENT OF SIGNIFICANCE: Tissue engineering of articular cartilage requires material scaffolds capable of driving the deposition of a coherent and specific ECM representative of articular cartilage. Materials explored so far account for low mechanical properties (hydrogels), or are too stiff to mimic the elasticity of the native tissue (traditional polyesters). Here, we fabricated 3D fibrous scaffolds via FDM with a biodegradable poly(ester)urethane. The compressive Young`s modulus and elastic limit of the scaffolds can be tuned by designed, mimicking those of the native tissue. The designed scaffolds showed an intrinsic potential to drive the formation of a GAG and collagen II rich ECM, and to drive a stable chondrogenic cell phenotype.

Keywords: Cartilage tissue engineering; Fused deposition modeling; Poly(ester)urethane.