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.