Design and characterization of porous poly(glycerol-dodecanedioate) scaffolds for cartilage repair

Abstract Synthetic polymeric scaffolds play an important role in establishing the microenvironment for chondrocytes in engineered cartilage. A three-dimensional pore network allows cell accommodation and supports extracellular matrix (ECM) production by chondrocytes. Ligand coating and biomechanical properties of scaffolds guide regeneration of functional cartilage by mediating cell attachment and establishing the local strain environment. Poly(glycerol-dodecanedioate) (PGD) is a novel biodegradable elastomer with nonlinear-elastic properties similar to native cartilage. However, its harsh curing environments limit the feasibility of common strategies for pore creation in polymeric scaffolds. Herein, we developed porous PGD (pPGD) scaffolds with tailorable pore structures using an inverse molding method and evaluated the range of scaffold structural parameters achievable and their subsequent mechanical properties. The influence of coating PGD with various ECM ligands on the cell shape, metabolic activity, and ECM production of human articular chondrocytes (hACs) was evaluated. pPGD scaffolds were created with pore sizes ranging from 250 – 1000 μm, resulting in 20 – 50% porosity. The morphology and metabolic activity of hACs on PGD were regulated by the type of ligand coating used. When compared to tissue culture plastic, PGD enhanced ECM production in monolayer cultures. Finite element analysis showed that the tensile strains that developed on the pores’ surfaces were at levels shown to be anabolic for hACs. The predicted strain profile varied with pore size and porosity under load, demonstrating that the pore structural parameters could be tuned to optimize cellular-level strains. These results suggest that pPGD scaffolds have the potential to guide cartilage regeneration. Statement of Significance Previous studies have established the importance of designing pore geometry and surface properties in engineered cartilage tissue constructs. This work reports the development and assessment of pPGD scaffolds with tunable pore and surface parameters for cartilage regeneration. The cellular-level strain that cells may experience inside the pores was influenced by the scaffolds’ pore geometry. Ligand coating on PGD balanced out the less ideal properties of the material itself and regulated the shape, attachment, metabolic activity, and ECM production of hACs during in vitro culture. These findings highlight how intelligent design of scaffold parameters can optimize chondrocyte function during 3D culture by tuning ligand presentation and cellular-level strain profiles.