title: Surface energy and stiffness discrete gradients in additive manufactured scaffolds for osteochondral regeneration.
abstract: Swift progress in biofabrication technologies has enabled unprecedented advances in the application of developmental biology design criteria in three-dimensional scaffolds for regenerative medicine. Considering that tissues and organs in the human body develop following specific physico-chemical gradients, in this study, we hypothesized that additive manufacturing (AM) technologies would significantly aid in the construction of 3D scaffolds encompassing such gradients. Specifically, we considered surface energy and stiffness gradients and analyzed their effect on adult bone marrow derived mesenchymal stem cell differentiation into skeletal lineages. Discrete step-wise macroscopic gradients were obtained by sequentially depositing different biodegradable biomaterials in the AM process, namely poly(lactic acid) (PLA), polycaprolactone (PCL), and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) copolymers. At the bulk level, PEOT/PBT homogeneous scaffolds supported a higher alkaline phosphatase (ALP) activity compared to PCL, PLA, and gradient scaffolds, respectively. All homogeneous biomaterial scaffolds supported also a significantly higher amount of glycosaminoglycans (GAGs) production compared to discrete gradient scaffolds. Interestingly, the analysis of the different material compartments revealed a specific contribution of PCL, PLA, and PEOT/PBT to surface energy gradients. Whereas PEOT/PBT regions were associated to significantly higher ALP activity, PLA regions correlated with significantly higher GAG production. These results show that cell activity could be influenced by the specific spatial distribution of different biomaterial chemistries in a 3D scaffold and that engineering surface energy discrete gradients could be considered as an appealing criterion to design scaffolds for osteochondral regeneration.
authors.affiliation: University of Twente, Tissue Regeneration Department, Drienerlolaan 5,7522 NB, Enschede, The Netherlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Luca
authors.forename: Alessia
authors.initials: A
authors.lastname: Longoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Criscenti
authors.forename: Ivan
authors.initials: I
authors.lastname: Lorenzo-Moldero
authors.forename: Michel
authors.initials: M
authors.lastname: Klein-Gunnewiek
authors.forename: Julius
authors.initials: J
authors.lastname: Vancso
authors.forename: Clemens
authors.initials: C
authors.lastname: van Blitterswijk
authors.forename: Carlos
authors.initials: C
authors.lastname: Mota
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moroni
mesh_terms: D001861:Bone Regeneration / Q000502:physiology; D018786:Bone Substitutes / Q000138:chemical synthesis*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D055119:Elastic Modulus; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D066330:Printing, Three-Dimensional; D013499:Surface Properties; D013718:Tensile Strength; D054457:Tissue Scaffolds
chemical_list: D018786:Bone Substitutes