title: Anisotropic Shape-Memory Alginate Scaffolds Functionalized with Either Type I or Type II Collagen for Cartilage Tissue Engineering.
abstract: Regenerating articular cartilage and fibrocartilaginous tissue such as the meniscus is still a challenge in orthopedic medicine. While a range of different scaffolds have been developed for joint repair, none have facilitated the development of a tissue that mimics the complexity of soft tissues such as articular cartilage. Furthermore, many of these scaffolds are not designed to function in mechanically challenging joint environments. The overall goal of this study was to develop a porous, biomimetic, shape-memory alginate scaffold for directing cartilage regeneration. To this end, a scaffold was designed with architectural cues to guide cellular and neo-tissue alignment, which was additionally functionalized with a range of extracellular matrix cues to direct stem cell differentiation toward the chondrogenic lineage. Shape-memory properties were introduced by covalent cross-linking alginate using carbodiimide chemistry, while the architecture of the scaffold was modified using a directional freezing technique. Introducing such an aligned pore structure was found to improve the mechanical properties of the scaffold, and promoted higher levels of sulfated glycosaminoglycans (sGAG) and collagen deposition compared to an isotropic (nonaligned) pore geometry when seeded with adult human stem cells. Functionalization with collagen improved stem cell recruitment into the scaffold and facilitated more homogenous cartilage tissue deposition throughout the construct. Incorporating type II collagen into the scaffolds led to greater cell proliferation, higher sGAG and collagen accumulation, and the development of a stiffer tissue compared to scaffolds functionalized with type I collagen. The results of this study demonstrate how both scaffold architecture and composition can be tailored in a shape-memory alginate scaffold to direct stem cell differentiation and support the development of complex cartilaginous tissues.
authors.affiliation: 1 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute , Trinity College Dublin, Dublin, Ireland .|2 Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin , Dublin, Ireland .
authors.forename: Henrique V
authors.initials: HV
authors.lastname: Almeida
authors.affiliation: 1 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute , Trinity College Dublin, Dublin, Ireland .|2 Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin , Dublin, Ireland .
authors.forename: Binulal N
authors.initials: BN
authors.lastname: Sathy
authors.affiliation: 1 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute , Trinity College Dublin, Dublin, Ireland .|3 School of Medicine, Trinity Biomedical Sciences Institute , Trinity College Dublin, Dublin, Ireland .
authors.forename: Ivan
authors.initials: I
authors.lastname: Dudurych
authors.affiliation: 1 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute , Trinity College Dublin, Dublin, Ireland .|2 Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin , Dublin, Ireland .
authors.forename: Conor T
authors.initials: CT
authors.lastname: Buckley
authors.affiliation: 1 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute , Trinity College Dublin, Dublin, Ireland .|4 Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland , Dublin, Ireland .|5 Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
authors.affiliation: 1 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute , Trinity College Dublin, Dublin, Ireland .|2 Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin , Dublin, Ireland .|4 Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland , Dublin, Ireland .|5 Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland , Dublin, Ireland .
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelly
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000464:Alginates; D016880:Anisotropy; D002356:Cartilage; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry*; D024043:Collagen Type II / Q000737:chemistry*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000464:Alginates; D024042:Collagen Type I; D024043:Collagen Type II; D006603:Hexuronic Acids; D020723:Glucuronic Acid
keywords: biomimetic materials; cartilage; extracellular matrix; meniscus; polymeric scaffolds