title: Solid freeform-fabricated scaffolds designed to carry multicellular mesenchymal stem cell spheroids for cartilage regeneration.
abstract: Three-dimensional (3D) cellular spheroids have recently emerged as a new trend to replace suspended single cells in modern cell-based therapies because of their greater regeneration capacities in vitro. They may lose the 3D structure during a change of microenvironment, which poses challenges to their translation in vivo. Besides, the conventional microporous scaffolds may have difficulty in accommodating these relatively large spheroids. Here we revealed a novel design of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC) spheroids were made by solid freeform fabrication (SFF) from the solution of poly(D,L-lactide-co-glycolide). Their internal surface was modified with chitosan following air plasma treatment in order to preserve the morphology of the spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds produced a significantly larger amount of cartilage-associated extracellular matrix in vitro and in NOD/SCID mice compared to single cells in the same scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral defects of rabbit knees showed superior cartilage regeneration. This study establishes new perspectives in designing the spheroid-sustaining microenvironment within a tissue engineering scaffold for in vivo applications.
authors.affiliation: Institute of Polymer Science and Engineering, National Taiwan University, No. 1, Sec. 4 Roosevelt Road, Taipei 10617, Taiwan, R.O.C.shhsu@ntu.edu.tw.
authors.forename: G S
authors.initials: GS
authors.lastname: Huang
authors.forename: C S
authors.initials: CS
authors.lastname: Tseng
authors.forename: B
authors.initials: B
authors.lastname: Linju Yen
authors.forename: L G
authors.initials: LG
authors.lastname: Dai
authors.forename: P S
authors.initials: PS
authors.lastname: Hsieh
authors.forename: S-h
authors.initials: SH
authors.lastname: Hsu
mesh_terms: D000328:Adult; D000818:Animals; D063566:Biodegradable Plastics / Q000737:chemistry / Q000494:pharmacology; D002356:Cartilage / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011098:Polyglactin 910 / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D012038:Regeneration; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000502:physiology; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D063566:Biodegradable Plastics; D011098:Polyglactin 910; D048271:Chitosan