title: Bioprinting of growth factors onto aligned sub-micron fibrous scaffolds for simultaneous control of cell differentiation and alignment.
abstract: The capability to spatially control stem cell orientation and differentiation simultaneously using a combination of geometric cues that mimic structural aspects of native extracellular matrix (ECM) and biochemical cues such as ECM-bound growth factors (GFs) is important for understanding the organization and function of musculoskeletal tissues. Herein, oriented sub-micron fibers, which are morphologically similar to musculoskeletal ECM, were spatially patterned with GFs using an inkjet-based bioprinter to create geometric and biochemical cues that direct musculoskeletal cell alignment and differentiation in vitro in registration with fiber orientation and printed patterns, respectively. Sub-micron polystyrene fibers (diameter ~ 655 nm) were fabricated using a Spinneret-based Tunable Engineered Parameters (STEP) technique and coated with serum or fibrin. The fibers were subsequently patterned with tendon-promoting fibroblast growth factor-2 (FGF-2) or bone-promoting bone morphogenetic protein-2 (BMP-2) prior to seeding with mouse C2C12 myoblasts or C3H10T1/2 mesenchymal fibroblasts. Unprinted regions of STEP fibers showed myocyte differentiation while printed FGF-2 and BMP-2 patterns promoted tenocyte and osteoblast fates, respectively, and inhibited myocyte differentiation. Additionally, cells aligned along the fiber length. Functionalizing oriented sub-micron fibers with printed GFs provides instructive cues to spatially control cell fate and alignment to mimic native tissue organization and may have applications in regenerative medicine.
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Elmer D F
authors.initials: ED
authors.lastname: Ker
authors.forename: Amrinder S
authors.initials: AS
authors.lastname: Nain
authors.forename: Lee E
authors.initials: LE
authors.lastname: Weiss
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.forename: Joseph
authors.initials: J
authors.lastname: Suhan
authors.forename: Cristina H
authors.initials: CH
authors.lastname: Amon
authors.forename: Phil G
authors.initials: PG
authors.lastname: Campbell
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size; D011137:Polystyrenes / Q000494:pharmacology; D044967:Serum / Q000378:metabolism; D013710:Tendons / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000469:Alkaline Phosphatase; D051792:Basic Helix-Loop-Helix Proteins; D055396:Bone Morphogenetic Protein 2; D016222:Fibroblast Growth Factor 2; D036341:Intercellular Signaling Peptides and Proteins; D011137:Polystyrenes; C503815:Scx protein, mouse