title: Embryonically inspired scaffolds regulate tenogenically differentiating cells.
abstract: Tendon injuries heal as scar tissue with significant dysfunction and propensity to re-injure, motivating efforts to develop stem cell-based therapies for tendon regeneration. For these therapies to succeed, effective cues to guide tenogenesis are needed. Our aim is to identify these cues within the embryonic tendon microenvironment. We recently demonstrated embryonic tendon elastic modulus increases during development and is substantially lower than in adult. Here, we examined how these embryonic mechanical properties influence tenogenically differentiating cells, by culturing embryonic tendon progenitor cells (TPCs) within alginate gel scaffolds fabricated with embryonic tendon mechanical properties. We showed that nano- and microscale moduli of RGD-functionalized alginate gels can be tailored to that of embryonic tendons by adjusting polymer concentration and crosslink density. These gels differentially regulated morphology of encapsulated TPCs as a function of initial elastic modulus. Additionally, higher initial elastic moduli elicited higher mRNA levels of scleraxis and collagen type XII but lower levels of collagen type I, whereas late tendon markers tenomodulin and collagen type III were unaffected. Our results demonstrate the potential to engineer scaffolds with embryonic mechanical properties and to use these scaffolds to regulate the behavior of tenogenically differentiating cells.
authors.affiliation: Tufts University, Department of Biomedical Engineering, 4 Colby St, Medford, MA 02155, United States.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Marturano
authors.affiliation: Tufts University, Department of Biomedical Engineering, 4 Colby St, Medford, MA 02155, United States.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Schiele
authors.affiliation: Tufts University, Department of Biomedical Engineering, 4 Colby St, Medford, MA 02155, United States.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Schiller
authors.affiliation: Tufts University, Department of Biomedical Engineering, 4 Colby St, Medford, MA 02155, United States.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Galassi
authors.affiliation: Tufts University, Department of Biomedical Engineering, 4 Colby St, Medford, MA 02155, United States.
authors.forename: Matteo
authors.initials: M
authors.lastname: Stoppato
authors.affiliation: Tufts University, Department of Biomedical Engineering, 4 Colby St, Medford, MA 02155, United States; University of Rochester, Department of Biomedical Engineering, Department of Orthopaedics, Center for Musculoskeletal Research, 215 Robert B. Goergen Hall, Rochester, NY 14627, United States. Electronic address: Catherine.K.Kuo@rochester.edu.
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Kuo
mesh_terms: D000464:Alginates / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002642:Chick Embryo; D024082:Collagen Type XII / Q000378:metabolism; D055119:Elastic Modulus / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D013710:Tendons / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D024082:Collagen Type XII; D006603:Hexuronic Acids; D008565:Membrane Proteins; D020723:Glucuronic Acid
keywords: Alginate gels; Elastic modulus; Embryonic; Tendon; Tissue Engineering