title: Fiber/collagen composites for ligament tissue engineering: influence of elastic moduli of sparse aligned fibers on mesenchymal stem cells.
abstract: Electrospun microfibers are attractive for the engineering of oriented tissues because they present instructive topographic and mechanical cues to cells. However, high-density microfiber networks are too cell-impermeable for most tissue applications. Alternatively, the distribution of sparse microfibers within a three-dimensional hydrogel could present instructive cues to guide cell organization while not inhibiting cell behavior. In this study, thin (∼5 fibers thick) layers of aligned microfibers (0.7 μm) were embedded within collagen hydrogels containing mesenchymal stem cells (MSCs), cultured for up to 14 days, and assayed for expression of ligament markers and imaged for cell organization. These microfibers were generated through the electrospinning of polycaprolactone (PCL), poly(ester-urethane) (PEUR), or a 75/25 PEUR/PCL blend to produce microfiber networks with elastic moduli of 31, 15, and 5.6 MPa, respectively. MSCs in composites containing 5.6 MPa fibers exhibited increased expression of the ligament marker scleraxis and the contractile phenotype marker α-smooth muscle actin versus the stiffer fiber composites. Additionally, cells within the 5.6 MPa microfiber composites were more oriented compared to cells within the 15 and 31 MPa microfiber composites. Together, these data indicate that the mechanical properties of microfiber/collagen composites can be tuned for the engineering of ligament and other target tissues. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1894-1901, 2016.
authors.affiliation: Virginia Tech/Wake Forest School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia, 24061.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Thayer
authors.affiliation: Virginia Tech/Wake Forest School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia, 24061.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Verbridge
authors.affiliation: Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, 24061.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Dahlgren
authors.affiliation: Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, 55905.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kakar
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, 37212.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Guelcher
authors.affiliation: Virginia Tech/Wake Forest School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia, 24061.|Department of Chemical Engineering, Virginia Tech, Blacksburg, Virginia, 24061.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000032:analysis; D055119:Elastic Modulus; D008022:Ligaments / Q000187:drug effects / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology; D011140:Polyurethanes / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D003094:Collagen; D004247:DNA; D011091:Polyesters; D011140:Polyurethanes; D012333:RNA, Messenger; C503819:Scx protein, rat; C081821:microthane foam; C016240:polycaprolactone
keywords: collagen; composite; electrospinning; ligament; stiffness