TY - JOUR
T1 - Programmed biomolecule delivery to enable and direct cell migration for connective tissue repair
AU - Qu, Feini
AU - Holloway, Julianne L.
AU - Esterhai, John L.
AU - Burdick, Jason A.
AU - Mauck, Robert L.
N1 - Funding Information:
This work was supported by the National Institutes of Health (R01 AR056624, T32 AR007132, F32 AR063598), the American Orthopaedic Society for Sports Medicine, the Penn Center for Musculoskeletal Disorders (P30 AR069619), and the Department of Veterans’ Affairs (I01 RX000174). We gratefully acknowledge Mr Michael Pintauro and Ms. Breanna Seiber for their technical assistance with the tissue Boyden chamber and mechanical testing, respectively.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Dense connective tissue injuries have limited repair, due to the paucity of cells at the wound site. We hypothesize that decreasing the density of the local extracellular matrix (ECM) in conjunction with releasing chemoattractive signals increases cellularity and tissue formation after injury. Using the knee meniscus as a model system, we query interstitial cell migration in the context of migratory barriers using a novel tissue Boyden chamber and show that a gradient of platelet-derived growth factor-AB (PDGF-AB) expedites migration through native tissue. To implement these signals in situ, we develop nanofibrous scaffolds with distinct fiber fractions that sequentially release active collagenase (to increase ECM porosity) and PDGF-AB (to attract endogenous cells) in a localized and coordinated manner. We show that, when placed into a meniscal defect, the controlled release of collagenase and PDGF-AB increases cellularity at the interface and within the scaffold, as well as integration with the surrounding tissue.
AB - Dense connective tissue injuries have limited repair, due to the paucity of cells at the wound site. We hypothesize that decreasing the density of the local extracellular matrix (ECM) in conjunction with releasing chemoattractive signals increases cellularity and tissue formation after injury. Using the knee meniscus as a model system, we query interstitial cell migration in the context of migratory barriers using a novel tissue Boyden chamber and show that a gradient of platelet-derived growth factor-AB (PDGF-AB) expedites migration through native tissue. To implement these signals in situ, we develop nanofibrous scaffolds with distinct fiber fractions that sequentially release active collagenase (to increase ECM porosity) and PDGF-AB (to attract endogenous cells) in a localized and coordinated manner. We show that, when placed into a meniscal defect, the controlled release of collagenase and PDGF-AB increases cellularity at the interface and within the scaffold, as well as integration with the surrounding tissue.
UR - http://www.scopus.com/inward/record.url?scp=85034982635&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-01955-w
DO - 10.1038/s41467-017-01955-w
M3 - Article
C2 - 29176654
AN - SCOPUS:85034982635
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1780
ER -