Growth Factor-Mediated Migration of Bone Marrow Progenitor Cells for Accelerated Scaffold Recruitment.
Tissue engineering approaches using growth factor-functionalized acellular scaffolds to support and guide repair driven by endogenous cells are thought to require a careful balance between cell recruitment and growth factor release kinetics. The objective of this study was to identify a growth factor combination that accelerates progenitor cell migration into self-assembling peptide hydrogels in the context of cartilage defect repair. A novel 3D gel-to-gel migration assay enabled quantification of the chemotactic impact of platelet-derived growth factor-BB (PDGF-BB), heparin-binding insulin-like growth factor-1 (HB-IGF-1), and transforming growth factor-β1 (TGF-β1) on progenitor cells derived from subchondral bovine trabecular bone (bone-marrow progenitor cells, BM-PCs) encapsulated in the peptide hydrogel [KLDL]3. Only the combination of PDGF-BB and TGF-β1 stimulated significant migration of BM-PCs over a 4-day period, measured by confocal microscopy. Both PDGF-BB and TGF-β1 were slowly released from the gel, as measured using their (125)I-labeled forms, and they remained significantly present in the gel at 4 days. In the context of augmenting microfracture surgery for cartilage repair, our strategy of delivering chemotactic and proanabolic growth factors in KLD may provide the necessary local stimulus to help increase defect cellularity, providing more cells to generate repair tissue.
1 Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.
Paul H
PH
Liebesny
1 Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.
Sangwon
S
Byun
1 Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.
Han-Hwa
HH
Hung
2 Brigham and Women's Hospital , Boston, Massachusetts.
James R
JR
Pancoast
3 Department of Mechanical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.
Keri A
KA
Mroszczyk
3 Department of Mechanical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.
Whitney T
WT
Young
2 Brigham and Women's Hospital , Boston, Massachusetts.
Richard T
RT
Lee
4 Colorado State University , Orthopaedic Research Center, Fort Collins, Colorado.
David D
DD
Frisbie
4 Colorado State University , Orthopaedic Research Center, Fort Collins, Colorado.
John D
JD
Kisiday
1 Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.|3 Department of Mechanical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.|5 Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology , Cambridge, Massachusetts.
Alan J
AJ
Grodzinsky
D000818:Animals; D000077214:Becaplermin; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D020574:Proto-Oncogene Proteins c-sis; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin; D007334:Insulin-Like Growth Factor I