title: Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.
abstract: Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects.
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
authors.forename: Anusuya
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Segar
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
authors.forename: Yihsuan
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
authors.forename: Tiffany W
authors.initials: TW
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, China.
authors.forename: Chunxi
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China.
authors.forename: Xeujun
authors.initials: X
authors.lastname: Du
authors.affiliation: School of Medical Diagnostic and Translational Sciences, Old Dominion University, Norfolk, VA, USA.
authors.forename: Roy C
authors.initials: RC
authors.lastname: Ogle
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA.
authors.forename: Quanjun
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA. Electronic address: Edward.botchwey@bme.gatech.edu.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Botchwey
mesh_terms: D064591:Allografts; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016025:Bone Transplantation; D001842:Bone and Bones / Q000502:physiology; D019070:Cell Lineage; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D007155:Immunologic Factors / Q000008:administration & dosage*; D019344:Lactic Acid / Q000008:administration & dosage; D008297:Male; D038042:Myelopoiesis / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011828:Radiation Chimera; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013314:Stress, Mechanical; D013977:Tibia / Q000293:injuries / Q000601:surgery; D055114:X-Ray Microtomography
chemical_list: D004337:Drug Carriers; D007155:Immunologic Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000068876:Fingolimod Hydrochloride
keywords: Bone graft; Bone marrow; Immunomodulation; Phospholipid; Progenitor cells