Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras

• Published in: Biomaterials Vol. 64; pp. 98 - 107
• Main Authors: Das, Anusuya, Segar, Claire E, Chu, Yihsuan, Wang, Tiffany W, Lin, Yong, Yang, Chunxi, Du, Xeujun, Ogle, Roy C, Cui, Quanjun, Botchwey, Edward A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-09-2015
• Subjects: Advanced Basic Science; Allografts; Animals; Biocompatibility; Biomedical materials; Bone and Bones - physiology; Bone graft; Bone marrow; Bone Marrow Cells - cytology; Bone Transplantation; Bones; Cell Lineage; Coating; Defects; Dentistry; Drug Carriers - administration & dosage; Drug Delivery Systems; Female; Fingolimod Hydrochloride - administration & dosage; Genes, Reporter; Green Fluorescent Proteins - genetics; Immunologic Factors - administration & dosage; Immunomodulation; Lactic Acid - administration & dosage; Lipids; Male; Myelopoiesis - drug effects; Neovascularization, Physiologic - drug effects; Osteogenesis - drug effects; Phospholipid; Polyglycolic Acid - administration & dosage; Progenitor cells; Radiation Chimera; Random Allocation; Rats; Rats, Sprague-Dawley; Regeneration; Strategy; Stress, Mechanical; Tibia - injuries; Tibia - surgery; X-Ray Microtomography; Phospholipid; Bone marrow; Immunomodulation; Bone graft; Progenitor cells
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2015.06.019

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.