title: Induction of the early inflammatory-mediated cellular responses of fracture healing in vitro using platelet releasate-containing alginate/CaPO4 biomaterials for early osteoarthritis prevention.
abstract: A significant gap exists in our understanding of subchondral and cancellous bone changes that may regulate osteoarthritis progression. Herein, we complement our prior osteochondrogenesis work with growth factor elution and monocyte and endothelial cell activation using two biomaterial formulations. The design of these biomaterials was inspired by the roles of a fracture hematoma, more specifically, the potential of significant cross-talk among cells and cellular factors that affect bone remodeling. Biomaterials, referred to herein as F1+ and F2+, are human concentrated platelet releasate-containing alginate/beta-tricalcium phosphate composites. F1+ has a higher calcium phosphate volume percentage and lower alginate polymer weight percent hydrogel versus F2+. The majority of releasate-derived platelet-derived growth factor eluted over 24 h for F1+ and 48 h for F2+, suggesting sustained release with an increase in alginate weight percentage. Simple monocyte and endothelial cell migration studies demonstrated 650% and 900% increases with F1+ eluate over medium alone, respectively. Induction of endothelial cell invasion over supplemented medium positive control was also shown for F2+ eluate (p = 0.03) with F1+ eluate being similar to the control. Monocyte transendothelial migration was increased over 300% and 400% for F1+ and F2+ eluates compared with medium alone, respectively. In addition, F1+ and F2+ eluates induced spontaneous endothelial tube formations similar to supplemented medium, demonstrating a well-formed network of capillary-like structures. This work demonstrated our biomaterial formulations ability to induce characteristics in vitro that parallel the in vivo behavior of fracture hematomas and potential to induce bone remodeling for the early treatment of osteoarthritic joints.
authors.affiliation: Biomedical Engineering Department, Herff College of Engineering, The University of Memphis, Memphis, Tennessee 38152-3210, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: McCanless
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Jennings
authors.forename: Judith A
authors.initials: JA
authors.lastname: Cole
authors.forename: Joel D
authors.initials: JD
authors.lastname: Bumgardner
authors.forename: Warren O
authors.initials: WO
authors.lastname: Haggard
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D017102:Fracture Healing / Q000187:drug effects*; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010003:Osteoarthritis / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D002130:Calcium Phosphates; D006603:Hexuronic Acids; D010982:Platelet-Derived Growth Factor; D020723:Glucuronic Acid; C020243:calcium phosphate