title: In vitro and in vivo evaluation of heparin mediated growth factor release from tissue-engineered constructs for anterior cruciate ligament reconstruction.
abstract: Anterior cruciate ligament (ACL) rupture is a common injury often necessitating surgical treatment with graft reconstruction. Due to limitations associated with current graft options, there is interest in a tissue-engineered substitute for use in ACL regeneration. While they represent an important step in translation to clinical practice, relatively few in vivo studies have been performed to evaluate tissue-engineered ACL grafts. In the present study, we immobilized heparin onto electrospun polycaprolactone scaffolds as a means of incorporating basic fibroblast growth factor (bFGF) onto the scaffold. In vitro, we demonstrated that human foreskin fibroblasts (HFFs) cultured on bFGF-coated scaffolds had significantly greater cell proliferation. In vivo, we implanted electrospun polycaprolactone grafts with and without bFGF into athymic rat knees. We analyzed the regenerated ACL using histological methods up to 16 weeks post-implantation. Hematoxylin and eosin staining demonstrated infiltration of the grafts with cells, and picrosirius red staining demonstrated aligned collagen fibers. At 16 weeks postop, mechanical testing of the grafts demonstrated that the grafts had approximately 30% the maximum load to failure of the native ACL. However, there were no significant differences observed between the graft groups with or without heparin-immobilized bFGF. While this study demonstrates the potential of a regenerative medicine approach to treatment of ACL rupture, it also demonstrates that in vitro results do not always predict what will occur in vivo.
authors.affiliation: Department of Orthopaedic Surgery, University of California, Los Angeles, California.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Leong
authors.forename: Armin
authors.initials: A
authors.lastname: Arshi
authors.forename: Nima
authors.initials: N
authors.lastname: Kabir
authors.forename: Azadeh
authors.initials: A
authors.lastname: Nazemi
authors.forename: Frank A
authors.initials: FA
authors.lastname: Petrigliano
authors.forename: Ben M
authors.initials: BM
authors.lastname: Wu
authors.forename: David R
authors.initials: DR
authors.lastname: McAllister
mesh_terms: D000818:Animals; D059549:Anterior Cruciate Ligament Reconstruction; D016025:Bone Transplantation; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006493:Heparin / Q000737:chemistry; D006801:Humans; D008297:Male; D011091:Polyesters; D051381:Rats; D011923:Rats, Nude; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D019737:Transplants
chemical_list: D011091:Polyesters; D016222:Fibroblast Growth Factor 2; C016240:polycaprolactone; D006493:Heparin
keywords: ACL; bFGF; drug delivery; heparin; scaffold