title: Three-Dimension-Printed Porous Poly(Propylene Fumarate) Scaffolds with Delayed rhBMP-2 Release for Anterior Cruciate Ligament Graft Fixation.
abstract: Anterior cruciate ligament (ACL) ruptures reconstructed with tendon grafts are commonly fixed with bioabsorbable implants, which are frequently complicated by incomplete bone filling upon degradation. Bone regeneration after ACL reconstruction could be enhanced by utilizing tissue engineering techniques and three-dimensional (3D) printing to create a porous bioabsorbable scaffold with delayed delivery of recombinant-human bone morphogenetic protein 2 (rhBMP-2). The first aim of this study was to design a 3D poly(propylene fumarate) (PPF) porous scaffold that maintained suitable pullout strength for future testing in a rabbit ACL reconstruction model. Our second aim was to determine the release kinetics of rhBMP-2 from PPF scaffolds that utilized both calcium-phosphate coatings and growth factor delivery on microspheres, both of which have been shown to decrease the initial burst release of rhBMP-2 and increase bone regeneration. To determine the degree of scaffold porosity that maintained suitable pullout strength, tapered scaffolds were fabricated with increasing porosity (0%, 20%, 35%, and 44%) and pullout testing was performed in a cadaveric rabbit ACL reconstruction model. Scaffolds were coated with carbonate hydroxyapatite (synthetic bone mineral [SBM]), and radiolabeled rhBMP-2 was delivered in four different experimental groups as follows: Poly(lactic-co-glycolic acid) microspheres only, microspheres and collagen (50:50), collagen only, and saline solution only. rhBMP-2 release was measured at day 1, 2, 4, 8, 16, and 32. The microsphere delivery groups had a smaller burst release and released a smaller percentage of rhBMP-2 over the 32 days than the collagen and saline only groups. In conclusion, a porous bioabsorbable scaffold with suitable strength for a rabbit ACL reconstruction was developed. Combining a synthetic bone mineral coating with microspheres had an additive effect, decreasing the initial burst release and cumulative release of rhBMP-2. Future studies need to evaluate this scaffold's fixation strength and bone filling capabilities in vivo compared to traditional bioabsorbable implants.
authors.affiliation: Department of Orthopaedic Surgery, Tissue Engineering and Biomaterials Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Joshua Alan
authors.initials: JA
authors.lastname: Parry
authors.affiliation: Department of Orthopaedic Surgery, Tissue Engineering and Biomaterials Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Maurits G L
authors.initials: MG
authors.lastname: Olthof
authors.affiliation: Department of Orthopaedic Surgery, Tissue Engineering and Biomaterials Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Shogren
authors.affiliation: Department of Orthopaedic Surgery, Tissue Engineering and Biomaterials Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mahrokh
authors.initials: M
authors.lastname: Dadsetan
authors.affiliation: Department of Orthopaedic Surgery, Tissue Engineering and Biomaterials Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andre
authors.initials: A
authors.lastname: Van Wijnen
authors.affiliation: Department of Orthopaedic Surgery, Tissue Engineering and Biomaterials Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Michael
authors.initials: M
authors.lastname: Yaszemski
authors.affiliation: Department of Orthopaedic Surgery, Tissue Engineering and Biomaterials Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kakar
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000166:cytology*; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects; D005650:Fumarates / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011126:Polypropylenes / Q000737:chemistry*; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D005650:Fumarates; D011126:Polypropylenes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C097850:poly(propylene fumarate); C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: anterior cruciate ligament; bioabsorbable; microspheres; poly(propylene fumarate); rhBMP-2