title: Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair.
abstract: The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formulations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair.
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77005-1892, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77005-1892, USA.
authors.forename: Johnny
authors.initials: J
authors.lastname: Lam
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77005-1892, USA.
authors.forename: Jordan E
authors.initials: JE
authors.lastname: Trachtenberg
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77005-1892, USA.
authors.forename: Esther J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77005-1892, USA.
authors.forename: Hajar
authors.initials: H
authors.lastname: Seyednejad
authors.affiliation: Department of Biomaterials, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Jeroen J J P
authors.initials: JJJP
authors.lastname: van den Beucken
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Department of Surgery, Division of Oral and Maxilofacial Surgery, The University of Texas School of Dentistry at Houston, Houston, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Wong
authors.affiliation: Department of Biomaterials, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77005-1892, USA. Electronic address: mikos@rice.edu.
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77005-1892, USA. Electronic address: kasper@rice.edu.
authors.forename: F Kurtis
authors.initials: FK
authors.lastname: Kasper
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000627:therapeutic use; D002356:Cartilage / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005269:Femur / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005650:Fumarates / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D055396:Bone Morphogenetic Protein 2; D005650:Fumarates; C508734:poly(ethylene glycol fumarate); D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D007334:Insulin-Like Growth Factor I
keywords: Bone morphogenetic protein-2; Cartilage repair; Insulin-like growth factor-1; Rabbit model; Subchondral bone