title: Cartilage repair by local delivery of transforming growth factor-β1 or bone morphogenetic protein-2 from a novel, segmented polyurethane/polylactic-co-glycolic bilayered scaffold.
abstract: This study aimed to analyze the in vitro and in vivo release kinetics and evaluate the grades of repair induced by either the release of 50 ng of transforming growth factor-β1 or 2.5 or 5 μg of bone morphogenetic protein-2 (BMP-2) from a bilayer scaffold of segmented polyurethane/polylactic-co-glycolic (SPU/PLGA) in osteochondral defects, in a rabbit model. The scaffold consisted of a porous, bone-directed PLGA layer, overlaid with a cartilage-directed layer of growth factor (GF)-loaded PLGA microspheres, dispersed in a matrix of SPU. The PLGA porous layer was fabricated by gas foaming. Microspheres were prepared by a double emulsion method. SPU was synthesized by following the two-step method. GF release kinetics were assessed using iodinated ((125)I) GFs. The in vivo release profiles of both GFs fitted to zero-order kinetics, demonstrating a consistently good control of their release rates by SPU. Cartilage-like tissue, characterized by histological analysis, scoring, and immunolabeling of chondrogenic differentiation markers, was observed only after 12 weeks, maintaining integrity up to at least 24 weeks, independently of the GF and the dose of BMP-2. The biocompatibility and the resulting good quality, hyaline repair cartilage convert this system into a promising candidate for future applications in osteochondral lesions.
authors.affiliation: Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, San Cristóbal de La Laguna 38200, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Reyes
authors.forename: Araceli
authors.initials: A
authors.lastname: Delgado
authors.forename: Raul
authors.initials: R
authors.lastname: Solis
authors.forename: Esther
authors.initials: E
authors.lastname: Sanchez
authors.forename: Antonio
authors.initials: A
authors.lastname: Hernandez
authors.forename: Julio
authors.initials: J
authors.lastname: San Roman
authors.forename: Carmen
authors.initials: C
authors.lastname: Evora
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects / Q000473:pathology*; D002452:Cell Count; D003094:Collagen / Q000378:metabolism; D005269:Femur / Q000187:drug effects / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011140:Polyurethanes / Q000737:chemistry*; D019919:Prosthesis Implantation; D011817:Rabbits; D051381:Rats; D014018:Tissue Distribution / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D053674:Aggrecans; D055396:Bone Morphogenetic Protein 2; D011140:Polyurethanes; D053773:Transforming Growth Factor beta1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen
keywords: BMP-2; SPU-PLGA scaffold; TGF-β1; controlled release; osteochondral repair