Repair of an osteochondral defect by sustained delivery of BMP-2 or TGFβ1 from a bilayered alginate-PLGA scaffold.
Regeneration of cartilage defects can be accelerated by localized delivery of appropriate growth factors (GFs) from scaffolds. In the present study we analysed the in vitro and in vivo release rates and delivery efficacies of transforming growth factor-β1 (TGFβ1) and bone morphogenetic protein-2 (BMP-2) from a bilayered system, applied for osteochondral defect repair in a rabbit model. A bone-orientated, porous PLGA cylinder was overlaid with GF containing PLGA microspheres, dispersed in an alginate matrix. Four microsphere formulations were incorporated: (a) blank ones; (b) microspheres containing 50 ng TGFβ1; (c) microspheres containing 2.5 µg BMP-2; and (d) microspheres containing 5 µg BMP-2. Release kinetics and tissue distributions were determined using iodinated ((125) I) GFs. Bioactivity of in vitro released BMP-2 and TGFβ1 was confirmed in cell-based assays. In vivo release profiles indicated good GF release control. 20% of BMP-2 and 15% of TGFβ1 were released during the first day. Virtually the total dose was delivered at the end of week 6. Significant histological differences were observed between untreated and GF-treated specimens, there being especially relevant short-term outcomes with 50 ng TGFβ1 and 5 µg BMP-2. Although the evaluation scores for the newly formed cartilage did not differ significantly, 5 µg BMP-2 gave rise to higher quality cartilage with improved surface regularity, tissue integration and increased collagen-type II and aggrecan immunoreactivity 2 weeks post-implantation. Hence, the bilayered system controlled GF release rates and led to preserved cartilage integrity from 12 weeks up to at least 24 weeks.
Department of Chemical Engineering and Pharmaceutical Technology and Institute of Biomedical Technologies (ITB), University of La Laguna, La Laguna, Spain.
R
R
Reyes
A
A
Delgado
E
E
Sánchez
A
A
Fernández
A
A
Hernández
C
C
Evora
D053674:Aggrecans / Q000378:metabolism; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D003692:Delayed-Action Preparations; D005269:Femur / Q000187:drug effects / Q000473:pathology*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019919:Prosthesis Implantation; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D053674:Aggrecans; D000464:Alginates; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D024043:Collagen Type II; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D053773:Transforming Growth Factor beta1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid