The stability of BMP loaded polyelectrolyte multilayer coatings on titanium

• Published in: Biomaterials 2013-07, Vol.34 (23), p.5737-5746
• Main Authors: Guillot, Raphael, Gilde, Flora, Becquart, Pierre, Sailhan, Frédéric, Lapeyrere, Aurélien, Logeart-Avramoglou, Delphine, Picart, Catherine
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Biotechnology; Bone morphogenetic protein 2; Bone Morphogenetic Proteins - pharmacology; Bone Regeneration - drug effects; Bone Regeneration - radiation effects; Cell Line; Chemical Sciences; Coated Materials, Biocompatible - pharmacology; Coating; Computer Science; Dentistry; Electrolytes - chemistry; Gamma Rays; Hyaluronic Acid - analogs & derivatives; Hyaluronic Acid - chemistry; Life Sciences; Material chemistry; Mice; Osteogenesis - drug effects; Osteogenesis - radiation effects; Osteoinduction; Polylysine - analogs & derivatives; Polylysine - chemistry; Porosity; Rats; Sterilization; Storage; Tissue Scaffolds - chemistry; Titanium - chemistry; Titanium - pharmacology; Titanium implant
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.03.067

Abstract Immobilization of bone morphogenetic proteins (BMP) onto material surfaces is a promising, but still challenging, strategy for achieving dependable and consistent osseointegration of long-term metal implants. In the present study, we have developed an osteoinductive coating of a porous titanium implant using biomimetic polyelectrolyte multilayer (PEM) films loaded with BMP-2. The amount of BMP-2 loaded in these films was tuned – over a large range – depending on the cross-linking extent of the film and of the BMP-2 initial concentration. The air-dried PEM films were stable for at least one year of storage at 4 °C. In addition, they resisted exposure to γ-irradiation at clinically approved doses. The preservation of the growth factor bioactivity upon long-term storage and sterilization were evaluated both in vitro (using C2C12 cells) and in vivo (in a rat ectopic model) for the perspective of industrial and clinical development. BMP-2 loaded in dried PEM films exhibited shelf-life stability over one year. However, their bioactivity in vitro decreased from 50 to 80% after irradiation depending on the γ-irradiation dose. Remarkably, the in vivo studies showed that the osteoinductive potential of BMP-2 contained in PEM-coated Ti implants was fully preserved after air-drying of the implants and sterilization at 25 kGy. Film drying or irradiation did not affect the amount of new bone tissue formation. This “off-the-shelf” novel technology of functionalized implants opens promising applications in prosthetic and tissue engineering fields.