Local and controlled release of growth factors (combination of IGF-I and TGF-beta I, and BMP-2 alone) from a polylactide coating of titanium implants does not lead to ectopic bone formation in sheep muscle.
The osteoinductive potential of growth factors leads not only to a stimulated bone formation in bony tissue but also in extra skeletal tissue. This potential depends on the dosage and potentially on the application method and may limit the clinical use. The aim of the present study was to investigate the potential of IGF-I, TGF-beta1 and BMP-2 released from a newly developed application systems of orthopaedic implants to induce ectopic bone formation in muscles. This bioactive coating showed a stimulating effect on fracture healing in several experimental studies before. Titanium discs were coated on one side with the drug carrier poly(d,l-lactide) (PDLLA), with the carrier plus IGF-I and TGF-beta1 or with the carrier plus BMP-2. The discs were implanted in the Musculus cleidomastoideus of sheep and followed up for 3 months. X-rays were taken after the operation and the day of sacrifice. The muscles plus implant were harvested and prepared for histology. Neither the radiology nor the histology revealed any signs of ectopic ossification in the implant/muscle interface or in a distance to the plate in any group. An influence of the locally applied growth factor, however, was seen in the formation of a soft tissue capsule. Histomorphometric analysis revealed a significantly larger capsule area over the growth factor coated side in comparison to the uncoated side or the pure titanium plate, indicating an effect of the applied growth factors on cells, however, not resulting in osteoinduction in muscle. The result showed that the local and controlled release of growth factors from PDLLA coated implants does not induce ectopic bone formation in sheep muscle and could be used in orthopaedic surgery to increase healing without the risk of ectopic bone formation in the surrounding soft tissue.
Wildemann
B
B
Center for Musculoskeletal Surgery, Charité-University Medicine, Campus Virchow-Clinic, Augustenburger Platz 1, D-13353, Berlin, Germany. britt.wildemann@charite.de
Kandziora
F
F
Krummrey
G
G
Palasdies
N
N
Haas
N P
NP
Raschke
M
M
Schmidmaier
G
G
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000009:adverse effects*; D001842:Bone and Bones; D002828:Choristoma / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology; D020099:Coated Materials, Biocompatible; D005079:Excipients; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000009:adverse effects*; D018482:Muscle, Skeletal / Q000502:physiology*; D009135:Muscular Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects*; D011091:Polyesters; D019736:Prostheses and Implants; D011859:Radiography; D012756:Sheep; D014025:Titanium; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020099:Coated Materials, Biocompatible; D005079:Excipients; D011091:Polyesters; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C033616:poly(lactide); D007334:Insulin-Like Growth Factor I; D014025:Titanium