Repair of Calvarial Defects with Flap Tissue: Role of Bone Morphogenetic Proteins and Competent Responding Tissues

• Published in: Plastic and reconstructive surgery (1963) Vol. 98; no. 1; pp. 103 - 109
• Main Authors: Khouri, Roger K, Brown, David M, Koudsi, Basem, Deune, Gene E, Gilula, Louis A, Cooley, Brian C, Reddi, Hari A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Society of Plastic Surgeons 01-07-1996; Lippincott Williams & Wilkins
• Subjects: Animals; Biological and medical sciences; Bone Morphogenetic Proteins; Fibroblast Growth Factor 2 - pharmacology; Growth Substances - pharmacology; Image Processing, Computer-Assisted; Insulin-Like Growth Factor I - pharmacology; Kidney - cytology; Liver - cytology; Medical sciences; Muscle, Skeletal - cytology; Muscle, Skeletal - transplantation; Organ Specificity; Osteogenesis; Platelet-Derived Growth Factor - pharmacology; Proteins - pharmacology; Rats; Rats, Inbred Lew; Skin plastic surgery; Skull - cytology; Skull - diagnostic imaging; Skull - radiation effects; Skull - surgery; Spleen - cytology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgical Flaps; Tomography, X-Ray Computed; Wound Healing - radiation effects; Rat; Rodentia; Diseases of the osteoarticular system; Plastic surgery; Injection; Experimental study; Vertebrata; Mammalia; Bone morphogenetic protein; Treatment; Surgery; Animal; Skull; Bone defect; Flap (surgery); Osteogenesis
• ISSN: 0032-1052; 1529-4242
• DOI: 10.1097/00006534-199607000-00017

Bone morphogenetic proteins 2 through 8 have the ability to induce the in vivo transformation of extraskeletal mesenchymal tissue into bone. The aims of this investigation were to determine the optimal responding tissue and the specificity of the inductive effect of bone morphogenetic protein 3. The optimal responding tissue was found to be skeletal muscle. The specificity of this response to bone morphogenetic protein 3 was compared with that of recombinant human basic fibroblast growth factor, recombinant platelet-derived growth factor, and recombinant insulin-like growth factor. Bone morphogenetic protein 3 was the only factor that induced de novo bone formation.This ability to transform muscle into bone was tested in 7 × 7 mm irradiated skull defects in the rat. After 1500 rads of exposure, these defects showed no significant signs of healing by 8 months. When these defects were treated with the microvascular transfer of a nonirradiated muscle flap, they had 8 percent healing at 4 months and 37 percent healing by 8 months. Defects treated with 30 μg bone morphogenetic protein 3 (without the muscle flap) achieved 50 percent healing by 4 months and 64 percent healing by 8 months. When the defects were treated with both the muscle flap and bone morphogenetic protein 3, there was 96 percent healing by 4 months and 100 percent healing by 8 months (p < 0.015, compared with bone morphogenetic protein 3 alone at both time points). At 8 months, the transplanted muscle was entirely transformed into bone and healed the skull defect with newly generated bone indistinguishable from the surrounding calvarial tissue. These findings suggest a potential clinical utility of bone morphogenetic protein 3-induced bone formation in skeletal reconstructions. Furthermore, they also show that there is a collaborative requirement for both the osteoinductive factor bone morphogenetic protein 3 and the presence of competent responsive cells in the wellperfused muscle.