Stimulation of fracture healing by local application of humoral factors integrated in biodegradable implants.
Growth stimulation by growth hormones or by IGF-1 is well known whereas publications about stimulation of fracture healing with these substances are rare. One of the main effects of IGF-1 is angiopoiesis which consequently may be expected to induce and accelerate the soft tissue callus formation. BMP-2 is a stimulator for osteoclasts and osteoblasts and prepares the osseous reparation. RhBMPs, mostly BMP-2, are already used in the reconstruction of the cranial vault. The main disadvantage of these proteins is the quick inactivation after about 20-30 minutes. Local stimulation without systemic effects might be avoided by releasing a low but constant dose of IGF-1 or BMP. We speculate that the combination of a reasonable implant with an integrated drug release system may enlarge the field of application of biodegradable implants in the treatment of fractures. Such an implant might remarkably reduce the time for fracture healing and also lower the costs of postoperative treatment. In this paper we report our animal models in which we have tested constructive principles of biodegradable implants, we present the first clinical experiences with polyactates (PLLA) in the osteosynthesis of children, and we describe our inventions concerning drug releasing implants. 1) PLLA-implants a) The animal models We performed on oblique osteotomy of the right metacarpal bone in 48 juvenile calves and osteoplastic reconstructions of the cranial vault in 28 juvenile Göttinger minipigs. Biodegradable osteosynthesis with PLLA implants led to results as good as with conventional materials in both animal models, so that we proceeded to clinical evaluation in children. b) The clinical application in children 35 children, aged 6 weeks to 17 years, had resorbable osteosynthesis of their cranioplasties for correction of congenital malformations and posttraumatic reconstructions. The follow-up ranged from 5-15 years. 2) Invention of a drug-releasing system IGF-1 or BMP-2 is planned to be incapsulated by evaporation technique into nanospheres of low PDLLA (Poly-DL-Lactite) with a molecular weight of about 20,000 and an expected resorption time of 2-3 weeks (patent pending). 3) Concept of our drug-releasing resorbable implants Plates could be built up in multilayers of PDLLA sheets, separated by a spongiform matrix containing the IGF-1- or BMP-2-loaded nanospheres. The screws are hollow due to an internal driving system. The specially designed thread could also contain nanospheres, which would be brought into the cortical bone and the medullary space. The cavity of the screw is filled up with nanospheres after tightening.
Department of Surgery, University Children's Hospital Zurich, Switzerland.
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Illi
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Feldmann
D020341:Absorbable Implants; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D001860:Bone Plates; D001863:Bone Screws; D002417:Cattle; D002648:Child; D016503:Drug Delivery Systems; D005383:Finger Injuries / Q000601:surgery; D005593:Fracture Fixation, Internal / Q000379:methods; D017102:Fracture Healing; D050723:Fractures, Bone / Q000601:surgery*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000627:therapeutic use; D019344:Lactic Acid; D008663:Metacarpus / Q000601:surgery; D010027:Osteotomy; D011091:Polyesters; D011108:Polymers; D012887:Skull Fractures / Q000601:surgery*; D013552:Swine; D013556:Swine, Miniature; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000627:therapeutic use
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011091:Polyesters; D011108:Polymers; D016212:Transforming Growth Factor beta; D019344:Lactic Acid; C033616:poly(lactide); D007334:Insulin-Like Growth Factor I