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 wherea s publications about stimulation of fracture healing with these substa nces 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 osteoblast s and prepares the osseous reparation. RhBMPs, mostly BMP-2, are alrea dy used in the reconstruction of the cranial vault. The main disadvant age of these proteins is the quick inactivation after about 20-30 minu tes. Local stimulation without systemic effects might be avoided by re leasing a low but constant dose of IGF-1 or BMP. We speculate that the combination of a reasonable implant with an integrated drug release s ystem may enlarge the field of application of biodegradable implants i n the treatment of fractures. Such an implant might remarkably reduce the time for fracture healing and also lower the costs of postoperativ e treatment. In this paper we report our animal models in which we hav e tested constructive principles of biodegradable implants, we present the first clinical experiences with polyactates (PLLA) in the osteosy nthesis of children, and we describe our inventions concerning drug re leasing implants. 1) PLLA-implants a) The animal models We performed o n oblique osteotomy of the right metacarpal bone in 48 juvenile calves and osteoplastic reconstructions of the cranial vault in 28 juvenile Gottinger minipigs. Biodegradable osteosynthesis with PLLA implants le d to results as good as with conventional materials in both animal mod els, so that we proceeded to clinical evaluation in children. b) The c linical 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 fol low-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 weig ht of about 20,000 and an expected resorption time of 2-3 weeks (paten t pending). 3) Concept of our drug-releasing resorbable implants Plate s could be built up in multilayers of PDLLA sheets, separated by a spo ngiform matrix containing the IGF-1- or BMP-2-loaded nanospheres. The screws are hollow due to an internal driving system. The specially des igned thread could also contain nanospheres, which would be brought in to the cortical bone and the medullary space. The cavity of the screw is filled up with nanospheres after tightening.