ABSTRACT
BACKGROUND: Irradiation results in impaired bone healing. Thus, osteosynthesis procedures are afflicted with increased failure rates. To improve osseointegration bone morphogenetic protein-2 (BMP-2) immobilized on nanocrystalline diamond (NCD)-coated implant surfaces might be 1 solution. METHODS: By 4 weeks after irradiation of pig's mandible with a dose of 60 Gy a fracture was accomplished. Osteosynthesis was performed either with titanium osteosynthesis screws or NCD-coated screws with immobilized BMP-2. Nonirradiated animals served as control. After 1, 2, 4, and 8 weeks screws were evaluated histologically. Bone biopsies were gained to extract mesenchymal stem or precursor cells (MSCs). RESULTS: MSCs after irradiation demonstrated a behavior comparable to that of unirradiated cells. Consequently, immobilized BMP-2 resulted in an initial increased bone contact ratio (p = .014) but demonstrated no sustainable effect compared with osseointegration in nonirradiated bone (p = .08). CONCLUSION: Immobilized BMP-2 demonstrates an osteoinductive effect in irradiated bone. MSCs as effector cells possess protective mechanisms to overcome the destructive effect of irradiation.
Subject(s)
Bone Morphogenetic Protein 2/pharmacology , Bone Screws , Coated Materials, Biocompatible/pharmacology , Mandible/radiation effects , Mandibular Fractures/surgery , Osseointegration/drug effects , Animals , Diamond/pharmacology , Disease Models, Animal , Fracture Fixation/instrumentation , Fracture Fixation/methods , Fracture Healing/physiology , Mandible/pathology , Mandible/surgery , Mandibular Fractures/diagnostic imaging , Radiation Dosage , Radiography , Random Allocation , Reference Values , Sensitivity and Specificity , Surface Properties , Sus scrofa , Swine , Titanium/pharmacologyABSTRACT
Irradiation impacts on the viability and differentiation capacity of tissue-borne mesenchymal stem cells (MSC), which play a pivotal role in bone regeneration. As a consequence of radiotherapy, bones may develop osteoradionecrosis. When irradiating human bone-derived MSC in vitro with increasing doses, the cells' self-renewal capabilities were greatly reduced. Mitotically stalled cells were still capable of differentiating into osteoblasts and pre-adipocytes. As a large animal model comparable to the clinical situation, pig mandibles were subjected to fractionized radiation of 2 χ 9 Gy within 1 week. This treatment mimics that of a standardized clinical treatment regimen of head and neck cancer patients irradiated 30 χ 2 Gy. In the pig model, fractures which had been irradiated, showed delayed osseous healing. When isolating MSC at different time points post-irradiation, no significant changes regarding proliferation capacity and osteogenic differentiation potential became apparent. Therefore, pig mandibles were irradiated with a single dose of either 9 or 18 Gy in vivo, and MSC were isolated immediately afterwards. No significant differences between the untreated and 9 Gy irradiated bone with respect to proliferation and osteogenic differentiation were unveiled. Yet, cells isolated from 18 Gy irradiated specimens exhibited a reduced osteogenic differentiation capacity, and during the first 2 weeks proliferation rates were greatly diminished. Thereafter, cells recovered and showed normal proliferation behaviour. These findings imply that MSC can effectively cope with irradiation up to high doses in vivo. This finding should thus be implemented in future therapeutic concepts to protect regenerating tissue from radiation consequences.
