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J Orthop Res ; 31(10): 1597-604, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23832813

RESUMO

Current strategies for bone regeneration after traumatic injury often fail to provide adequate healing and integration. Here, we combined the poly (ethylene glycol) diacrylate (PEGDA) hydrogel with allogeneic "carrier" cells transduced with an adenovirus expressing BMP2. The system is unique in that the biomaterial encapsulates the cells, shielding them and thus suppressing destructive inflammatory processes. Using this system, complete healing of a 5 mm-long femur defect in a rat model occurs in under 3 weeks, through secretion of 100-fold lower levels of protein as compared to doses of recombinant BMP2 protein used in studies which lead to healing in 2-3 months. New bone formation was evaluated radiographically, histologically, and biomechanically at 2, 3, 6, 9, and 12 weeks after surgery. Rapid bone formation bridged the defect area and reliably integrated into the adjacent skeletal bone as early as 2 weeks. At 3 weeks, biomechanical analysis showed the new bone to possess 79% of torsional strength of the intact contralateral femur. Histological evaluation showed normal bone healing, with no infiltration of inflammatory cells with the bone being stable approximately 1 year later. We propose that these osteoinductive microspheres offer a more efficacious and safer clinical option over the use of rhBMP2.


Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Fraturas do Fêmur/tratamento farmacológico , Consolidação da Fratura/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Fenômenos Biomecânicos/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Composição de Medicamentos/métodos , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/fisiopatologia , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Fibroblastos/citologia , Consolidação da Fratura/fisiologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Microesferas , Radiografia , Ratos , Ratos Wistar , Pele/citologia , Células Estromais/citologia
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