RESUMO
Biomaterials developed to treat bone defects have classically focused on bone healing via direct, intramembranous ossification. In contrast, most bones in our body develop from a cartilage template via a second pathway called endochondral ossification. The unsolved clinical challenge to regenerate large bone defects has brought endochondral ossification into discussion as an alternative approach for bone healing. However, a biomaterial strategy for the regeneration of large bone defects via endochondral ossification is missing. Here we report on a biomaterial with a channel-like pore architecture to control cell recruitment and tissue patterning in the early phase of healing. In consequence of extracellular matrix alignment, CD146+ progenitor cell accumulation and restrained vascularization, a highly organized endochondral ossification process is induced in rats. Our findings demonstrate that a pure biomaterial approach has the potential to recapitulate a developmental bone growth process for bone healing. This might motivate future strategies for biomaterial-based tissue regeneration.
Assuntos
Materiais Biocompatíveis/farmacologia , Osso e Ossos/patologia , Consolidação da Fratura/efeitos dos fármacos , Animais , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Feminino , Humanos , Osteogênese/efeitos dos fármacos , Porosidade , Ratos Sprague-Dawley , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Alicerces Teciduais/químicaRESUMO
There is at present a clear trend in the study of psychoneuroimmunoregulatory events. Different experimental models have demonstrated: a) the participation of stress, psychosocial factors and the central nervous system in the regulation of the immune response; b) an extensive innervation by the autonomic nervous system of the lymphatic organs; c) the presence of receptors for the neuroendocrine mediators in the mononuclear peripheral cells; d) the activity of neuropeptides, hormones and neurotransmitters in lymphocyte activation and function; e) the production of neuroendocrine substances by lymphocytes; f) the existence of feedback pathways in the immune system. In our laboratory we have contributed to these studies with the description of: a) the regulatory activity of different neuroendocrine substances on interferon-gamma production; b) the characterization of the immune regulation exercised by the muscarinic cholinergic system; c) the in vitro activity of the indoleamines, serotonin and melatonin on the immune response, and the production of these indoleamines by lymphocytes and monocytes, thus establishing a model of paracrine regulation.
Assuntos
Formação de Anticorpos , Sistema Nervoso Central/fisiologia , Linfócitos/fisiologia , Sistemas Neurossecretores/fisiologia , Corticosteroides/fisiologia , Animais , Encefalinas/fisiologia , Interferon gama/biossíntese , Ativação Linfocitária , Camundongos , Neuropeptídeos/fisiologia , RatosRESUMO
There is at present a clear trend in the study of psychoneuroimmunoregulatory events. Different experimental models have demonstrated: a) the participation of stress, psychosocial factors and the central nervous system in the regulation of the immune response; b) an extensive innervation by the autonomic nervous system of the lymphatic organs; c) the presence of receptors for the neuroendocrine mediators in the mononuclear peripheral cells; d) the activity of neuropeptides, hormones and neurotransmitters in lymphocyte activation and function; e) the production of neuroendocrine substances by lymphocytes; f) the existence of feedback pathways in the immune system. In our laboratory we have contributed to these studies with the description of: a) the regulatory activity of different neuroendocrine substances on interferon-gamma production; b) the characterization of the immune regulation exercised by the muscarinic cholinergic system; c) the in vitro activity of the indoleamines, serotonin and melatonin on the immune response, and the production of these indoleamines by lymphocytes and monocytes, thus establishing a model of paracrine regulation.