RESUMO
Electrical stimulation (EStim) has been shown to promote bone healing and regeneration both in animal experiments and clinical treatments. Therefore, incorporating EStim into promising new bone tissue engineering (BTE) therapies is a logical next step. The goal of current BTE research is to develop combinations of cells, scaffolds, and chemical and physical stimuli that optimize treatment outcomes. Recent studies demonstrating EStim's positive osteogenic effects at the cellular and molecular level provide intriguing clues to the underlying mechanisms by which it promotes bone healing. In this review, we discuss results of recent in vitro and in vivo research focused on using EStim to promote bone healing and regeneration and consider possible strategies for its application to improve outcomes in BTE treatments. Technical aspects of exposing cells and tissues to EStim in in vitro and in vivo model systems are also discussed.
Assuntos
Regeneração Óssea , Osso e Ossos , Terapia por Estimulação Elétrica/métodos , Estimulação Elétrica/métodos , Consolidação da Fratura , Regeneração Tecidual Guiada/métodos , Engenharia Tecidual/métodos , Trifosfato de Adenosina/metabolismo , Apoptose , Sinalização do Cálcio , Adesão Celular , Diferenciação Celular , Movimento Celular , Proliferação de Células , Condrogênese , Polpa Dentária/citologia , Proteínas de Choque Térmico/metabolismo , Humanos , Técnicas In Vitro , Inflamação , Sistema de Sinalização das MAP Quinases , Mecanotransdução Celular , Microdomínios da Membrana , Células-Tronco Mesenquimais , Neovascularização Fisiológica , Osteoblastos , Osteogênese , Espécies Reativas de Oxigênio/metabolismo , Receptores de Superfície Celular/metabolismo , Transdução de Sinais , Alicerces TeciduaisRESUMO
BACKGROUND: Electrochemical signals play an important role in cell communication and behavior. Electrically charged ions transported across cell membranes maintain an electrochemical imbalance that gives rise to bioelectric signaling, called membrane potential or Vmem. Vmem plays a key role in numerous inter- and intracellular functions that regulate cell behaviors like proliferation, differentiation and migration, all playing a critical role in embryonic development, healing, and regeneration. METHODS: With the goal of analyzing the changes in Vmem during cell proliferation and differentiation, here we used direct current electrical stimulation (EStim) to promote cell proliferation and differentiation and simultaneously tracked the corresponding changes in Vmem in adipose derived mesenchymal stem cells (AT-MSC). RESULTS: We found that EStim caused increased AT-MSC proliferation that corresponded to Vmem depolarization and increased osteogenic differentiation that corresponded to Vmem hyperpolarization. Taken together, this shows that Vmem changes associated with EStim induced cell proliferation and differentiation can be accurately tracked during these important cell functions. Using this tool to monitor Vmem changes associated with these important cell behaviors we hope to learn more about how these electrochemical cues regulate cell function with the ultimate goal of developing new EStim based treatments capable of controlling healing and regeneration.
RESUMO
Approximately 6.3 million fractures occur each year in the United States alone. Accurately monitoring the progression of fracture healing is essential to be able to advise patients when it is safe to return to normal activity. The most common method used to confirm and monitor fracture healing is the acquisition of multiple radiographic images over the many months required for healing. This imaging method uses large expensive equipment and exposes patients to high levels of ionizing radiation. In the study described here, we tested another technology for monitoring fracture healing that could minimize the need for multiple radiographic images. We tested a piezoelectric transducer fixed to the surface of a bone that uses electromechanical impedance spectroscopy to measure simulated fractures and transmits the measurement data to an acoustic receiver located externally on the skin surface.
Assuntos
Fraturas Ósseas/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Sinais Assistido por Computador , Ultrassonografia/métodos , Animais , Modelos Animais de Doenças , Extremidades/diagnóstico por imagem , Extremidades/lesões , SuínosRESUMO
BACKGROUND: Electrical stimulation (ES) has been successfully used to treat bone defects clinically. Recently, both cellular and molecular approaches have demonstrated that ES can change cell behavior such as migration, proliferation and differentiation. METHODS: In the present study we exposed rat bone marrow- (BM-) and adipose tissue- (AT-) derived mesenchymal stem cells (MSCs) to direct current electrical stimulation (DC ES) and assessed temporal changes in osteogenic differentiation. We applied 100 mV/mm of DC ES for 1 h per day for three, seven and 14 days to cells cultivated in osteogenic differentiation medium and assessed viability and calcium deposition at the different time points. In addition, expression of osteogenic genes, Runx2, Osteopontin, and Col1A2 was assessed in BM- and AT-derived MSCs at the different time points. RESULTS: Results showed that ES changed osteogenic gene expression patterns in both BM- and AT-MSCs, and these changes differed between the two groups. In BM-MSCs, ES caused a significant increase in mRNA levels of Runx2, Osteopontin and Col1A2 at day 7, while in AT-MSCs, the increase in Runx2 and Osteopontin expression were observed after 14 days of ES. DISCUSSION: This study shows that rat bone marrow- and adipose tissue-derived stem cells react differently to electrical stimuli, an observation that could be important for application of electrical stimulation in tissue engineering.
