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.

Limb loss is a devastating disability and while current treatments provide aesthetic and functional restoration, they are associated with complications and risks. The optimal solution would be to harness the body’s regenerative capabilities to regrow new limbs. Several methods have been tried to regrow limbs in mammals, but none have succeeded. One such attempt, in the early 1970s, used electrical stimulation and demonstrated partial limb regeneration. Several researchers reproduced these findings, applying low voltage DC electrical stimulation to the stumps of amputated rat forelimbs reporting “blastema and new bone, bone marrow, cartilage, nerve, skin, muscle and epiphyseal plate formation”. In spite of these encouraging results this research was discontinued. Recently there has been renewed interest in studying electrical stimulation, primarily at a cellular and subcellular level and studies have demonstrated changes in stem cell behavior with increased proliferation, differentiation, matrix formation and migration, all important in tissue regeneration. We applied electrical stimulation, in vivo, to the stumps of amputated rat limbs and observed significant new bone, cartilage and vessel formation and prevention of neuroma formation. These findings demonstrate that electricity stimulates tissue regeneration and form the basis for further research leading to possible new treatments for regenerating limbs.

Despite a remarkable expansion of microsurgery, there is still no international consensus about routinely used prophylactic antithrombotic agents. Most treatment regimens still use aspirin, heparin (low-molecular-weight and unfractionated heparin) or colloids (hydroxyphenylacetate 6%/dextran); however, clear evidence for the clinical benefit of an ideal administration regimen or one agent over the other has not yet been established. Instead of searching for the one regime that fits all, an increasing number of reviews from different disciplines describe multistep approaches that optimize what has been shown to be most promising. This includes the use of antithrombotic agents, proper risk assessment, secondary prevention and professional training to optimize microsurgical skills. In this review, we describe factors included in traditional approaches and also emphasize the value of good surgical technique, which while recognized by all to be one of the most important factors for success, receives less emphasis in reviews describing thrombosis prophylaxis in microvascular surgery.

Large bone defects are a major problem in trauma and orthopedic surgery. Tissue engineering based treatments have emerged as promising alternatives of traditional bone grafting techniques. Critical size bone defect animal models had been developed and widely used to evaluate and compare therapeutic effectiveness in bone tissue engineering treatments. To measure healing in a given defect, after treatment histological assessment methods are commonly used. These histological methods are typically either qualitative and/or measure the amount of newly formed bone. In this study, we introduce a new histological scoring method that in addition to new bone formation also measures newly formed “cartilage”, “fibrous tissue”, and “remnant bone defect size”. Using Kappa analysis and inter- class correlation analysis, we verified the reliability of our new scoring method. These additional parameters make it possible to differentiate between the hard callus and soft callus phases of healing and thus derive more valuable information about the effect different tissue-engineering treatments have on the healing process.

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 V_mem. V_mem 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 V_mem 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 V_mem in adipose derived mesenchymal stem cells (AT-MSC). Results: We found that EStim caused increased AT-MSC proliferation that corresponded to V_mem depolarization and increased osteogenic differentiation that corresponded to V_mem hyperpolarization. Taken together, this shows that V_mem changes associated with EStim induced cell proliferation and differentiation can be accurately tracked during these important cell functions. Using this tool to monitor V_mem 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.