Histotripsy - hype or hope? Review of innovation and future implications.

BACKGROUND: Histotripsy is a novel, ultrasound-based ablative technique that was recently approved by the Food and Drug Administration for hepatic targets. It has several promising additional theoretical applications that need to be further investigated. Its basis as a nonthermal cavitational technology presents a unique advantage over existing thermal ablation techniques in maximizing local effects while minimizing adjacent tissue destruction. This review discusses the technical basis and current preclinical and clinical data surrounding histotripsy. METHODS: This was a comprehensive review of the literature surrounding histotripsy and the clinical landscape of existing ablative techniques using the PubMed database. A technical summary of histotripsy's physics and cellular effect was described. Moreover, data from recent clinical trials, including Hope4Liver, and future implications regarding its application in various benign and malignant conditions were discussed. RESULTS: Preclinical data demonstrated the efficacy of histotripsy ablation in various organ systems with minimal tissue destruction when examined at the histologic level. The first prospective clinical trial involving histotripsy in hepatocellular carcinoma and liver metastases, Hope4Liver, demonstrated a primary efficacy of 95.5% with minimal complications (6.8%). This efficacy was replicated in similar trials involving the treatment of benign prostatic hypertrophy. DISCUSSION: In addition to the noninvasive ability to ablate lesions in the liver, histotripsy offers additional therapeutic potential. Early data suggest a potential complementary therapeutic effect when combining histotripsy with existing immunologic therapies because of the technology's theoretical ability to sensitize tumors to adaptive immunity. As with most novel therapies, the effect of histotripsy on the oncologic therapeutic landscape remains uncertain.

Utilization of Natural Language Processing Software to Identify Worrisome Pancreatic Lesions.

BACKGROUND: Computed tomography (CT) imaging is routinely obtained for diagnostics, especially in trauma and emergency rooms, often identifying incidental findings. We utilized a natural language processing (NLP) algorithm to quantify the incidence of clinically relevant pancreatic lesions in CT imaging. PATIENTS AND METHODS: We utilized the electronic medical record to perform a retrospective chart review of adult patients admitted for trauma to a level 1 tertiary care center between 2010 and 2020 who underwent abdominal CT imaging. An open-source NLP software was used to identify patients with intrapapillary mucinous neoplasms (IPMN), pancreatic cysts, pancreatic ductal dilation, or pancreatic masses after optimizing the algorithm using a test group of patients who underwent pancreatic surgery. RESULTS: The algorithm identified pancreatic lesions in 27 of 28 patients who underwent pancreatic surgery and excluded 1 patient who had a pure ampullary mass. The study cohort consisted of 18,769 patients who met our inclusion criteria admitted to the hospital. Of this population, 232 were found to have pancreatic lesions of interest. There were 48 (20.7%) patients with concern for IPMN, pancreatic cysts in 36 (15.5%), concerning masses in 30 (12.9%), traumatic findings in 44 (19.0%), pancreatitis in 41 (17.7%), and ductal abnormalities in 19 (18.2%) patients. Prior pancreatic surgery and other findings were identified in 14 (6.0%) patients. CONCLUSIONS: In this study, we propose a novel use of NLP software to identify potentially malignant pancreatic lesions annotated in CT imaging performed for other purposes. This methodology can significantly increase the screening and automated referral for the management of precancerous lesions.

Medicaid expansion is associated with earlier diagnosis of gastric cancer.

INTRODUCTION: The 2014 Medicaid expansion was intended to improve access to care. We hypothesized that Medicaid expansion would be associated with improved gastric cancer (GC) outcomes. METHODS: We selected patients with a new primary diagnosis of GC from the National Cancer Database. We compared states that expanded Medicaid in 2014 to those that did not. We compared pre-and post-expansion intervals 2012-2013 and 2015-2016. RESULTS: There was an increase in patients diagnosed with stage 0-2 GC from 38% to 41.5% [p < 0.01] in expansion states (ES), but no change at 38.9% in non-expansion states (NES). Uninsured and Medicaid patients diagnosed with stages 0-2 GC increased in ES from 32.4% to 37.8% [p = 0.01] and decreased in NES from 29.7% to 27.3% [p = n.s.]. Uninsured and Medicaid patients receiving treatment rose from 87.0% to 90.3% in ES [p < 0.01] and in NES 83.9%-84.9% [p = n.s.]. Twelve-month survival for ES rose from 68.1% to 70.6% [p = 0.03] and in NES decreased 65.2%-65.1% [p = n.s.]. CONCLUSION: Increased healthcare access may be related to earlier diagnosis and improved outcomes in GC.

Cost-Benefit Analysis of Robotic vs. Laparoscopic Hepatectomy: A Propensity-Matched Retrospective Cohort Study of American College of Surgeons National Surgical Quality Improvement Program Database.

BACKGROUND: Robotic and laparoscopic hepatectomies having increased utilization as minimally invasive techniques are explored for hepatobiliary malignancies. Although the data on outcomes from these 2 approaches are emerging, the cost-benefit analysis of these approaches remains sparse. This study compares the costs associated with robotic vs. laparoscopic liver resections, taking into account 30-day complications. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, a propensity-matched cohort of patients with laparoscopic or robotic liver resections between 2014 and 2017 was identified. Costs were assigned to perioperative variables, including operating room (OR) time, length of stay, blood transfusions, and 30-day complications. Cost estimates were obtained from the Centers for Medicare and Medicaid Services billing data (2017), American Hospital Association data (2017), relevant literature, and local institutional cost data. RESULTS: In our matched cohort of 454 patients (227 per group), total costs associated with laparoscopic liver resections were estimated at $5.5 M ($24 K per patient) vs. $6.8 M ($29.8 K per patient) for robotic liver resections (21.3% difference, P < .001). The higher cost associated with robotic hepatectomies was related to blood transfusions ($22.0 K vs. $12.1 K, P = .02), length of stay ($2.05 M vs. $1.76 M, P = .046), and OR time ($4.01 M vs. $3.24 M, P < .0001). DISCUSSION: Robotic hepatectomies were associated with higher costs compared to laparoscopic hepatectomies. The 2 major contributors to the cost disparity were increased OR time and increased length of stay. Future studies are warranted to analyze high-volume Minimally Invasive Surgery surgeons' impact in specialty centers on potentially mitigating this current cost disparity.

Curcumin and Carnosic Acid Cooperate to Inhibit Proliferation and Alter Mitochondrial Function of Metastatic Prostate Cancer Cells.

Anticancer activities of plant polyphenols have been demonstrated in various models of neoplasia. However, evidence obtained in numerous in vitro studies indicates that proliferation arrest and/or killing of cancer cells require quite high micromolar concentrations of polyphenols that are difficult to reach in vivo and can also be (geno)toxic to at least some types of normal cells. The ability of certain polyphenols to synergize with one another at low concentrations can be used as a promising strategy to effectively treat human malignancies. We have recently reported that curcumin and carnosic acid applied at non-cytotoxic concentrations synergistically cooperate to induce massive apoptosis in acute myeloid leukemia cells, but not in normal hematopoietic and non-hematopoietic cells, via sustained cytosolic calcium overload. Here, we show that the two polyphenols can also synergistically suppress the growth of DU145 and PC-3 metastatic prostate cancer cell cultures. However, instead of cell killing, the combined treatment induced a marked inhibition of cell proliferation associated with G0/G1 cell cycle arrest. This was preceded by transient elevation of cytosolic calcium levels and prolonged dissipation of the mitochondrial membrane potential, without generating oxidative stress, and was associated with defective oxidative phosphorylation encompassing mitochondrial dysfunction. The above effects were concomitant with a significant downregulation of mRNA and protein expression of the oncogenic kinase SGK1, the mitochondria-hosted mTOR component. In addition, a moderate decrease in SGK1 phosphorylation at Ser422 was observed in polyphenol-treated cells. The mTOR inhibitor rapamycin produced a similar reduction in SGK1 mRNA and protein levels as well as phosphorylation. Collectively, our findings suggest that the combination of curcumin and carnosic acid at potentially bioavailable concentrations may effectively target different types of cancer cells by distinct modes of action. This and similar combinations merit further exploration as an anticancer modality.

Mitochondrial responses to organelle-specific drug delivering nanoparticles composed of polypeptide and peptide complexes.

Aims: The mechanistic study of the drug carrier-target interactions of mitochondria-unique nanoparticles composed of polypeptide-peptide complexes (mPoP-NPs). Materials & methods: The isolated organelles were employed to address the direct effects of mPoP-NPs on dynamic structure and functional wellbeing of mitochondria. Mitochondria morphology, respiration, membrane potential, reactive oxygen species generation, were examined by confocal microscopy, flow cytometry and oxygraphy. Lonidamine-encapsulated formulation was assessed to evaluate the drug delivery capacity of the naive nanoparticles. Results: The mPoP-NPs do not alter mitochondria structure and performance upon docking to organelles, while successfully delivering drug that causes organelle dysfunction. Conclusion: The study gives insight into interactions of mPoP-NPs with mitochondria and provides substantial support for consideration of designed nanoparticles as biocompatible and efficient mitochondria-targeted platforms.

Implications for Telemedicine for Surgery Patients After COVID-19: Survey of Patient and Provider Experiences.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has expanded the utilization of telemedicine in clinical practice to minimize potential risks to both patients and providers. We aim to describe the perception of telemedicine by both surgical patients and providers to understand the preferences for future incorporation in future surgical practice. METHODS: An anonymous survey was administered to providers that transitioned clinic visits to telemedicine encounters since the start of the COVID-19 pandemic. In the second part of the study, patients who underwent video telemedicine appointments answered survey questions via telephone. RESULTS: Twenty-six out of 36 (72.7%) providers responded. Over 75% reported that they could effectively communicate with patients over telemedicine. Six (23.1%) reported that they could adequately assess surgical sites. Of 361 patients, 187 consented to the study (consent rate 51.8%). Among patients, the most common result to choose a telemedicine appointment was to avoid the risk of COVID-19 transmission (84, 44.9%), though the minority reported that they would choose telemedicine after the pandemic (64, 34.2%). Those patients who would choose an in-person visit were more likely to have a higher Charlson Comorbidity Score, body mass index, and use friends or family for transportation. In open-ended feedback, patients suggested that telemedicine would be better suited for long-term follow-up rather than the immediate postoperative setting. CONCLUSIONS: Patients and providers reported a high degree of satisfaction using telemedicine during the COVID-19 pandemic but noted concern with limited physical examinations. Telemedicine may be suited for preoperative evaluation and medium-term and long-term postoperative follow-up for surgical patients.

Induction of Myogenic Differentiation Improves Chemosensitivity of Chemoresistant Cells in Soft-Tissue Sarcoma Cell Lines.

Rhabdomyosarcoma (RMS) and rhabdoid tumors (RT) are rare soft-tissue malignancies with the highest incidence in infants, children, and adolescents. Advanced, recurrent, and/or metastatic RMS and RT exhibit poor response to treatment. One of the main mechanisms behind resistance to treatment is believed to be intratumoral heterogeneity. In this study, we investigated the myogenic determination factor 1 (MYOD1) and Noggin (NOG) markers in an embryonal RMS (ERMS) cell line and an RT cell line and the differential response of the MYOD1 and NOG expressing subpopulations to chemotherapy. Importantly, we found that these markers together identify a subpopulation of cells (MYOD1+ NOG+ cells) with primary resistance to Vincristine and Doxorubicin, two commonly used chemotherapies for ERMS and RT. The chemoresistant MYOD1+ NOG+ cells express markers of undifferentiated cells such as myogenin and ID1. Combination of Vincristine with TPA/GSK126, a drug combination shown to induce differentiation of RMS cell lines, is able to partially overcome MYOD1/NOG cells chemoresistance.

Danazol alters mitochondria metabolism of fibrocystic breast Mcf10A cells.

Fibrocystic Breast Disease (FBD) or Fibrocystic change (FC) affects about 60% of women at some time during their life. Although usually benign, it is often associated with pain and tenderness (mastalgia). The synthetic steroid danazol has been shown to be effective in reducing the pain associated with FBD, but the cellular and molecular mechanisms for its action have not been elucidated. We investigated the hypothesis that danazol acts by affecting energy metabolism. Effects of danazol on Mcf10A cells homeostasis, including mechanisms of oxidative phosphorylation, cytosolic calcium signaling and oxidative stress, were assessed by high-resolution respirometry and flow cytometry. In addition to fast physiological responses the associated genomic modulations were evaluated by Affimetrix microarray analysis. The alterations of mitochondria membrane potential and respiratory activity, downregulation of energy metabolism transcripts result in suppression of energy homeostasis and arrest of Mcf10A cells growth. The data obtained in this study impacts the recognition of direct control of mitochondria by cellular mechanisms associated with altered energy metabolism genes governing the breast tissue susceptibility and response to medication by danazol.

In Situ Operating Room-Based Simulation: A Review.

OBJECTIVE: To systematically review the literature surrounding operating room-based in situ training in surgery. METHODS: A systematic review was conducted of MEDLINE. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, and employed the Population, Intervention, Comparator, Outcome (PICO) structure to define inclusion/exclusion criteria. The Kirkpatrick model was used to further classify the outcome of in situ training when possible. RESULTS: The search returned 308 database hits, and ultimately 19 articles were identified that met the stated PICO inclusion criteria. Operating room-based in situ simulation is used for a variety of purposes and in a variety of settings, and it has the potential to offer unique advantages over other types of simulation. Only one randomized controlled trial was conducted comparing in situ simulation to off-site simulation, which found few significant differences. One large-scale outcome study showed improved perinatal outcomes in obstetrics. CONCLUSIONS: Although in situ simulation theoretically offers certain advantages over other types of simulation, especially in addressing system-wide or environmental threats, its efficacy has yet to be clearly demonstrated.

Magnetic Nanoparticle-Mediated Targeting of Cell Therapy Reduces In-Stent Stenosis in Injured Arteries.

Although drug-eluting stents have dramatically reduced the recurrence of restenosis after vascular interventions, the nonselective antiproliferative drugs released from these devices significantly delay reendothelialization and vascular healing, increasing the risk of short- and long-term stent failure. Efficient repopulation of endothelial cells in the vessel wall following injury may limit complications, such as thrombosis, neoatherosclerosis, and restenosis, through reconstitution of a luminal barrier and cellular secretion of paracrine factors. We assessed the potential of magnetically mediated delivery of endothelial cells (ECs) to inhibit in-stent stenosis induced by mechanical injury in a rat carotid artery stent angioplasty model. ECs loaded with biodegradable superparamagnetic nanoparticles (MNPs) were administered at the distal end of the stented artery and localized to the stent using a brief exposure to a uniform magnetic field. After two months, magnetic localization of ECs demonstrated significant protection from stenosis at the distal part of the stent in the cell therapy group compared to both the proximal part of stent in the cell therapy group and the control (stented, nontreated) group: 1.7-fold (p < 0.001) less reduction in lumen diameter as measured by B-mode and color Doppler ultrasound, 2.3-fold (p < 0.001) less reduction in the ratios of peak systolic velocities as measured by pulsed wave Doppler ultrasound, and 2.1-fold (p < 0.001) attenuation of stenosis as determined through end point morphometric analysis. The study thus demonstrates that magnetically assisted delivery of ECs is a promising strategy for prevention of vessel lumen narrowing after stent angioplasty procedure.

Can Simulated Team Tasks be Used to Improve Nontechnical Skills in the Operating Room?

OBJECTIVE: The purpose of this study was to understand the effect of a team-based surgical skills intervention on the technical and nontechnical skills of surgery residents. DESIGN: This was a prospective cohort study with pretesting or posttesting. We designed basic tasks for the assessment and learning of nontechnical skills in the operating room (OR). A total of 15 postgraduate year 1 residents performed an open gastrojejunostomy in a simulated OR setting (pretest), followed by training in the 3 team-based tasks designed to teach communication and teamwork, followed by performance of a gastrojejunostomy in the simulated OR (posttest). SETTING: Tertiary care, university-based teaching institution. PARTICIPANTS: A total of 15 general surgery residents at the intern level. RESULTS: The mean nontechnical skills for surgeons (NOTSS) score improved postteam task training (10.04 ± 0.33 vs. 12.14 ± 1.33). There was a concomitant increase in the objective structured assessment of technical skills (OSATS) score (18.56 ± 0.86 vs. 22.86 ± 0.15, p = 0.006). The percentage increases in OSATS and NOTSS score for each resident was similar (19.49 ± 4.8 % for NOTSS vs. 21.22 ± 4.92 % for OSATS, p = 0.502). CONCLUSION: Nontechnical skills positively correlate with the technical performance of a surgeon. Simple, easily designed tasks can be used to improve NOTSS in the OR. These team tasks and development of curricula based on them can be used to explicitly address one of the most important components of ACGME core competencies for surgical residents, namely interpersonal skills and communication.

Mitochondria-Mediated Anticancer Effects of Non-Thermal Atmospheric Plasma.

Non-thermal atmospheric pressure plasma has attracted great interest due to its multiple potential biomedical applications with cancer treatment being among the most urgent. To realize the clinical potential of non-thermal plasma, the exact cellular and molecular mechanisms of plasma effects must be understood. This work aimed at studying the prostate cancer specific mechanisms of non-thermal plasma effects on energy metabolism as a central regulator of cell homeostasis and proliferation. It was found that cancer cells with higher metabolic rate initially are more resistant to plasma treated phosphate-buffered saline (PBS) since the respiratory and calcium sensitive signaling systems were not responsive to plasma exposure. However, dramatic decline of cancer oxidative phosphorylation developed over time resulted in significant progression of cell lethality. The normal prostate cells with low metabolic activity immediately responded to plasma treated PBS by suppression of respiratory functions and sustained elevation of cytosolic calcium. However, over time the normal cells start recovering their mitochondria functions, proliferate and restore the cell population. We found that the non-thermal plasma induced increase in intracellular ROS is of primarily non-mitochondrial origin. The discriminate non-thermal plasma effects hold a promise for clinical cancer intervention.

Tumor microenvironment promotes dicarboxylic acid carrier-mediated transport of succinate to fuel prostate cancer mitochondria.

Prostate cancer cells reprogram their metabolism, so that they support their elevated oxidative phosphorylation and promote a cancer friendly microenvironment. This work aimed to explore the mechanisms that cancer cells employ for fueling themselves with energy rich metabolites available in interstitial fluids. The mitochondria oxidative phosphorylation in metastatic prostate cancer DU145 cells and normal prostate epithelial PrEC cells were studied by high-resolution respirometry. An important finding was that prostate cancer cells at acidic pH 6.8 are capable of consuming exogenous succinate, while physiological pH 7.4 was not favorable for this process. Using specific inhibitors, it was demonstrated that succinate is transported in cancer cells by the mechanism of plasma membrane Na(+)-dependent dycarboxylic acid transporter NaDC3 (SLC13A3 gene). Although the level of expression of SLC13A3 was not significantly altered when maintaining cells in the medium with lower pH, the respirometric activity of cells under acidic condition was elevated in the presence of succinate. In contrast, normal prostate cells while expressing NaDC3 mRNA do not produce NaDC3 protein. The mechanism of succinate influx via NaDC3 in metastatic prostate cancer cells could yield a novel target for anti-cancer therapy and has the potential to be used for imaging-based diagnostics to detect non-glycolytic tumors.

Metabolic and structural integrity of magnetic nanoparticle-loaded primary endothelial cells for targeted cell therapy.

AIM: To successfully translate magnetically mediated cell targeting from bench to bedside, there is a need to systematically assess the potential adverse effects of magnetic nanoparticles (MNPs) interacting with 'therapeutic' cells. Here, we examined in detail the effects of internalized polymeric MNPs on primary rat endothelial cells' structural intactness, metabolic integrity and proliferation potential. MATERIALS & METHODS: The intactness of cytoskeleton and organelles was studied by fluorescent confocal microscopy, flow cytometry and high-resolution respirometry. RESULTS: MNP-loaded primary endothelial cells preserve intact cytoskeleton and organelles, maintain normal rate of proliferation, calcium signaling and mitochondria energy metabolism. CONCLUSION: This study provides supportive evidence that MNPs at doses necessary for targeting did not induce significant adverse effects on structural integrity and functionality of primary endothelial cells - potential cell therapy vectors.

Patient-specific risk factors are predictive for postoperative adverse events in colorectal surgery: an American College of Surgeons National Surgical Quality Improvement Program-based analysis.

BACKGROUND: Pay-for-performance measures incorporate surgical site infection rates into reimbursement algorithms without accounting for patient-specific risk factors predictive for surgical site infections and other adverse postoperative outcomes. METHODS: Using American College of Surgeons National Surgical Quality Improvement Program data of 67,445 colorectal patients, multivariable logistic regression was performed to determine independent risk factors associated with various measures of adverse postoperative outcomes. RESULTS: Notable patient-specific factors included (number of models containing predictor variable; range of odds ratios [ORs] from all models): American Society of Anesthesiologists class 3, 4, or 5 (7 of 7 models; OR 1.25 to 1.74), open procedures (7 of 7 models; OR .51 to 4.37), increased body mass index (6 of 7 models; OR 1.15 to 2.19), history of COPD (6 of 7 models; OR 1.19 to 1.64), smoking (6 of 7 models; OR 1.15 to 1.61), wound class 3 or 4 (6 of 7 models; OR 1.22 to 1.56), sepsis (6 of 7 models; OR 1.14 to 1.89), corticosteroid administration (5 of 7 models; OR 1.11 to 2.24), and operation duration more than 3 hours (5 of 7 models; OR 1.41 to 1.76). CONCLUSIONS: These findings may be used to pre-emptively identify colorectal surgery patients at increased risk of experiencing adverse outcomes.

Unique risks for mortality in patients with end-stage renal disease undergoing nonemergent colorectal surgery.

BACKGROUND: The aim of this study was to identify unique risk factors for mortality in patients with end-stage renal disease undergoing nonemergent colorectal surgery. METHODS: A multivariate logistic regression model predicting 30-day mortality was constructed for patients with end-stage renal disease undergoing nonemergent colorectal procedures. Data were obtained from the National Surgical Quality Improvement Program (2005-2010). RESULTS: Among the 394 patients analyzed, those with serum creatinine levels >7.5 mg/dL had .07 times the adjusted mortality risk of those with levels <3.5 mg/dL. For colorectal surgery patients, the average serum creatinine level was 5.52 ± 2.6 mg/dL, and mortality was 13% (n = 50). CONCLUSIONS: High serum creatinine was associated with a lower risk for mortality in patients with end-stage renal disease, even though creatinine is often considered a risk factor for surgery. These results show how variables from a patient-centered subpopulation can differ in meaning from the general population.

Breast tumor detection using piezoelectric fingers: first clinical report.

BACKGROUND: Mammography is key to detection of breast cancer in high-risk populations. Currently, aside from palpation and risk-assessment questionnaires, there is no prescreening test that can improve the accuracy, safety, and cost effectiveness of screening low-risk populations. The piezoelectric finger (PEF) is a radiation-free, portable, and low-cost breast tumor detector we developed to be used as a prescreening tool. STUDY DESIGN: Patients presenting with breast abnormalities detected by palpation or imaging were enrolled in this IRB-approved study. The PEF testing was performed with the patient in supine position before undergoing biopsy or surgical excision. The locations of the lesions detected by PEF were compared with those confirmed on imaging or pathology. RESULTS: A total of 40 patients were enrolled and 46 lesions were confirmed by imaging or pathology. The PEF reported 55 lesions, with 9 false positives and 2 true positives not originally found on imaging or palpation. The overall sensitivity of the PEF test was 87% (40 of 46). In women 40 years old or younger, overall sensitivity was or 100% (19 of 19). In women who had a lesion visible on mammography, PEF had a sensitivity of 83% (24 of 29). Of these, in women aged 40 years or younger, PEF identified all 7 mammographically visible lesions, including 2 malignant lesions. When compared with ultrasound, PEF correctly identified 87% (34 of 39) in this group. Of these, in women aged 40 years or younger, PEF identified 100% (19 of 19) of all ultrasound-visible lesions. CONCLUSIONS: The PEF identified abnormalities in all 39 patients who presented with breast abnormalities and did not demonstrate any false negatives that would prevent the patients from additional evaluation, which makes it a good prescreening tool. In addition, PEF demonstrated 100% sensitivity in women aged 40 years or younger, a traditionally low-risk population.

Magnetic nanoparticle-based approaches to locally target therapy and enhance tissue regeneration in vivo.

Magnetic-based systems utilizing superparamagnetic nanoparticles and a magnetic field gradient to exert a force on these particles have been used in a wide range of biomedical applications. This review is focused on drug targeting applications that require penetration of a cellular barrier as well as strategies to improve the efficacy of targeting in these biomedical applications. Another focus of this review is regenerative applications utilizing tissue engineered scaffolds prepared with the aid of magnetic particles, the use of remote actuation for release of bioactive molecules and magneto-mechanical cell stimulation, cell seeding and cell patterning.