Cardiovascular disease is the leading cause of mortality in the world. While reperfusion therapy is vital for patient survival post-heart attack, it also causes further tissue injury, known as myocardial ischemia/reperfusion (I/R) injury in clinical practice. Exploring ways to attenuate I/R injury is of clinical interest for improving post-ischemic recovery. A platelet-inspired nano-cell (PINC) that incorporates both prostaglandin E2 (PGE 2 )-modified platelet membrane and cardiac stromal cellsecreted factors to target the heart after I/R injury is introduced. By taking advantage of the natural infarct-homing ability of platelet membrane and the overexpression of PGE 2 receptors (EPs) in the pathological cardiac microenvironment after I/R injury, the PINCs can achieve targeted delivery of therapeutic payload to the injured heart. Furthermore, a synergistic treatment efficacy can be This article is protected by copyright. All rights reserved. 3 achieved by PINC, which combines the paracrine mechanism of stem cell therapy with the PGE 2 /EP receptor signaling that is involved in the repair and regeneration of multiple tissues. In a mouse model of myocardial I/R injury, intravenous injection of PINCs results in augmented cardiac function and mitigated heart remodeling, which is accompanied by the increase in cycling cardiomyocytes, activation of endogenous stem/progenitor cells, and promotion of angiogenesis. This approach represents a promising therapeutic delivery platform for treating I/R injury.

The vascularized cardiac patch strategy is promising for ischemic heart repair after myocardial infarction (MI), but current fabrication processes are quite complicated. Vascularized cardiac patches that can promote concurrent restoration of both the myocardium and vasculature at the injured site in a large animal model remain elusive. The safety and therapeutic benefits of a cardiac stromal cell patch integrated with engineered biomimetic microvessels (BMVs) were determined for treating MI. By leveraging a microfluidic method employing hydrodynamic focusing, we constructed the endothelialized microvessels and then encapsulated them together with therapeutic cardiosphere-derived stromal cells (CSCs) in a fibrin gel to generate a prevascularized cardiac stromal cell patch (BMV–CSC patch). We showed that BMV–CSC patch transplantation significantly promoted cardiac function, reduced scar size, increased viable myocardial tissue, promoted neovascularization, and suppressed inflammation in rat and porcine MI models, demonstrating enhanced therapeutic efficacy compared to conventional cardiac stromal cell patches. BMV–CSC patches did not increase renal and hepatic toxicity or exhibit immunogenicity. We noted a significant increase in endogenous progenitor cell recruitment to the peri-infarct region of the porcine hearts treated with BMV–CSC patch as compared to those that received control treatments. These findings establish the BMV–CSC patch as a novel engineered-tissue therapeutic for ischemic tissue repair.

To assess the prevalence of myofascial pain in women undergoing uncomplicated, minimally invasive hysterectomy for chronic pelvic pain, to identify clinical and demographic factors associated with preoperative myofascial pain, and examine the association between myofascial pain and postoperative pain in hysterectomy patients. Design: A retrospective cohort study. Setting: A tertiary care teaching hospital. Patients: A total of 353 adult women who underwent uncomplicated, minimally invasive hysterectomy between January 2014 and 2016. Interventions: All women underwent a preoperative pelvic floor examination. Myofascial pain was diagnosed as tenderness and reproduction of pain symptoms in at least 2 of 6 pelvic floor muscles. Demographics, comorbidities, and intraoperative characteristics were compared between women with and without preoperative myofascial pain. Measurements and Main Results: Of the 353 women who underwent hysterectomy, the prevalence of myofascial pain was 42.7% (86.0% in patients with chronic pelvic pain [CPP] compared with 13.7% without CPP). Women with myofascial pain were more likely younger, Caucasian, sexually active, and with comorbid pain conditions. Patients with myofascial pain used a greater number of adjuvant pain medications before surgery including opiates (29.5%) but were only half as likely to use muscle relaxants (12.1%) for preoperative pain control. Contrastingly, in women without myofascial pain before surgery, controlled substances such as opiates (8%, p <.01) and benzodiazepines (3%, p <.01) were used at a three-fold lower frequency. Postoperative pain score was higher in patients with myofascial pain, with 37% reporting a visual analog scale score greater than 5 at the routine postoperative visit compared with only 1% of patients without myofascial pain. Conclusion: Myofascial pelvic pain must be considered in the evaluation of CPP, especially in surgical candidates. Women with myofascial pelvic use a greater amount of pain medication preoperatively and have higher pain scores postoperatively. Identification of these high-risk patients before surgery may improve pre and postoperative pain management with a multimodal therapy approach.

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