Bioengineered endometrial hydrogels with growth factors promote tissue regeneration and restore fertility in murine models.

Extracellular matrix (ECM) hydrogels obtained from decellularized tissues are promising biocompatible materials for tissue regeneration. These biomaterials may provide important options for endometrial pathologies such as Asherman's syndrome and endometrial atrophy, which lack effective therapies thus far. First, we performed a proteomic analysis of a decellularized endometrial porcine hydrogel (EndoECM) to describe the specific role of ECM proteins related to regenerative processes. Furthermore, we investigated the ability of a bioengineered system-EndoECM alone or supplemented with growth factors (GFs)-to repair the endometrium in a murine model of endometrial damage. For this model, the uterine horns of female C57BL/6 mice were first injected with 70% ethanol, then four days later, they were treated with: saline (negative control); biotin-labeled EndoECM; or biotin-labeled EndoECM plus platelet-derived GF, basic fibroblast GF, and insulin-like GF 1 (EndoECM+GF). Endometrial regeneration and fertility restoration were evaluated by assessing the number of glands, endometrial area, cell proliferation, neaoangiogenesis, reduction of collagen deposition, and fertility restoration. Interestingly, regenerative effects such as an increased number of endometrial glands, increased area, high cell proliferative index, development of new blood vessels, reduction of collagen deposition, and higher pregnancy rate occurred in mice treated with EndoECM+GF. Thus, a bioengineered system based on EndoECM hydrogel supplemented with GFs may be promising for the clinical treatment of endometrial conditions such as Asherman's syndrome and endometrial atrophy. STATEMENT OF SIGNIFICANCE: In the last years, the bioengineering field has developed new and promising approaches to regenerate tissues or replace damaged and diseased tissues. Bioengineered hydrogels offer an ideal option because these materials can be used not only as treatments but also as carriers of drugs and other therapeutics. The present work demonstrates for the first time how hydrogels derived from pig endometrium loaded with growth factors could treat uterine pathologies in a mouse model of endometrial damage. These findings provide scientific evidence about bioengineered hydrogels based on tissue-specific extracellular matrix offering new options to treat human infertility from endometrial causes such as Asherman's syndrome or endometrial atrophy.

Ciprofloxacin prophylaxis in patients with acute leukemia and granulocytopenia in an area with a high prevalence of ciprofloxacin-resistant Escherichia coli.

BACKGROUND: Infection remains the major cause of morbidity and mortality in patients with neutropenia, and the beneficial effects of oral prophylaxis remain controversial. METHODS: From 1993 to December 1999, the authors analyzed the clinical and microbiologic outcomes of 144 episodes of febrile neutropenia among adult patients with acute leukemia. RESULTS: Forty-three consecutive episodes occurred among patients who were on ciprofloxacin prophylaxis during 1993-1996 (ciprofloxacin group), and 101 subsequent episodes occurred among patients who were not exposed to ciprofloxacin prophylaxis (control group). There were no differences in clinical presentation, antibiotic treatment received for the episode, or a worse outcome between groups. The rate of bacteremia was similar (12 of 43 patients [28%] vs. 26 of 101 patients [26%], respectively). There was a trend toward a higher rate of Gram positive bacteremia in the control group (12 of 101 patients [12%] vs. 2 of 43 patients [5%]) and a higher rate of Gram negative bacteremia in the ciprofloxacin group (11 of 43 patients [26%] vs. 15 of 101 patients [15%]). Resistance to fluoroquinolones was greater in Escherichia coli blood isolates from patients in the ciprofloxacin group (7 of 8 patients vs. 2 of 9 patients; P = 0.02). CONCLUSIONS: The current results suggest that fluoroquinolone prophylaxis for patients with febrile neutropenia may be abandoned safely in areas with a high prevalence of ciprofloxacin-resistant enterobacteria.