Vascularization and tissue infiltration of a biodegradable polyurethane matrix

Urethanes are frequently used in biomedical applications because of their excellent biocompatibility. However, their use has been limited to bioresistant polyurethanes. The aim of this study was to develop a nontoxic biodegradable polyurethane and to test its potential for tissue compatibility. A matrix was synthesized with pentane diisocyanate (PDI) as a hard segment and sucrose as a hydroxyl group donor to obtain a microtextured spongy urethane matrix. The matrix was biodegradable in an aqueous solution at 37 degrees C in vitro as well as in vivo. The polymer was mechanically stable at body temperatures and exhibited a glass transition temperature (Tg) of 67 degrees C. The porosity of the polymer network was between 10 and 2000 microm, with the majority of pores between 100 and 300 microm in diameter. This porosity was found to be adequate to support the adherence and proliferation of bone-marrow stromal cells (BMSC) and chondrocytes in vitro. The degradation products of the polymer were nontoxic to cells in vitro. Subdermal implants of the PDI-sucrose matrix did not exhibit toxicity in vivo and did not induce an acute inflammatory response in the host. However, some foreign-body giant cells did accumulate around the polymer and in its pores, suggesting its degradation is facilitated by hydrolysis as well as by giant cells. More important, subdermal implants of the polymer allowed marked infiltration of vascular and connective tissue, suggesting the free flow of fluids and nutrients in the implants. Because of the flexibility of the mechanical strength that can be obtained in urethanes and because of the ease with which a porous microtexture can be achieved, this matrix may be useful in many tissue-engineering applications.     

Angiopoietins as promising biomarkers and potential therapeutic targets in brain injury

Traumatic brain injury (TBI) and sub-arachnoid hemorrhage (SAH) are major causes of long-term disability, mortality, and enormous economic costs to society. The full spectrum of neurological damage created by TBI or SAH is not usually manifested at the time of injury, but evolves gradually over the course of hours to days (or weeks) following these injuries. Angiopoietins, important regulators of vascular structure and function, are hallmark indicators of vascular injury and may therefore represent promising targets in the treatment of SAH and TBI. In animal models and human tissues, normal intracerebral and pial vessels show strong expression of Angiopoietin-1 (Ang-1), but only minimal expression or presentation of Angiopoietin-2 (Ang-2). After several types of neurotrauma, the ratios of Ang-1 and Ang-2 expression in brain microvessel are disturbed and appear to contribute to the remarkable loss of blood–brain barrier (BBB) in these injuries. Angiopoietins levels, and perhaps more importantly, Angiopoietin ratios (1:2) may have novel and important diagnostic and prognostic uses in TBI and SAH brain injury. Ang-1/2 evaluation in plasma, serum and cerebrospinal fluid may provide new therapeutic modalities which can modify ‘secondary’ forms of brain injury after TBI and SAH.     

Primary anterior cruciate ligament reconstruction: perioperative considerations and complications

Anterior cruciate ligament (ACL) injuries are among the most commonly studied orthopaedic injuries. Despite having an excellent prognosis, complications do occur. The timely recognition and management of complications is imperative to ensure the success of reconstruction. Avoiding such complications requires thorough preoperative planning, proficient technical skills to properly manage intraoperative complications, and an extensive knowledge of possible postoperative complications.     

History,indications, and advantages of orthopaedic operating room tables: a review

European Journal of Orthopaedic Surgery & Traumatology - Although surgical procedures have been occurring as early at 6500 BC, the modern sense of the operating room (OR) did not exist until...     

Development of EGFR-Targeted Nanoemulsion for Imaging and Novel Platinum Therapy of Ovarian Cancer

Purpose

Platinum-based chemotherapy is the treatment of choice for malignant epithelial ovarian cancers, but generalized toxicity and platinum resistance limits its use. Theranostic nanoemulsion with a novel platinum prodrug, myrisplatin, and the pro-apoptotic agent, C₆-ceramide, were designed to overcome these limitations.

Methods

The nanoemulsions, including ones with an EGFR binding peptide and gadolinium, were made using generally regarded as safe grade excipients and a high shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3, A2780 and A2780_CP.

Results

The nanoemulsion with particle size <150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and EGFR-targeted nanoemulsions; improved cytotoxicity was observed for the these nanoemulsions with the latter showing a 50-fold drop in the IC₅₀ in SKOV3 cells as compared to cisplatin alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist^®.

Conclusion

The myrisplatin/C₆-ceramide nanoemulsion synergistically enhanced in vitro cytotoxicity. An EGFR binding peptide addition further increased in vitro cytotoxicity in EGFR positive cancer cells. The diagnostic version showed MR imaging similar to the clinically relevant Magnevist® and may be suitable as a theranostic for ovarian cancer.     

Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields

The use of stents for vascular disease has resulted in a paradigm shift with significant improvement in therapeutic outcomes. Polymer-coated drug-eluting stents (DES) have also significantly reduced the incidence of reobstruction post stenting, a disorder termed in-stent restenosis. However, the current DESs lack the capacity for adjustment of the drug dose and release kinetics to the disease status of the treated vessel. We hypothesized that these limitations can be addressed by a strategy combining magnetic targeting via a uniform field-induced magnetization effect and a biocompatible magnetic nanoparticle (MNP) formulation designed for efficient entrapment and delivery of paclitaxel (PTX). Magnetic treatment of cultured arterial smooth muscle cells with PTX-loaded MNPs caused significant cell growth inhibition, which was not observed under nonmagnetic conditions. In agreement with the results of mathematical modeling, significantly higher localization rates of locally delivered MNPs to stented arteries were achieved with uniform-field–controlled targeting compared to nonmagnetic controls in the rat carotid stenting model. The arterial tissue levels of stent-targeted MNPs remained 4- to 10-fold higher in magnetically treated animals vs. control over 5 days post delivery. The enhanced retention of MNPs at target sites due to the uniform field-induced magnetization effect resulted in a significant inhibition of in-stent restenosis with a relatively low dose of MNP-encapsulated PTX (7.5 μg PTX/stent). Thus, this study demonstrates the feasibility of site-specific drug delivery to implanted magnetizable stents by uniform field-controlled targeting of MNPs with efficacy for in-stent restenosis.     

An unusual presentation of metastatic testicular tumour

We report a unique case of metastatic malignant teratoma from an undescended testis which presented with acute pulmonary embolism. After chemotherapy, the undescended right testicle was resected along with a cord of non- obstructing inferior venal caval tumour which extended into the right atrium with tumour floating free within the atrium at the end of the cord of tumour. The presentation, diagnosis and treatment of testicular tumours is described and the literature pertaining to testicular tumours in military personnel reviewed.     

Caecocystoplasty for intractable interstitial cystitis: long-term results

OBJECTIVE: To evaluate the role of orthotopic substitution caecocystoplasty in intractable interstitial cystitis refractory to conservative measures by looking at long-term follow-up results. PATIENTS AND METHODS: We present a retrospective review of eleven patients who underwent a trigone-preserving orthotopic substitution caecocystoplasty for intractable classical interstitial cystitis. All patients received conservative treatment for a mean period of three years. They were followed up for a mean period of nine years (range 4-14 years) with evaluation of symptoms, biochemistry, ultrasound scan and flexible cystoscopy. RESULTS: Symptomatic relief was universal with an increase of bladder capacity to normal. There was no mortality and the postoperative morbidity was minimal. Intermittent self-catheterisation due to high residual volumes was necessary in two patients. There was no significant urinary reflux or metabolic complications noted. Two patients required a cystectomy after four and six years respectively due to recurrent trigonal disease in one and urethro-trigonal hypersensitivity following intermittent self-catheterisation in the other patient. One patient developed an advanced adenocarcinoma in the caecal segment seven years following the primary operation. CONCLUSION: A sustained relief of symptoms is noted after trigone-preserving orthotopic substitution caecocystoplasty in intractable classical interstitial cystitis. It may not be appropriate in patients with urethro-trigonal disease or hypersensitivity. There is low long-term morbidity due to the operation but is associated with malignancy in the augmentate. Long-term follow-up is necessary to identify malignant change in the bladder.