Impact of Secondary Reactive Species on the Apparent Decoupling of Poly(Ethylene Glycol) Diacrylate Hydrogel Average Mesh Size and Modulus

Poly(ethylene glycol) diacrylate (PEGDA) hydrogels are widely used in biotechnology due to their in situ crosslinking capacity and tunable physical properties. However, as with all single component hydrogels, the modulus of PEGDA networks cannot be tailored independently of mesh size. This interdependence places significant limitations on their use for defined, 3D cell-microenvironment studies and for certain controlled release applications. The incorporation of secondary reactive species (SRS) into PEGDA hydrogels has previously been shown to allow the identification of up to 6 PEGDA hydrogel formulations for which distinct moduli can be obtained at consistent average mesh size (or vice versa). However, the modulus and mesh size ranges which can be probed by these formulations are quite restricted. This work presents an in-depth study of SRS incorporation into PEGDA hydrogels, with the goal of expanding the space for which decoupled examination of modulus and mesh size effects is achievable. Towards this end, over 100 PEGDA hydrogels containing either N-vinyl pyrrolidone or star PEG-tetraacrylate as SRS were characterized. To our knowledge, this is the first study to demonstrate that SRS incorporation allows for the identification of a number of modulus ranges that can be probed at consistent average mesh size (or vice versa)

Collagen-Mimetic Hydrogels Promote Human Endothelial Cell Adhesion, Migration and Phenotypic Maturation

This work evaluates the response of human aortic endothelial cells (HAECs) to thromboresistant collagen-mimetic hydrogel coatings toward improving the biocompatibility of existing off-the-shelf small-caliber vascular grafts. Specifically, bioactive hydrogels-previously shown to support α1/α2 integrin-mediated cell adhesion but to resist platelet activation-were fabricated by combining poly(ethylene glycol) (PEG) with a 120 kDa, triple-helical collagen-mimetic protein (Scl2-2) containing the GFPGER adhesion sequence. Analysis of HAECs seeded onto the resulting PEG-Scl2-2 hydrogels demonstrated that HAEC adhesion increased with increasing Scl2-2 concentration, while HAEC migration rate decreased over this same concentration range. In addition, evaluation of HAEC phenotype at confluence indicated significant differences in the gene expression of NOS3, thrombomodulin, and E-selectin on the PEG-Scl2-2 hydrogels relative to PEG-collagen controls. At the protein level, however, only NOS3 was significantly different between the PEG-Scl2-2 and PEG-collagen surfaces. Furthermore, PECAM-1 and VE-cadherin expression on PEG-Scl2-2 hydrogels versus PEG-collagen controls could not be distinguished at either the gene or protein level. Cumulatively, these data indicate the PEG-Scl2-2 hydrogels warrant further investigation as off-the-shelf graft coatings. In future studies, the Scl2-2 protein can potentially be modified to include additional extracellular matrix or cytokine binding sites to further improve endothelial cell responses

PERIOPERATIVE AND ONCOLOGICAL OUTCOMES IN HIGH RISK ELDERLY PATIENTS

Aim of the study ontroversy continues to exist concerning the treatment of choice for D\u2019Amico high risk elderly patients. The purpose of this study is to compare the perioperative and oncologic outcomes of robotic assisted radical prostatectomy (RARP) in D\u2019Amico high risk, propensity score-matched elderly and younger cohorts. Materials and methods From January 2008 through August 2012, 3818 patients underwent RARP at our institution by a single surgeon (VP). Retrospective analysis of prospectively collected data from our Institutional Review Board approved registry identified 80 D\u2019Amico high risk patients, 70 years of age and over. A propensity scorematch analysis was conducted using multivariable analysis to compare elderly patients (age 70 and over) to those under 70. The final two study cohorts \u2013 D\u2019Amico high risk elderly patients (n=80) and D\u2019Amico high risk younger patients (n=80) constituted the clinical material for this comparative study of perioperative and oncologic outcomes. Results Preoperative clinical characteristics were similar for the two matched groups. The operative time, transfusion rate and intra-operative complications were similar for the two groups.The mean estimated blood loss was significantly greater in younger patients (156.1 \ub1 84.2 mLvs 113.6 \ub1 67.7; p=0.002). No significant differences were observed in laterality, ease of nerve sparing or surgeon subjectively assessed anastomosis and pathological outcomes between the groups. No significant differences were found in postoperative complication rates, overall pain scores, length of stay or duration of indwelling catheterization. At follow-up, freedom from biochemical recurrence (BCR) in elderly patients was 85.0% vs. 83.8% in younger patients. The mean time to BCR in elderly patients was 15.0 months (range, 2.3 to 38.8) and 14.5 months (range, 5.2 to 35.1) in younger patients. Discussion Conclusions This study clearly demonstrates that RARP can be performed in D\u2019Amico high risk elderly patients without increasing perioperative morbidity and with oncologic outcomes comparable to high risk younger patients. RARP in elderly patients presenting with localized prostate cancer should be considered a viable treatment alternative based on the individual\u2019s life expectancy

3D printing for the development of in vitro cancer models

In vitro engineering of tumor milieus is complex because cancer progression and metastasis involve spatio-temporally evolving cell-matrix interactions, myriad interactions between tumor cells and auxiliary cells, hypoxic cores, leaky unorganized vasculature and a host of signaling molecules. Recent advances in 3D printing approaches enable the precise placement of cells, bioactive factors and biomaterials, thus permitting the recapitulation of several features associated with the in vivo tumor microenvironment. 3D printed in vitro tumor models can serve as robust platforms to study mechanisms of disease progression, enable high throughput screening of drugs and aid the development of next generation molecular therapies. This focused review discusses the importance and relevance of 3D printing technologies in building 3D tumor models in vitro. Several recent 3D printed cancer models are discussed, as also the evolution and features of next-generation models

Experimental investigation of instabilities in charged polymer solutions

Electrospinning is a process that utilizes electric fields to create non-woven fibrous matrices. The main goal of the work is to determine the effect of potential drop

Fabrication of electrospun meshes from natural polymers for biomedical applications

Diabetic retinopathy (DR) involves a progressively worsening cycle of microglial cell activation and inflammation that leads to severe retinal damage. While the inflammatory nature of DR is well-established, the exact role of microglial cells in contributing to disease progression is not clear. Towards the long-term goal of creating in vitro platforms to understand microglial cells responses in health/disease, the objective of this work is to create electrospun substrates from natural polymers with systematically varying properties for the in vitro culture of microglial cells. Accordingly, gelatin and composite nanofibers with different diameters and architectures were successfully electrospun. Increasing the concentration of gelatin in solution resulted in a slight increase in fiber diameter. Concurrently, a 10% (w/v) gelatin solution was mixed with 10% polycaprolactone (PCL) solution at a ratio of 50:50 and electrospun to produce gelatin/ PCL composite nanofibers. In a parallel study, fiber architecture was varied by changing the collector geometry. While randomly oriented gelatin and PCL fibers (with angular standard deviation >50°) were generated by electrospinning onto a flat plate collector, semi-aligned (with angular standard deviation >30°) and highly aligned fibers (with angular standard deviation <20°) were collected by using a drum collector rotating at 750 rpm and 1500 rpm respectively. To improve the stability of gelatin in aqueous environments, nanofibers were crosslinked with glutaraldehyde (GTA) vapor at room temperature for different time periods, namely 2h, 6h, 12h and 24h. While the non-crosslinked control fibers almost entirely degraded within 1 day of exposure to aqueous buffer at 37 °C, fibers crosslinked with GTA for 2h or more remained stable for at least four days in buffer, indicating that 2h was sufficient to retard degradation. Culture of primary mixed retinal cells on randomly oriented and aligned fibers resulted in randomly oriented and highly aligned vimentin and cell nuclei. In summary, the work demonstrates that the properties of gelatin meshes can be changed by systematically varying electrospinning parameters. In the future, the effects of fiber diameter and chemistry on cell phenotypic activation will be studied. Furthermore, fibers will be tethered with cytokines that can be released in a controlled manner through fiber degradation

Bladder Cancer After Radiotherapy for Prostate Cancer: Detailed Analysis of Pathological Features and Outcome After Radical Cystectomy

We reviewed outcomes and features in patients with bladder cancer who underwent cystectomy and had a history of radiation for prostate cancer. We performed a retrospective analysis of the University of Miami cystectomy database and identified 34 patients with a history of radiotherapy for prostate cancer. An age and stage matched control group was used to compare survival. Our entire male cystectomy population was used to compare clinicopathological features. Mean age in the 34 patients with cystectomy was 75 years with a mean latency of 5 years from prostate cancer radiation. Radiotherapy was the primary treatment modality for prostate cancer in 32 of 34 patients and 2 received adjuvant radiation. Of the patients 86% received external beam radiation. Hematuria was the initial symptom in 86% of the cases. In 53% of the patients the initial diagnosis was muscle invasive bladder cancer. An ileal conduit was the method of urinary diversion in 33 cases. Major perioperative complications developed in 9% of the patients. There was 1 perioperative death, resulting in a mortality rate of 2.9%. Of the patients 54% presented with a locally advanced (pT3-4) tumor. Patients with a history of radiation therapy for prostate cancer had significantly poorer overall and bladder cancer specific survival than the matched control group. Most bladder cancers in patients with a history of radiation for prostate cancer present as locally advanced tumors and patients have poorer survival than age and stage matched controls

Current Status Of Various Neurovascular Bundle-Sparing Techniques In Robot-Assisted Radical Prostatectomy

Nerve-sparing procedures during robot-assisted radical prostatectomy (RARP) have demonstrated improved postoperative functional outcomes. This article provides an overview of clinically applied prostatic neuro-anatomy, various techniques of nerve sparing (NS), and recent innovations in NS and potency outcomes of NS RARP. We retrieved and reviewed all listed publications within PubMed using keywords: nerve sparing, robotic radical prostatectomy, prostate cancer, outcomes, pelvic neuroanatomy and potency. Studies reporting potency outcomes of NS RARP (comparative and non-comparative) were analysed using the Delphi method with an expert panel of urological robotic surgeons. Herein, we outline the published techniques of NS during RARP. Potency and continence outcomes of individual series are discussed in light of the evidence provided by case series and published trials. The potency outcomes of various comparative and non-comparative series of NS RARP have also been mentioned. There are numerous NS techniques reported for RARP. Each method is complimented with benefits and constrained by idiosyncratic caveats, and thus, careful patient selection, a wise intraoperative clinical judgment and tailored approach for each patient is required, when decision for nerve sparing is made. Further large prospective multi-institutional randomized controlled trials are required to evaluate potency and continence outcomes of these techniques, using a rigid standard patient selection criteria and definition of potency are warranted in the new era of functional outcome-driven research