Conducting Informal Discovery of a Party\u27s Former Employees: Legal and Ethical Concerns and Constraints

This Article identifies and critiques existing sources of confusion in the law and proposes revised and alternative discovery procedures to provide equal access to information possessed by ex-employees, while simultaneously safeguarding the integrity of that information. Its primary emphasis is on federal jurisprudence, although important points of consensus and departure between state and federal law are noted, as appropriate. Part I explains the issues that arise in informal discovery, and the difficulties with clearly resolving those issues given the conflicting state of the law. Part II discusses application of the attorney-client privilege to communications between corporate counsel and former employees, concluding that the privilege should not shield the content of such communications from discovery by opposing counsel. Because the attorney-client privilege issue and the debate over ex parte contact both turn on whether a former employee is a party to the litigation, an exposition of the ethical concerns of ex parte contact follows in Part III, which concludes that ex parte contact by opposing counsel should be allowed. Part IV examines the applicability of the work product doctrine in shielding from discovery certain tangible materials related to the interview. This Article advocates absolute immunity from discovery for attorney notes and memoranda, and for collections of documents selected by counsel for discussion with former employees; limited discovery of signed witness statements generated pursuant to the interview; and fairly broad discovery of the content of counsel\u27s questions and statements during the interview. The proposed discovery guidelines in the Conclusion are offered with the ambitious, if not elusive, goal of reconciling the competing interests and policies that rouse litigants to battle when informal discovery is conducted of former employees, while simultaneously giving due regard to the pragmatic impact that new or revised rules may have on the litigants and the adversarial process. The overriding objective is to provide equal access by all parties to the information possessed by former employees, while at the same time providing mechanisms to deter, and if necessary to reveal, inappropriate manipulation of these potential witnesses by counsel

Biomaterials: from molecules to engineered tissue

Proceedings of BIOMED 2003, the 10th International Symposium on Biomedical Science and Technology, held October 10-12, 2003, in Northern Cyprus

Bone Tissue Engineering

The requirement for new bone to replace or restore the function of damaged or lost bone is a major clinical and social need. Bone tissue engineering has been considered as the alternative strategy to produce artificial bone grafts. The strategy of the method is to combine progenitor or mature cells isolated from desired cell source with biodegradable scaffolds to produce 3-D viable artificial bone in the laboratory conditions. Incorporation of growth factors that are regulators of cellular activities in vivo into the construct would protect these fragile molecules from degradation while sustaining their local concentration over a given period of time at the target site. Therefore, activities have been concentrated on the development of multi functional tissue engineering scaffolds capable of delivering the required bioactive agents to initiate and control cellular activities. This article reviews the recent developments in the production of functional artificial bone constructs via tissue engineering technique. [Archives Medical Review Journal 2010; 19(4.000): 206-219

Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering

WOS: 000399256500014PubMed ID: 28343005The aim of this study was to design a dermal substitute containing adipose derived stem cells (ADSC) that can be used to improve the regeneration of skin on difficult wound beds by stimulating rapid neovascularization. This was achieved by first synthesizing methacrylated gelatin (GeIMA) and methacrylated hyaluronic acid (HAMA) precursors which could be stored at -80 degrees C after lyophilisation. Polymer precursors were then dissolved in media (in 15:1 ratio), ADSCs added together with the photoinitiator and crosslinked with 40 s of W. Hydrogels degraded by 50% over 3 weeks in an in vitro environment. ADSC loaded hydrogels could be easily handled with forceps (compressive modulus was 6 kPa). Transparency of the gel would allow a full field-of-view of a wound site. The hydrogels provided a suitable microenvironment for ADSC proliferation as shown by the filopodia observed in confocal micrographs. In vivo studies demonstrated that stem cell loaded hydrogels increased vascularization by up to 3 fold compared to their cell free counterparts. In conclusion, GelMA/HAMA hydrogels loaded with ADSC showed the desired proliferative and angiogenic properties essential to promote angiogenesis for wound healing and improving survival of tissue engineered skin. (C) 2017 Elsevier Ltd. All rights reserved.Middle East Technical University Center of Excellence in Biomaterials and Tissue Engineering (BIOMATEN); TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [2211-C, 2214-A]; European Association of Urology Scholarship Programme (EUSP); Rosetrees TrustRosetrees Trust; Urology Foundation; Rosetrees TrustRosetrees Trust [M537]The authors acknowledge Middle East Technical University Center of Excellence in Biomaterials and Tissue Engineering (BIOMATEN) for the use of the facilities and for the financial support, and METU Central Laboratory for SEM analysis. The authors also acknowledge TUBITAK 2211-C and 2214-A scholarships and Menekse Ermis Sen, MD, PhD, for statistical analysis. Naside Mangir was funded by the European Association of Urology Scholarship Programme (EUSP), The Rosetrees Trust and The Urology Foundation. We thank Dr. Sabiniano Roman for providing the cultured ADSC used in this study

Nuclear targeting peptide-modified, DOX-loaded, PHBV nanoparticles enhance drug efficacy by targeting to Saos-2 cell nuclear membranes

WOS: 000424943700004PubMed ID: 29297759The aim of this study was to target nano sized (266 +/- 25nm diameter) poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) particles carrying Doxorubicin (DOX), an anticancer agent, to human osteosarcoma cells (Saos-2). A nuclear targeting molecule (Nuclear Localization Signal, NLS), a 17 a.a. peptide, was attached onto the doxorubicin loaded nanoparticles. NLS conjugated nanoparticles surrounded the cell nuclei, but did not penetrate them. Free doxorubicinand doxorubicin loadednanoparticles entered the cytoplasm and were evenly distributed within the cytoplasm. The localization of the NLS-targetedparticles around the nuclear membrane caused a significantly higher decrease in the cancer cell numbers due to apoptosis or necrosis than the untargeted and free doxorubicin formulations showing the importance of targeting the nanoparticles to the nuclear membrane in the treatment of cancer.Middle East Technical University Center of Excellence in Biomaterials and Tissue Engineering (BIOMATEN)This work was financially supported by Middle East Technical University Center of Excellence in Biomaterials and Tissue Engineering (BIOMATEN)

A bilayer scaffold prepared from collagen and carboxymethyl cellulose for skin tissue engineering applications

WOS: 000448728400008PubMed ID: 30189766Treatment of chronic skin wound such as diabetic ulcers, burns, pressure wounds are challenging problems in the medical area. The aim of this study was to design a bilayer skin equivalent mimicking the natural one to be used as a tissue engineered skin graft for use in the treatments of problematic wounds, and also as a model to be used in research related to skin, such as determination of the efficacy of transdermal bioactive agents on skin cells and treatment of acute skin damages that require immediate response. In this study, the top two layers of the skin were mimicked by producing a multilayer construct combining two different porous polymeric scaffolds: as the dermis layer a sodium carboxymethyl cellulose (NaCMC) hydrogel on which fibroblasts were added, and as the epidermis layer collagen (Coll) or chondroitin sulfate-incorporated collagen (CollCS) on which keratinocytes were added. The bilayer construct was designed to allow cross-talk between the two cell populations in the subsequent layers and achieves paracrine signalling. It had interconnected porosity, high water content, appropriate stability and elastic moduli. Expression of vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (bFGF) and Interleukin 8 (IL-8), and the production of collagen I, collagen III, laminin and transglutaminase supported the attachment and proliferation of cells on both layers of the construct. Attachment and proliferation of fibroblasts on NaCMC were lower compared to performance of keratinocyte on collagen where keratinocytes created a dense and a stratified layer similar to epidermis. The resulting constructs succesfully mimicked in vitro the natural skin tissue. They are promising as grafts for use in the treatment of deep wounds and also as models for the study of the efficacy of bioactive agents on the skin.TUBITAK through 1002 project [213M651]; Turkish Ministry of DevelopmentTurkiye Cumhuriyeti Kalkinma Bakanligi [BAP08-11-DPT-2011K120350]Authors acknowledge the support by TUBITAK through 1002 project 213M651 and Turkish Ministry of Development for the establishment of BIOMATEN through BAP08-11-DPT-2011K120350. Authors also would like to thank Prof. Seda Vatansever and Hilal Kabadayi from Celal Bayar University for their contribution in histology and immunohistochemistry analyses

A cost-effective and simple culture method for primary hepatocytes

WOS: 000288661400003Hepatocytes, the major epithelial cells of the liver, maintain their morphology in culture dishes coated with extracellular matrix (ECM) components such as collagen and fibronectin or biodegradable polymers (e.g. chitosan, gelatin). In these coated dishes, survival of cells and maintaining of liver-specific functions may increase. The aim of this study was to determine a suitable, cost-effective and simple system for hepatocyte isolation and culture which may be useful for various applications such as in vitro toxicology studies, hepatocyte transplantation and bioartificial liver (BAL) systems. In order to obtain primary cultures, hepatocytes were isolated from liver by an enzymatic method and cultured on plates coated with collagen, chitosan or gelatin. Collagen, gelatin-sandwich and gelatin-cell mixture methods were also evaluated. Morphology and attachment of the cells were observed by inverted microscope and scanning electron microscope (SEM). An MTT assay was used to determine cell viability and mitochondrial activity.Ege University Science and Technology Society (EBILTET)Ege University [E18/03/06]The authors received partial support from Ege University Science and Technology Society (EBILTET) under the Project No. E18/03/06. In addition, we are grateful to Assoc. Prof. Seda Vatansever, Dr. Feyzan Ozdal Kurt and Dr. Elgin Turkoz from Celal Bayar University for their help in the study

Biocompatibility of Dead Sea Water and retinyl palmitate carrying poly(3-hydroxybutyrate-co-3-hydroxyvalerate) micro/nanoparticles designed for transdermal skin therapy

WOS: 000360829900001In this study, novel drug carriers were developed for the treatment of skin conditions such as psoriasis, aging, or ultraviolet damage using micro/nanocapsules and micro/nanospheres of poly(3-hydroxybutyrate-co-3-hydroxyvalerate). The sizes of the particles were in the micron range and were loaded with retinyl palmitate and Dead Sea Water. In some tests, MgCl2 was used as a substitute for Dead Sea Water for accurate determination of released ions of Dead Sea Water. Encapsulation efficiency and loading of water-soluble excipients Dead Sea Water and MgCl2 were almost eight times lower than the hydrophobic compound retinyl palmitate. The particles were not cytotoxic as determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test using L929 mouse fibroblasts, BALB/3T3 mouse embryo fibroblasts, and HaCaT human keratinocytes. Ames test showed that the carriers were not genotoxic. The particles penetrated the membrane of human osteosarcoma cells Saos 2 and accumulated in their cytoplasm. No reactive oxygen species production could be detected which indicated low or no inflammatory response toward the particles. In the tests with intact human skin, 1.2% of the retinyl palmitate-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) particles penetrated into the human skin, but when the skin was without stratum corneum and increased to 6.9%. In conclusion, these carriers have shown a significant potential as topical drug delivery systems in the personalized treatment of skin diseases because their contents could be modified according to a patient's needs and several drugs could be loaded in one type of microparticle, or several populations, each carrying a different drug, can be used in the treatment.FP7-NMP "SkinTreat" project [213202-2]; METUMiddle East Technical University [BAP-07-02-2012-101-91]The research was performed within the framework of the FP7-NMP "SkinTreat" project theme under grant agreement no. 213202-2. The authors also acknowledge the support of METU through the project BAP-07-02-2012-101-91

Covalent immobilization of Aspergillus niger on pHEMA membrane: Application to continuous flow reactors

Poly(2‐hydroxyethyl methacrylate) (pHEMA) membrane was prepared via photopolymerization and activated with epichlorohydrin. The conidia of Aspergillus niger strains (wild type ‘NRRL‐3’ and genetically improved strain ‘NRRL‐3/2‐2A’) were covalently‐immobilized on the membranes. Uniform growth of A. niger cells on membrane surfaces was verified by SEM. The glucose oxidase (GOD) activity of the immobilized cells was determined in a continuous flow membrane reactor (CFMR) by assaying for hydrogen peroxide produced. The activity was also determined in the culture fluids of A. niger strains, freely grown in batch cultures. The CFMR was run with 0.1 mol dm−3 glucose with a fixed flow rate of 20 cm3 h−1 for 60 h during which a 10% loss of the original activity was detected. The loss of the activity with the freely cultivated mycelia was about 50% after 30 h. The GOD activity of the improved strain NRRL

Covalent immobilization of invertase on chemically activated poly (styrene-2-hydroxyethyl methacrylate) microbeads

HASIRCI, Nesrin/0000-0002-4497-0194WOS: 000256156800002A carrier for invertase enzyme was synthesized from styrene (S) and 2- hydroxyethyl methacrylate (HEMA) in the form of microbeads. These poly (styrene-2-hydroxyethyl methacrylate), P(S-HEMA) microbeads were activated by epichlorohydrin (ECH) treatment for covalent immobilization. The free and immobilized invertase were assayed in the hydrolysis of sucrose to glucose, and the obtained results were compared. The optimum pH was 4.5 for free and 5.5 for immobilized invertase. The optimum temperature of invertase shifted from 45C to 55C upon immobilization. For free and immobilized enzymes, kinetic parameters were calculated as 4.1 x 10(-3) mol L(-1)and 9.2 x 10(-3) mol L(-1)for K-m, and 6.6 x 10(-2) mol L-1 min(-1)and 4.1 x 10(-1) mol L-1 min(-1)for V-max, respectively. After 1 month of storage at 4C, free enzyme retained 36% of its initial activity, while for the ECH-activated P(S-HEMA) immobilized enzyme, P(S-HEMA)-E, this value was observed as 67%. In repeated batch use, i.e., 20 times in 3 days, 78% retention of the initial activity was observed for P(S-HEMA)-E system