Bioadhesion and biocompatibility evaluations of gelatin and polyacrylic acid as a crosslinked hydrogel in vitro

This study describes the potentiality of crosslinked hydrogels comprised of gelatin and polyacrylic acid (CHGP) as a biological glue for soft tissues and compares its bonding strength with that of fibrin glue. Water-soluble carbodimide (WSC) was used to crosslink the mixture of gelatin and polyacrylic acid (PAA). An addition of PAA to gelatin increases bonding strength and reduces the gelation time and WSC concentration. Increasing the gelatin, WSC and PAA concentration increases the bonding strength. There is a critical concentration to have a maximum bonding strength. The cured hydrogel exhibited sufficient adhesion to mouse skin with a higher bonding strength than fibrin glue. The in vitro test has been done for evaluating CHGP toxicity.     

The continuing important role of radionuclide generator systems for nuclear medicine

In this review, the continuing importance and status of development of radionuclide generator systems for nuclear medicine are discussed. Radioisotope costs and availability are two important factors, and both nuclear reactors and accelerator facilities are required for production of the parent radioisotopes. Radionuclide generator research is currently focused on the development of generators which provide radioisotopes for positron emission tomography (PET) applications and daughter radioisotopes for various therapeutic applications which decay primarily by particle emission. Generator research continues to be influenced by developments and requirements of complementary technologies, such as the increasing availability of PET. In addition, the availability of a wide spectrum of tumor-specific antibodies, fragments, and peptides for radio-immunodiagnosis and radioimmunotherapy has stimulated the need for generator-derived radioisotopes. The advantages of treatment of arthritis of the synovial joints with radioactive particles (radiation synovectomy) may be expected to be of increasing importance as the elderly population increases, and many of these agents are prepared using generator-derived radioisotopes such as yttrium-90 and rhenium-188. Therapeutic use of the in vivo generator is a new approach, where the less radio-toxic parent radioisotope is used to prepare tissue-speciic therapeutic agents. Following in vivo site localization, decay of the parent provides the daughter for therapy at the target site. The principal foundation of most diagnostic agents will continue to require technetium-99m from the molybdenum-99/technetium-99m (Moly) generator. With the limited availability of nuclear reactors and facilities necessary for production and processing of fission ^99mTc and the significant issues and problems associated with radioactive waste processing, however, the possibility of utilizing lower specific activity ⁹⁹Mo produced from neutron activation of enriched ⁹⁸Mo may become practical in the future. Correspondence to: RE Knapp, Jr.     

Molecular survey of ITS1 spacer and Rickettsia infection in human flea,Pulex irritans

Parasitology Research - The human flea is an important ectoparasite causing serious public health problems worldwide. Planning and monitoring the control programs against this vector require the...     

Evaluation of 225Ac for vascular targeted radioimmunotherapy of lung tumors

Several alpha particle emitting radioisotopes have been studied for use in radioimmunotherapy. Ac-225 has the potential advantages of a relatively long half life of 10 days, and a yield of 4 alpha emissions in its decay chain with a total energy release of approximately 28 MeV. A new, 12 coordination site chelating ligand, HEHA, has been chemically modified for coupling to targeting proteins without loss of chelating ability. HEHA was coupled with MAb 201B which binds to thrombomodulin and accumulates efficiently in murine lung. Ac-225 was bound to the HEHA-MAb 201B conjugate and injected into BALB/c mice bearing lung tumor colonies of EMT-6 mammary carcinoma. Biodistribution data at 1 and 4 h postinjection indicated that, as expected, 225Ac was delivered to lung efficiently (> 300% ID/g). The 225Ac was slowly released from the lung with an initial t1/2 = 49 h, and the released 225Ac accumulated in the liver. Injection of free HEHA was only partially successful in scavenging free 225Ac. In addition to the slow release of 225Ac from the chelate, data indicated that decay daughters of 225Ac were also released from the lung. Immediately after organ harvest, the level of 213Bi, the third alpha-decay daughter, was found to be deficient in the lungs and to be in excess in the kidney, relative to equilibrium values. Injected doses of 225Ac MAb 201B of 1.0 microCi, delivering a minimum calculated absorbed dose of about 6 Gy to the lungs, was effective in killing lung tumors, but also proved acutely radiotoxic. Animals treated with 1.0 microCi or more of the 225Ac radioconjugate died of a wasting syndrome within days with a dose dependent relationship. We conclude that the potential for 225Ac as a radioimmunotherapeutic agent is compromised not only by the slow release of 225Ac from the HEHA chelator, but most importantly by the radiotoxicity associated with decay daughter radioisotopes released from the target organ.     

Segmented detachable structure of cochlear-implant electrodes for close-hugging engagement with the modiolus

Surface and bulk modification techniques of polydimethylsiloxane (PDMS) polymers were used to develop a new intracochlear electrode that can closely hug the inner wall of scala tympani. Laser-induced surface grafting of poly (2-hydroxyethyl methacrylate) (PHEMA) and sequential method for preparation of interpenetrating polymer networks (IPNs) of PDMS/PHEMA were, respectively, used for surface and bulk modifications. The hydrogel content and water-uptake capability of the modified samples were optimized by Taguchi method for experimental design. The modified PDMS samples were examined by performing attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, water contact-angle measurement, and peel strength tests. The performances of actual-sized fabricated electrodes were assessed inside a transparent model of scala tympani, which was filled with saline. After a swelling process, the hydrophilic branch begins to elongate and detach from hydrophobic branch and pushes it toward the inner wall.     

A review of key challenges of electrospun scaffolds for tissue‐engineering applications

Tissue engineering holds great promise to develop functional constructs resembling the structural organization of native tissues to improve or replace biological functions, with the ultimate goal of avoiding organ transplantation. In tissue engineering, cells are often seeded into artificial structures capable of supporting three‐dimensional (3D) tissue formation. An optimal scaffold for tissue‐engineering applications should mimic the mechanical and functional properties of the extracellular matrix (ECM) of those tissues to be regenerated. Amongst the various scaffolding techniques, electrospinning is an outstanding one which is capable of producing non‐woven fibrous structures with dimensional constituents similar to those of ECM fibres. In recent years, electrospinning has gained widespread interest as a potential tissue‐engineering scaffolding technique and has been discussed in detail in many studies. So why this review? Apart from their clear advantages and extensive use, electrospun scaffolds encounter some practical limitations, such as scarce cell infiltration and inadequate mechanical strength for load‐bearing applications. A number of solutions have been offered by different research groups to overcome the above‐mentioned limitations. In this review, we provide an overview of the limitations of electrospinning as a tissue‐engineered scaffolding technique, with emphasis on possible resolutions of those issues. Copyright © 2015 John Wiley & Sons, Ltd.     

Particle size design of PLGA microspheres for potential pulmonary drug delivery using response surface methodology

The large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium are unique features of the lung facilitating systemic drug delivery via pulmonary administration. The efficacy and safety of many new and existing inhaled therapies may be enhanced through advanced controlled-release systems by using polymer particles. Poly (D,L-lactic-co-glycolic acid) (PLGA) is well known by its safety in biomedical preparations which has been approved for human use by the FDA. The optimum aerodynamic particle size distribution for most inhalation aerosols has generally been recognized to be in the range of 1-5 microns. PLGA microspheres, therefore, were prepared by a developed oil-in-oil solvent evaporation method and characterized. A four-factor, three levels Box-Behnken design was used for the optimization procedure with temperature, stirring speed, PLGA and surfactant concentration as independent variables. Particle size and polydispersity of microspheres were considered as dependent variables. PLGA microparticles were prepared successfully in desired size for pulmonary delivery by solvent evaporation method. It was found that the particle size of microspheres could be easily controlled. It was also proved that response surface methodology could efficiently be applied for size characterization and optimization of PLGA microparticles for pulmonary drug delivery.     

Bone differentiation of marrow-derived mesenchymal stem cells using beta-tricalcium phosphate-alginate-gelatin hybrid scaffolds

The aim of the present study was to establish a 3D culture system for bone differentiation of mesenchymal stem cells (MSCs), using a new hybrid sponge. To manufacture the scaffold, a composite of beta-tricalcium phosphate-alginate-gelatin was prepared and cast as pellets of 1 cm diameter. The sponge was then fabricated by drying in freeze-dryer for 12 h. The porosity, mean pore size, compressive modulus and strength of the composite sponge fabricated in this study were 89.7%, 325.3 microm, 1.82 and 0.196 MPa, respectively. To establish a 3D culture system, the rat bone marrow-derived MSCs were suspended in 500 microl diluted collagen gel, loaded into the porous sponge and provided with medium with or without osteogenic supplements for 3 weeks. The day after loading, the cells appeared in the scaffold's internal spaces, where later some of them from either culture survived by anchoring on the surfaces. At the end of cultivation period, individually adhered cells from both cultures were observed to be replaced by cell aggregates, in which mineralized matrix was detected by alizarin red staining. Furthermore, RT-PCR analysis indicated that the bone-specific gene osteocalcin was expressed in cultures in both the presence and absence of the osteogenic supplements. Taken together, it seems that the studied scaffolds are cell-compatible and, more importantly, possess some osteo-inductive properties.     

Hydrophilic interpenetrating polymer networks of poly(dimethyl siloxane) (PDMS) as biomaterial for cochlear implants

Poly(dimethyl siloxane) (PDMS) was bulk-modified to develop a new intra-cochlear electrode that can closely hug the inner wall of scala tympani (ST). The hydrophilicity of bulk and surface of PDMS was changed using a sequential method for preparation of interpenetrating polymer networks (IPNs). A series of IPNs, based on PDMS and poly(acrylic acid) (PAAc), was synthesized and characterized by means of attenuated total reflectance Fourier transform infrared spectroscopy, water contact-angle measurement, dynamic mechanical thermal analysis and peel strength tests. The performances of actual-sized fabricated electrodes were assessed inside a transparent model of ST, which was filled with saline. The cell behavior of L929 fibroblasts on materials was studied in vitro.