Enhanced femoral nerve regeneration after tubulization with a tyrosine-derived polycarbonate terpolymer: effects of protein adsorption and independence of conduit porosity.

Following complete nerve transection, entubulation of the nerve stumps helps guide axons to reconnect distally. In this study, a biodegradable and noncytotoxic tyrosine-derived polycarbonate terpolymer composed of 89.5 mol% desaminotyrosyl tyrosine ethyl ester (DTE), 10 mol% desaminotyrosyl tyrosine (DT), and 0.

Functionalized nanospheres for targeted delivery of paclitaxel.

Targeted delivery of anti-cancer agents to cancer cells is a mature line of investigation that has yet to realize its full potential. In this study we report on the development of a delivery platform with the future goal of merging two thus far parallel methods for selective elimination of cancer cells: targeted nanospheres and pretargeted radioimmunotherapy. Several clinical trials have shown the promise of pretargeted radioimmunotherapy, which leverages the specificity of antibodies for targeted cell populations and delivers a localized dose of a biotinylated radionuclide that is most often administered following binding of a biotinylated antibody and streptavidin (StA) to the target cells.

Tyrosine-derived polycarbonate-silica xerogel nanocomposites for controlled drug delivery.

Biodegradable polymer-ceramic composites offer significant potential advantages in biomedical applications where the properties of either polymers or ceramics alone are insufficient to meet performance requirements. Here we demonstrate the highly tunable mechanical and controlled drug delivery properties accessible with novel biodegradable nanocomposites prepared by non-covalent binding of silica xerogels and co-polymers of tyrosine-poly(ethylene glycol)-derived poly(ether carbonate). The Young's moduli of the nanocomposites exceed by factors of 5-20 times those of the co-polymers or of composites made with micron scale silica particles.

Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases.

Human skin not only functions as a permeation barrier (mainly because of the stratum corneum layer) but also provides a unique delivery pathway for therapeutic and other active agents. These compounds penetrate via intercellular, intracellular, and transappendageal routes, resulting in topical delivery (into skin strata) and transdermal delivery (to subcutaneous tissues and into the systemic circulation). Passive and active permeation enhancement methods have been widely applied to increase the cutaneous penetration.

Ethylene oxide's role as a reactive agent during sterilization: effects of polymer composition and device architecture.

Sterilization conditions need to be optimized to effectively neutralize the bioburden while using short exposure times for minimizing the changes in chemical composition, material properties and device architecture. Towards this goal, effects of ethylene oxide (EtO) exposure parameters such as time, temperature, humidity, and EtO concentration on the polymer properties were investigated by monitoring the changes in composition, and the morphology of different types of structures in a family of poly(ethylene glycol) (PEG)-containing tyrosine-derived polycarbonates. EtO was found to esterify the carboxyl groups present in the desaminotyrosyl-tyrosine groups.

One-step synthesis of biodegradable curcumin-derived hydrogels as potential soft tissue fillers after breast cancer surgery.

A one-step synthesis of a curcumin-derived hydrogel (curcumin content of 25-75 mol %) is reported. Curcumin is incorporated into the hydrogel backbone and cross-linked through biodegradable carbonate linkages. Curcumin as a part of the polymer backbone is protected from oxidation and degradation, while hydrogel hydrolysis results in the release of active curcumin.

Multiscale analysis of water uptake and erosion in biodegradable polyarylates.

The role of hydration in degradation and erosion of materials, especially biomaterials used in scaffolds and implants, was investigated by studying the distribution of water at length scales from 0.1 nm to 0.1 mm using Raman spectroscopy, small-angle neutron scattering (SANS), Raman confocal imaging, and scanning electron microscopy (SEM).

Study of nanoscale structures in hydrated biomaterials using small-angle neutron scattering.

Distribution of water in three classes of biomedically relevant and degradable polymers was investigated using small-angle neutron scattering. In semicrystalline polymers, such as poly(lactic acid) and poly(glycolic acid), water was found to diffuse preferentially into the non-crystalline regions. In amorphous polymers, such as poly(d,l-lactic acid) and poly(lactic-co-glycolic acid), the scattering after 7 days of incubation was attributed to water in microvoids that form following the hydrolytic degradation of the polymer.

Gas-Foamed Scaffold Gradients for Combinatorial Screening in 3D.

Current methods for screening cell-material interactions typically utilize a two-dimensional (2D) culture format where cells are cultured on flat surfaces. However, there is a need for combinatorial and high-throughput screening methods to systematically screen cell-biomaterial interactions in three-dimensional (3D) tissue scaffolds for tissue engineering. Previously, we developed a two-syringe pump approach for making 3D scaffold gradients for use in combinatorial screening of salt-leached scaffolds.

Hydration-induced phase separation in amphiphilic polymer matrices and its influence on voclosporin release.

Voclosporin is a highly potent, new cyclosporine-A derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. We therefore selected it as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption.

Tissue engineered human skin equivalents.

Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening.

Paclitaxel in tyrosine-derived nanospheres as a potential anti-cancer agent: in vivo evaluation of toxicity and efficacy in comparison with paclitaxel in Cremophor.

Paclitaxel (PTX) has gained widespread clinical use yet its administration is associated with significant toxicity. In the present study, the toxicity and anti-tumor efficacy of tyrosine-derived nanospheres (NSP) for the delivery of PTX was compared to a clinical formulation of PTX in PBS-diluted Cremophor® EL (PTX-CrEL-D). Maximum tolerated dose was determined using a concentration series of PTX in NSP and CrEL-D, with toxicity assessed by measuring changes in body weight.

The fiber diameter of synthetic bioresorbable extracellular matrix influences human fibroblast morphology and fibronectin matrix assembly.

Background: The ideal scaffold material should provide immediate capacity to bear mechanical loads and also permit eventual resorption and replacement with native tissue of similar mechanical integrity. Scaffold characteristics such as fiber diameter provide environmental cues that can influence cell function and differentiation. In this study, the impact of fiber diameter of scaffolds constructed from a tyrosine-based bioresorbable polymer on cellular response was investigated.

The fate of ultrafast degrading polymeric implants in the brain.

We have recently reported on an ultrafast degrading tyrosine-derived terpolymer that degrades and resorbs within hours, and is suitable for use in cortical neural prosthetic applications. Here we further characterize this polymer, and describe a new tyrosine-derived fast degrading terpolymer in which the poly(ethylene glycol) (PEG) is replaced by poly(trimethylene carbonate) (PTMC). This PTMC containing terpolymer showed similar degradation characteristics but its resorption was negligible in the same period.

Logical Analysis of Data in Structure-Activity Investigation of Polymeric Gene Delivery.

To date semi-empirical or surrogate modeling has demonstrated great success in the prediction of the biologically relevant properties of polymeric materials. For the first time, a correlation between the chemical structures of poly(β-amino esters) and their efficiency in transfecting DNA was established using the novel technique of logical analysis of data (LAD). Linear combination and explicit representation models were introduced and compared in the framework of the present study.

Ultrafast resorbing polymers for use as carriers for cortical neural probes.

We have identified a polymeric system based on a novel tyrosine-derived terpolymer that offers desirable insertion capability for flexible neural prosthetic devices. To test this concept, flexible films were coated with this terpolymer and their suitability for peranchyma insertion was visualized. The effect of the polymer on neural recording was evaluated using coated microwire probes.

Control of surface chemistry, substrate stiffness, and cell function in a novel terpolymer methacrylate library.

A focused library of methacrylate terpolymers was synthesized to explore the effects of varying surface chemistry and adhesive peptide ligands on cell function. The chemical diversity of methacrylate monomers enabled construction of a library of polymers in which one can systematically vary the chemical composition to achieve a wide range of contact angle, Young's modulus, and T(g) values. Furthermore, the materials were designed to allow surface immobilization of bioactive peptides.

Plasma-micropatterning of albumin nanoparticles: Substrates for enhanced cell-interactive display of ligands.

The authors demonstrate a novel, efficient, and widely applicable approach to direct the patterning of ligand-functionalized organic nanoparticles derived from albumin on nonconductive, biodegradable polymeric substrates. In contrast to traditional deposition methods for inorganic nanoparticles, the approach involves oxygen plasma treatment of spatially restricted regions on a nonbiopermissive polymer. Albumin nanoparticles conjugated with a truncated fragment of fibronectin containing the Arg-Gly-Asp domain were successfully patterned and used as templates to elicit adhesion and spreading of human mesenchymal stem cells and fibroblasts.

Designing tyrosine-derived polycarbonate polymers for biodegradable regenerative type neural interface capable of neural recording.

Next-generation neuroprosthetic limbs will require a reliable long-term neural interface to residual nerves in the peripheral nervous system (PNS). To this end, we have developed novel biocompatible materials and a fabrication technique to create high site-count microelectrodes for stimulating and recording from regenerated peripheral nerves. Our electrodes are based on a biodegradable tyrosine-derived polycarbonate polymer system with suitable degradation and erosion properties and a fabrication technique for deployment of the polymer in a porous, degradable, regenerative, multiluminal, multielectrode conduit.

Topical drug delivery by a polymeric nanosphere gel: Formulation optimization and in vitro and in vivo skin distribution studies.

Tyrosine-derived nanospheres have demonstrated potential as effective carriers for the topical delivery of lipophilic molecules. In this investigation, a gel formulation containing nanospheres was developed for effective skin application and enhanced permeation. Carbopol and HPMC hydrophilic gels were evaluated for dispersion of these nanospheres.

UV laser-ablated surface textures as potential regulator of cellular response.

Textured surfaces obtained by UV laser ablation of poly(ethylene terephthalate) films were used to study the effect of shape and spacing of surface features on cellular response. Two distinct patterns, cones and ripples with spacing from 2 to 25 μm, were produced. Surface features with different shapes and spacings were produced by varying pulse repetition rate, laser fluence, and exposure time.

Microphase separation in copolymers of hydrophilic PEG blocks and hydrophobic tyrosine-derived segments using simultaneous SAXS/WAXS/DSC.

Hydration- and temperature-induced microphase separations were investigated by simultaneous small- and wide-angle X-ray scattering (SAXS and WAXS) and differential scanning calorimetry (DSC) in a family of copolymers in which hydrophilic poly(ethylene glycol) (PEG) blocks are inserted randomly into a hydrophobic polymer made of either desaminotyrosyl-tyrosine ethyl ester (DTE) or iodinated I(2)DTE segments. Iodination of the tyrosine rings in I(2)DTE increased the X-ray contrast between the hydrophobic and hydrophilic segments in addition to facilitating the study of the effect of iodination on microphase separation. The formation of phase-separated, hydrated PEG domains is of considerable significance as it profoundly affects the polymer properties.

Monitoring the viscoelastic properties of skin in liquid environments using quartz crystal microbalance.

Quartz crystal microbalance (QCM) with dissipation can be used to measure the response of the human stratum corneum (SC) attached to the QCM crystal, as it adsorbs or desorbs active ingredients from a liquid medium. The method was demonstrated with the sorption of poly(diallyl dimethyl ammonium chloride), a cationic polymer widely used in formulations for topical and transdermal applications. Using 14-mm diameter SC coupons attached to the QCM crystals with an adhesive, up to five overtones (up to 11th harmonic) were obtained and the response was analyzed using a Voigt model.