Novel Guidewire Design and Coating for Continuous Delivery of Adenosine During Interventional Procedures.

Background The "no-reflow phenomenon" compromises percutaneous coronary intervention outcomes. There is an unmet need for a device that prevents no-reflow phenomenon. Our goal was to develop a guidewire platform comprising a nondisruptive hydrophilic coating that allows continuous delivery of adenosine throughout a percutaneous coronary intervention.

Complexation Hydrogels as Oral Delivery Vehicles of Therapeutic Antibodies: An in Vitro and ex Vivo Evaluation of Antibody Stability and Bioactivity.

Oral administration of monoclonal antibodies (mAbs) may enable the localized treatment of infections or other conditions in the gastrointestinal tract (GI) as well as systemic diseases. As with the development of oral protein biotherapeutics, one of the most challenging tasks in antibody therapies is the loss of biological activity due to physical and chemical instabilities. New families of complexation hydrogels with pH-responsive properties have demonstrated to be excellent transmucosal delivery vehicles.

Interfacial optimization of fiber-reinforced hydrogel composites for soft fibrous tissue applications.

Meniscal tears are the most common orthopedic injuries to the human body, yet the current treatment of choice is a partial meniscectomy, which is known to lead to joint degeneration and osteoarthritis. As a result, there is a significant clinical need to develop materials capable of restoring function to the meniscus following an injury. Fiber-reinforced hydrogel composites are particularly suited for replicating the mechanical function of native fibrous tissues due to their ability to mimic the native anisotropic property distribution present.

Assessing the transport of receptor-mediated drug-delivery devices across cellular monolayers.

Receptor-mediated endocytosis (RME) has been extensively studied as a method for augmenting the transport of therapeutic devices across monolayers. These devices range from simple ligand-therapeutic conjugates to complex ligand-nanocarrier systems. However, characterizing the uptake of these carriers typically relies on their comparisons to the native therapeutic, which provides no understanding of the ligand or cellular performance.

Implications of poly(N-isopropylacrylamide)-g-poly(ethylene glycol) with codissolved brain-derived neurotrophic factor injectable scaffold on motor function recovery rate following cervical dorsolateral funiculotomy in the rat.

Object: In a follow-up study to their prior work, the authors evaluated a novel delivery system for a previously established treatment for spinal cord injury (SCI), based on a poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with a polyethylene glycol (PEG) injectable scaffold. The primary aim of this work was to assess the recovery of both spontaneous and skilled forelimb function following a cervical dorsolateral funiculotomy in the rat. This injury ablates the rubrospinal tract (RST) but spares the dorsal and ventral corticospinal tract and can severely impair reaching and grasping abilities.

Aging behavior of PVA hydrogels for soft tissue applications after in vitro swelling using osmotic pressure solutions.

The osmotic pressure of the medium used for in vitro swelling evaluation has been shown to have a significant effect on the swelling behavior of a material. In this study, the effect of osmotic pressure during swelling on poly(vinyl alcohol) hydrogel material properties was evaluated in vitro. Osmotic pressure solutions are necessary in order to mimic the swelling pressure observed in vivo for soft tissues present in load-bearing joints.

A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: controlled release for cartilage tissue engineering.

Because of similar mechanical properties to native cartilage, synthetic hydrogels based on poly(vinyl alcohol) (PVA) have been proposed for replacement of damaged articular cartilage, but they suffer from a complete lack of integration with surrounding tissue. In this study, insulin-like growth factor-1 (IGF-1), an important growth factor in cartilage regeneration, was encapsulated in degradable poly(lactic-co-glycolic acid) (PLGA) microparticles embedded in the PVA hydrogels in a single step based on a double emulsion. The release of IGF-1 from these hydrogels was sustained over 6 weeks in vitro.

A pilot study of poly(N-isopropylacrylamide)-g-polyethylene glycol and poly(N-isopropylacrylamide)-g-methylcellulose branched copolymers as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord.

Object: The authors investigated the feasibility of using injectable hydrogels, based on poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with polyethylene glycol (PEG) or methylcellulose (MC), to serve as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord. The primary aims of this work were to assess the biocompatibility of the scaffolds by evaluating graft cell survival and the host tissue immune response. The scaffolds were also evaluated for their ability to promote axonal growth through the action of released brain-derived neurotrophic factor (BDNF).

Design of semi-degradable hydrogels based on poly(vinyl alcohol) and poly(lactic-co-glycolic acid) for cartilage tissue engineering.

Articular cartilage damage is a persistent challenge in biomaterials and tissue engineering. Poly(vinyl alcohol) (PVA) hydrogels have shown promise as implants, but their lack of integration with surrounding cartilage prevents their utility. We sought to combine the advantages of PVA hydrogels with poly(lactic-co-glycolic acid) (PLGA) scaffolds, which have been successful in facilitating the integration of neocartilage with surrounding tissue.

Biodegradable nanoparticles for protein delivery: analysis of preparation conditions on particle morphology and protein loading, activity and sustained release properties.

PLGA particles have been extensively used as a sustained drug-delivery system, but there are multiple drawbacks when delivering proteins. The focus of this work is to address the most significant disadvantages to the W/O/W double emulsion procedure and demonstrate that simple changes to this procedure can have significant changes to particle size and dispersity and considerable improvements to protein loading, activity and sustained active protein release. A systematic approach was taken to analyze the effects of the following variables: solvent miscibility (dichloromethane (DCM), ethyl acetate, acetone), homogenization speed (10 000-25 000 rpm), PLGA concentration (10-30 mg/ml) and additives in both the organic (sucrose acetate isobutyrate (SAIB)) and aqueous (bovine serum albumin (BSA)) phases.

Hydrogels for the repair of articular cartilage defects.

The repair of articular cartilage defects remains a significant challenge in orthopedic medicine. Hydrogels, three-dimensional polymer networks swollen in water, offer a unique opportunity to generate a functional cartilage substitute. Hydrogels can exhibit similar mechanical, swelling, and lubricating behavior to articular cartilage, and promote the chondrogenic phenotype by encapsulated cells.

Enhanced mucoadhesive capacity of novel co-polymers for oral protein delivery.

Graft co-polymer networks have shown promise as devices for oral delivery of proteins. By increasing adhesion of these networks at the delivery site of the upper small intestine by utilizing small covalent chemical linkages caused by the addition of an aldehyde functional group we can make them more viable. These aldehydes bind covalently by way of a condensation reaction with the amines of the amino acids found in the glycoprotein network of the mucus layer of the small intestine to form imines.

Analysis of the in vitro swelling behavior of poly(vinyl alcohol) hydrogels in osmotic pressure solution for soft tissue replacement.

An osmotic solution was used to evaluate poly(vinyl alcohol) (PVA) hydrogels as potential non-degradable soft tissue replacements in vitro. Osmotic solutions are necessary in order to mimic the swelling pressure observed in vivo for soft tissues present in load-bearing joints. In vitro studies indicated that PVA hydrogels experience minimal changes in swelling with a polymer concentration of 20 wt.

Mechanical evaluation of poly(vinyl alcohol)-based fibrous composites as biomaterials for meniscal tissue replacement.

In this study, poly(vinyl alcohol) (PVA) hydrogels were reinforced with ultrahigh molecular weight polyethylene (UHMWPE) and PP fibers and evaluated as potential nondegradable meniscal replacements. An investigation of hydrogel and composite mechanical properties indicates that fiber-reinforced PVA hydrogels could replicate the unique anisotropic modulus distribution present in the native meniscus; the most commonly damaged orthopedic tissue. More specifically, fibrous reinforcement successfully increased the tensile modulus of the biomaterial from 0.

Synthesis and recovery characteristics of branched and grafted PNIPAAm-PEG hydrogels for the development of an injectable load-bearing nucleus pulposus replacement.

A family of injectable poly(N-isopropyl acrylamide) (PNIPAAm) copolymer hydrogels has been fabricated in order to tune mechanical properties to support load-bearing function and dimensional recovery for possible use as load-bearing medical devices, such as a nucleus pulposus replacement for the intervertebral disc. PNIPAAm-polyethylene glycol (PEG) copolymers were synthesized with varying hydrophilic PEG concentrations as grafted or branched structures to enhance dimensional recovery of the materials. Polymerizations were confirmed with attenuated total reflectance-Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy studies.

Characterization of the behavior of porous hydrogels in model osmotically-conditioned articular cartilage systems.

The evaluation of hydrogel swelling behavior is a vital step in development of new materials for biomedical applications. Phosphate-buffered saline (PBS) is the most commonly chosen swelling medium to model hydrogel behavior in articular cartilage (AC). However, the use of PBS does not fully elucidate the osmotic pressure hydrogels will face in many tissues in vivo.

Synthesis, characterization and in vivo efficacy of PEGylated insulin for oral delivery with complexation hydrogels.

Purpose: This work evaluated the feasibility of combining insulin PEGylation with pH responsive hydrogels for oral insulin delivery.

Methods: A mono-substituted PEG-insulin conjugate was synthesized and purified. The site of conjugation was determined by MALDI-TOF MS.

In vitro analysis of PNIPAAm-PEG, a novel, injectable scaffold for spinal cord repair.

Nervous tissue engineering in combination with other therapeutic strategies is an emerging trend for the treatment of different CNS disorders and injuries. We propose to use poly(N-isopropylacrylamide)-co-poly(ethylene glycol) (PNIPAAm-PEG) as a minimally invasive, injectable scaffold platform for the repair of spinal cord injury (SCI). The scaffold allows cell attachment, and provides mechanical support and a sustained release of neurotrophins.

Semi-degradable scaffold for articular cartilage replacement.

Existing technologies have not met the challenge of designing a construct for the repair of focal cartilage defects such that it mimics the mechanical properties of and can integrate with native cartilage. Herein we describe a novel construct consisting of a non-degradable poly-vinyl alcohol (PVA) scaffold to provide long-term mechanical stability, interconnected pores to allow for the infiltration of chondrocytes, and poly-lactic glycolic acid (PLGA) microspheres for the incorporation of growth factors to enhance cellular migration. The objective of this study was to characterize the morphological features and mechanical properties of our porous PVA-PLGA construct as a function of PLGA content.

Key functions in polymer carriers for intestinal absorption of insulin.

This work aimed to clarify the relationship between polymer function and insulin absorption, and to evaluate the optimized preparative formulation predicted from this relationship. Insulin-loaded polymer (ILP) carrier systems were prepared following a two-factor composite second-order spherical experimental design. To investigate the polymer function, we evaluated its insulin release, bioadhesiveness, and protective effect.

Superporous hydrogels for cartilage repair: Evaluation of the morphological and mechanical properties.

Despite extensive research in the design of biomaterials for articular cartilage repair, there remains a need for the development of materials with the mechanical compliance to function synergistically with healthy cartilage, but porous enough to allow for tissue integration. In this study, superporous hydrogels of poly(vinyl alcohol) and poly(vinyl pyrrolidone) were prepared using a novel technique consisting of a double emulsion process. The hydrogel emulsions were physically cross-linked by freeze-thaw cycling.

Complexation hydrogels for oral protein delivery: an in vitro assessment of the insulin transport-enhancing effects following dissolution in simulated digestive fluids.

The insulin-transport enhancing effects of a pH-sensitive poly((methacrylic acid)-grafted-poly(ethylene glycol)) hydrogel system were studied using Caco-2 monolayers as an in vitro model of intestinal transport. Further, the ability of the hydrogel system to protect entrapped proteins through the upper gastrointestinal tract via digestion in simulated gastric and simulated intestinal fluids with digestive enzymes was confirmed. Caco-2 cell monolayers were exposed to a series of formulations including insulin alone, the polymer in insulin solution, insulin-loaded polymer (ILP) and ILP previously subjected to simulated digestive fluids with enzymes.

Complexation hydrogels for oral insulin delivery: effects of polymer dosing on in vivo efficacy.

Hydrogels comprised of poly(methacrylic acid) grafted with poly(ethylene glycol) (P(MAA-g-EG)) were characterized and examined for their potential as oral insulin carriers. Insulin loaded polymer (ILP) samples were made using two different polymer formulations. The values for the effective molecular weight between crosslinks, M _e , and the network mesh size, xi, were characterized and increased with increasing pH levels for both formulations.

In situ apatite forming injectable hydrogel.

Injectable polymers are attractive materials for tissue augmentation or replacement. Thermosensitive hydrogels, especially poly(N-isopropylacryamide), have been investigated for these applications to exploit the lower critical solution temperature (LCST) which falls between room and body temperatures. Some practical limitations to the material are the load-bearing capabilities and the ability to bond to the host tissue.

Quantitation of humalog insulin by reversed-phase high-performance liquid chromatography.

Introduction: The methodology for in vitro testing of insulin delivery systems for long-term infusion of lispro insulin requires insulin flow studies over time, with the measurement of lispro concentrations in wells or other laboratory fluid collection systems. We postulated that the efficiency of the insulin assay could be improved if the insulin collected in the wells could be measured without having to perform dilutions of insulin samples. The manufacturer's method for the identification of Humalog(R) insulin by high-performance liquid chromatography (HPLC) does not provide a detailed method for the quantitation of the clinical formulation.