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Central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia, used to prevent disease recurrence in the brain, is essential for survival. Systemic and intrathecal methotrexate, commonly used for CNS-directed treatment, have been associated with cognitive problems during and after treatment. The cortex, hippocampus, and caudate putamen, important brain regions for learning and memory, may be involved in methotrexate-induced brain injury. Objectives of this study were to (1) quantify neuronal degeneration in selected regions of the cortex, hippocampus, and caudate putamen and (2) measure changes in the expression of genes with known roles in oxidant defense, apoptosis/inflammation, and protection from injury. Male Sprague Dawley rats were administered 2 or 4 mg/kg of methotrexate diluted in artificial cerebrospinal fluid (aCSF) or aCSF only into the left cerebral lateral ventricle. Gene expression changes were measured using customized reverse transcription (RT)2 polymerase chain reaction arrays. The greatest percentage of degenerating neurons in methotrexate-treated animals was in the medial region of the cortex; percentage of degenerating neurons in the dentate gyrus and cornu ammonis 3 regions of the hippocampus was also greater in rats treated with methotrexate compared to perfusion and vehicle controls. There was a greater percentage of degenerating neurons in the inferior cortex of control versus methotrexate-treated animals. Eight genes involved in protection from injury, oxidant defense, and apoptosis/inflammation were significantly downregulated in different brain regions of methotrexate-treated rats. To our knowledge, this is the first study to investigate methotrexate-induced injury in selected brain regions and gene expression changes using a rat model of intraventricular drug administration.

Biodegradable hydrogels have become a rapidly expanding area of research for biomedical applications. Poly(β-amino ester) (PBAE) biodegradable hydrogels, in particular, have been studied extensively because of the ease of synthesis and range of properties exhibited. In this work, PBAE macromers were created with poly(ethylene glycol) diacrylate (PEGDA), diethylene glycol diacrylate (DEGDA), and isobutylamine. Many methods have been presented that allow control over the resulting hydrogel behavior. Here, properties were varied by combining multiple diacrylate components in the macromer synthesis step (single macromer (SM)) or through the combination of multiple macromers prior to polymerization (double macromer (DM)). The exhibited properties are a result of the hydrophilic/hydrophobic contributions of the different diacrylate molecules to the macromer. The SM systems exhibited linear degradation profiles, the rate of degradation increased as the PEGDA concentration increased. DM systems exhibited a multiphase degradation profile as a result of the combination of macromers with different hydrophilic properties.

Poly(β-amino ester) (PBAE) biodegradable hydrogel systems have garnered much attention in recent years due to their appealing properties for biomedical applications. These hydrogel systems exhibit properties similar to natural soft tissue, degrade in aqueous environments, and have easily tunable properties that have been well studied and understood. In most cases, tissue engineering scaffolds must possess a three-dimensional interconnected porous network for tissue ingrowth and construct vascularization. Here, PBAE properties were explored and systems were selected to serve as both the pore-forming agent and the outer matrix of a scaffold that exhibits controlled pore opening upon degradation. To our knowledge, this is the first demonstration of a biodegradable hydrogel porogen system entrapped in a degradable hydrogel outer matrix. Scaffolds were prepared, and the degradation, compressive moduli, and porosity were analyzed. An added advantage of a degradable porogen is the potential for controlled drug release, and a model protein was released from the porogen particles to demonstrate this application. Finally, pluripotent cells seeded onto predegraded scaffolds were viable during the first 24 h of exposure, and furthermore, cell tracking confirmed the presence of cells within the pores of the scaffold. Overall, these present studies demonstrate the possibility of using these biodegradable hydrogel porogen-matrix systems as tissue engineering scaffolding materials. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 400–412, 2014.

Poly(β-amino ester) biodegradable hydrogels are common in biomedical applications because of their tunable properties and similarities to natural soft tissue. Previous work has shown property adjustments through the choice of monomers, the ratio between monomers and the addition of a crosslinking component. Here, we show that the reaction time for the creation of the macromer can affect the resulting hydrogel properties, and thus provides another method of tuning properties. Macromer was created through the reaction of isobutylamine with poly(ethylene glycol) diacrylate (n = 400). The reaction progress was analyzed using IR and GPC analysis. Hydrogels were created through UV photopolymerization from macromers synthesized for 24, 36, and 48 h. The degradation, compressive moduli, and swelling were measured in an aqueous solution. All showed significant differences between hydrogels of different macromer synthesis times. These differences likely stem from the incomplete macromer synthesis reaction and resulting PEG-rich regions in hydrogels from shorter synthesis times. These regions will not readily degrade, but do increase the mechanical properties and extent of swelling. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Poly(β-amino ester) (PBAE) biodegradable hydrogel systems have garnered much attention in recent years due to their appealing properties for biomedical applications. These hydrogel systems exhibit properties similar to natural soft tissue, degrade in aqueous environments, and have easily tunable properties that have been well studied and understood. In most cases, tissue engineering scaffolds must possess a three-dimensional interconnected porous network for tissue ingrowth and construct vascularization. Here, PBAE properties were explored and systems were selected to serve as both the pore-forming agent and the outer matrix of a scaffold that exhibits controlled pore opening upon degradation. To our knowledge, this is the first demonstration of a biodegradable hydrogel porogen system entrapped in a degradable hydrogel outer matrix. Scaffolds were prepared, and the degradation, compressive moduli, and porosity were analyzed. An added advantage of a degradable porogen is the potential for controlled drug release, and a model protein was released from the porogen particles to demonstrate this application. Finally, pluripotent cells seeded onto predegraded scaffolds were viable during the first 24 h of exposure, and furthermore, cell tracking confirmed the presence of cells within the pores of the scaffold. Overall, these present studies demonstrate the possibility of using these biodegradable hydrogel porogen-matrix systems as tissue engineering scaffolding materials.

The remote heating of iron oxide nanoparticles in an alternating magnetic field is used to drive a thermoresponsive sol-gel block copolymer, Pluronic® F-127, through the upper phase transition temperature. This phase change triggers an accelerated release rate of a model drug. Actuation and return to baseline levels are demonstrated for multiple AMF doses.

Hydrogel nanocomposites are a new class of biomaterials that have recently attracted a lot of attention for applications in medical and pharmaceutical areas. The nanocomposites may consist of various types of nanoparticles, such as clay, ceramic, metallic, or metal oxides dispersed in a hydrogel matrix. The hydrogel nanocomposites have been investigated for various biological applications including drug delivery, tissue engineering, antimicrobial materials, and thermal therapy. In particular, different techniques to control the drug release rate from the nanocomposite matrix have been highlighted. In this chapter, various tissue-engineering areas are discussed, including bone, articular cartilage, and cornea repair. Biological interactions with nanocomposites, including cell adhesion and pertinent cytotoxicity studies, are also discussed.

To demonstrate remote controlled degradation of degradable nanocomposite hydrogels by application of an alternating magnetic field (AMF). Further, it was desired to study the AMF effect on the drug release properties of these systems.Degradable nanocomposite hydrogels were synthesized by incorporating iron oxide nanoparticles into a degradable hydrogel that exhibited temperature dependent degradation. Heating, degradation, and drug release studies were conducted by application of an AMF to determine if modulation of degradation and drug release could be attained.Hydrogels were successfully prepared, shown to have temperature dependent degradation, and shown to heat when exposed to the AMF. The degradation rate of the exposed samples was demonstrated to be higher than control samples, thus modulation of degradation was obtained. The release of a model drug from the system was modulated by exposure to the AMF.This is the first demonstration of remote controlled degradation using an AMF stimulus. Here, the proof of the concept has been presented, and there is great potential to enhance this effect through various methods. The ability to remotely control degradation of an implanted device opens a new area of improved medical devices.

A young teen asthma camp was developed as a 3-day residential experience in a traditional camp setting offering activities such as swimming, canoeing, horseback riding, ropes, course crafts, and games. The overall purpose, goals and plans for the camp experience were developed by a team of nurse educators, nurse practitioners, clinicians (nurses and physicians) with experience in asthma management, and camp directors. Feasibility and outcomes were measured for the camp using materials in the Power Breathing Program for teens developed by the Asthma and Allergy Foundation of America (AAFA) and questionnaires developed by the Consortium of Children's Asthma Camps.