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.
Poly(b-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 ¼ 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.
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.
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.
We have isolated cDNAs coding for the complete amino acid sequences of cholinesterase 1 (ChE1) and cholinesterase 2 (ChE2) from amphioxus. Both ChE transcripts have the characteristics of H-type catalytic subunits, which are inserted in the membrane via an ethanolamine-glycan-phosphatidylinositol anchor. The members of the catalytic triad of ChEs, the three pairs of cysteine residues involved in intrachain disulfide bonding, a cysteine near the carboxy terminal of both sequences, which could mediate interchain disulfide bonding, and 11 of the 14 aromatic amino acids that line the catalytic gorge of AChE are conserved. A remarkable difference between the two enzymes is in the region of the acyl-binding pocket, which plays an important role in determining substrate specificity in cholinesterases. ChE2 contains a sequence that resembles the acyl pocket of invertebrate ChE, while the acyl-binding site of ChE1 is novel. There are also differences between the two enzymes in the peripheral anionic site, which mediates inhibition by certain ligands. In vitro expression in COS-7 cells demonstrates that ChE2 hydrolyzes acetylthiocholine almost exclusively, while ChE1 hydrolyzes both acetylthiocholine and butyrylthiocholine. Both enzymes are inhibited comparably by BW284c51, but ChE1 is considerably more resistant to inhibition by propidium, ethopropazine, and eserine than is ChE2. Velocity sedimentation indicates that ChE1 and ChE2 are present as amphiphilic and nonamphiphilic G 2 forms in vivo and in vitro. Another molecular form, which sediments at 17 S, is also present in vivo. Nondenaturing gel electrophoresis in conjunction with digestion by phosphatidylinositol-specific phospholipase C demonstrates that the vast majority of ChE1 and ChE2 is present as ethanolamine-glycan-phosphatidylinositol-anchored G 2 forms in vivo. ChE1 also possesses an ethanolamine-glycan-phosphatidylinositol-anchor in vitro; however, ChE2 produced in vitro could not be detected on nondenaturing gels.
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