Gel Point Suppression in RAFT Polymerization of Pure Acrylic Cross-Linker Derived from Soybean Oil.

Here we report the reversible addition-fragmentation chain transfer (RAFT) polymerization of acrylated epoxidized soybean oil (AESO), a cross-linker molecule, to high conversion (>50%) and molecular weight (>100 kDa) without macrogelation. Surprisingly, gelation is suppressed in this system far beyond the expectations predicated both on Flory-Stockmeyer theory and multiple other studies of RAFT polymerization featuring cross-linking moieties. By varying AESO and initiator concentrations, we show how intra- versus intermolecular cross-linking compete, yielding a trade-off between the degree of intramolecular linkages and conversion at gel point. We measured polymer chain characteristics, including molecular weight, chain dimensions, polydispersity, and intrinsic viscosity, using multidetector gel permeation chromatography and NMR to track polymerization kinetics. We show that not only the time and conversion at macrogelation, but also the chain architecture, is largely affected by these reaction conditions. At maximal AESO concentration, the gel point approaches that predicted by the Flory-Stockmeyer theory, and increases in an exponential fashion as the AESO concentration decreases. In the most dilute solutions, macrogelation cannot be detected throughout the entire reaction. Instead, cyclization/intramolecular cross-linking reactions dominate, leading to microgelation. This work is important, especially in that it demonstrates that thermoplastic rubbers could be produced based on multifunctional renewable feedstocks.

Dissolvable microgel-templated macroporous hydrogels for controlled cell assembly.

Mesenchymal stem cells (MSCs)-based therapies have been widely used to promote tissue regeneration and to modulate immune/inflammatory response. The therapeutic potential of MSCs can be further improved by forming multi-cellular spheroids. Meanwhile, hydrogels with macroporous structures are advantageous for improving mass transport properties for the cell-laden matrices. Herein, we report the fabrication of MSC-laden macroporous hydrogel scaffolds through incorporating rapidly dissolvable spherical cell-laden microgels. Dissolvable microgels were fabricated by tandem droplet-microfluidics and thiol-norbornene photopolymerization using a novel fast-degrading macromer poly(ethylene glycol)-norbornene-dopamine (PEGNB-Dopa). The cell-laden PEGNB-Dopa microgels were subsequently encapsulated within another bulk hydrogel matrix, whose porous structure was generated efficiently by the rapid degradation of the PEGNB-Dopa microgels. The cytocompatibility of this in situ pore-forming approach was demonstrated with multiple cell types. Furthermore, adjusting the stiffness and cell adhesiveness of the bulk hydrogels afforded the formation of solid cell spheroids or hollow spheres. The assembly of solid or hollow MSC spheroids led to differential activation of AKT pathway. Finally, MSCs solid spheroids formed in situ within the macroporous hydrogels exhibited robust secretion of HGF, VEGF-A, IL-6, IL-8, and TIMP-2. In summary, this platform provides an innovative method for forming cell-laden macroporous hydrogels for a variety of future biomedical applications.

Injectable Acylhydrazone-Linked RAFT Polymer Hydrogels for Sustained Protein Release and Cell Encapsulation.

A new class of temperature responsive polymer, termed PADO, is synthesized by reversible addition-fragmentation chain-transfer polymerization. Synthesized from copolymerization of diacetone acrylamide (DAAM), di(ethylene glycol) ethyl ether acrylate, and oligo(ethylene glycol) methyl ether acrylate, PADO polymer phase separates at temperature above its lower critical solution temperature (36-42 °C) due to enhanced hydrophobic interactions between the short ethylene glycol side chains. Solution of PADO polymers exhibit injectable shear-thinning properties and reach sol-gel transition rapidly (<5 min) at 37 °C. When the ketone moieties on DAAM are linked by adipic acid dihydrazdie, PADO polymers form crosslinked and injectable acylhydrazone hydrogels, which are hydrolytically degradable at a mild acidic environment owing to the pH sensitive acylhydrazone bonds. The pH-responsive degradation kinetics can be controlled by tuning polymer contents and ketone/hydrazide ratio. Importantly, the injectable PADO hydrogels are highly cytocompatible and can be easily formulated for pH-responsive sustained protein delivery.

Facile Synthesis of Rapidly Degrading PEG-Based Thiol-Norbornene Hydrogels.

An alternate synthesis route was developed to prepare norbornene-functionalized poly(ethylene glycol) (PEG) from reacting multiarm PEG with carbic anhydride. The macromer, PEGNBCA, permits photo-cross-linking of thiol-norbornene hydrogels with kinetics comparable to conventional PEGNB macromer. In addition, PEGNBCA provides an additional carboxylate group for further conjugation with amine-bearing molecules. Interestingly, PEGNBCA thiol-norbornene hydrogels are highly susceptible to hydrolytic degradation through enhanced ester hydrolysis. The ester linkage is further weakened after the secondary conjugation, resulting in extremely rapid degradation of PEGNB hydrogels. More importantly, the degradation can be readily adjusted via tuning macromer compositions, with complete degradation time ranging from hours to weeks. The PEGNBCA hydrogels are also highly cytocompatible toward various cell types, providing opportunities for future applications in tissue engineering and advanced biofabrication.

Sensitivity enhancement of methacrylic acid gel dosimeters by incorporating iodine for computed tomography scans.

PURPOSE: Polymer gel dosimeters provide three-dimensional absorbed dose information and have gradually become a popular tool for quality assurance in radiotherapy. This study aims to incorporate iodine into the MAGAT-based gel as radiation sensitizer and investigate whether it can be used to measure the radiation dose and slice thickness for CT scans. METHODS: The nMAGAT(I) gel was doped with 0.03, 0.05, and 0.07-M iodine. The absorbed dose was delivered using a CT scanner (Alexion 16, Toshiba Medical Systems, Japan) with tube voltages of 80, 100, 120, and 135 kVp. The irradiated nMAGAT(I) gel was read using a cone beam optical CT scanner to produce dose-response curves. The nMAGAT(I) gel was used to obtain the slice sensitivity profile (SSP) and the CT dose index (CTDI) for quality assurance of CT scans. RESULTS: The 0.07-M iodine-doped nMAGAT(I) gel exhibited maximum sensitivity with the dose enhancement ratio of 2.12. The gel was chemically stable 24 h after its preparation, and the polymerization process was completed 24-48 h after the irradiation. For CT quality assurance, the full width at half maximum measured by the nMAGAT(I) gel matched the nominal slice thickness of CT. The CTDI at center, CTDI at peripheral, and weighted CTDI obtained by the nMAGAT(I) gel differed from those obtained by the ionization chamber by -4.2%, 3.1%, and 0.7%, respectively. CONCLUSIONS: The nMAGAT(I) gel can be used to assess radiation doses and slice thickness in CT scans, thus rendering it a potential quality assurance tool for CT and other radiological diagnostic applications.