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To develop an understanding of thenature of complex, spatiotemporalinteractions between cells and the extracellular matrix (ECM), artificialECMs formed from hydrogels with a particular spectrum of propertiesare being developed at a rapid pace. We report the microfluidic generationof small, monodisperse composite agarose–gelatin hydrogel modules(microgel particles) that can be used for cell encapsulation and canserve as instructive cellular microenvironments. The agarose componentof the microgels gelled under reduced temperature, while gelatin modifiedwith phenolic hydroxyl groups underwent peroxidase-catalyzed gelation.Microgel composition, structure, morphology, and rigidity were tunedin a high-throughput manner. The results of this work are importantfor the generation of libraries of cell-laden polymer microgels forsingle-cell analysis, tissue engineering, and fundamental studiesof the role of local microenvironments in cell fate. [ABSTRACT FROM AUTHOR]

We describe the synthesis of metal chelating polymersbased onpolyaspartamide and polyglutamide backbones as carriers for 111In in radioimmunoconjugates. These polymers [PAsp(DTPA), PGlu(DTPA)]have a biotin end group and diethylenetriaminepentaacetic acid (DTPA)chelators attached to the primary amines of the diethylenetriamine(DET) pendant groups of biotin-poly{N′-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)] andof biotin-poly{N′-[N-(2-aminoethyl)-2-aminoethyl]glutamide}[PGlu(DET)]. Like Asn-containing proteins and polypeptides, polyaspartamidesundergo uncatalyzed degradation under model physiological conditions(10 mM phosphate buffer, pH 7.4, 150 mM NaCl). We studied the uncatalyzeddegradation of the polyaspartamide polymers by size exclusion chromatographyand found that the degradation rate was sensitive to the nature ofthe pendant groups. The metal-free polymer underwent somewhat slowerdegradation than the corresponding polymers in which the DTPA groupswere saturated with Eu3+or In3+, but even after14 days, substantial fractions of the polymers survived. We concludethat these polymers undergo negligible degradation on the time scale(24–48 h) of radioimmunotherapy treatment of tumors with 111In. From a mechanistic perspective, we note that these degradationrates are on the order of the deamidation rates reported [J. Peptide Res. 2004, 63,426] for Asn-containing pentapeptides, with half-times on the orderof 10 days, but much slower than the rapid decay (hours) reportedrecently [Biomaterials2010, 31, 3707] for poly{N′-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} itself. This variationin degradation rate can be explained in terms of the influence ofpositive charges on the pendant group enhancing the acidity of theside-chain amide nitrogen of the aspartamide repeat unit. The DETpendant group is positively charged at pH 7, but in indium-loadedPAsp(DTPA) this charge is offset by the net negative charge of theDTPA-In complex. [ABSTRACT FROM AUTHOR]