Jennifer (Goldenberg) Klarer, M.Sc.Eng.

Organoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing selforganized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy… Show more

Organoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing selforganized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. As cell therapy transforms into a new class of therapeutic modality, this simple method—by making use of the dynamic nature of hydrogels—could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures. Show less

This publication is in print in volume 100 of the American Mineralogist Journal.

The recent definitive deuterium solid state NMR spectroscopic evidence for structural water in fluor- and hydroxylapatites has prompted our study of the conditions necessary for the removal and reincorporation of this important structural feature of apatites. Thermal gravimetric analysis of 20 synthetic carbonated calcium hydroxylapatite (CCaApOH) samples and nine carbonated calcium fluorapatite (CCaApF) samples has been used to determine the amount of structural and adsorbed water in each… Show more

The recent definitive deuterium solid state NMR spectroscopic evidence for structural water in fluor- and hydroxylapatites has prompted our study of the conditions necessary for the removal and reincorporation of this important structural feature of apatites. Thermal gravimetric analysis of 20 synthetic carbonated calcium hydroxylapatite (CCaApOH) samples and nine carbonated calcium fluorapatite (CCaApF) samples has been used to determine the amount of structural and adsorbed water in each sample. No correlation between the weight percent and number of moles of structural water and the weight percent carbonate in CCaApOH and CCaApF has been found. In contrast, there appears to be a relationship between the amount of adsorbed water and the carbonate concentration in the fluorapatites prepared with a two hour digestion time, as well as in the hydroxylapatites prepared with one hour digestion periods, presumably due to the effect of carbonate on crystallite size. Structural water can be removed from the apatite lattice, primarily above 200 °C, but heating to over 550 °C is required for complete removal. This water can be partly reincorporated through an apparently kinetically-controlled process that is enhanced by an increase in time and/or temperature. We speculate that the incorporation of structural water occurs at the beginning of the formation of the apatite structure, approximately coincident with the incorporation of carbonate. We also speculate that water is both removed and reincorporated by proton transfers from water molecules to
hydroxide ions. Show less