Copolymers with varying compositions of 2-ethoxy-2-oxo-1,3,2-dioxaphospholane (EEP) and 2-ethoxy-4-methyl-2-oxo-1,3,2-dioxaphospholane (EMEP) have been synthesized via 1,5,7-triazabicyclo[4.4.0]dec-5-ene-catalyzed anionic ring-opening polymerization. The molecular weights and comonomer ratios were well controlled and polymers with reasonable molecular weight distributions (<1.5) were obtained in all cases. The copolymers were investigated by 1 H and 31 P NMR spectroscopies to determine the underlying microstructure via detailed dyad analysis. The copolymers were found to be nontoxic to HeLa cells. Furthermore, the obtained copolymers of EEP and EMEP show thermoresponsive properties, i.e., exhibit a lower critical solution temperature (LCST).

Biomimetic materials have been gaining increasing importance for use as bone biomaterials, because they may provide regenerative alternatives for the use of autologous tissues for bone regeneration. We demonstrate a promising alternative for the use of biomimetic materials based on a biodegradable PEG hydrogel loaded with vaterite nanoparticles as mineral storage. Vaterite, the least stable CaCO 3 polymorph, is stable enough to ensure the presence of a potential ion buffer for bone regeneration, but still has sufficient reactivity for the transformation from CaCO 3 to hydroxyapatite (HA). A combination of powder X-ray diffraction (PXRD), electron microscopy, and Fourier-transform infrared (FT-IR) and Raman spectroscopy showed the transformation of vaterite nanoparticles incorporated in a PEG-acetal-DMA hydrogel to hydroxycarbonate apatite (HCA) crystals upon incubation in simulated body fluid at human body temperature within several hours. The transformation in the PEG-acetal-DMA hydrogel scaffold in simulated body fluid or phosphate saline buffer proceeded significantly faster than for free vaterite. The vaterite-loaded hydrogels were free of endotoxin and did not exhibit an inflammatory effect on endothelial cells. These compounds may have prospects for future applications in the treatment of bone defects and bone degenerative diseases. † Electronic supplementary information (ESI) available: Fig. S1, quantitative phase analysis and determination of the crystallite size based on the XRD data after soaking vaterite nanoparticles in SBF at 37 1C for (a) 24 h (b) 48 h and (c) 72 h. See

Vaterite, a metastable modification of calcium carbonate, embedded in a flexible microgel packaging with adjustable mechanical properties, functionality, and biocompatibility, provides a powerful scaffolding for bone tissue regeneration, as it is easily convertible to bone-like hydroxyapatite (HA). In this study, the synthesis and physical analysis of a packaging material to encapsulate vaterite particles and osteoblast cells into monodisperse, sub-millimeter-sized microgels, is described whereby a systematic approach is used to tailor the microgel properties. The size and shape of the microgels is controlled via droplet-based microfluidics. Key requirements for the polymer system, such as absence of cytotoxicity as well as biocompatibility and biodegradability, are accomplished with functionalized poly(ethylene glycol) (PEG), which reacts in a cytocompatible thiol-ene Michael addition. On a mesoscopic level, the microgel stiffness and gelation times are adjusted to obtain high cellular viabilities. The co-encapsulation of living cells provides i) an in vitro platform for the study of cellular metabolic processes which can be applied to bone formation and ii) an in vitro foundation for novel tissue-regenerative therapies. Finally, the degradability of the microgels at physiological conditions caused by hydrolysis-sensitive ester groups in the polymer network is examined.