The organometallic-inorganic diblock copolymer poly(ferrocenyldimethylsilane-b-dimethylsiloxane) (PFDMS-b-PDMS) with a 1:6 block ratio unexpectedly forms long rodlike micelles rather than spherical structures in a variety of PDMS-selective n-alkane solvents when the solutions are prepared at or near ambient temperature. The cylindrical structures represent the thermodynamically preferred morphology and consist of an iron-rich PFDMS core and a corona of PDMS. The length of the micelles can be varied from 70 nm to 10 µm by altering the method of sample preparation. In addition, the dimensions of the micellar core can be controlled through variations in the length of the PFDMS block, which is achieved by altering the molecular weight of the diblock copolymer while maintaining a constant block ratio. In contrast, when micelles are formed above the T m of PFDMS (ca. 120-145°C), spherical aggregates are formed, which suggests that crystallization of the core polymer is the driving force for the formation of wormlike micelles below T m . Furthermore, the analogues with amorphous polyferrocene blocks, poly(ferrocenylmethylphenylsilane-bdimethylsiloxane) (PFMPS-b-PDMS) and poly(ferrocenylmethylethylsilane-b-dimethylsiloxane) (PFMES-b-PDMS), form spherical micelles in hexane at room temperature. This lends further support to the proposition that the crystalline nature of the PFDMS block plays a pivotal role in the unexpected formation of cylindrical micelles. To provide an application of this concept, an analogous PFDMS block copolymer with polyisoprene, PI-b-PFDMS, was prepared and, as predicted, was found to form cylindrical micelles in hexane.

One of the breakthroughs in biomaterials and regenerative medicine in the latest decade is the finding that matrix stiffness affords a crucial physical cue of stem cell differentiation. This statement was recently challenged by another understanding that protein tethering on material surfaces instead of matrix stiffness was the essential cue to regulate stem cells. Herein, we employed nonfouling poly(ethylene glycol) (PEG) hydrogels as the matrix to prevent nonspecific protein adsorption, and meanwhile covalently bound cell-adhesive arginine-glycine-aspartate (RGD) peptides onto the hydrogel surfaces in the form of well-defined nanoarrays to control specific cell adhesion. This approach enables the decoupling of the effects of matrix stiffness and surface chemistry. Mesenchymal stem cells (MSCs) were cultured on four substrates (two compressive moduli of the PEG hydrogels multiplied by two RGD nanospacings) and incubated in the mixed osteogenic and adipogenic medium. The results illustrate unambiguously that matrix stiffness is a potent regulator of stem cell differentiation. Moreover, we reveal that RGD nanospacing affects spreading area and differentiation of rat MSCs, regardless of the hydrogel stiffness. Therefore, both matrix stiffness and nanoscale spatial organization of cell-adhesive ligands direct stem cell fate.

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In this study, a muti-benzaldehyde functionalized poly(ethylene glycol) analogue, poly(ethylene oxide-co-glycidol)-CHO (poly(EO-co-Gly)-CHO), was designed and synthesized for the first time, and applied as a cross-linker to develop an injectable hydrogel system. Simply mixing two aqueous precursor solutions of glycol chitosan (GC) and poly(EO-co-Gly)-CHO led to the in situ formation of chemically cross-linked hydrogels under physiological conditions. The cross-linking was attributed to a Schiff's base reaction between amino groups of GC and aldehyde groups of poly(EO-co-Gly)-CHO. The gelation time, water uptake, mechanical properties and network morphology of the GC/poly(EO-co-Gly) hydrogels were well modulated by varying the concentration of poly(EO-co-Gly)-CHO. Degradation of the in situ formed hydrogels was confirmed both in vitro and in vivo. The integrity of the GC/poly(EO-co-Gly) hydrogels was maintained for up to 12 weeks subcutaneously in ICR mice. The feasibility of encapsulating chondrocytes in the GC/poly(EO-co-Gly) hydrogels was assessed. Live/Dead staining assay demonstrated that the chondrocytes were highly viable in the hydrogels, and no dedifferentiation of chondrocytes was observed after 2 weeks of in vitro culture. Cell counting kit-8 assay gave evidence of the remarkably sustained proliferation of the encapsulated chondrocytes. Maintenance of the chondrocyte phenotype was also confirmed with an examination of characteristic gene expression. These features suggest that GC/poly(EO-co-Gly) hydrogels hold potential as an artificial extracellular matrix for cartilage tissue engineering.

Stem cells are capable of sensing and responding to the mechanical properties of extracellular matrixes (ECMs). It is well-known that, while osteogenesis is promoted on the stiff matrixes, adipogenesis is enhanced on the soft ones. Herein, we report an "abnormal" tendency of matrix-stiffness-directed stem cell differentiation. Well-defined nanoarrays of cell-adhesive arginine-glycine-aspartate (RGD) peptides were modified onto the surfaces of persistently nonfouling poly(ethylene glycol) (PEG) hydrogels to achieve controlled specific cell adhesion and simultaneously eliminate nonspecific protein adsorption. Mesenchymal stem cells were cultivated on the RGD-nanopatterned PEG hydrogels with the same RGD nanospacing but different hydrogel stiffnesses and incubated in the induction medium to examine the effect of matrix stiffness on osteogenic and adipogenic differentiation extents. When stem cells were kept at a low density during the induction period, the differentiation tendency was consistent with the previous reports in the literature; however, both lineage commitments were favored on the stiff matrices at a high cell density. We interpreted such a complicated stiffness effect at a high cell density in two-dimensional culture as the interplay of matrix stiffness and cell-cell contact. As a result, this study strengthens the essence of the stiffness effect and highlights the combinatory effects of ECM cues and cell cues on stem cell differentiation.

The diblock copolymers, poly(isoprene‐block‐ferrocenyldimethylsilane) (PI‐b‐PFDMS) and poly(ferrocenyldimethylsilane‐block‐dimethylsiloxane) (PFDMS‐b‐PDMS), form cylindrical micelles with an organometallic polyferrocenylsilane core in a solvent of hexanes. These cylindrical micelles were deposited onto a Si substrate from solution by either spin or dip coating, and upon reactive ion etching, continuous ceramic nanolines with lengths of micrometers and widths as small as 8 nm were created. The nanolines were characterized by scanning force microscopy (SFM) and transmission electron microscopy (TEM), and were shown to contain Fe, Si, and O from X‐ray photoelectron spectroscopy (XPS) studies. The widths of the nanolines could be varied from ca. 8 to 30 nm, depending on the composition of the corona (PI or PDMS). The oriented deposition of these cylindrical micelles can be achieved along pre‐patterned grooves on a resist film using capillary forces. Following treatment with hydrogen or oxygen plasma, oriented ceramic nanolines can be fabricated. The approach reported here represents a relatively simple method to create ceramic nanolines with large aspect ratio on semiconducting substrates.

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In this study, we suggest a novel strategy of constituting an in situ-formed hydrogel composed of polymer-platinum(IV) conjugate to realize a long-term delivery of cisplatin. A unique conjugate was designed and synthesized by covalent linking of Pt(IV) complex to the hydrophobic end of two methoxyl poly(ethylene glycol)-b-poly(d,l-lactide) (mPEG-PLA) copolymer chains, resulting in the formation of Bi(mPEG-PLA)-Pt(IV). The conjugate could self-assemble into micelles in water, and its concentrated solution exhibited a thermoreversible sol-gel transition and formed a semisolid thermogel at body temperature. The incorporation of the cisplatin analogue Pt(IV) prodrug into the conjugate had a significant influence on its thermogelling properties and the conjugate thermogelation was attributed to the micellar aggregation. In vitro release experiments of Pt(IV)-conjugated thermogel showed that the platinum release lasted as long as two months. Furthermore, we demonstrated that the Pt(IV) prodrug was released mainly in the form of micelles and micellar aggregates from the gel depot. Compared with free cisplatin, the formation of conjugate micelles led to the enhanced in vitro cytotoxicity against cancer cells due to the effective accumulation into cells via endocytosis.