Carbon nanodots (CDs) with a low cytotoxicity have been synthesized by one-step microwave-assisted pyrolysis of citric acid in the presence of various amine molecules. The primary amine molecules have been confirmed to serve dual roles as N-doping precursors and surface passivation agents, both of which considerably enhanced the fluorescence of the CDs.

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Targeted disruption of core binding factor α1 (Cbfa1) showed that Cbfa1 is an essential transcription factor in osteoblast differentiation and bone formation. Furthermore, both in vitro and in vivo studies showed that Cbfa1 plays important roles in matrix production and mineralization. However, it remains to be clarified how Cbfa1 controls osteoblast differentiation, bone formation, and bone remodelling. To understand fully the physiological functions of Cbfa1, we generated transgenic mice that overexpressed Cbfa1 in osteoblasts using type I collagen promoter. Unexpectedly, Cbfa1 transgenic mice showed osteopenia with multiple fractures. Cortical bone, which was thin, porous, and enriched with osteopontin, was invaded by osteoclasts, despite the absence of acceleration of osteoclastogenesis. Although the number of neonatal osteoblasts was increased, their function was impaired in matrix production and mineralization. Furthermore, terminally differentiated osteoblasts, which strongly express osteocalcin, and osteocytes were diminished greatly, whereas less mature osteoblasts expressing osteopontin accumulated in adult bone. These data indicate that immature organization of cortical bone, which was caused by the maturational blockage of osteoblasts, led to osteopenia and fragility in transgenic mice, demonstrating that Cbfa1 inhibits osteoblast differentiation at a late stage.

is greatly decreased or even eliminated. For instance, the widely used cyanoacrylate adhesives exhibit strong adhesion in air, but when applied in water environment, they are hardened quickly to form a layer of stiff plastics, eventually resulting in the loss of adhesion. [9] The commercially available epoxy resins [10] and polyurethanes [11] are reported to demonstrate strong underwater adhesion, but long time of curing is usually required. Recently, host-guest chemistry strategy was reportedly employed to prepare underwater adhesives; however, the substrate surface needs to be modified in advance. [5,12] In addition, electrostatic and hydrophobic interactions were also proved to contribute to enhanced underwater adhesion, but the adhesion strength was relatively poor. [13,14] In nature, many organisms, such as mussels, barnacles, and castle worms, have evolved an unparalleled mechanism to perfectly tackle the underwater adhesion problem. [15][16][17] The finding of universality of catechol chemistry for wet adhesion has provided a valuable biomimetic source to develop diverse adhesives for use in aqueous environments. However, several problems, such as the complexity of administration, release of harmful organic solvents, [18,19] long-term curing, [2] need for oxidant addition, [20,21] and low adhesion strength, [18,22] may hamper the actual applications of these bioinspired adhesives. Although numerous dopamine-based adhesives have been reported and shown to bond various material surfaces, strong adhesion in water and particularly blood environment, remains nonexistent so far.Increasing studies on bioadhesives secreted by molluscs and insects have suggested that liquid coacervation plays a critical role in achieving underwater adhesion. [13] In this process, phase separation and concurrently increased hydrophobicity induced by coacervation can dispel the hydrated water on the interface, leading to much enhanced interaction of adhesive groups with the adherent and thus stable underwater adhesion. Up to date, several complex coacervate adhesives with linear structure have been reported, but the occurrence of those coacervations in water needs external triggers, such as temperature, [13] pH, [20,23] and iron strength. [24] Compared to linear counterparts, hyperbranched polymer (HBP) has a unique highly branched Despite recent advance in bioinspired adhesives, achieving strong adhesion and sealing hemostasis in aqueous and blood environments is challenging. A hyperbranched polymer (HBP) with a hydrophobic backbone and hydrophilic adhesive catechol side branches is designed and synthesized based on Michael addition reaction of multi-vinyl monomers with dopamine.It is demonstrated that upon contacting water, the hydrophobic chains selfaggregate to form coacervates quickly, displacing water molecules on the adherent surface to trigger increased exposure of catechol groups and thus rapidly strong adhesion to diverse materials from low surface energy to high energy in various environments, such as deionized water, sea ...

The emerging 3D printing technique allows for tailoring hydrogel‐based soft structure tissue scaffolds for individualized therapy of osteochondral defects. However, the weak mechanical strength and uncontrollable swelling intrinsic to conventional hydrogels restrain their use as bioinks. Here, a high‐strength thermoresponsive supramolecular copolymer hydrogel is synthesized by one‐step copolymerization of dual hydrogen bonding monomers, N‐acryloyl glycinamide, and N‐[tris(hydroxymethyl)methyl] acrylamide. The obtained copolymer hydrogels demonstrate excellent mechanical properties—robust tensile strength (up to 0.41 MPa), large stretchability (up to 860%), and high compressive strength (up to 8.4 MPa). The rapid thermoreversible gel ⇔ sol transition behavior makes this copolymer hydrogel suitable for direct 3D printing. Successful preparation of 3D‐printed biohybrid gradient hydrogel scaffolds is demonstrated with controllable 3D architecture, owing to shear thinning property which allows continuous extrusion through a needle and also immediate gelation of fluid upon deposition on the cooled substrate. Furthermore, this biohybrid gradient hydrogel scaffold printed with transforming growth factor beta 1 and β‐tricalciumphosphate on distinct layers facilitates the attachment, spreading, and chondrogenic and osteogenic differentiation of human bone marrow stem cells (hBMSCs) in vitro. The in vivo experiments reveal that the 3D‐printed biohybrid gradient hydrogel scaffolds significantly accelerate simultaneous regeneration of cartilage and subchondral bone in a rat model.

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Runx2 is an essential transcription factor for osteoblast differentiation. However, the functions of Runx2 in postnatal bone development remain to be clarified. Introduction of dominant-negative (dn)-Runx2 did not inhibit Col1a1 and osteocalcin expression in mature osteoblastic cells. In transgenic mice that expressed dn-Runx2 in osteoblasts, the trabecular bone had increased mineralization, increased volume, and features of compact bone, and the expression of major bone matrix protein genes was relatively maintained. After ovariectomy, neither osteolysis nor bone formation was enhanced and bone was relatively conserved. In wild-type mice, Runx2 was strongly expressed in immature osteoblasts but downregulated during osteoblast maturation. These findings indicate that the maturity and turnover rate of bone are determined by the level of functional Runx2 and Runx2 is responsible for bone loss in estrogen deficiency, but that INTRODUCTIONBone is composed of compact bone and cancellous bone. In long bones, the shaft (cortical bone) consists of compact bone, and the inside of the shaft (trabecular bone), which is a threedimensional lattice of branching bony spicules, consists of cancellous bone. Compact bone is mature bone, because it is composed of densely packed, highly organized collagen fibrils with high mineralization, and is relatively resistant to osteolysis. In contrast, cancellous bone is less mature, because it is composed of loosely organized collagen fibrils with low mineralization, and it is easily resorbed and plays an important role in calcium homeostasis (Marks and Odgren, 2002). Runt-related transcription factor 2 (Runx2) is a transcription factor that belongs to the Runx family and is involved in many aspects of skeletal development (Komori, 2005). Upon forming a heterodimer with core binding factor ␤ (Cbf␤), Runx2 acquires DNA-binding activity and regulates transcriptional activity (Kundu et al., 2002;Miller et al., 2002;Yoshida et al., 2002;Kanatani et al., 2006). There are two Runx2 isoforms, type I Runx2 and type II Runx2, which have different N-termini, and type I Runx2 is more dependent on Cbfb than type II Runx2 for their functional activities (Kanatani et al., 2006). Runx2-deficient mice lack osteoblasts and show a complete lack of bone formation, demonstrating that Runx2 is essential for osteoblast differentiation (Komori et al., 1997;Otto et al., 1997). Runx2 also plays important roles in chondrocyte maturation, maintenance of the chondrocyte phenotype, and vascular invasion into cartilage (Komori, 2005;Zelzer et al., 2001). Furthermore, Runx2 regulates RANKL and OPG expression stimulating osteoclast differentiation (Enomoto et al., 2003). These findings indicate that Runx2 functions as a key molecule in skeletal development.The DNA-binding sites of Runx2 in major bone matrix protein genes including the Col1a1, osteopontin, bone sialoprotein, and osteocalcin genes, have been identified, and Runx2 induced the expression of these genes or activated their promoters (Ducy et al., 1997(Ducy et...

Despite rapid development of adhesive hydrogels, the typical double-sided adhesives fail to adhere to wet tissues and concurrently prevent postoperative tissue adhesion, thus severely limiting their applications in repair of internal tissues. Herein, a negatively charged carboxyl-containing hydrogel is gradiently, electrostatically complexed with a cationic oligosaccharide by a one-sided dipping method to form a novel Janus hydrogel wet adhesive whose two-side faces demonstrate strikingly distinct adhesive and nonadhesive properties. The lightly complexed surface demonstrates instant robust adhesion to various wet biological tissues even under water since the phase separation induced by electrostatic complexation increases the hydrophobicity and water drainage capacity. Intriguingly, the highly complexed surface is non-adhesive due to complete neutralization of carboxyls in the hydrogels. The Janus hydrogel can be used to replace traditional sutures to treat gastric perforation of rabbits. Animal experiment outcomes reveal that one side of the Janus hydrogel is firmly glued to the stomach tissue, and other side facing outward can efficiently prevent the postoperative adhesion. Molecular simulation elucidates the importance for selecting cationic polymer species. It is believed that gradient polyelectrolyte complexation establish a new direction to create Janus adhesives for internal tissue/organ repair and simultaneous prevention of post-operative adhesion.