Molecular co-assembled strategy tuning protein conformation for cartilage regeneration.

The assembly of oligopeptide and polypeptide molecules can reconstruct various ordered advanced structures through intermolecular interactions to achieve protein-like biofunction. Here, we develop a "molecular velcro"-inspired peptide and gelatin co-assembly strategy, in which amphiphilic supramolecular tripeptides are attached to the molecular chain of gelatin methacryloyl via intra-/intermolecular interactions. We perform molecular docking and dynamics simulations to demonstrate the feasibility of this strategy and reveal the advanced structural transition of the co-assembled hydrogel, which brings more ordered ß-sheet content and 10-fold or more compressive strength improvement. We conduct transcriptome analysis to reveal the role of co-assembled hydrogel in promoting cell proliferation and chondrogenic differentiation. Subcutaneous implantation evaluation confirms considerably reduced inflammatory responses and immunogenicity in comparison with type I collagen. We demonstrate that bone mesenchymal stem cells-laden co-assembled hydrogel can be stably fixed in rabbit knee joint defects by photocuring, which significantly facilitates hyaline cartilage regeneration after three months. This co-assembly strategy provides an approach for developing cartilage regenerative biomaterials.

Hierarchical Scaffold with Directional Microchannels Promotes Cell Ingrowth for Bone Regeneration.

Bone regenerative scaffolds with a bionic natural bone hierarchical porous structure provide a suitable microenvironment for cell migration and proliferation. Here, a bionic scaffold (DP-PLGA/HAp) with directional microchannels is prepared by combining 3D printing and directional freezing technology. The 3D printed framework provides structural support for new bone tissue growth, while the directional pore embedded in the scaffolds provides an express lane for cell migration and nutrition transport, facilitating cell growth and differentiation. The hierarchical porous scaffolds achieve rapid infiltration and adhesion of bone marrow mesenchymal stem cells (BMSCs) and improve the expression of osteogenesis-related genes. The rabbit cranial defect experiment presents significant new bone formation, demonstrating that DP-PLGA/HAp offers an effective means to guide cranial bone regeneration. The combination of 3D printing and directional freezing technology might be a promising strategy for developing bone regenerative biomaterials.

Engineered Microchannel Scaffolds with Instructive Niches Reinforce Endogenous Bone Regeneration by Regulating CSF-1/CSF-1R Pathway.

Structural and physiological cues provide guidance for the directional migration and spatial organization of endogenous cells. Here, a microchannel scaffold with instructive niches is developed using a circumferential freeze-casting technique with an alkaline salting-out strategy. Thereinto, polydopamine-coated nano-hydroxyapatite is employed as a functional inorganic linker to participate in the entanglement and crystallization of chitosan molecules. This scaffold orchestrates the advantage of an oriented porous structure for rapid cell infiltration and satisfactory immunomodulatory capacity to promote stem cell recruitment, retention, and subsequent osteogenic differentiation. Transcriptomic analysis as well as its in vitro and in vivo verification demonstrates that essential colony-stimulating factor-1 (CSF-1) factor is induced by this scaffold, and effectively bound to the target colony-stimulating factor-1 receptor (CSF-1R) on the macrophage surface to activate the M2 phenotype, achieving substantial endogenous bone regeneration. This strategy provides a simple and efficient approach for engineering inducible bone regenerative biomaterials.

Hydrophobic Tetracycline Immobilized in Fibrous Hyaluronan Regulates Adhesive Collagen-Based Hydrogel Stability for Infected Wound Healing.

Collagen-based hydrogels have a significant impact on wound healing, but they suffer from structural instability and bacterial invasion in infected wounds. Here, electrospun nanofibers of esterified hyaluronan (HA-Bn/T) are developed to immobilize the hydrophobic antibacterial drug tetracycline by π-π stacking interaction. Dopamine-modified hyaluronan and HA-Bn/T are employed simultaneously to stabilize the structure of collagen-based hydrogel by chemically interweaving the collagen fibril network and decreasing the rate of collagen degradation. This renders it injectable for in situ gelation, with suitable skin adhesion properties and long-lasting drug release capability. This hybridized interwoven hydrogel promotes the proliferation and migration of L929 cells and vascularization in vitro. It presents satisfactory antibacterial ability against Staphylococcus aureus and Escherichia coli. The structure also retains the functional protein environment provided by collagen fiber, inhibits the bacterial environment of infected wounds, and modulates local inflammation, resulting in neovascularization, collagen deposition, and partial follicular regeneration. This strategy offers a new solution for infected wound healing.

Tailorable 3DP Flexible Scaffolds with Porosification of Filaments Facilitate Cell Ingrowth and Biomineralized Deposition.

Facilitating cell ingrowth and biomineralized deposition inside filaments of 3DP scaffolds are an ideal bone repair strategy. Here, 3D printed PLGA/HA scaffolds with hydroxyapatite content of 50% (P5H5) and 70% (P3H7) were prepared by optimizing 3D printing inks, which exhibited good tailorability and foldability to meet clinical maneuverability. The supercritical CO2 foaming technology further endowed the filaments of P5H5 with a richer interconnected pore structure (P5H5-C). The finite element and computational fluid dynamics simulation analysis indicated that the porosification could effectively reduce the stress concentration at the filament junction and improved the overall permeability of the scaffold. The results of in vitro experiments confirmed that P5H5-C promoted the adsorption of proteins on the surface and inside of filaments, accelerated the release of Ca and P ions, and significantly upregulated osteogenesis (Col I, ALP, and OPN)- and angiogenesis (VEGF)-related gene expression. Subcutaneous ectopic osteogenesis experiments in nude mice further verified that P5H5-C facilitated cell growth inside filaments and biomineralized deposition, as well as significantly upregulated the expression of osteogenesis- and angiogenesis-related genes (Col I, ALP, OCN, and VEGF) and protein secretion (ALP, RUNX2, and VEGF). The porosification of filaments by supercritical CO2 foaming provided a new strategy for accelerating osteogenesis of 3DP implants.

[Role of Stem Cells and Their Biomimetic Matrix Microenvironment in Regenerative Repair of Articular Cartilage: A Review].

It is difficult for the articular cartilage to self-heal any damage it may incur due to its lack of nerves and blood vessels. Development in stem cell technology provides new prospects for articular cartilage regeneration. Currently, stem cells from different sources and their diverse applications have demonstrated different degrees of therapeutic effect and potential in articular cartilage repair. However, stem cells are highly sensitive to their microenvironment. Therefore, more and more researchers are focusing their attention on regulating stem cells and thus accelerating cartilage regeneration through the biomimetic microenvironment constructed by biologically functional scaffolds. We reviewed in this paper the sources of the stem cells used for cartilage repair, the application method of these stem cells, as well as the therapeutic effect, mechanism and limitations in the application of stem cells synergizing with the biomimetic microenvironment in promoting articular cartilage repair and regeneration. We hoped to provide suggestions for practical clinical research in the design and improvement of biofunctional cartilage repair scaffolds that synergize with stem cells.

Bioinspired polysaccharide hybrid hydrogel promoted recruitment and chondrogenic differentiation of bone marrow mesenchymal stem cells.

Cartilage regeneration by biomimetic cartilage matrix with synchronously recruited stem cells was one of ideal strategies. Inspired by catechol for proteins adhesion, dopamine modified polysaccharide hybrid hydrogel (HD-C) was prepared by integrating collagen I (Col I) and hyaluronic acid derivatives (HA-DN) with sulfhydryl modified polysaccharide hybrid hydrogel (HS-C) as control. Because of double-crosslinking architecture, HD-C hydrogel was endowed with a more compact pore structure, higher mechanical properties and water retention ability in comparison with those of HS-C hydrogel. Meanwhile, it significantly promoted the proliferation and spread of rabbit bone marrow stem cells (rBMSCs), and accelerated cartilaginous matrix secretion. RT-PCR results also verified higher related gene expression of chondrogenesis (Sox 9, Agg and Col II). Moreover, HD-C hydrogel could enhance the enrichment and migration of rBMSCs in vitro by potential functional protein adsorption mechanisms, and this phenomenon was further confirmed by more rBMSCs migration in short-term joint implantation experiments in vivo.

Redox and pH dual-responsive injectable hyaluronan hydrogels with shape-recovery and self-healing properties for protein and cell delivery.

In this work, 3, 3'-dithiobis (propanoic dihydrazide) modified and aldehyde-modified hyaluronic acid were respectively synthesized as precursor solutions to form redox and pH dual-responsive injectable hydrogels through dynamic acylhydrazone and disulfide linkages without exogenous stimulus conditions. The reversible sol-gel transition behavior of hydrogels could be repeated multiple times by adjusting DTT/H2O2 or HCl/TEA. Interestingly, the hydrogels shrank gradually when pH decreased, which improved significantly the storage modulus up to 8.4 times at pH 2. Furthermore, the hydrogel presented acid-switchable shape-recovery characteristics of self-healing by a dynamic recombination of acylhydrazone bonds. Moreover, the osmotic driving force derived from inner and outer concentration difference also affected the characteristic. The controlled release of bovine serum albumin (BSA) encapsulated in this hydrogel could be achieved in vitro under simulated pH/redox intracellular and intercellular microenvironment. This hydrogel could also promote chondrocytes proliferation.

Light curve measurements with a superconducting nanowire single-photon detector.

The superconducting nanowire single-photon detector (SNSPD) is used to detect the sunlight reflected by the artificial satellite and space debris. In the process, light curves of the satellite and space debris are successfully measured. In 2017, a space-debris laser ranging system with a four-element SNSPD is developed by Yunnan Observatories in China. During the ranging experiments, the detector works in a freely detecting state. It can detect photons not only of the laser echo, but also of the sunlight reflected by the target. After separating the data triggered by background light from the whole detected data set, the light curves of satellites, including Topex and several types of debris, are acquired. The apparent rotation rate of the satellite Topex is determined by analyzing the light curves by Fourier transform and phase dispersion minimization. On the basis of a laser ranging system using SNSPDs, the simultaneous measurement of the laser ranging and light curves of some space targets without any additional equipment is realized for the first time, to the best of our knowledge.

Mechanistic Insight into Etching Chemistry and HF-Assisted Etching of MgO-Al2O3-SiO2 Glass-Ceramic.

The present study focuses on the etching conditions and mechanism of MgO-Al2O3-SiO2 glass-ceramic (MAS) in hydrofluoric acid (HF). The results show that the amorphous phase has 218 times higher etching rate than pure cordierite crystal at room temperature. In addition, the activation energies of cordierite and amorphous phases in the HF solution are 52.5 and 30.6 kJ/mol, respectively. The time (tad) taken for complete dissolution of the amorphous phase depends on the HF concentration (CHF). Based on the etching experiments, a new model is established and refined to assess the tad evolution. In addition, a highly crystalline cordierite phase, with the high specific surface area (59.4 m²·g-1) and mesoporous structure, has been obtained by HF etching. This paper presents novel insights into the etching chemistry and opens up avenues for further research in the area of cordierite-based catalytic ceramics.

Satellite laser ranging using superconducting nanowire single-photon detectors at 1064 nm wavelength.

Satellite laser ranging operating at 1064 nm wavelength using superconducting nanowire single-photon detectors (SNSPDs) is successfully demonstrated. A SNSPD with an intrinsic quantum efficiency of 80% and a dark count rate of 100 cps at 1064 nm wavelength is developed and introduced to Yunnan Observatory in China. With improved closed-loop telescope systems (field of view of about 26''), satellites including Cryosat, Ajisai, and Glonass with ranges of 1600 km, 3100 km, and 19,500 km, respectively, are experimentally ranged with mean echo rates of 1200/min, 4200/min, and 320/min, respectively. To the best of our knowledge, this is the first demonstration of laser ranging for satellites using SNSPDs at 1064 nm wavelength. Theoretical analysis of the detection efficiency and the mean echo rate for typical satellites indicate that it is possible for a SNSPD to range satellites from low Earth orbit to geostationary Earth orbit.