Ralstonengberg2285
Patients with bone defects suffer from a high rate of disability and deformity. Poor contact of grafts with defective bones and insufficient osteogenic activities lead to increased loose risks and unsatisfied repair efficacy. Although self-expanding scaffolds were developed to enhance bone integration, the limitations on the high transition temperature and the unsatisfied bioactivity hindered greatly their clinical application. Herein, we report a near-infrared-responsive and tight-contacting scaffold that comprises of shape memory polyurethane (SMPU) as the thermal-responsive matrix and magnesium (Mg) as the photothermal and bioactive component, which fabricated by the low temperature rapid prototyping (LT-RP) 3D printing technology. As designed, due to synergistic effects of the components and the fabrication approach, the composite scaffold possesses a homogeneously porous structure, significantly improved mechanical properties and stable photothermal effects. The programmed scaffold can be heated to recover under near infrared irradiation in 60s. With 4 wt% Mg, the scaffold has the balanced shape fixity ratio of 93.6% and shape recovery ratio of 95.4%. The compressed composite scaffold could lift a 100 g weight under NIR light, which was more than 1700 times of its own weight. The results of the push-out tests and the finite element analysis (FEA) confirmed the tight-contacting ability of the SMPU/4 wt%Mg scaffold, which had a signficant enhancement compared to the scaffold without shape memory effects. Furthermore, The osteopromotive function of the scaffold has been demonstrated through a series of in vitro and in vivo studies. We envision this scaffold can be a clinically effective strategy for robust bone regeneration.Laser powder bed fusion (L-PBF) of magnesium (Mg) alloy porous scaffolds is expected to solve the dual challenges from customized structures and biodegradable functions required for repairing bone defects. However, one of the key technical difficulties lies in the poor L-PBF process performance of Mg, contributed by the high susceptibility to oxidation, vaporization, thermal expansion, and powder attachment etc. This work investigated the influence of L-PBF energy input and scanning strategy on the formation quality of porous scaffolds by using WE43 powder, and characterized the microstructure, mechanical properties, biocompatibility, biodegradation and osteogenic effect of the as-built WE43 porous scaffolds. With the customized energy input and scanning strategy, the relative density of struts reached over 99.5%, and the geometrical error between the designed and the fabricated porosity declined to below 10%. Massive secondary phases including intermetallic precipitates and oxides were observed. The compressive strength (4.37-23.49 MPa) and elastic modulus (154.40-873.02 MPa) were comparable to those of cancellous bone. Good biocompatibility was observed by in vitro cell viability and in vivo implantation. The biodegradation of as-built porous scaffolds promoted the osteogenic effect, but the structural integrity devastated after 12 h by the immersion tests in Hank's solution and after 4 weeks by the implantation in rabbits' femur, indicating an excessively rapid degradation rate.This study investigated the osteogenic performance of new brushite cements obtained from Li+-doped β-tricalcium phosphate as a promising strategy for bone regeneration. Lithium (Li+) is a promising trace element to encourage the migration and proliferation of adipose-derived stem cells (hASCs) and the osteogenic differentiation-related gene expression, essential for osteogenesis. In-situ X-ray diffraction (XRD) and in-situ 1H nuclear magnetic resonance (1H NMR) measurements proved the precipitation of brushite, as main phase, and monetite, indicating that Li+ favored the formation of monetite under certain conditions. Li+ was detected in the remaining pore solution in significant amounts after the completion of hydration. Kenpaullone in vivo Isothermal calorimetry results showed an accelerating effect of Li+, especially for low concentration of the setting retarder (phytic acid). A decrease of initial and final setting times with increasing amount of Li+ was detected and setting times could be well adjusted by varying the setting retarder concentration. The cements presented compressive mechanical strength within the ranges reported for cancellous bone. In vitro assays using hASCs showed normal metabolic and proliferative levels. The immunodetection and gene expression profile of osteogenic-related markers highlight the incorporation of Li+ for increasing the in vivo bone density. The osteogenic potential of Li-doped brushite cements may be recommended for further research on bone defect repair strategies.Lipid-based boundary layers formed on liposome-containing hydrogels can facilitate lubrication. However, these boundary layers can be damaged by shear, resulting in decreased lubrication. Here, a shear-responsive boundary-lubricated drug-loaded hydrogel is created by incorporating celecoxib (CLX)-loaded liposomes within dynamic covalent bond-based hyaluronic acid (HA) hydrogels (CLX@Lipo@HA-gel). The dynamic cross-linked network enables the hydrogel to get restructured in response to shear, and the HA matrix allows the accumulation of internal liposome microreservoirs on the sliding surfaces, which results in the formation of boundary layers to provide stable lubrication. Moreover, hydration shells formed surrounding the hydrogel can retard the degradation process, thus helping in sustaining lubrication. Furthermore, in vitro and in vivo experiments found that CLX@Lipo@HA-gels can maintain anabolic-catabolic balance, alleviate cartilage wear, and attenuate osteoarthritis progression by delivering CLX and shear-responsive boundary lubrication. Overall, CLX@Lipo@HA-gels can serve as shear-responsive boundary lubricants and drug-delivery vehicles to alleviate friction-related diseases like osteoarthritis.The inevitable gap between in vitro and in vivo degradation rate of biomaterials has been a challenging factor in the optimal designing of scaffold's degradation to be balanced with new tissue formation. To enable non-/minimum-invasive tracking of in vivo scaffold degradation, chemical modifications have been applied to label polymers with fluorescent dyes. However, the previous approaches may have limited expandability due to complicated synthesis processes. Here, we introduce a simple and efficient method to fluorescence labeling of polymeric scaffolds via blending with near-infrared (NIR) quantum dots (QDs), semiconductor nanocrystals with superior optical properties. QDs-labeled, 3D-printed PCL scaffolds showed promising efficiency and reliability in quantitative measurement of degradation using a custom-built fiber-optic imaging modality. Furthermore, QDs-PCL scaffolds showed neither cytotoxicity nor secondary labeling of adjacent cells. QDs-PCL scaffolds also supported the engineering of fibrous, cartilaginous, and osteogenic tissues from mesenchymal stem/progenitor cells (MSCs). In addition, QDs-PCL enabled a distinction between newly forming tissue and the remaining mass of scaffolds through multi-channel imaging. Thus, our findings suggest a simple and efficient QDs-labeling of PCL scaffolds and minimally invasive imaging modality that shows significant potential to enable in vivo tracking of scaffold degradation as well as new tissue formation.Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility, antibacterial property and pro-healing bioactivity. Yet, the inadequate mechanical properties and bio-adhesion limit their applications. Herein, based on dynamic covalent bonds, photo-triggered covalent bonds and hydrogen bonds, multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan, modified sodium alginate and tannic acid are developed. Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously. Owing to cohesion enhancement strategy and self-healing ability, considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa, 12.3-fold that of commercial fibrin glue. Based on bio-adhesion and pro-coagulant activity (e.g., the stimulative aggregation and adhesion of erythrocytes and platelets), the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g, only 54.2% of that in fibrin glue. The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag+ Gel due to the enhanced antibacterial and antioxidant properties. Through the multi-crosslinking strategy, the hydrogels show enhanced mechanical properties, fabulous bio-adhesion, superior hemostatic performance and promoting healing ability, thereby have an appealing application value for the first-aid hemostasis and infected wound healing.Moderately regulating vascularization and immune microenvironment of wound site is necessary to achieve scarless wound healing of the skin. Herein, we have prepared an angiogenesis-promoting and scar-preventing band-aid with a core-shell structure, that consists of MXene-loaded nanofibers (MNFs) as the core and dopamine-hyaluronic acid hydrogel (H) as the shell (MNFs@V-H@DA) to encapsulate a growth factor (vascular endothelial growth factor, VEGF, abbreviated as V) and H2S donor (diallyl trisulfide, DATS, abbreviated as DA). The continuous release of DA from this system produced H2S, which would successfully induce macrophages to polarize into M2-lile phenotype, regulating the immune microenvironment and inhibiting an excessive inflammatory response at the wound sites. It is conducive to the proliferation of skin cells, facilitating the wound healing. In addition, an appropriate amount of VEGF can be released from the MXene nanofibrous skeleton by adjusting the time of near-infrared (NIR) light exposure, preventing excessive neovascularization and extracellular matrix deposition at the wound sites. Collectively, this NIR photothermal-responsive band-aid achieved scarless wound healing through gradient-controlled vascularization and a related immune sequential reaction of damaged skin tissue.Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature, thereby causing massive blood loss and significantly increased mortality. Inspired by the attack action of torpedoes, we synthesized microcluster (MC) colloidosomes equipped with magnetic-mediated navigation and "blast" systems to deliver hemostats into the cavity of vase-type wounds. CaCO3/Fe2O3 (CF) microparticles functionalized with Arg-Gly-Asp (RGD) modified polyelectrolyte multilayers were co-assembled with oppositely charged zwitterionic carbon dots (CDs) to form MC colloidosomes, which were loaded with thrombin and protonated tranexamic acid (TXA-NH3 +). The composite microparticles moved against blood flow under magnetic mediation and simultaneously disassembled for the burst release of thrombin stimulated by TXA-NH3 +. The CO2 bubbles generated during disassembly produced a "blast" that propelled thrombin into the wound cavity. Severe bleeding in a vase-type hemorrhage model in the rabbit liver was rapidly controlled within ∼60 s.