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As cartilage tissue lacks the innate ability to mount an adequate regeneration response, damage to it is detrimental to the quality of life of the subject. The emergence of three-dimensional bioprinting (3DBP) technology presents an opportunity to repair articular cartilage defects. However, widespread adoption of this technique has been impeded by difficulty in preparing a suitable bioink and the toxicity inherent in the chemical crosslinking process of most bioinks. Diphenhydramine Our objective was to develop a crosslinker-free bioink with the same biological activity as the original cartilage extracellular matrix (ECM) and good mechanical strength. We prepared bioinks containing different concentrations of silk fibroin and decellularized extracellular matrix (SF-dECM bioinks) mixed with bone marrow mesenchymal stem cells (BMSCs) for 3D bioprinting. SF and dECM interconnect with each other through physical crosslinking and entanglement. A porous structure was formed by removing the polyethylene glycol from the SF-dECM bioink. The results showed the SF-dECM construct had a suitable mechanical strength and degradation rate, and the expression of chondrogenesis-specific genes was found to be higher than that of the SF control construct group. Finally, we confirmed that a SF-dECM construct that was designed to release TGF-β3 had the ability to promote chondrogenic differentiation of BMSCs and provided a good cartilage repair environment, suggesting it is an ideal scaffold for cartilage tissue engineering.Mechanical aspects of printable hydrogels can impact cell behavior in 3D-bioprinted constructs, and in this context the stiffness of hydrogel-based bioink can serve as an important physical cue in regulating cell differentiation. Here we bioprinted mesenchymal stem cells (MSCs) by the commonly used bioink alginate-gelatin (Alg-Gel) blends and investigated the influence of stiffness on MSC differentiation toward sweat glands. Mechanical properties were assessed through compression testing and it was found that higher compressive modulus was associated with the higher Alg-Gel concentrations. Using these Alg-Gel blends for bioprinting, we demonstrated that stiffness variance cannot cause differences in cell spreading, adhesion and viability. However, MSCs bioprinted by stiffer hydrogels were found to further upregulate the protein and gene expression of sweat gland cell phenotype, function and development of signaling pathways. Furthermore, we found that the increased Yes-associated protein (YAP) localization of nuclei in MSCs when bioprinted by stiffer hydrogels. These results illustrated that the stiffness of Alg-Gel blends is a potent regulator of MSC differentiation, which was possibly achieved through a YAP-dependent mechanotransduction mechanism.Diabetic foot ulcer, one of the most common diabetic complications, is a progressive wound occurred on the skin with irregularly delayed wound healing rate due to impaired metabolism and weak immune responses. Such chronic wound remains a serious healthcare burden to the diabetics since it is often associated with high risk of limb loss due to amputation and leads to a reduced survival consequently. To improve the efficiency of diabetic wound healing, a synthetic chitosan-based composite hydrogel named SNPECHG incorporating silver ions (Ag+) and nanoparticle-encapsulated epidermal growth factor (EGF) was developed in this study. The optimal effective dosages of 24-mM Ag+ and 60-μg mL-1 EGF for the SNPECHG manufacture were first determined based on the results of antibacterial, cytotoxicity, and cell growth examinations. We then characterized the optimized SNPECHG and found that the composite hydrogel was able to provide sustained release of Ag+ and EGF, and exhibited a significantly higher hydration capacities, including the swelling degree and equilibrium water content, in PBS than those in deionized water, showing that the developed SNPECHG is highly applicable in the ion-rich environment such as chronic wound site. According to the results of in vivo study using diabetic rats, the one with SNPECHG exhibited a markedly enhanced wound healing effect compared with the other settings since day 3, and may reach a degree of wound closure of 97% at day 14 that was 7.4% (P less then 0.05) and 18.9% (P less then 0.05) higher than the values gained from the groups with the commercial dressing HeraDerm and gauze, respectively. Moreover, the wound treated with the SNPECHG exhibited thorough re-epithelization, sufficient collagen deposition, and accelerated collagen maturation confirmed by the histological analysis. Taken all together, we anticipate that the SNPECHG is highly advantageous for use in the clinical diabetic/chronic wound treatment.Temperature-responsive drug-loaded electrospun nanofibers have gained huge critical attention as efficient localized implantable devices in preventing cancer local recurrence. In this regard, a smart hyperthermia nanofiber with the simultaneous heat-generation and dual-stage drug release ability in response to 'ON-OFF' switching of an alternating magnetic field (AMF) for improved hyperthermic chemotherapy has been developed. The smart hyperthermia nanofibrous scaffolds are fabricated via electrospinning a temperature-responsive copolymer blended with iron oxide (II, III) magnetic nanoparticles (MNPs, 10 nm), metformin (MET), and mesoporous silica nanoparticles (MSNs) loaded with MET (MSNs@MET). It was found that all the magnetic nanofibers (MNFs) possess heat generation property and 'ON-OFF' switchable heating ability. The swelling ratio with reversible alterations and the corresponding drug discharge in response to AMF application with 'ON-OFF' switching was also demonstrated. MET-MNFs showed an initial rapid discharge in the 1st cycle of AMF application while MET released from MET@MSNs-MNFs exhibited a sustained release without the initial rapid discharge. It was found that MET-MET@MSNs-MNFs displayed a blend of initial rapid discharge and late prolonged drug discharge. In a magnetic field for 300 s during the second and third days, the metabolic activity of B16F10 skin melanoma cells incubated with all types of MNFs was decreased. Importantly, MET-MET@MSNs-MNFs had enhanced cytotoxicity than the MET-MNFs and MET@MSNs-MNFs (P less then .05), due to the double effects of heat and dual-stage drug release. These results demonstrated that the proposed two-stage drug discharge approach plus hyperthermia is more desirable to standard chemotherapy regimens and might effectively induce cytotoxicity via a synergistic effect over a relatively long time.
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