Hagengunter4770

Extrusion bioprinting is a popular method for fabricating tissue engineering scaffolds because of its potential to rapidly produce complex, bioactive or cell-laden scaffolds. However, due to the relatively high viscosity required to maintain shape fidelity during printing, many extrusion-based inks lack the ability to achieve precise structures at scales lower than hundreds of micrometers. In this work, we present a novel poly(N-isopropylacrylamide) (PNIPAAm)-based ink and poloxamer support bath system that produces precise, multi-layered structures on the tens of micrometers scale. The support bath maintains the structure of the ink in a hydrated, heated environment ideal for cell culture, while the ink undergoes rapid thermogelation followed by a spontaneous covalent crosslinking reaction. Through the combination of the PNIPAAm-based ink and poloxamer bath, this system was able to produce hydrogel scaffolds with uniform fibers possessing diameters tunable from 80 to 200 μm. A framework of relationships between several important printing factors involved in maintaining support and thermogelation was also elucidated. As a whole, this work demonstrates the ability to produce precise, acellular and cell-laden PNIPAAm-based scaffolds at high-resolution and contributes to the growing body of research surrounding the printability of extrusion-based bioinks with support baths.Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues. However, the application of these fluorescence contrast agents in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) was dramatically hammered as a result of lacking active targeting and poor retention time in tumor, which limited the Signal to Noise Ratio (SNR) and narrowed the imaging window for complicated surgery. Herein, we reported an activated excretion-retarded tumor imaging (AERTI) strategy, which could be in situ activated with MMP-2 and self-assembled on the surface of tumor cells, thereby resulting in a promoted excretion-retarded effect with an extended tumor retention time and enhanced SNR. Briefly, the AERTI strategy could selectively recognize the Integrin αvβ3. Afterwards, the AERTI strategy would be activated and in situ assembled into nanofibrillar structure after specifically cleaved by MMP-2 upregulated in a variety of human tumors. We demonstrated that the AERTI strategy was successfully accumulated at the tumor sites in the 786-O and HepG2 xenograft models. More importantly, the modified modular design strategy obviously enhanced the SNR of AERTI strategy in the imaging of orthotopic RCC and HCC. Taken together, the results presented here undoubtedly confirmed the design and advantage of this AERTI strategy for the imaging of tumors in metabolic organs.Early childhood caries (ECC) is a public healthcare concern that greatly reduces the quality of life of young children. As a leading factor of ECC, cariogenic biofilms are composed of acidogenic/aciduric pathogens and extracellular polysaccharides (EPSs), creating an acidic and protected microenvironment. Antimicrobial photodynamic therapy (aPDT) is a noninvasive, painless, and efficient therapeutic approach that is suitable for treating ECC. However, due to the hyperfine structure of cariogenic biofilms, most photosensitizers (PSs) could not access and penetrate deeply in biofilms, which dramatically hamper their efficiency in the clinic. Herein, bioresponsive nanoparticle loaded with chlorin e6 (MPP-Ce6) is developed, which largely increases the penetration depth (by over 75%) and retention (by over 100%) of PS in the biofilm compared with free Ce6. Furthermore, MPP-Ce6-mediated aPDT not only kills the bacteria in preformed biofilms but also inhibits multispecies biofilm formation. A rampant caries model is established to mimic ECC in vivo, where the population of cariogenic bacteria is decreased to 10% after MPP-Ce6-mediated aPDT. Importantly, the number and severity of carious lesions are efficiently reduced via Keyes' scoring and micro-CT analysis. This simple but effective strategy can serve as a promising approach for daily oral hygiene in preventing ECC.Nanosized extracellular vesicles derived from bacteria contain diverse cargo and transfer intercellular bioactive molecules to cells. Due to their favorable intercellular interactions, cell membrane-derived bacterial extracellular vesicles (BEVs) have great potential to become novel drug delivery platforms. In this review, we summarize the biogenesis mechanism and compositions of various BEVs. In addition, an overview of effective isolation and purification techniques of BEVs is provided. In particular, we focus on the application of BEVs as bioactive nanocarriers for drug delivery. Finally, we summarize the advances and challenges of BEVs after providing a comprehensive discussion in each section. We believe that a deeper understanding of BEVs will open new avenues for their exploitation in drug delivery applications.Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drug-eluting stents for the treatment of obstructive coronary artery disease. Any bioresorbable or biodegradable scaffold material needs to possess optimal mechanical properties and uniform degradation behavior that avoids local and systemic toxicity. Recently, molybdenum (Mo) has been investigated as a potential novel biodegradable material for this purpose. With its proven moderate degradation rate and excellent mechanical properties, Mo may represent an ideal source material for clinical cardiac and vascular applications. The present study was performed to evaluate the mechanical performance of metallic Mo in vitro and the biodegradation properties in vivo. The results demonstrated favorable mechanical behavior and a uniform degradation profile as desired for a new generation ultra-thin degradable endovascular stent material. Moreover, Mo implants in mouse arteries avoided the typical cellular response that contributes to restenosis. There was minimal neointimal hyperplasia over 6 months, an absence of excessive smooth muscle cell (SMC) proliferation or inflammation near the implant, and avoidance of significant harm to regenerating endothelial cells (EC). Qualitative inspection of kidney sections showed a potentially pathological remodeling of kidney Bowman's capsule and glomeruli, indicative of impaired filtering function and development of kidney disease, although quantifications of these morphological changes were not statistically significant. Together, the results suggest that the products of Mo corrosion may exert beneficial or inert effects on the activities of inflammatory and arterial cells, while exerting potentially toxic effects in the kidneys that warrant further investigation.Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration. Decalcified bone matrix (DBM) is considered as an ideal bone regeneration scaffold, but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration. To address these problems, we proposed a novel strategy of bone regeneration units (BRUs) based on microgels produced by photo-crosslinkable and microfluidic techniques, containing both the osteogenic ingredient DBM and vascular endothelial growth factor (VEGF) for accurate biomimic of an osteoinductive microenvironment. The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. BRUs were successfully constructed by seeding BMSCs onto microgels, which achieved reliable bone regeneration in vivo. Finally, by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength, a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia. The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair..The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics. This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest (CNC)-like cells (CNCLCs); these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells (iPSCs). CNC is the anterior region of the neural crest in vertebrate embryos, which contains the primordium of dental pulp cells or odontoblasts. The produced CNCLCs showed approximately 2.5-12,000-fold upregulations of major CNC marker genes. Furthermore, the CNCLCs exhibited remarkable odontoblastic differentiation ability, especially when treated with a combination of the fibroblast growth factors (FGFs) FGF4 and FGF9. The FGFs induced odontoblast marker genes by 1.7-5.0-fold, as compared to bone morphogenetic protein 4 (BMP4) treatment. In a mouse subcutaneous implant model, the CNCLCs briefly fated with FGF4 + FGF9 replicated dental pulp tissue characteristics, such as harboring odontoblast-like cells, a dentin-like layer, and vast neovascularization, induced by the angiogenic self-assembling peptide hydrogel (SAPH), SLan. SLan acts as a versatile biocompatible scaffold in the canal space. This study demonstrated a successful collaboration between regenerative medicine and SAPH technology.Approximately 25% of patients with congenital heart disease require implantation of patches to repair. However, most of the currently available patches are made of inert materials with unmatched electrical conductivity and mechanical properties, which may lead to an increased risk for arrhythmia and heart failure. In this study, we have developed a novel Polyurethane/Small intestinal submucosa patch (PSP) with mechanical and electrical properties similar to those of the native myocardial tissue, and assessed its feasibility for the reconstruction of right ventricular outflow tract. A right ventricular outflow tract reconstruction model was constructed in 40 rabbits. Compared with commercially available bovine pericardium patch, the PSP patch has shown better histocompatibility and biodegradability, in addition with significantly improved cardiac function. To tackle the significant fibrosis and relatively poor vascularization during tissue remodeling, we have further developed a bioactive patch by incorporating the PSP composites with urine-derived stem cells (USCs) which were pretreated with hypoxia. The results showed that the hypoxia-pretreated bioactive patch could significantly inhibit fibrosis and promote vascularization and muscularization, resulting in better right heart function. Our findings suggested that the PSP patch combined with hypoxia-pretreated USCs may provide a better strategy for the treatment of congenital heart disease.