Tissue Engineering Part A最新文献

Tracheal reconstruction remains challenged in clinical. We aimed to fabricate scaffolded cartilage sheets with rigid and elastic supports for tracheal reconstruction. The chondrocyte cell infiltration activity was examined in poly-caprolactone sheet scaffolds with various thicknesses and pore sizes after seeding cells on the top surface of the sheet scaffolds. The expression of cartilage-related genes and accumulation of sulfated glycosaminoglycans were elevated in the cell-scaffold composites upon chondrogenic induction. The thicker cartilage sheets represented stronger mechanical properties than the thinner cartilage sheets. Two different cartilage sheets were orthotopically implanted into a trachea in a rabbit model for 2, 4, and 16 weeks. Cartilage-related sulfated glycosaminoglycans and type II collagen macromolecules were stably expressed in the tracheal implants. However, the invasive migration of fibrous tissue and profibrotic collagen fibers into cartilage implants and the peripheral space surrounding the implants were elevated in a time-dependent manner. At week 16 postimplantation, airway stenosis was noticed under the thicker sheet implants, but not the thinner implants, suggesting that the thinner (1 mm thick) scaffolded cartilage sheet was an optimal candidate for tracheal reconstruction in this study. Finally, cartilage sheets could be a reconstructive therapy candidate applied to reconstruct defects in the trachea and other tissues composed of cartilage. Impact statement Tissue engineering is a promising approach to generate biological substitutes. We aimed to develop cartilage sheets as tracheal prosthesis used in tracheal reconstruction or regional repairing in the animal model. The formation of microvessels and the dynamics of reepithelialization were monitored for 16 weeks in tracheal implants of the engineered cartilage sheets. In this study, it was demonstrated that the tissue-engineered cartilage sheets are potential substitutes applied in the reconstruction of the trachea and other tissues composed of cartilage tissue. The cartilage sheets were thought of as biomaterials for personalized regenerative medicine since the dimensions, thickness, and pore sizes of cartilage sheets were tunable to fit the lesions that need to be reconstructed.

The combination of three-dimensional (3D) printed scaffold materials and various cytokines can achieve the purpose of tissue reconstruction more efficiently. In this study, we prepared platelet-rich plasma (PRP)/gelatin microspheres combined with 3D printed polycaprolactone/β-tricalcium phosphate scaffolds to solve the key problem that PRP cannot be released under control and the release time is too short, and thus better promote bone repair. Consequently, the composite scaffold displayed a good mechanical property and sustained cytokine release for ∼3 weeks. Increased survival, proliferation, migration, and osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells were observed compared with the control groups. The in vivo study demonstrated that the composite scaffold with PRP/gelatin microspheres led to greater positive effects in promoting large bone defect repair. In conclusion, in this study, a new type of PRP long-term sustained-release composite scaffold material was constructed that effectively improved the survival, proliferation, and differentiation of cells in the transplanted area, thereby better promoting the repair of large bone defects. Impact statement Reconstruction of bone tissue and blood vessels at bone defects takes time. Platelet-rich plasma (PRP) has been widely used in bone defect repair because it contains a variety of cytokine that can promote local osteogenesis and angiogenesis. In this study, we constructed a new type of polycaprolactone/β-tricalcium phosphate/PRP/gelatin scaffold to solve the predicament of short cytokine release time in PRP-related materials. We proved that this scaffold can not only achieve long-term PRP-related cytokine release (more than 3 weeks) but also promote osteogenesis and bone defect repair. We believe that this is a novel concept of developing the sustained PRP-related cytokine releasing bioscaffold for treating large bone defect.

Renal fibrosis (RF) predisposes patients to an increased risk of progressive chronic kidney disease, and effective treatments remain elusive. Mesenchymal stem cell (MSC)-derived exosomes are considered a new treatment for tissue damage. Our study aimed to investigate the in vitro effects of bone marrow MSC-derived exosomes (BM-MSC-Exs) on transforming growth factor-β1 (TGF-β1)-induced fibrosis in renal tubular epithelial cells (HK-2 cells) and the associated mechanisms. Herein, we found BM-MSC-Exs could inhibit TGF-β1-induced epithelial-mesenchymal transition (EMT) in HK-2 cells, and may involve autophagy activation of BM-MSC-Exs. Moreover, we first reported that after ceria nanoparticles (CeNPs) treatment, the improvements induced by BM-MSC-Ex on EMT were significantly enhanced by upregulating the expression of Nedd4Lof MSCs and promoting the secretion of exosomes, which contained Nedd4L. In addition, Nedd4L could activate autophagy in HK-2 cells. In conclusion, BM-MSC-Ex prevents the TGF-β1-induced EMT of renal tubular epithelial cells by transporting Nedd4L, which activates autophagy. The results of this in vitro experiment may extend to RF, whereby BM-MSC-Ex may also be used as a novel treatment for improving RF. Impact statement Renal fibrosis (RF) is an important pathological change in chronic kidney disease that ultimately leads to end-stage renal failure, and effective treatments remain elusive. In this study, there are two contributions. First, our results suggest that bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exs) can prevent transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells through Nedd4L trafficking, which activates autophagy. Second, the improvement effects of BM-MSC-Ex on TGF-β1-induced HK-2 EMT can be enhanced by ceria nanoparticles (CeNPs). The findings in this study may be extended to RF: BM-MSC-Exs may be used as a novel treatment to improve RF.

The nasal mucosa functions as a frontline biological defense against various foreign substances and pathogens. Maintaining homeostasis of the nasal epithelium is necessary to promote good health. Nasal epithelia are constantly replaced under normal conditions. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Since there is no treatment for this underlying condition, extrinsic manipulation is necessary to recover and maintain nasal epithelia in cases of hereditary diseases. In this study, we explored the use of airway epithelial cells (AECs), including multiciliated airway cells, derived from human induced pluripotent stem cells (iPSCs) on porcine atelocollagen vitrigel membranes, as a candidate of a therapeutic method for irreversible nasal epithelial disorders. To confirm the regenerative capacity of iPSC-derived AECs, we transplanted them into nasal cavities of nude rats. Although the transplanted cells were found within cysts isolated from the recipient nasal respiratory epithelia, they survived in some rats. Furthermore, the surviving cells were composed of multiple cell types similar to the human airway epithelia. The results could contribute to the development of novel transplantation-related technologies for the treatment of severe irreversible nasal epithelial disorders. Impact Statement Nasal respiratory epithelia are important for the functions of nasal cavity, including humidifying the air and filtering various toxic substances. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Our novel method to transplant airway epithelial cells derived from human induced pluripotent stem cells will be a candidate method to replace malfunctioned nasal respiratory epithelia in such a situation. To secure our method's safety, we used porcine atelocollagen vitrigel membranes, which prevent the immune response and bovine spongiform encephalopathy, as a scaffold.