The skin is the largest human organ, and defects in the skin with a diameter greater than 4 cm do not heal without treatment. Allogeneic skin transplantation has been used to allow wound healing, but many grafts do not survive after implantation, due to multiple complications in the procedure. In the present study, the vascularization of three-dimensional (3D) printed full-thickness skin grafts was investigated. Dermal-epithelial grafts were transplanted into a nude mouse model to evaluate integration with the host tissue and the extent of wound healing. To create microvessels in the skin grafts, a bilayer structure consisting of human dermal fibroblasts, keratinocytes, and microvascular endothelial cells was designed and fabricated using an extruded 3D printer. Human dermal fibroblasts and human microvascular endothelial cells were mixed with gelatin-sodium alginate composite hydrogel as the dermis, and human keratinocytes were mixed with gel as the epithelium. Confocal imaging allowed visualization of the location of the cells in the double-layer skin grafts. A full-thickness wound was created on the backs of nude mice and then covered with a double-layer skin graft. Various groups of mice were tested. Animals were euthanized and tissue samples collected after specified time points. Compared with the control group, wound contraction improved by approximately 10%. Histological analysis demonstrated that the new skin had an appearance similar to that of normal skin and with a significant degree of angiogenesis. The results of the immunohistochemical analysis demonstrated that the transplanted cells survived and participated in the healing process.
Introduction: Hypertensive nephropathy is characterized by glomerular and tubulointerstitial damage, but we know little about changes in cell-specific gene expression in the early stages of hypertensive kidney injury, which usually has no obvious pathological changes. Methods: We performed unbiased single-cell RNA sequencing of rat kidney samples from hypertensive kidney injury to generate 10602 single-cell transcriptomes from 2 control and 2 early stage of hypertensive kidney injury samples. Results: All major cell types of the kidney were represented in the final dataset. Side-by-side comparisons showed that cell type-specific changes in gene expression are critical for functional impairment of glomeruli and tubules and activation of immune cells. In particular, we found a significantly reduced gene expression profile of maintaining vascular integrity in glomerular cells of hypertensive kidney injury. Meanwhile, the expression of genes associated with oxidative stress injury and fibrosis in the renal tubules and collecting ducts was elevated, but the degree of tubular cells response to injury differed between parts. We also found a signature of immune cell infiltration in hypertensive kidney injury. Discussion/Conclusion: Exploring the changes of gene expression in hypertension-injured kidneys may be helpful to identify the early biomarkers and signal pathways of this disease. Our data provide rich resources for understanding the pathogenesis of hypertensive renal injury and formulating effective treatment strategies.
In recent years, with the development of biological 3D printing technology, especially the development of soft tissue engineering, new hope has been brought to solve clinical problems such as soft tissue defects and functional loss. The blood vessels network is essential in large pieces of tissue because blood can nourish the ambient cells proliferation and metabolism. Currently, most bio-printing technologies can only print single-size micro-channels, which affect the normal proliferation and metabolism of internal cells. In our previous study, a multi-level and multi-size bionic vascular network was molded by mould. The bionic structure could promote cells endothelialization but the preparation process was complex and the precision was very low. In this paper, a 3D vascular network/soft tissue and multi-material dual-nozzle cells printing platform is developed and then, a FDM 3D collaborative printing method is proposed to fabricate self-assembled scaffold within multi-level and multi-size bionic vascular network. The forming process is fast and sterile with the highprecision self-assembled scaffold structure printed. It is envisioned that this technology can be used to study the basis of composite tissue technology with multi-material supply and multi-nozzle printing, and to establish the theoretical basis of the correlation between vascular/soft tissue symbiosis system and the performance of artificial soft tissue.
Valved conduits often correct the blood flow of congenital heart disease by connecting the right ventricle to the pulmonary artery (RV-PA). The homograft valved conduit was invented in the 1960s, but its wide application is limited due to the lack of effective sterilization and preservation methods. Modern cryopreservation prolongs the preservation time of homograft valved conduit, which makes it become the most important treatment at present, and is widely used in Ross and other operations. However, homograft valved conduit has limited biocompatibility and durability and lacks any additional growth capacity. Therefore, decellularized valved conduit has been proposed as an effective improved method, which can reduce immune response and calcification, and has potential growth ability. In addition, as a possible substitute, commercial xenograft valved conduit has certain advantages in clinical application, and tissue engineering artificial valved conduit needs to be further studied.
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