The simultaneous regeneration of avascular cartilage ring and vascular connective tissue in one biomimetic tracheal substitute has remained a remarkable challenge in the clinical breakthrough of tissue-engineered trachea for repairing segmental trachea defect. Herein, an unprecedented strategy based on bidirectional modulation of vascular niches is developed through tailoring the tissue-specific scaffolds with programmable functional nucleic acids. Namely, the antiangiogenic characteristic of cartilage-specific scaffold enables development of an avascular niche, and thereby facilitating the regeneration of biomimetic cartilage. Conversely, the angiogenic capability of connective tissue-specific scaffold fosters the creation of a vascular niche, and thus enhancing the regeneration of biomimetic connective tissue. Importantly, the steadily immobilized nucleic acids in specific scaffolds enable the seamless integration of angiogenic and antiangiogenic functions without mutual interference. As such, biomimetic tracheas are successfully engineered with the vascular connective tissue scattering between avascular cartilage rings using the assembly of tissue-specific scaffolds. The results from in vivo trachea regeneration and the in situ trachea reconstruction demonstrate the satisfactory tissue-specific regeneration of (a)vascular niches along with optimal structural, mechanical, and physiological features. This study represents the first demonstration of trachea regeneration promoted by modulation of tissue-specific vascular niches, which adds an additional dimension for the clinical trachea reconstruction.
Zeyang Liu,Haochen Nan,Yi Shiou Chiou,Zhen Zhan,Peter E. Lobie,Chengzhi Hu
Tissue-engineered periosteum substitutes (TEPSs) incorporating hierarchical architecture with osteoprogenitor and vascular niches are drawing much attention as a promising tool to support functional cells in defined zones and nourish the cortical bone. Current TEPSs usually lack technologies to closely observe cell performance, especially at the cell contact interface between distinct compartments containing defined biological configurations and functions. Here, an electrodeposition strategy is reported, which enables the selective formation of TEPSs with osteoprogenitor and vascular niches in a multiphasic scaffold in combination with different human cell types for cartilage regeneration in an in vivo osteochondral defect model. Human umbilical vein endothelial cells (HUVECs), dermal fibroblasts (HDFs), and bone marrow mesenchymal stem cells (hMSCs) are used to mirror both the vascular and osteogenic niches, respectively. It is observed that the intrinsic viscoelastic nature of the porous solid matrix is essential to successfully induce angiogenesis. Coculture of hMSCs with functional cells (HUVECs/HDFs) in TEPSs also effectively promoted periosteal regeneration, including osteogenic and angiogenic processes. The osteoarthritis cartilage histopathology assessment and histologic/histochemical grading system data indicate that the TEPSs containing hMSCs/HUVECs/HDFs exhibit superior potential for cartilage regeneration.
危险品化学品经营许可证（带存储）