Vascularized silk electrospun fiber for promoting oral mucosa regeneration

Chunyu Qian,Tianwen Xin,Zhen Wang,Ruoyu Cheng,Wenguo Cui,Zili Ge,Qiang Zhang,Lili Liu,Wanshu Xiao,Huajun Zhu

doi:10.1038/s41427-020-0221-z

Abstract

Electrospun fiber membranes have been extensively researched for tissue repair; however, fiber angiogenesis has been a difficult problem because the biomaterials used to prepare the fiber cannot promote angiogenesis by themselves. To endow the fiber with the function of promoting angiogenesis and oral mucosa regeneration, surface-aminated liposomes (NH2-LIPs) encapsulating leptin, as well as silk fiber (SF) membranes that have been immersed overnight in polydopamine (PDA) solution were synthesized. The NH2-LIPs were then grafted onto the surfaces of SF through reactions between the catechol groups of PDA and the amino groups of NH2-LIPs to induce angiogenesis on the fiber surface and thus promote oral mucosa regeneration. The PDA-modified and NH2-LIP-modified SF retained the original fibrous morphology but increased the SF tensile strength from 1.95 MPa to 2.87 MPa. PDA changed the hydrophilicity of the fibers and improved the adhesion of fibroblasts on the fibrous membranes. Leptin loaded onto SF via PDA had no significant effect on cell proliferation and formed 162.7-node tubes in human umbilical vein endothelial cells (HUVECs) within 10 h, which demonstrated that leptin loaded onto SF can promote angiogenesis. Wound closure of mucosa covered in leptin-loaded fibrous membranes reached 99% at 14 days postsurgery. Histologic analysis showed that leptin-loaded SFs exhibited clear stratification of new mucosa, as well as a strong CD34 signal that indicated the presence of new blood vessels and confirmed the successful loading of leptin on the fiber. Therefore, this work successfully showed that NH2-LIPs grafted onto the surface of SFs via PDA endow the fibers with angiogenic abilities and promote oral mucosa regeneration.

Highlights

Angiogenesis is a highly complex process that plays a vital role in the normal development of the human body and the pathophysiology of various diseases[1,2,3]
NH2-LIPs encapsulating leptin were fabricated by thin film dispersion of DSPE-PEG-NH2, lecithin and cholesterol (Scheme 1a)
NH2-LIPs grafted onto the surfaces of electrospinningproduced silk fiber (SF) membranes via conjugation with PDA can locally release leptin to stimulate blood vessel regeneration and promote healing of damaged oral mucosa

Summary

Introduction

Angiogenesis is a highly complex process that plays a vital role in the normal development of the human body and the pathophysiology of various diseases[1,2,3]. The surface of the fiber membrane is difficult to vascularize due to a lack of factors for angiogenesis induction. Electrospun fibers can load bioactive factors to promote angiogenesis[22]. Leptin promotes angiogenesis during tumor formation by stimulating the high expression of angiogenic factors through pathways including STAT3 and MAPK23,26. The loading of leptin into electrospun fiber membranes is expected to solve the problem of fiber membrane angiogenesis. When producing fibers for subsequent drug loading, the types of electrospinning used are blend electrospinning[27,28], coaxial electrospinning[29,30], emulsion electrospinning[31,32], and microsol electrospinning[33]. There is an urgent need for electrospun fiber membranes capable of being loaded with leptin but without the above disadvantages in order to enable vascularization of the fiber membrane

Methods

Results

Conclusion