HA-coated collagen nanofibers for urethral regeneration via in situ polarization of M2 macrophages

Yuqing Niu,Florian J Stadler,Guochang Liu,Fuming Deng,Xu Yang,Huimin Xia

doi:10.1186/s12951-021-01000-5

Yuqing Niu, Florian J Stadler + Show 4 more

Open Access

https://doi.org/10.1186/s12951-021-01000-5

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Abstract

In situ tissue engineering utilizes the regenerative potential of the human body to control cell function for tissue regeneration and has shown considerable prospect in urology. However, many problems are still to be understood, especially the interactions between scaffolds and host macrophages at the wound site and how these interactions direct tissue integration and regeneration. This study was designed to evaluate the efficacy of hyaluronic acid (HA) functionalized collagen nanofibers in modulating the pro-healing phenotype expression of macrophages for urethral regeneration. Tubular HA-collagen nanofibers with HA-coating were prepared by coaxial electrospinning. The formation of a thin HA-coating atop each collagen nanofiber endowed its nanofibrous mats with higher anisotropic wettability and mechanical softness. The macrophages growing on the surface of HA-collagen nanofibers showed an elongated shape, while collagen nanofibers’ surface exhibited a pancake shape. Immunofluorescence and ELISA analysis showed that elongation could promote the expression of M2 phenotype marker and reduce the secretion of inflammatory cytokines. In vivo experiments showed that tubular HA-collagen nanofibers significantly facilitate male puppy urethral regeneration after injury. In the regenerated urethra bridged by tubular HA-collagen nanofibers, anti-inflammatory M2 macrophages are recruited to the surface of the scaffold, which can promote angiogenesis and endogenous urothelial progenitor cell proliferation.

Highlights

Regenerative medicine (RM) of tubular or hollow organs is a developing field of multi-disciplinary including materials science, engineering, biomedical and clinical research [1]
There is no significant difference in the distribution of elements on the surface of collagen and hyaluronic acid (HA)-collagen nanofibers
The results showed that the expression of IL-10 in the grafted urethra bridged by tubular HA-collagen nanofibers was significantly higher than that in the tubular collagen nanofibers group (Fig. 5B), indicating that HA-collagen nanofibers can regulate macrophage polarization to M2 phenotype to guide the recruitment of endogenous urothelial progenitor cells

Summary

Introduction

Regenerative medicine (RM) of tubular or hollow organs is a developing field of multi-disciplinary including materials science, engineering, biomedical and clinical research [1]. Tubular HA‐collagen nanofibers recruit endogenous urothelial progenitor cells in wound site via in situ polarization of M2 macrophages Studies have shown that the phenotypic polarization of macrophages determines the immune response shortly after the implantation of biomaterial scaffolds.

Results

Conclusion