Bioinspired and osteopromotive polydopamine nanoparticle-incorporated fibrous membranes for robust bone regeneration

Yi Deng,Shi-Cheng Wei,Xiao-Ling Xiong,Minjie Wu,Dong Shi,Zhi-Gang Chen,Wei-Zhong Yang

doi:10.1038/s41427-019-0139-5

Abstract

Due to their inherent hydrophobic and bioinert nature, synthetic degradable polymer-based membranes show inferior stem cell attachment, proliferation, and even differentiation. To overcome these limitations, bioinspired and osteopromotive polydopamine nanoparticle-incorporated fibrous membranes are developed via a two-step route: pH-induced polymerization of dopamine and co-electrospinning of polycaprolactone (PCL) with polydopamine nanoparticles (PDA NPs). Hybrid membranes with optimized PDA NP content exhibit high quantities of apatite deposition and prominent cytocompatibility (cell attachment, spreading and reproduction) and osteo-differentiation potential (alkaline phosphatase activity, calcium mineralization, and osteogenesis-related genes and protein expression) of human mesenchymal stem cells cultured without any growth factors. Importantly, in vivo assessments using a mouse calvarial critical-sized defect demonstrate that the engineered fibrous membranes remarkably boost bone reconstruction and regeneration. Accordingly, our bioinspired PCL-based hybrid fibrous membranes with robust osteoinductive ability can potentially be utilized as a clinically applicable candidate in guided tissue regeneration applications.

Highlights

IntroductionBone defects and injuries (e.g., surgical resections, nonunions, and fractures) are common microscopic defects because of diseases, congenital abnormalities, accidents, and military injuries[1,2,3]
Bone defects and injuries are common microscopic defects because of diseases, congenital abnormalities, accidents, and military injuries[1,2,3]
Electrospun membranes have captured tremendous attention in recent years for guided tissue engineering applications considering the following advantages: (1) the membranes can mimic the niche where stem cells reside[7]; (2) the porous fibers possess a large surface area, which provides a friendly environment to support cell attachment and growth; and (3) the 3D fibrous micromilieu of membranes dramatically accelerates the osteogenic potential of numerous stem cell lines, including mouse osteoblastic progenitor cells, rat/human mesenchymal stem cells, human adipose stem cells, and human pluripotent stem cells[8,9,10]

Summary

Introduction

Bone defects and injuries (e.g., surgical resections, nonunions, and fractures) are common microscopic defects because of diseases, congenital abnormalities, accidents, and military injuries[1,2,3]. Most of these cannot be healed spontaneously via a self-repairing mechanism. Electrospun membranes have captured tremendous attention in recent years for guided tissue engineering applications considering the following advantages: (1) the membranes can mimic the niche where stem cells reside[7]; (2) the porous fibers possess a large surface area, which provides a friendly environment to support cell attachment and growth; and (3) the 3D fibrous micromilieu of membranes dramatically accelerates the osteogenic potential of numerous stem cell lines, including mouse osteoblastic progenitor cells, rat/human mesenchymal stem cells, human adipose stem cells (hASCs), and human pluripotent stem cells (hPSCs)[8,9,10]. A composite nanofibrous membrane consisting of poly(L-lactic acid)/poly(benzyl-L-glutamate)/collagen (PLLA/PBLG/ Col) was prepared through electrospinning, possessing the capability to enhance the osteogenic conversion of

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Conclusion