Creating Biomimetic Anisotropic Tissue Engineering Scaffolds with Co-Aligned Nanofibers and Macrochannels by Manipulating Ice Growth


Most scientific and technological advancements have been achieved through the successful mimicking of various natures’ ingenious systems. Specifically, scaffolds formed by natural polymers play vital roles in tissue engineering owing to their excellent biodegradability and biocompatibility. Ideally, a scaffold ought to not only provide a 3D environment and support, but also direct cell behavior and functions. Therefore, it is imperative for a scaffold to mimic the structural features and functions of the natural extracellular matrix which is a nanofibrous web. In particular, a combination of aligned nanofibers and interconnected macrochannels is very important for the development of functional scaffolds mimicking the natural extracellular matrix of anisotropic tissues such as nerve and tendon tissues. So far, various techniques, especially 3D printing, lyophilization and electrospinning have been used to produce scaffolds for tissue engineering applications. Unfortunately, none of these techniques is capable of coupling aligned nanofibers with aligned interconnected macrochannels which always go in the opposite direction.

Against the challenge, recently, Deakin University researchers: Dr. Linpeng Fan, A/Prof. Jing-Liang Li, Dr. Zengxiao Cai, and Prof. Xungai Wang developed a facile guided ice-crystal growth and nanofiber assembly strategy to create a biomimetic scaffold composed of oriented nanofibers and interconnected macrochannels in the same direction. They utilized various biomacromolecules, including silk fibroin, hand in hand with this facile strategy to create various types of biomimetic anisotropic nanofibrous scaffolds. Their work is currently published in the research journal, ACS Nano.

The research technique employed entailed, first, the creation of oriented fine ice crystals to guide the assembly of oriented nanofibers. This was achieved by immersing a solution of silk fibroin in a medium with a very low temperature. Next, the researchers utilized the oriented nanofibers to guide the oriented growth of large ice crystals along the fiber direction into the scaffold, which in turn led to further assembly of the nanofibers to form aligned macrochannels in their long-axis direction.

The researchers found that the biomimetic anisotropic 3D silk fibroin nanofibrous scaffold showed significantly higher cell capture and growth-promoting capability than the widely used porous 3D silk fibroin scaffolds and the 3D aligned silk fibroin nano-fibrous scaffold without macrochannels for both non-adherent dorsal root ganglion neurons and adherent human umbilical vein endothelial cells (HUVECs). Moreover, the co-aligned nanofibers and macrochannels of the biomimetic anisotropic 3D scaffold were seen to not only direct the neurite growth of dorsal root ganglion neurons in the 3D space similar to the natural nerve conduit but also regulate the growth, migration, alignment, elongation, and interaction of HUVECs to assemble into blood vessel-like structures as well as the deposition of collagen in their direction in vitro.

The researchers demonstrated that the scaffold they developed served as an excellent model platform for the proof of concept that the creation of the extracellular matrix-mimicking 3D structure is very important for providing insight into cell behaviors and functions. In the scaffold, the macrochannels provide space for cell and tissue growth as well as exchange and transport of oxygen, nutrients, and waste. And the aligned nanofibers direct cells to grow in their direction. This is a type of active scaffolds which can direct the healthy cells or tissues to grow towards the target site. This is very important to accelerate the regeneration of damaged tissues. For example, for the healing of chronic skin ulcers, a scaffold with radially coaligned nanofibers and macrochannels can direct the peripheral healthy cells to grow inwards and thus accelerate the regeneration of local skin tissues. 

Creating Biomimetic Anisotropic Tissue Engineering Scaffolds with Co-Aligned Nanofibers and Macrochannels by Manipulating Ice Growth - Advanced Engineering
Fabricating 3D Scaffolds with Radially Co-Aligned Nanofibers and Interconnected Macrochannels (A(F&C) Scaffolds) by a Facilely Guided Ice-Crystal Growth and Nanofiber Assembly Strategy, with Silk Fibroin (SF) as an Example. (Reprinted with permission from (ACS Nano 2018, 12, 6, 5780-5790). Copyright (2018) American Chemical Society.)


About the author

Dr.Linpeng Fan received his PhD degree in Materials Science and Engineering from Deakin University, Australia. Currently he is a Research Fellow in Institute for Frontier Materials, Deakin University. Dr. Fan is an active researcher in the field of Biomaterials and Tissue Engineering.

His research is primarily focused on the development of innovative nano/microfibers and porous materials for application in cell culture, drug delivery, personal skin care, tissue regeneration etc. He has published over 20 peer-reviewed articles in journals such as ACS Nano, Journal of Controlled Release, Journal of Materials Chemistry etc. He has been invited to submit 10 papers for some professional international conferences.

Indeed Dr. Fan has more interest in transforming his research outcomes into practical applications. He has issued 10 patents and some of them have been transferred to industrials. Dr. Fan’s achievements have been recognized by numerous highly prestigious awards including Innovation and Entrepreneurship Award.

E-mail: [email protected]

About the author

A/Prof. Jingliang Li received his PhD degree from the National University of Singapore (NUS) in 2004. He is an Australia Research Council (ARC) Future Fellow and associate professor at Deakin University, Australia. Before moving to Deakin University in 2011, he has been research fellows at the Physics department of NUS and Swinburne University of Technology (Australia). His expertise covers soft materials (gels, nature protein and related biomaterials) and bionanotechnology. He has published over 100 peer-reviewed journal articles, a number of book chapters, and edited one book (Soft Fibrillar Material: fabrication and applications).

His current research focuses on the formation mechanisms of fibers in soft materials and their applications for energy and biomedical applications. He is a chief investigator on a number of projects supported by the ARC.


Linpeng Fan, Jing-Liang Li, Zengxiao Cai, Xungai Wang. Creating Biomimetic Anisotropic Architectures with Co-Aligned Nanofibers and Macrochannels by Manipulating Ice Crystallization. ACS Nano 2018, volume 12, 5780−5790

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