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Electrospun Polycaprolactone 3D Nanofibrous Scaffold with Interconnected and Hierarchically Structured Pores for Bone Tissue Engineering.

Significance Statement

Ultrathin fibers (with diameters from tens to hundreds of nanometers, commonly known as electrospun nanofibers) prepared via the electrospinning method are of great interests for tissue engineering applications, because electrospun nanofibers have diameters similar to those of fibrous structures in natural extracellular matrix (ECM).  The major limitation of electrospun scaffolds is owing to their morphological structure of overlaid nanofiber mats with apparent/equivalent pore sizes in sub-micrometers; in other words, electrospun nanofibrous mats lack the needed macropores (with sizes from tens to hundreds of micrometers) for cell growth and tissue formation.

In the reported studies, novel electrospun three-dimensional (3D) nanofibrous scaffold has been developed by an innovative and convenient approach (i.e., thermally induced nanofiber self-agglomeration followed by freeze drying) from a biopolymer of polycaprolactone (PCL) for the first time, and the scaffold possesses interconnected and hierarchically structured pores (in specific, the macropores with sizes in hundreds of micrometers would maintain the structural stability of scaffold, support cell proliferation, ECM deposition, and tissue formation; the medium pores with sizes in tens of micrometers or smaller would facilitate the diffusion of nutrients and promote the formation of vascularization, while the small pores with sizes in micrometers or smaller would have impacts on some cell behaviors such as seeding and genes expressions).  The novel polycaprolactone 3D scaffold is soft and elastic with very high porosity of ~96.4%, thus it is morphologically/structurally similar to natural ECM and well-suited for cell functions (e.g., adhesion, proliferation, migration, and differentiation) and tissue formation.

The in vitro studies reveal that the novel scaffold can lead to high cell viability; more importantly, it is able to promote more potent bone morphogenetic protein 2 (BMP2) induced chondrogenic (rather than osteogenic) differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs).  Consistent to the in vitro findings, the in vivo results indicate that electrospun polycaprolactone 3D scaffold acts as a favorable synthetic ECM for functional bone regeneration through the physiological endochondral ossification process (i.e., through formation of cartilage intermediate), which is a new strategy of “developmental tissue engineering” to mimic natural endochondral bone repair process.  Hence, it is envisioned that the developed electrospun polycaprolactone 3D nanofibrous scaffold would be very promising for tissue engineering applications including the regenerations of bone, cartilage, and their composite tissue of osteochondral (an especially challenged tissue repair in clinics).

About The Author

Dr. Hongli Sun is an Assistant Professor in the Biomedical Engineering program at the University of South Dakota (USD).  Prior to joining the faculty at the USD, he worked as a Research Fellow in the Department of Biologic and Materials Sciences at the University of Michigan.  Dr. Sun earned his Ph.D. in Cell Biology from the Chinese Academy of Sciences (Shanghai, China) in 2007.  Inspired by the fundamental findings in stem cell and developmental biology, Dr. Sun’s research has been focusing on the development of novel stem cell/nano-biomaterials based translational strategies for challenged bone regeneration.  Dr. Sun has authored many articles in peer-reviewed journals including Biomaterials, Stem Cells, and Tissue Engineering.  In addition, he has been serving as a manuscript/grant reviewer in the fields related to bone, stem cells, and tissue engineering.

 

About The Author

Dr. Hao Fong is one of the pioneers and renowned scientists worldwide in the field of “Electrospinning and Nanofibers”.  Presently, he is a tenured Full Professor in the Department of Chemistry and Applied Biological Sciences at the South Dakota School of Mines and Technology (SDSM&T); and he is also an important faculty member in the SDSM&T’s multidisciplinary graduate programs of Materials Engineering and Science (MES), Nanoscience and Nanoengineering (NANO), and Biomedical Engineering (BME).  His highest degree is a Ph.D. earned in 1999 from the Department of Polymer Science at the University of Akron (in Ohio, USA).  Prior to joining the faculty at the SDSM&T in 2003, he worked as a guest research scientist in the Polymer Branch of the Air Force Research Laboratory (AFRL) in the Wright-Patterson Air Force Base, and as a staff research scientist in the Paffenbarger Research Center of the American Dental Association (PRC-ADA) and/or the Polymer Division at the National Institute of Standards and Technology (NIST) in Maryland, for a total of three years.  In the recent years, Dr. Hao Fong’s research interests have been focused on “The Materials-processing Technique of Electrospinning and Various Applications of Electrospun Polymer, Ceramic, Carbon/Graphite, Metallic, Composite, and Hierarchically-structured Nanofibers and/or Nanofibrous Materials”.  The applications include, but not limited to, (1) filtration/separation applications (e.g., separation of biopharmaceutical therapeutics such as proteins, purification of air/water, microfiltration, ultrafiltration, nanofiltration, and reverse osmosis), (2) energy-related applications (e.g., solar cells, batteries, fuel cells, and supercapacitors), (3) biomedical applications (e.g., tissue engineering, drug delivery, and antimicrobial wound dressing), (4) microelectronics-related applications (e.g., sensors/detectors and transistors), (5) composite applications (e.g., hybrid multi-scale composites and dental restorative composites).

Electrospun Polycaprolactone 3D Nanofibrous Scaffold with Interconnected and Hierarchically Structured Pores for Bone Tissue Engineering

Journal Reference

Adv Healthc Mater. 2015;4(15):2238-46.

Xu T1, Miszuk JM2, Zhao Y1, Sun H2, Fong H1.

Show Affiliations
  1. Program of BiomedicalEngineering, South Dakota School of Mines and Technology, Rapid City, SD, 57701, USA.
  2. Program of BiomedicalEngineering, University of South Dakota, Sioux Falls, SD, 57107, USA.

Abstract

For the first time, electrospun polycaprolactone (PCL) 3D nanofibrous scaffold has been developed by an innovative and convenient approach (i.e., thermally induced nanofiber self-agglomeration followed by freeze drying), and the scaffold possesses interconnected and hierarchically structured pores including macropores with sizes up to ≈300 μm. The novel polycaprolactone 3D scaffold is soft and elastic with very high porosity of ≈96.4%, thus it is morphologically/structurally similar to natural extracellular matrix and well suited for cell functions and tissue formation. The in vitro studies reveal that the scaffold can lead to high cell viability; more importantly, it is able to promote more potent BMP2-induced chondrogenic than osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Consistent to the in vitro findings, the in vivo results indicate that the electrospun polycaprolactone 3D scaffold acts as a favorable synthetic extracellular matrix for functional bone regeneration through the physiological endochondral ossification process.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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