Rational Design of Nanofiber Scaffolds for Orthopedic Tissue Repair and Regeneration

Authors and Disclosures

Bing Ma¹, Jingwei Xie*¹, Jiang Jiang¹, Franklin D Shuler² & David E Bartlett<sup>1

1</sup>Marshall Institute for Interdisciplinary Research & Center for Diagnostic Nanosystems, Marshall University, Huntington, WV 25755, USA
²Department of Orthopaedic Surgery, Joan C Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA.

Financial & competing interests disclosure
The authors are supported in part by the National Center for Research Resources (grant number UL1RR033173), funded by the Office of the Director, NIH (grant number 1R15 AR063901-01), supported by the NIH roadmap for Medical Research and receive start-up funds from Marshall Institute for Interdisciplinary Research and Center for Diagnostic Nanosystems at Marshall University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

*Author for correspondence xiej@marshall.edu

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Executive Summary

Background

• Current approaches for the treatment of orthopedic injury are associated with a number of limitations.

• Rationally designed nanofiber scaffolds may hold promise for the repair and regeneration of orthopedic tissues.

• Electrospinning is a simple and versatile technique for producing nanofiber scaffolds.

Why Electrospun Nanofibers?

• Studies have demonstrated the control of diameter, composition, structure, alignment and order of electrospun nanofiber scaffolds.

• The mechanical properties of electrospun nanofibers can be tailored in different ways, which could be used for regulating cell response and matching the mechanical property of musculoskeletal tissue.

• Electrospun nanofibers can be used as carriers for topically sustained drug/gene delivery.

• Electrospun nanofibers can be used as substrates for regulating cell behaviors, including morphology, proliferation, migration, differentiation and gene expression.

Nanofiber Scaffolds for Orthopedic Tissue Repair & Regeneration

• Nanofiber scaffolds have been shown to support osteogenic differentiation of progenitor and stem cells in vitro. Nanofiber scaffolds with different combinations (i.e., incorporating hydroxyapatite, and incorporating collagen and signaling molecule delivery systems) have been tested for repairing bone defects in vivo.

• A combination of nanofiber scaffolds, cells and signaling molecules is used for tendon injury repair and regeneration. Nanofiber scaffolds are also used for the prevention of rerupture and adhesion after tendon surgery.

• Studies are limited to the examination of nanofiber scaffolds made of random nanofibers on articular cartilage regeneration, although these scaffolds show the potential for regeneration in vivo.

• No literature has reported on the use of electrospun nanofibers for meniscal tissue regeneration in vivo. A novel electrospinning method has been developed to produce scaffolds composed of circumferentially aligned nanofibers using a rotated plate as a collector, which can mimic the circumferentially aligned collagen fibers in menisci' extracellular matrix.

• Anisotropic nanofiber laminates seeded with mesenchymal stem cells are developed using a layer-by-layer stacking strategy, which could to some degree mimic the fibrous architecture of annulus fibrosus tissue.

• Nanofiber scaffolds with gradations in fiber organization and mineral content are fabricated for mimicking both the fiber orientation and composition at the tendon-to-bone insertion site.