Rational Design of Nanofiber Scaffolds for Orthopedic Tissue Repair and Regeneration

Bing Ma; Jingwei Xie; Jiang Jiang; Franklin D Shuler; David E Bartlett;


Nanomedicine. 2013;8(9):1459-1481. 

In This Article

Abstract and Introduction


This article reviews recent significant advances in the design of nanofiber scaffolds for orthopedic tissue repair and regeneration. It begins with a brief introduction on the limitations of current approaches for orthopedic tissue repair and regeneration. It then illustrates that rationally designed scaffolds made up of electrospun nanofibers could be a promising solution to overcome the problems that current approaches encounter. The article also discusses the intriguing properties of electrospun nanofibers, including control of composition, structures, orders, alignments and mechanical properties, use as carriers for topical drug and/or gene sustained delivery, and serving as substrates for the regulation of cell behaviors, which could benefit musculoskeletal tissue repair and regeneration. It further highlights a few of the many recent applications of electrospun nanofiber scaffolds in repairing and regenerating various orthopedic tissues. Finally, the article concludes with perspectives on the challenges and future directions for better design, fabrication and utilization of nanofiber scaffolds for orthopedic tissue engineering.


Injuries frequently occur in the musculoskeletal system, accounting for 60–67% of all unintentional injuries in the USA per annum.[1] It has been reported that more than 34 million musculoskeletal-related surgeries are performed each year in the USA.[2] Clinically, the main options available for the surgical treatment of musculoskeletal injuries include: transplantation of autografts/allografts and utilization of synthetic substitutes composed of metals, ceramics and/or polymers. However, each strategy suffers from a number of limitations. For example, the benefits of autografts are counterbalanced by function loss at the donor sites, scar tissue formation, structural differences between donor and recipient grafts preventing successful regeneration, and the shortage of graft material for extensive repair. Patients receiving transplantation of allografts are at risk of immune rejection and transmitting infectious diseases. Synthetic substitutes, such as metal transplants, mainly serve as a replacement for damaged tissues or organs rather than as a platform for repair and regeneration of tissue defects, and they are often associated with issues such as poor integration with surrounding tissue and infection.[3,4]

To overcome the limitations associated with these approaches, regenerative medicine has emerged as a promising strategy for developing functional tissue constructs to repair, regenerate and restore damaged musculoskeletal tissues or organs.[5] Three general strategies have been adopted for the creation of tissue constructs: to use isolated cells or cell substitutes; to use acellular biomaterials/scaffolds that are capable of inducing tissue regeneration in vivo; and to use a combination of cells and materials typically in the form of scaffolds.[6,7] It is critical to design and fabricate a suitable scaffold for use in specific tissue regeneration, as it directly comes into contact with cells, and provides structural support and guidance for subsequent tissue development.[8] Towards this end, more and more attention has been paid to the design of scaffolds for guiding cell behaviors and tissue regeneration. One effective approach to obtain scaffolds is to harvest the remaining extracellular matrix (ECM) from a decellularized donor organ. The harvested ECM seeded with patient-specific cells could create functional tissue constructs. However, the availability of donor organs remains a stringent limitation. This limitation has encouraged researchers to develop tissue constructs using synthetically derived biomaterials/scaffolds.

The design of scaffolds should be based on knowledge learned from native tissues, such as their anatomic structures, compositions and functions. Generally, the ECM is composed of a complex meshwork of proteins and proteoglycans. Collagen is one of the major components of the ECM, existing in many different types depending on its tissue of origin, and often forming nanofibers. Integrating nanofiber features is particularly important for recapitulating the ECM architecture in the design and fabrication of scaffolds that host multiple cell types, and precisely define cell–cell and cell–matrix interactions in a 3D environment. Thus, nanofiber materials play a paramount role in tissue repair and regeneration. The development of nanotechnology allows for the fabrication of nanofiber scaffolds that are characterized by a nanoscale diameter, high surface area:volume ratio and high porosity. The interconnected porous structure of nanofiber scaffolds provides a large surface area for cell attachment and sufficient space for nutrient and waste exchange. Until now, several approaches have been developed for fabricating nanofiber scaffolds, such as temperature-induced phase separation, molecular self-assembly, template synthesis, drawing and electrospinning. Among these, electrospinning is a cost-effective approach for producing polymeric fibers from a variety of polymer melts and solutions. This is a simple, robust and versatile technique that is capable of producing fibers with nanoscale diameters.[9] Studies have shown that electrospun nanofiber scaffolds hold great promise for musculoskeletal tissue repair and regeneration.[10–12]

The aim of this article is to provide a review of recent studies that are related to the use of electrospun nanofiber scaffolds for orthopedic tissue repair and regeneration. We first describe how electrospun nanofibers can be designed to meet the specific requirements for repairing and regenerating musculoskeletal tissues. We also highlight the recent applications of electrospun nanofibers in repairing and regenerating a number of musculoskeletal tissues, including bone, tendon, cartilage, meniscus, intervertebral disc (IVD) and the tendon-to-bone insertion site. We conclude this article with a perspective on the challenges and future directions in designing better nanofiber scaffolds for orthopedic tissue engineering.