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P&F Grant Awards

Year 1

Grant # 1

Putting Electrospun Nanofibers to Work for Musculoskeletal Research

PI: Younan Xia, Ph.D., Professor of Biomedical Engineering;
Co-PI: Jingyi Chen, Ph.D., Research Assistant Professor of Biomedical Engineering;
Co-Investigator: Jingwei Xie, Ph.D., Research Associate of Biomedical Engineering;
Co-PI: Stavros Thomopoulos, Ph.D., Assistant Professor of Orthopaedic Surgery and Biomedical Engineering


Specific Aims

This project is a collaborative effort involving investigators from the Departments of Biomedical Engineering and Orthopaedic Surgery at Washington University in St. Louis. The major goal of this project is to develop and validate electrospun nanofibers as a new platform for musculoskeletal research, with an initial focus on the demonstration of hierarchical scaffolds for tissue engineering at the tendon-to-bone insertion site.

Owing to the high porosity and large surface area, a scaffold derived from electrospun nanofibers can mimic the hierarchical structure of extracellular matrix (ECM) critical for cell attachment and nutrient transportation. The nanofibers can be routinely prepared from a broad range of biocompatible and biodegradable polymers (both natural and synthetic), as well as composites containing inorganic solids such as hydroxyapatite (HA). The nanofibers can also be conveniently functionalized via encapsulation or attachment of bioactive species such as ECM proteins, enzymes, DNAs, and growth factors to control the proliferation and differentiation of cells seeded on the scaffolds. In addition, the fibers can be assembled into a variety of arrays or hierarchically structured films by manipulating their alignment, stacking, and/or folding. All these attributes make electrospun nanofibers a class of enabling materials for biomedical research, with notable examples including tissue engineering, targeted delivery, and controlled release of biofactors. Our global hypothesis is that fibrous scaffolds can be engineered with specific structural order, surface chemistry, degradation profile, mineral composition, biomechanical property, and bioactivity for manipulating the attachment, proliferation, and differentiation of cells and thus serve as a new framework for repairing the tendon-to-bone insertion site and other musculoskeletal tissues.

The specific aims of this proposal are to:

  1. Fabricate nanofibers by electrospinning and then optimize their properties for use as scaffolds for tissue engineering by in vitro cell culture studies. We will initially focus on poly(lactic-co-glycolic acid) (PLGA), whose mechanical properties and degradation profiles can be controlled by varying the copolymer composition. In addition to the use of fibers with various diameters, we will compare two different types of scaffolds constructed from randomly oriented and uniaxially aligned nanofibers, respectively. In one set of experiments, fibroblasts isolated from rat rotator cuff tendons will be used to investigate the proliferation and morphology of cells seeded on these scaffolds. In another set of experiments, mesenchymal stem cells (MSCs) derived from rat bone marrow will be used to examine how their proliferation and differentiation can be manipulated by engineering the properties of the scaffolds. We will systematically evaluate the biomechanical and cellular properties of these scaffolds in an effort to develop an optimal system for the in vivo animal study.
  2. Evaluate the performance of the engineered nanofibrous scaffolds in vivo using a clinically relevant animal model for rotator cuff repair. The scaffolds will be seeded with the fibroblast cells and then patched onto the tendon-to-bone repair site. The scaffold is expected to serve as a graft to provide mechanical stability and potentially to guide cell activity during the healing process. We will test and compare three different types of scaffolds: randomly oriented, uniaxially aligned, and specially designed with a gradation in the alignment. We will systematically investigate the progress of healing using structural, compositional, and biomechanical assays at the Washington University Core Center for Musculoskeletal Biology and Medicine.