This multidisciplinary program involves well-established and productive experts in nanotechnology and tendon-to-bone testing, analysis, and surgical application from Washington University's Departments of Biomedical Engineering and Orthopaedic Surgery. Our goal is to design, fabricate, and validate novel nanostructures for use in the surgical repair of rotator cuff tears to restore the torn tendon to its bony insertion. We will take a biomimetic approach to this problem by applying knowledge of the natural tendon-to-bone insertion to design and fabricate novel nanofiber scaffolds from a biodegradable polymer by electrospinning, followed by coating with calcium phosphate in a continuous gradation. The scaffolds will be combined with mesenchymal stem cells (MSCs) and implanted in our well-established rat rotator cuff injury-and-repair model to enhance tendon- to-bone healing. The scaffolds we will develop have gradations in mineral content to mimic the natural insertion site, and can serve as grafts to guide tissue regeneration in vivo for tendon-to-bone healing. Our long-term objective is that these scaffolds will be used in a clinical setting for successful repair of soft tissue (meniscus-, ligament-, and cartilage-) to bone interface. The scope of this research includes: i) Fabricating nanofiber scaffolds with different structural orders and continuous gradations in mineral content by a combination of electrospinning and biomineralization;ii) testing and then optimizing the mechanical properties of the graded scaffolds for use in tendon-to-bone repair;iii) examining and quantifying the cellular response to a graded scaffold;and iv) determining the effect of a mineral gradient and seeding of MSCs on tendon-to-bone healing.

Public Health Relevance

We will design, fabricate, and validate a novel class of scaffolds based on electrospun nanofibers and with continuous gradations in mineral content for rotator cuff repair - that is, surgical reattachment of the torn tendons to their bony insertions. It is a clinically significant problem that affects approximately 30% of the population over the age of 60. The current failure rates range from 30% to 94%. Reducing these failure rates will have a major impact on shoulder function in these patients. This research will improve the health and quality of life for individuals afflicted with rotator cuff injuries, having significant impact on the treatment of diseases at rotator cuff and other soft tissue-to-bone interfaces (e.g., anterior cruciate ligament reconstruction).

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
7R01AR060820-02
Application #
8227988
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Panagis, James S
Project Start
2011-04-01
Project End
2016-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$444,942
Indirect Cost
$153,559
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
Zhu, Chunlei; Qiu, Jichuan; Pongkitwitoon, Suphannee et al. (2018) Inverse Opal Scaffolds with Gradations in Mineral Content for Spatial Control of Osteogenesis. Adv Mater :e1706706
Zhu, Chunlei; Pongkitwitoon, Suphannee; Qiu, Jichuan et al. (2018) Design and Fabrication of a Hierarchically Structured Scaffold for Tendon-to-Bone Repair. Adv Mater 30:e1707306
Xue, Jiajia; Xie, Jingwei; Liu, Wenying et al. (2017) Electrospun Nanofibers: New Concepts, Materials, and Applications. Acc Chem Res 50:1976-1987
Zhang, Yu Shrike; Zhu, Chunlei; Xia, Younan (2017) Inverse Opal Scaffolds and Their Biomedical Applications. Adv Mater 29:
Lipner, Justin; Boyle, John J; Xia, Younan et al. (2017) Toughening of fibrous scaffolds by mobile mineral deposits. Acta Biomater 58:492-501
Zhang, Yu Shrike; Wang, Lihong V; Xia, Younan (2016) Seeing Through the Surface: Non-invasive Characterization of Biomaterial-Tissue Interactions Using Photoacoustic Microscopy. Ann Biomed Eng 44:649-66
Li, Jianhua; Linderman, Stephen W; Zhu, Chunlei et al. (2016) Surgical Sutures with Porous Sheaths for the Sustained Release of Growth Factors. Adv Mater 28:4620-4
Lipner, Justin; Shen, Hua; Cavinatto, Leonardo et al. (2015) In Vivo Evaluation of Adipose-Derived Stromal Cells Delivered with a Nanofiber Scaffold for Tendon-to-Bone Repair. Tissue Eng Part A 21:2766-74
Zhang, Yu Shrike; Xia, Younan (2015) Multiple facets for extracellular matrix mimicking in regenerative medicine. Nanomedicine (Lond) 10:689-92
Thomopoulos, Stavros; Parks, William C; Rifkin, Daniel B et al. (2015) Mechanisms of tendon injury and repair. J Orthop Res 33:832-9

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