Lesions of the articular surface do not heal spontaneously and are often intractable clinical problems that are managed symptomatically. The progressive loss of articular cartilage is a pathologic hallmark of the degenerative joint disease osteoarthritis (OA). OA is one of the most common joint disorders afflicting humans, and it is estimated that over 60% of the United States population develop radiographic evidence of OA by 55 years of age. Given the aging American population and increasing physical activity among the elderly this estimate is likely to increase over time. The objective of this proposal is to design and characterize a novel fibrous-hydrogel composite to enhance the repair of cartilage defects in a normal and OA environment. The goals of this proposal are both hypothesis and design driven and will be addressed in the following specific aims:
Aim 1. Development and characterization of novel fibrous-hydrogel composites to promote cartilage repair. Specifically, we will incorporate a three dimensional electrospun poly(caprolactone) fibrous network into a photopolymerizable polyethylene-glycol hydrogel. Fiber diameter and density within the hydrogel will be modulated in order to optimize the bulk properties and chondrogenic potential of the composite. Physical properties of the composite will be evaluated. The chondrogenic potential will be studied in vitro through encapsulation experiments with primary chondrocytes and MSCs. The regenerative potential of this material will be investigated using an in vitro OA model based on Interleukin 1B exposure. Cartilage formation will be assessed on the basis of ECM production, gene expression, and histology.
Aim 2. Translate the fiber-hydrogel composites and cell-based repair strategies to a rodent model of a normal and osteoarthritic joint. The appropriate material from Aim 1 will be applied to a critical sized cartilage defect on the rat femoral trochlea in combination with a marrow stimulation procedure. A rat surgical destabilization model of OA will be used to evaluate the repair potential of these materials in the context of a degradative joint environment. Cartilage development and integration of our constructs will be evaluated by gross lesion grading scales and histology.

Public Health Relevance

Load bearing joint surfaces do not heal spontaneously and over time small cartilage lesions progress to full blown osteoarthritis which adversely affects the lives of 60% of people over 55 years of age.
The aims of this proposal seek to develop a novel technology platform for the treatment of cartilage defects both in a healthy joint and in the context of a diseased joint environment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30AG034807-02
Application #
8197972
Study Section
Special Emphasis Panel (ZRG1-F10B-S (20))
Program Officer
Joseph, Lyndon
Project Start
2010-12-01
Project End
2013-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
2
Fiscal Year
2012
Total Cost
$47,232
Indirect Cost
Name
Johns Hopkins University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Gibson, Matthew; Li, Hanwei; Coburn, Jeannine et al. (2014) Intra-articular delivery of glucosamine for treatment of experimental osteoarthritis created by a medial meniscectomy in a rat model. J Orthop Res 32:302-9
Coburn, Jeannine; Gibson, Matt; Bandalini, Pierre Alain et al. (2011) Biomimetics of the Extracellular Matrix: An Integrated Three-Dimensional Fiber-Hydrogel Composite for Cartilage Tissue Engineering. Smart Struct Syst 7:213-222