Degenerative joint disease accounts for substantial human suffering at tremendous social and economic cost. While prosthetic joint replacement is a well-established procedure, a finite life span makes this treatment unacceptable for younger or active individuals who often require progressively complicated revision surgeries. The goal of this Phase II STTR is to develop an osteochondral implant suitable for complete resurfacing of the osteoarthritic femoral head of the hip joint and proven ability to integrate with bone. The two novelties of this work are: (i) accelerated generation of an osteochondral implant within a brief period of in vitro culture and (ii) resurfacing of an entire joint instead of a focal defect. We will create a hemispherical layer of cartilage that replicates the load-bearing properties of the native tissue by combining adult human stem cells with a three- dimensionally woven scaffold in a new bioreactor. In vitro growth of the osteochondral implant will be quantified by histomolecular and biomechanical testing, and functional integration with vital bone will be assessed using a subcutaneous pouch model in an immunodeficient rodent. The combination of these emergent regenerative medical technologies is expected to provide a novel means of developing functional, complex tissue engineered constructs that can resurface large segments of joints that have been affected by degenerative diseases such as osteoarthritis.

Public Health Relevance

This project represents a Phase II STTR project to develop a novel tissue engineering approach to create osteochondral implants for joint resurfacing as a treatment for hip osteoarthritis. The technologic basis involves a combination of adult human mesenchymal stem cells grown on an anatomically shaped, three-dimensionally woven scaffold, which is cultured in a novel bioreactor system that can accelerate the generation of mechanically functional cartilage. The ultimate goal of this study is to develop a tissue engineering approach that can be used to resurface large segments of joints that have been affected by degenerative diseases such as osteoarthritis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
2R42AR055414-02
Application #
7804715
Study Section
Special Emphasis Panel (ZRG1-MOSS-L (10))
Program Officer
Wang, Fei
Project Start
2007-09-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$775,801
Indirect Cost
Name
Cytex Therapeutics Inc.
Department
Type
DUNS #
783502466
City
Durham
State
NC
Country
United States
Zip Code
27715
Valonen, Piia K; Moutos, Franklin T; Kusanagi, Akihiko et al. (2010) In vitro generation of mechanically functional cartilage grafts based on adult human stem cells and 3D-woven poly(epsilon-caprolactone) scaffolds. Biomaterials 31:2193-200
Abrahamsson, Christoffer K; Yang, Fan; Park, Hyoungshin et al. (2010) Chondrogenesis and mineralization during in vitro culture of human mesenchymal stem cells on three-dimensional woven scaffolds. Tissue Eng Part A 16:3709-18
Freed, Lisa E; Engelmayr Jr, George C; Borenstein, Jeffrey T et al. (2009) Advanced material strategies for tissue engineering scaffolds. Adv Mater 21:3410-8