Arthritis is the most widespread debilitating disease in the United States affecting over 13% of the population. As the population ages the prevalence which is currently nearly 50% for people 55 and older will increase. Lower extremity impairments (in particular arthritis) represent over 50% of reported impairments and accounts for the placement of more than 50% of all implants. In addition, arthritis related complaints account for over 3% of all hospital stays. Although orthopaedic implants, particularly artificial joints, improve patient function and reduce pain, they often involve radical procedures mandating a hospital stay and reduce proprioception and stability which can lead to an increased incidence of falls. The overall goal of this research program is the development of a sensate scaffold with a functional cartilage layer on one surface that can easily be implanted into a joint to replace damaged tissue and precluding the need for artificial joint placement. Since nearly half of the US population over 25 years of age experiences knee pain, and the knee is the most common joint for which joint pain and arthritis like symptoms are reported, a knee model will be used to study scaffold development. First, direct measurements will be collected proximal to, distal to and from within joints utilizing a novel in vivo sensing technique in conjunction with radio telemetry to better understand loading of tissues in joints and the way in which scaffolds (designed to carry engineered tissues into joints) affect loading patterns. This strain data will be used to engineer tissue covered scaffolds for cartilage repair. The in vivo measurements will be compared in animals with and without cartilage coated scaffolds. Measurements from the joint will be correlated with surface pressure to better understand cartilage loading and viability. Bone strain patterns during ingrowth into the scaffolds will be correlated with quantitative histomorphometry and radiography to define relationships between loading and tissue structure. Finally, this information will be used to develop cell culture loading systems to produce functional engineered tissues. Within the framework of the overall goal, the specific aims of this research are: ? 1. Prepare and calibrate a series of scaffolds with wired sensors in them for placement in a dog model and collect strain information from the distal femur of a dog using an existing measurement system prior to and following scaffold placement. ? 2. Test combinations of osteoconductive coatings and osteoinductive proteins and loading to establish conditions which provide rapid segregated cell growth and appropriate tissue formation in call culture. ? 3. Place sensate scaffolds with layers of functionally loaded cells into dogs and monitor loading of the scaffold during healing and for several months following healing. Compare the loading pattern changes to the tissue response using histomorphometry. An understanding of loads acting on cartilage will allow development of functional tissues for implantation and an in vivo monitoring system which could eventually be used in patients. A system of this type will provide a means of monitoring healing and rehabilitation in patients. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
3R01EB000660-02S1
Application #
6763587
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kelley, Christine A
Project Start
2002-09-30
Project End
2006-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$36,951
Indirect Cost
Name
University of Arizona
Department
Orthopedics
Type
Schools of Medicine
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Tellis, B C; Szivek, J A; Bliss, C L et al. (2009) Trabecular scaffolds created using micro CT guided fused deposition modeling. Mater Sci Eng C Mater Biol Appl 28:171-178
Geffre, Chris P; Margolis, David S; Ruth, John T et al. (2009) A novel biomimetic polymer scaffold design enhances bone ingrowth. J Biomed Mater Res A 91:795-805
Geffre, Chris P; Bliss, Cody L; Szivek, John A et al. (2008) Sensate scaffolds coupled to telemetry can monitor in vivo loading from within a joint over extended periods of time. J Biomed Mater Res B Appl Biomater 84:263-70
Szivek, Ja; Nandakumar, Vs; Geffre, Cp et al. (2008) A handheld computer as part of a portable in vivo knee joint load monitoring system. J Med Device 2:350011-350019
Szivek, J A; Margolis, D S; Schnepp, A B et al. (2007) Selective cell proliferation can be controlled with CPC particle coatings. J Biomed Mater Res A 81:939-47
Bliss, C L; Szivek, J A; Tellis, B C et al. (2007) Sensate scaffolds can reliably detect joint loading. J Biomed Mater Res B Appl Biomater 81:30-9
Szivek, J A; Bliss, C L; Geffre, C P et al. (2006) An instrumented scaffold can monitor loading in the knee joint. J Biomed Mater Res B Appl Biomater 79:218-28
Margolis, David S; Kim, Devin; Szivek, John A et al. (2006) Functionally improved bone in calbindin-D28k knockout mice. Bone 39:477-84
Szivek, J A; Margolis, D S; Garrison, B K et al. (2005) TGF-beta1-enhanced TCP-coated sensate scaffolds can detect bone bonding. J Biomed Mater Res B Appl Biomater 73:43-53