The overall goal of this 3-year project is to improve the outcome of a ?marrow stimulation? procedure for cartilage repair (viz., ?microfracture?) through the use of: 1) extracorporeal shock wave (ESW) treatment to enhance marrow stimulation; and 2) an injectable hyaluronic acid-gelatin (HA-Gtn) matrix to initially contain the fibrin clot and cells infiltrating the defect from the stimulated subchondral bone marrow. This proposal is based on the prior findings in which ESWs have been found to substantially enhance the critical processes underlying the success of microfracture: neovascularization and the stimulation of MSCs. The principal objective of this study is to investigate the effects of ESWs in enhancing the outcome of microfracture for cartilage repair in a goat model, for 2 select doses of SWs. A 2nd objective is to determine if there is a benefit to injecting into the microfracture-treated defects an absorbable Gtn matrix, with and without ESW treatment. A 3rd objective is to determine the change with time in the distribution of two basement membrane proteins, laminin and type IV collagen, recently described in articular cartilage. A 4th objective is to correlate the mechanical properties of reparative tissue in microfracture-treated sites with the types of tissues comprising the reparative material, 12 month after treatment. A total of 66 adult goats will be used in the study, allocated to 11 groups of 6 animals each. Two cylindrical full-thickness chondral defects will be produced in the articular cartilage in the patella groove of distal femur of the left stifle (knee) joint of each animal, and all defects will receive microfracture. The proximal and distal defects of the left knee joint of each animal will receive the same treatment and the results from the 2 defects averaged for the statistical analysis. There will be 3 variables investigated: ESW treatment (0, SW1 and SW2); the presence or absence of a Gtn matrix; and survival time (2 wks, and 3 and 12 months). The defects in all groups will be allocated for histomorphometric evaluation. An additional group of animals will be included to generate samples for mechanical testing 12 months postoperative. The right knee joints will all undergo sham operation and serve as controls.

Public Health Relevance

The objective of the research is to determine if the repair of injuries to the knee joint can be improved if short pulses of high pressure waves (shock waves) delivered from outside the body, currently used to treat other orthopedic problems, are used in addition to a method in which small holes are poked into the bone underlying the location of the lost articular cartilage. In addition, the research will determine if a hyaluronic acid-gelatin matrix is injected into the defect in the cartilage defect, can improve healing. The work will be performed in goats. The potential benefit of the research to the veteran population is that a better treatment for knee joint injuries will have been developed. If the work in the goat is successful, it is likely that the procedure can be introduced for human trial in 2 years. The strenuous activities in the military put individuals at risk for knee injury. This project will be of help to those individuals.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01RX001991-04
Application #
10086004
Study Section
Translational Rehab (Basic) (RRD0)
Project Start
2017-01-01
Project End
2020-12-31
Budget Start
2020-01-01
Budget End
2020-12-31
Support Year
4
Fiscal Year
2021
Total Cost
Indirect Cost
Name
VA Boston Health Care System
Department
Type
DUNS #
034432265
City
Boston
State
MA
Country
United States
Zip Code
02130