Ligament injuries cause joint instability and can lead to chronic joint disorders. The underlying cause of these functional deficits is the poor structural quality of the repaired matrix. Improvements to clinical outcomes require a mechanistic understanding ofthe physical mechanisms that instruct the restoration of matrix structure and function. The development and validation of mechanistic models would support the application and design of targeted interventions, such as soft-tissue mobilization, that apply mechanical stimuli directly to the remodeling matrix. The primary objective of this research proposal is to characterize physical mechanisms for matrix remodeling during ligament wound healing. The central hypothesis is that mechanical stimulation during wound healing can improve ligament repair by enhancing matrix composition and organization. To test this hypothesis, an experimental and computational methodology will be employed to measure and predict the structural and functional effect of mechanical stimulation on ligament reparative tissue.
In Aims 1 and 2, a computational framework will be developed to predict matrix remodeling from mechanical stimulation using tissue-equivalent materials.
In Aim 3, an in-vivo experiment will validate the predictive ability of this new model in a three-dimensional finite element simulation. Two potential projects stemming from this work include the design of soft tissue mobilization methods for use in human subjects (clinical trial);and the formulation of a new hypothesis on mechanotransduction mechanisms during repair. This may improve our ability to instruct signaling pathways during tissue repair, and help further our long-term goal of developing therapies for fast and full restoration of soft-tissue function after injury. As a Junior Investigator in the COBRE in Matrix Biology, I will work with my scientific mentor to complete the scientific aims and to develop a grant proposal for future R01 funding.

Public Health Relevance

Successful completion ofthe proposed aims will improve our understanding ofthe importance of mechanical stimuli in the functional restoration of the extracellular matrix during ligament repair. We anticipate that results from this project will advance targeted treatment strategies for ligament injuries

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
1P20GM109095-01
Application #
8653276
Study Section
Special Emphasis Panel (ZGM1)
Project Start
2014-08-01
Project End
2019-05-31
Budget Start
2014-08-01
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Boise State University
Department
Type
DUNS #
City
Boise
State
ID
Country
United States
Zip Code
83725
Pinkaew, Decha; Chattopadhyay, Abhijnan; King, Matthew D et al. (2017) Fortilin binds IRE1? and prevents ER stress from signaling apoptotic cell death. Nat Commun 8:18
Doumas, Diana M; Esp, Susan; Flay, Brian et al. (2017) A Randomized Controlled Trial Testing the Efficacy of a Brief Online Alcohol Intervention for High School Seniors. J Stud Alcohol Drugs 78:706-715
Rohn, Troy T; Moore, Zachary D (2017) Nuclear Localization of Apolipoprotein E4: A New Trick for an Old Protein. Int J Neurol Neurother 4:
Thurston, John H; Hunter, Necia M; Wayment, Lacey J et al. (2017) Urea-derived graphitic carbon nitride (u-g-C3N4) films with highly enhanced antimicrobial and sporicidal activity. J Colloid Interface Sci 505:910-918
Styner, Maya; Pagnotti, Gabriel M; McGrath, Cody et al. (2017) Exercise Decreases Marrow Adipose Tissue Through ß-Oxidation in Obese Running Mice. J Bone Miner Res 32:1692-1702
Misra, Neha; Wines, Tyler F; Knopp, Colton L et al. (2017) Expression, immunogenicity and variation of iron-regulated surface protein A from bovine isolates of Staphylococcus aureus. FEMS Microbiol Lett 364:
Shrestha, Nisha; Bryant, Sheenah L; Thomas, Christopher et al. (2017) Stochastic sensing of Angiotensin II with lysenin channels. Sci Rep 7:2448
Miller, Robert A; Bond, Laura; Migas, Patrick N et al. (2017) CONTRASTING HABITAT ASSOCIATIONS OF SAGEBRUSH-STEPPE SONGBIRDS IN THE INTERMOUNTAIN WEST. West Birds 48:35-55
Love, Julia E; Day, Ryan J; Gause, Justin W et al. (2017) Nuclear uptake of an amino-terminal fragment of apolipoprotein E4 promotes cell death and localizes within microglia of the Alzheimer's disease brain. Int J Physiol Pathophysiol Pharmacol 9:40-57
Grassley, Jane S; Connor, Kelley C; Bond, Laura (2017) Game-based online antenatal breastfeeding education: A pilot. Appl Nurs Res 33:93-95

Showing the most recent 10 out of 53 publications