Achilles tendon ruptures are common and devastating injuries, resulting in significant pain, disability, and healthcare costs. Despite the higher risk for complications and increased costs, operative treatment is often assumed to provide superior outcomes compared to non-operative treatment. However, a recent comprehensive review by the American Academy of Orthopaedic Surgeons concluded that the scientific evidence supporting current clinical paradigms, such as operative or non-operative care, and particular rehabilitation protocols, was weak and/or inconclusive. Further, a 2012 meta-analysis of randomized clinical trials concluded that outcomes for Achilles ruptures are not superior with surgical treatment, depending on the rehabilitation protocol, further calling into question the common belief of a preferred surgical treatment. The overall goal of this study is to define the tissue-level properties of healing Achilles tendon, in a targeted set of clinically-relevant conditions, that govern the mechanical mechanisms of successful tissue remodeling, and, ultimately, to relate these tissue-level properties to in vivo measures. In particular, we propose that the healing tendon environment is governed by specific structural and biologic properties which drive tendon fatigue mechanical parameters, which in turn, govern successful progression of rehabilitation. An animal model will be used to carefully control the injury and treatment strategies, rigorously analyze tissue properties, and, through our innovative methods determine clinically relevant measures which define tissue healing. Our overall hypothesis is that there are specific tissue-level properties, in clinically-relevant conditions, that govern a successful versus failed healing response of injured Achilles tendon and that these properties will not relate to currently used in vivo measures. To provide high impact and innovation, two novel aims are designed to directly challenge two commonly-accepted paradigms for Achilles tendon treatment and healing. 1: To determine whether a repaired Achilles tendon has superior tendon mechanical, structural and biological properties compared to a non-repaired tendon, and confirm the necessary measures which define successful healing for a set of six clinically relevant conditions. 2: Define the in vivo measurement techniques that are surrogates for Achilles tendon healing through our innovative ex vivo assays. As noted, this project has high impact by determining rigorous scientific and mechanistic mechanical data governing Achilles tendon healing, supporting or refuting clinically accepted paradigms regarding 1) the role of repair and specific rehabilitation paradigms and 2) the use of functional measures for return to activity criteria following Achilles tendon rupture. Furthermore, our innovative, non-invasive techniques that parallel clinical assays, coupled with our direct measures of tissue healing, such as tendon fatigue behavior from mechanical testing and collagen alignment through ultrasound, provide data to guide post-injury treatment progression and return to activity criteria in patients Thus, this study has direct translation to clinical practice and patient care.

Public Health Relevance

Achilles tendon ruptures are common and devastating injuries, resulting in significant pain, disability, and healthcare costs. The overall goal of this study is to define the tissue-level properties of healing Achilles tendon, in a targeted set of clinically-relevant conditions, that govern the mechanical mechanisms of successful tissue remodeling, and, ultimately, to relate these tissue-level properties to in vivo measures. This project has high impact by determining rigorous scientific and mechanistic mechanical data governing Achilles tendon healing, supporting or refuting clinically accepted paradigms regarding 1) the role of repair and specific rehabilitation paradigms and 2) the use of functional measures for return to activity criteria following Achilles tendon rupture.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR064216-03
Application #
8879048
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Tyree, Bernadette
Project Start
2013-09-17
Project End
2016-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
3
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Orthopedics
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Freedman, Benjamin R; Salka, Nabeel S; Morris, Tyler R et al. (2017) Temporal Healing of Achilles Tendons After Injury in Rodents Depends on Surgical Treatment and Activity. J Am Acad Orthop Surg 25:635-647
Freedman, Benjamin R; Fryhofer, George W; Salka, Nabeel S et al. (2017) Mechanical, histological, and functional properties remain inferior in conservatively treated Achilles tendons in rodents: Long term evaluation. J Biomech 56:55-60
Pardes, A M; Beach, Z M; Raja, H et al. (2017) Aging leads to inferior Achilles tendon mechanics and altered ankle function in rodents. J Biomech 60:30-38
Fryhofer, George W; Freedman, Benjamin R; Hillin, Cody D et al. (2016) Postinjury biomechanics of Achilles tendon vary by sex and hormone status. J Appl Physiol (1985) 121:1106-1114
Freedman, Benjamin R; Gordon, Joshua A; Bhatt, Pankti R et al. (2016) Nonsurgical treatment and early return to activity leads to improved Achilles tendon fatigue mechanics and functional outcomes during early healing in an animal model. J Orthop Res 34:2172-2180
Pardes, A M; Freedman, B R; Fryhofer, G W et al. (2016) Males have Inferior Achilles Tendon Material Properties Compared to Females in a Rodent Model. Ann Biomed Eng 44:2901-2910
Riggin, Corinne N; Sarver, Joseph J; Freedman, Benjamin R et al. (2014) Analysis of collagen organization in mouse achilles tendon using high-frequency ultrasound imaging. J Biomech Eng 136:021029
Freedman, Benjamin R; Sarver, Joseph J; Buckley, Mark R et al. (2014) Biomechanical and structural response of healing Achilles tendon to fatigue loading following acute injury. J Biomech 47:2028-34