The objective of this study is to improve the functional healing of an anterior curiae ligament reconstruction (ACLR) by using a collagen-platelet composite to enhance the biologic incorporation of the graft. The current """"""""standard of care"""""""" for an anterior cruciate ligament (ACL) tear is ACLR using an autograft tendon. Despite short-term success of ACLR, increases in joint laxity occur after surgery, which may place the knee at risk for subsequent damage and early osteoarthritis (OA). Thus, techniques to enhance graft healing which reduce laxity, protect the joint, and preserve articular cartilage would provide better long-term outcome for the ACL injured patient. A collagen-platelet composite was recently developed by this research team to enhance the healing response of the ACLR graft. Platelets are known to release various growth factors and cytokines that stimulate intra-articular ligament healing. We hypothesized that they will improve graft healing as well. We have developed a method to contain the platelets around the graft using a collagen sponge. In the work funded by the parent R01, we have found significant improvements in both graft performance (300% increases in modulus and 250% improvement in yield stress) as well as significant reductions in knee laxity after 15 weeks of healing. Due to the relatively short follow-up evaluation (15 weeks), we have been unable to detect whether these improvements will significantly impact cartilage health after an ACL reconstruction. In this competitive revision, we propose to include two longer-term groups of animals (ACL reconstruction with collagen-platelet composite vs traditional ACL reconstruction) with survivals of 6 and 12 months. These groups will expand our original proposal and provide information as to whether the collagen-platelet composite, which significantly improves graft quality and knee laxity in the short-term, will continue in the long term and prevent the development of premature osteoarthritis. If successful, these data will provide the foundation for subsequent clinical studies to further delineate the role of biologic scaffolds in improving graft healing and promoting long- term joint stability and articular cartilage health, thus reducing OA after ACLR.

Public Health Relevance

The use of a collagen scaffold with autologous platelets (a collagen-platelet composite) to improve the functional healing of an anterior cruciate ligament (ACL) autograft could decrease rehabilitation time, promote a more stable knee and significantly reduce the risk of premature osteoarthritis for 250,000 ACL reconstructed patients in the US annually. We are hopeful that the results of this study will inspire new fields of inquiry into cell-based therapies for intra-articular healing, and may result in a paradigm shift from use of a single growth factor toward the use of cells that can deliver multiple growth factors and cytokines over time as adjuncts to intra-articular healing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
3R01AR056834-01S1
Application #
7807720
Study Section
Special Emphasis Panel (ZRG1-MOSS-A (95))
Program Officer
Wang, Fei
Project Start
2009-09-28
Project End
2013-09-30
Budget Start
2009-09-28
Budget End
2013-09-30
Support Year
1
Fiscal Year
2009
Total Cost
$1,491,790
Indirect Cost
Name
Rhode Island Hospital
Department
Type
DUNS #
075710996
City
Providence
State
RI
Country
United States
Zip Code
02903
Sieker, Jakob T; Proffen, Benedikt L; Waller, Kimberly A et al. (2018) Transcriptional profiling of articular cartilage in a porcine model of early post-traumatic osteoarthritis. J Orthop Res 36:318-329
Sieker, Jakob T; Proffen, Benedikt L; Waller, Kimberly A et al. (2018) Transcriptional profiling of synovium in a porcine model of early post-traumatic osteoarthritis. J Orthop Res :
Waller, Kimberly A; Chin, Kaitlyn E; Jay, Gregory D et al. (2017) Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage After Destabilization of the Medial Meniscus in the Yucatan Minipig. Am J Sports Med 45:1512-1521
Kiapour, Ata M; Fleming, Braden C; Murray, Martha M (2017) Structural and Anatomic Restoration of the Anterior Cruciate Ligament Is Associated With Less Cartilage Damage 1 Year After Surgery: Healing Ligament Properties Affect Cartilage Damage. Orthop J Sports Med 5:2325967117723886
Perrone, Gabriel S; Proffen, Benedikt L; Kiapour, Ata M et al. (2017) Bench-to-bedside: Bridge-enhanced anterior cruciate ligament repair. J Orthop Res 35:2606-2612
Sieker, Jakob T; Ayturk, Ugur M; Proffen, Benedikt L et al. (2016) Immediate Administration of Intraarticular Triamcinolone Acetonide After Joint Injury Modulates Molecular Outcomes Associated With Early Synovitis. Arthritis Rheumatol 68:1637-47
Proffen, Benedikt L; Sieker, Jakob T; Murray, Martha M et al. (2016) Extracellular matrix-blood composite injection reduces post-traumatic osteoarthritis after anterior cruciate ligament injury in the rat. J Orthop Res 34:995-1003
Chin, K E; Karamchedu, N P; Patel, T K et al. (2016) Comparison of micro-CT post-processing methods for evaluating the trabecular bone volume fraction in a rat ACL-transection model. J Biomech 49:3559-3563
Kiapour, Ata M; Shalvoy, Matthew R; Murray, Martha M et al. (2015) Validation of porcine knee as a sex-specific model to study human anterior cruciate ligament disorders. Clin Orthop Relat Res 473:639-50
Fleming, Braden C; Proffen, Benedikt L; Vavken, Patrick et al. (2015) Increased platelet concentration does not improve functional graft healing in bio-enhanced ACL reconstruction. Knee Surg Sports Traumatol Arthrosc 23:1161-70

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