The objective of this study is to improve the functional performance of an anterior cruciate ligament reconstruction (ACLR) by using a platelet hydrogel to enhance the early biologic incorporation of the graft. The current """"""""standard of care"""""""" for an anterior cruciate ligament (ACL) tear is ACLR using autograft tendon. Despite short-term success of ACLR, temporal increases in joint laxity occur after surgery, which may place the knee at risk for subsequent damage and early arthritis. Thus, techniques to enhance graft healing to reduce early laxity, protect the joint, and preserve articular cartilage would provide better long-term outcome for the ACL injured patient. A platelet hydrogel was recently developed by the 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, and thus we hypothesize they will improve graft healing as well. A method has been developed to contain the platelets around the graft using a hydrogel.
Aim 1 is to define the effects of platelet concentration (5X vs 3X vs 0X) on the structural properties (failure load/linear stiffness) and histology (cellularity/vascularity) of the ACL graft after 12 weeks of healing when the graft is treated with the hydrogel at the time of surgery.
Aim 2 is to delineate the effects of the platelet hydrogel on knee joint laxity and the articular cartilage material properties after 12 weeks of healing. A translational model, which has been developed by this research team to study intra-articular ACL healing, will be used. The primary outcomes to address the study hypotheses will be the structural properties of the graft, graft histology, knee joint laxity and cartilage mechanics. Secondary outcome variables include the material properties of the graft, MRI assessments of vascularity and graft properties, meniscal status, and articular cartilage integrity via India ink staining and histology. If successful, these data will provide the foundation for a long-term translational study, and then subsequent clinical studies to further delineate the role of autologous platelets in improving graft healing and promoting long-term joint stability and articular cartilage health, thus reducing OA after ACLR.
The use of autologous platelets to improve the functional healing of an ACL autograft (as evidenced by the faster return of graft strength and a reduction in knee laxity) could reduce rehabilitation time and promote a more stable knee, which in turn could reduce the risk of premature osteoarthritis for 200,000 ACLR patients annually. The results of this study will also stimulate entirely 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 which can deliver multiple growth factors and cytokines over time as adjuncts to intra-articular healing.
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|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|
|Proffen, Benedikt L; Vavken, Patrick; Haslauer, Carla M et al. (2015) Addition of autologous mesenchymal stem cells to whole blood for bioenhanced ACL repair has no benefit in the porcine model. Am J Sports Med 43:320-30|
|Proffen, Benedikt L; Sieker, Jakob T; Murray, Martha M (2015) Bio-enhanced repair of the anterior cruciate ligament. Arthroscopy 31:990-7|
|Kiapour, Ata M; Fleming, Braden C; Murray, Martha M (2015) Biomechanical Outcomes of Bridge-enhanced Anterior Cruciate Ligament Repair Are Influenced by Sex in a Preclinical Model. Clin Orthop Relat Res 473:2599-608|
|Biercevicz, Alison M; Proffen, Benedikt L; Murray, Martha M et al. (2015) T2* relaxometry and volume predict semi-quantitative histological scoring of an ACL bridge-enhanced primary repair in a porcine model. J Orthop Res 33:1180-7|
|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|
|Proffen, Benedikt L; Perrone, Gabriel S; Fleming, Braden C et al. (2015) Effect of low-temperature ethylene oxide and electron beam sterilization on the in vitro and in vivo function of reconstituted extracellular matrix-derived scaffolds. J Biomater Appl 30:435-49|
|Proffen, Benedikt L; Perrone, Gabriel S; Fleming, Braden C et al. (2015) Electron beam sterilization does not have a detrimental effect on the ability of extracellular matrix scaffolds to support in vivo ligament healing. J Orthop Res 33:1015-23|
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