Effect of PRP Versus BMC in Anterior Cruciate Ligament Reconstruction

Study Overview
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Brief Summary
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Anterior cruciate ligament (ACL) is an important stabilizer of knee during daily activity and exercise. The ruptured ACL need to be reconstructed by a new tendon graft which passed the bone tunnel and joint during operation. How to enhance the tendon graft to bone tunnel healing is critical important to prevent recurrent ligament laxity, avoid secondary osteoarthritis, and achieve early return to sports and work. Platelet Rich Plasma (PRP)，harvest from peripheral blood, is rich in multiple growth factors(i.e. VEGF, PDGD, TGFB, IGF, EGF) which help the injured tissue regeneration. Bone marrow stem cell has been demonstrated to enhance the injured tissue repair both in vitro and in vivo study. However, there is no prospective study in comparing the PRP and BMC to enhance interfacial healing between graft and bone tunnel in ACL reconstruction. Investigators hypothesize that the combination of PRP and BMC has synergetic effect in interfacial healing in ACL reconstruction. Aim of this study： To investigate the result of clinical functional scoring, MRI, and biomechanical study between PRP augmentation, PRP+BMC augmentation and traditional ACL reconstruction.

Detailed Description
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Anterior cruciate ligament (ACL) is an important stabilizer of knee during daily activity and exercise. According to literature, there are 100,000- 200,000 ACL tear case annually in US. The patients with ACL tear will sustain with joint pain, muscle weakness, giving way sensation, other knee ligaments or meniscus injury, and consequent osteoarthritis change. However, the ruptured ACL cannot heal by itself due to limited vascularity supply, intraarticular inflammatory factors which inhibit the ACL cells migration and proliferation. The ruptured ACL need to be reconstructed by a new tendon graft which passed the bone tunnel and joint during operation. How to enhance the tendon graft to bone tunnel healing is critical important to prevent recurrent ligament laxity, avoid secondary osteoarthritis, and achieve early return to sports and work. Platelet Rich Plasma (PRP)，harvest from peripheral blood, is rich in multiple growth factors(i.e. VEGF, PDGD, TGFB, IGF, EGF) which help the injured tissue regeneration. The PRP has been applied in treating tendinitis, osteoarthritis, cartilage injury, and bone nonunion. Bone marrow contains lots of stem cell and progenitor cells with capability of self-renewal and multi-differentiation. Bone marrow stem cell has been demonstrated to enhance the injured tissue repair both in vitro and in vivo study. The bone marrow concentrate (BMC) can be isolated from the bone marrow through the centrifuge procedure at one time which contains multiple stem cells. The bone marrow can regenerate itself around 1 week. In recent years, many authors uses the combination of RPP and BMC to treat injured tissue. However, there is no prospective study in comparing the PRP and BMC to enhance interfacial healing between graft and bone tunnel in ACL reconstruction. Investigators hypothesize that the combination of PRP and BMC has synergetic effect in interfacial healing in ACL reconstruction. The purpose of this study is to investigate the clinical outcome of autologous PRP, and combined BMC+PRP in tendon graft augmentation in the ACL reconstruction surgery with functional score and MRI evaluation. Investigators will analyze the therapeutic effect using one-way ANOVA. To investigate the result of clinical functional scoring, MRI, and biomechanical study between PRP augmentation, PRP+BMC augmentation and traditional ACL reconstruction.

Official Title
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The Therapeutic Effect of Autologous Platelet-Rich Plasma Versus Bone Marrow Concentrate in Anterior Cruciate Ligament Reconstruction - A Prospective, Double-Blind Randomized Controlled Study

Conditions
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Anterior Cruciate Ligament Reconstruction

Intervention / Treatment
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* Combination Product: Platelet-Rich Plasma; Bone marrow concentrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≧ 20 year-old the patient has been confirmed ACL rupture and the reconstruction is indicated sign IRB and operation consent Exclusion Criteria: combined other ligament or extremities injury prior the same knee surgery open wound or operation history at knee joint Severe knee osteoarthritis history of multiple joint arthritis or rheumatoid arthritis Systemic diseases (infections, malignancies, immunodepression) patients with bleeding tendency, anticoagulant or antiaggregant therapies patients with Hb values < 11 g/dl and/or platelet values < 150,000/mm refuse to sign Informed Consent Form and operation consent

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: To investigate the result of clinical functional scoring, MRI, and biomechanical study between PRP augmentation, PRP+BMC augmentation and traditional ACL reconstruction.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRP augmentation ACL reconstruction group<br>Platelet-rich plasma (PRP) (Dosage form: APA-15) | Combination Product: Platelet-Rich Plasma; Bone marrow concentrate<br>* Platelet-rich plasma (PRP) (Dosage form: APA-15) Bone marrow concentrate (BMC) (Dosage form: APA-15Q)<br>|
| Experimental: PRP+BMC augmentation ACL reconstruction group<br>Bone marrow concentrate (BMC) (Dosage form: APA-15Q) | Combination Product: Platelet-Rich Plasma; Bone marrow concentrate<br>* Platelet-rich plasma (PRP) (Dosage form: APA-15) Bone marrow concentrate (BMC) (Dosage form: APA-15Q)<br>|
| No Intervention: Traditional ACL reconstruction group<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| X-ray | X-ray to evaluate the joint space, graft to bone healing status and graft incorporation. | preoperative | 
| X-ray | X-ray to evaluate the joint space, graft to bone healing status and graft incorporation. | 3 months after ACL reconstruction. | 
| X-ray | X-ray to evaluate the joint space, graft to bone healing status and graft incorporation. | 6 months after ACL reconstruction. | 
| X-ray | X-ray to evaluate the joint space, graft to bone healing status and graft incorporation. | 12 months after ACL reconstruction. | 
| MRI | MRI to evaluate the joint space, graft to bone healing status and graft incorporation. | preoperative | 
| MRI of operated knee | MRI to evaluate the joint space, graft to bone healing status and graft incorporation. | 3 months after ACL reconstruction. | 
| MRI of operated knee | MRI to evaluate the joint space, graft to bone healing status and graft incorporation. | 6 months after ACL reconstruction. | 
| MRI of operated knee | MRI to evaluate the joint space, graft to bone healing status and graft incorporation. | 12 months after ACL reconstruction. | 
| Lysholm score | Lysholm score to evaluate the knee function recovery | preoperative | 
| Lysholm score | Lysholm score to evaluate the knee function recovery | 3 months after ACL reconstruction. | 
| Lysholm score | Lysholm score to evaluate the knee function recovery | 6 months after ACL reconstruction. | 
| Lysholm score | Lysholm score to evaluate the knee function recovery | 12 months after ACL reconstruction. | 
| IKDC 2000 | IKDC 2000 to evaluate the knee function recovery | preoperative | 
| IKDC 2000 | IKDC 2000 to evaluate the knee function recovery | 3 months after ACL reconstruction. | 
| IKDC 2000 | IKDC 2000 to evaluate the knee function recovery | 6 months after ACL reconstruction. | 
| IKDC 2000 | IKDC 2000 to evaluate the knee function recovery | 12 months after ACL reconstruction. | 
| Muscle power (N.m/kg) | muscle power test by Biodex System 3 Pro | preoperative | 
| Muscle power (N.m/kg) | muscle power test by Biodex System 3 Pro | 3 months after ACL reconstruction. | 
| Muscle power (N.m/kg) | muscle power test by Biodex System 3 Pro | 6 months after ACL reconstruction. | 
| Muscle power (N.m/kg) | muscle power test by Biodex System 3 Pro | 12 months after ACL reconstruction. | 
| Proprioception (degree) | Proprioception test by Biodex System 3 Pro | preoperative | 
| Proprioception (degree) | Proprioception test by Biodex System 3 Pro | 3 months after ACL reconstruction. | 
| Proprioception (degree) | Proprioception test by Biodex System 3 Pro | 6 months after ACL reconstruction. | 
| Proprioception (degree) | Proprioception test by Biodex System 3 Pro | 12 months after ACL reconstruction. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anterior cruciate ligament reconstruction, Platelet-Rich Plasma, Bone marrow concentrate, Hamstring tendon