Clinical Outcome of Intra-articular Injection of PRP in ACL Injury.

Introduction

Background

The anterior cruciate ligament (ACL) plays a central role in limiting forward movement of the tibia and in controlling rotational motion at the knee. Functionally, it is formed by anteromedial and posterolateral bundles that become tensioned differently as the knee moves through flexion and extension. Injury to this ligament can therefore disturb more than passive stability; proprioceptive input, neuromuscular control and confidence during weight-bearing, cutting or pivoting may also be affected. ACL trauma is seen frequently in young, active people and may lead to pain, time away from employment or sport, prolonged rehabilitation costs and, for some patients, reconstructive surgery. Sanders et al. (2016) estimated the population incidence at about 68.6 ACL tears per 100,000 person-years, with substantially greater rates in sports characterised by abrupt slowing, landing, directional change and physical contact. In many sports, the injury occurs without a direct blow or after indirect contact, often when a relatively extended knee is subjected simultaneously to valgus loading, rotation and anterior shear.

Typical early complaints after ACL injury include a popping sensation or sound, rapid effusion, pain, limited knee motion and later episodes of perceived instability. Diagnosis is based on the history and mechanism together with examination findings from tests such as Lachman, anterior drawer and pivot shift. MRI helps demonstrate disruption of the ligament and can identify accompanying meniscal, cartilage or collateral-ligament pathology. This imaging is particularly useful when a partial tear is suspected, because preserved fibres, bundle involvement and indirect signs may be difficult to define confidently on examination alone (Al Mohammad and Gharaibeh, 2024). Published estimates suggest that partial injuries comprise roughly 10-28% of isolated ACL tears. Definitions, however, are inconsistent and have relied on the proportion of fibres torn, the bundle affected, arthroscopic appearance, MRI features and the amount of remaining functional stability (Sonnery-Cottet and Colombet, 2016; Giummarra et al., 2022). These differing definitions complicate diagnosis, treatment planning, and comparison between studies.

Partial disruption of the ACL does not invariably follow a mild clinical course. Some patients regain acceptable stability with rehabilitation, whereas others develop repeated giving-way, reduce their activity or sustain additional meniscal injury. Among young, active individuals managed without surgery, Management should therefore be guided by symptoms, functional stability, activity goals and preservation of joint health rather than by MRI appearance in isolation.

Direct evidence for rehabilitation-based management of partial ACL tears is still sparse. Giummarra et al. (2022) found only two small randomised rehabilitation studies in their systematic review; exercise appeared capable of improving pain, strength and proprioception, but the authors called for larger trials with longer observation. At the same time, the longstanding belief that the intra-articular ACL has almost no capacity to heal spontaneously has been reconsidered.

Because intrinsic ACL healing is uncertain, attention has shifted toward biological treatments that might improve the local repair environment without sacrificing intact native fibres. Platelet-rich plasma (PRP) is prepared from the patient's own blood and contains platelets at concentrations above those in circulating plasma. Once activated, these platelets release mediators such as platelet-derived growth factor, transforming growth factor-beta, vascular endothelial growth factor and insulin-like growth factor. Through these signals, PRP may affect fibroblast migration, collagen formation, angiogenesis, inflammatory activity and extracellular-matrix remodelling. A systematic review of tendon and ligament studies supports the biological rationale for PRP, although clinical effects differ by tissue type and by the way the product is prepared and delivered (Chen et al., 2018).

For partial ACL injury, PRP is appealing because the product is autologous, can be delivered with minimal invasiveness and may be injected under ultrasound guidance into the joint or near injured fibres. Real-time ultrasonography allows the operator to visualise relevant structures while directing the needle, potentially improving placement accuracy. You et al. (2019) described symptomatic and MRI improvement after ultrasound-guided PRP in a patient with a partial ACL tear. In a randomised study of athletes, Laimujam et al. (2022) also reported improvement in pain and functional measures when PRP was added to conservative rehabilitation, although statistically significant differences between groups were not sustained consistently. Hada et al. (2024) later reported return to sport and apparent restoration of ligament continuity in a small retrospective series of highly active patients treated early with PRP-based conservative care; the small, uncontrolled design prevents firm conclusions about causation.

Published findings are not uniformly favourable. Zicaro et al. (2021), in a prospective comparison of partial ACL tears, found that adding PRP to rehabilitation did not yield better MRI appearances, clinical results, stability or failure rates than rehabilitation alone. Research using PRP during or after ACL reconstruction has likewise produced mixed results. The meta-analysis by Lv et al. (2022) suggested possible early or intermediate improvements in pain and function, but did not show a clinically meaningful long-term advantage for stability, graft healing or tunnel enlargement. Delcogliano et al. (2024) concluded from a scoping review that differences in platelet concentration, leucocyte content, activation, injection location, timing, dose and outcome measurement made the evidence too heterogeneous to justify routine augmentation.

PRP appears to have an acceptable safety profile when prepared and administered under appropriate sterile conditions. The most frequently reported adverse effects are transient pain, swelling, stiffness or discomfort at the injection site. Serious complications such as septic arthritis are uncommon. A systematic review of 91 randomised trials involving 5,914 intra-articular knee injections found no evidence that open PRP preparation techniques increased the risk of joint infection compared with closed techniques when appropriate sterile procedures were followed (Alazzeh et al., 2024). Nevertheless, adequate patient selection, sterile preparation, image-guided administration and post-procedural monitoring remain necessary.

PRP is therefore better viewed as an investigational adjunct than as a substitute for properly structured rehabilitation or reconstruction when surgery is indicated. This study compared conventional conservative care alone with the same care supplemented by one ultrasound-guided intra-articular injection of autologous PRP in adults who had MRI-confirmed partial ACL injury. Pain, knee symptoms, daily activities, sport and recreation, knee-related quality of life and clinical stability were selected as outcomes and were measured with the Visual Analogue Scale, the Knee Injury and Osteoarthritis Outcome Score, Lachman testing and the anterior drawer test.

Rationale of the Study ACL injury affects both athletes and other physically active people in Bangladesh. Management usually involves a rehabilitation-based conservative approach, reconstruction, or a combination determined by clinical need. Reconstructive surgery, however, requires specialist facilities and substantial expenditure, which can limit access for people living in rural or resource-constrained settings. PRP is a minimally invasive biological intervention intended to expose injured tissue to a concentrated mixture of platelet-derived mediators that may support repair and modulate inflammation. This has created interest in its use as an adjunct to conservative care for early or partial ACL tear. Evidence from Bangladesh remains scarce, while financial and infrastructure barriers continue to restrict availability of surgical treatment. Less invasive and more affordable strategies are therefore of practical interest to sports medicine, Physical Medicine and Rehabilitation services and orthopaedic clinics. Evaluating PRP in this setting may generate locally relevant evidence on effectiveness, feasibility and safety, help refine treatment protocols, and clarify whether it can improve outcomes without the cost and burden of an operative pathway for selected patients.

Research Question

Does addition of PRP to conventional conservative treatment improve clinical outcome of patients with partial tear

Research Objectives

General Objective To determine the clinical outcomes associated with intra-articular autologous PRP administration in patients with ACL injury of the knee.

Specific Objectives

1. To quantify post-treatment pain in patients with ACL injury receiving PRP by using a standardized measure, the "Visual Analogue Scale".
2. To determine whether knee function changes after PRP treatment by comparing pre and post-intervention clinical scores by using the "Knee Injury and Osteoarthritis Outcome Score" scale.
3. To compare outcomes between participants treated with PRP and those receiving the control or standard-care regimen. Study Design An open-label, parallel-arm randomized controlled design was used for this study. 3.2 Place of Study The research took place in the Department of Physical Medicine and Rehabilitation at Bangladesh Medical University, Dhaka, Bangladesh, and included participants seen in its outpatient, inpatient and Sports Medicine Clinic services. Study Period Data collection and follow-up extended for 12 months after the research protocol received Institutional Review Board approval from Bangladesh Medical University. Study Population Eligible patients were adults with partial ACL tears confirmed by MRI who presented to the outpatient, inpatient, or Sports Medicine Clinic services of the Department of Physical Medicine and Rehabilitation, Bangladesh Medical University. Sampling Technique Potential participants were recruited purposively from patients attending the study centre. Once eligibility, enrolment and baseline assessment had been completed, allocation to the experimental or control arm was determined randomly by a lottery method. No blinding was performed because of the nature of the intervention. Sample-Size Determination The number of participants required was estimated with the formula for comparing two independent group means: Values used in the calculation were obtained from Liao et al. (2023), who reported KOOS outcomes after anterior cruciate ligament reconstruction. At the one-month assessment, the intervention group had a mean KOOS score of 65.85 ± 6.57, compared with 60.56 ± 6.61 in the comparator group. Where: n = required sample size in each group u = Z-value at 5% level of significance = 1.96 v = Z-value at 80% statistical power = 0.84 μ1 = mean KOOS score in the intervention group = 65.85 μ0 = mean KOOS score in the comparison group = 60.56 σ1= standard deviation of KOOS score in the intervention group = 6.57 σ0= standard deviation of KOOS score in the comparison group = 6.61 Therefore, n=24.33 Considering an anticipated 5% dropout or loss to follow-up, the adjusted sample size was: Therefore, 26 participants were required in each group. Hence, the final planned sample size was: N=26+26=52 The calculation therefore yielded a planned total of 52 participants, allocated as 26 in Group A and 26 in Group B. Study Variables Independent variables:

• Autologous PRP in addition to conventional conservative treatment Dependent variables
• Severity of pain assessment with VAS score
• ADL, Quality of life and other symptoms assessment by KOOS scale Additional demographic and clinical characteristics recorded were:
• Age;
• Sex;
• Occupation;
• Body mass index (BMI);
• Affected knee;
• Duration since injury;
• Level of physical activity;
• MRI grade of ACL injury;
• Associated PCL injury;
• Associated meniscal injury; Intervention method: Group A, in this study, will get one intra-articular autologous PRP treatment guided by ultrasound in addition to conventional conservative therapy (physical therapy, functional bracing and lifestyle modification) while group B will only receive conventional conservative therapy (physical therapy, functional bracing and lifestyle modification). Group A (Experimental group): This group will be given one intra-articular autologous PRP guided by ultrasound, along with conventional conservative therapy (physical therapy, functional bracing, and lifestyle modification). The conventional method has three phases of exercise which will be identical to that of group B, described later. Preparation of PRP (engelenortho.com): PRP is prepared by a process known as differential centrifugation. There are two methods for PRP preparation: PRP method and Buffy-coat method. Here I shall use the Buffy coat method. In this method, whole blood (WB) is centrifuged at a 'high speed' with subsequent collection of the buffy coat. A buffy coat contains a high concentration of leucocytes and platelets. From 40 mL volume of Whole blood a very thin layer of a buffy coat can be produced. Buffy coat method:

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1. A volume of 40 ml of whole blood, collected by two 20 ml disposable syringe holding 2 ml anticoagulant acid citrate dextrose in each at 20°C to 24°C room temperature.
2. Transfer the blood into 2 PRP kit.
3. Centrifuge the whole blood at a high speed (3400 rpm) for 6 minutes
4. Three layers are formed because of its density: The bottom layer consisting of RBCs, the middle layer consisting of buffy coat (Platelets and WBCs) and the top Platelet Poor Plasma (PPP) layer.
5. Remove supernatant plasma from the top of the container.
6. Transfer the buffy-coat layer to another sterile tube.
7. Centrifuge at low speed (1500 rpm) for 5-6 minutes to separate platelets from WBC.
8. Gently aspirate the upper portion (platelet-rich plasma) and avoid disturbing the leukocyte layer.
9. The final volume is usually 6-8 mL of PRP, with a platelet concentration typically 4 -5 times. Injection of PRP: The patient will be positioned supine with knee 70° flexion. A linear transducer (L18-5, 5 MHz to 18 MHz) was placed parallel to the patellar tendon with the proximal end rotated counterclockwise in 30° to clarify the origin of both anteromedial and posterolateral bundles over tibial plateau. The needle tip will be inserted at the site of the injured ACL, and 6-8 milliliters of PRP will be injected into the joint under ultrasound guidance. (Laimujam et al., 2022). Figure: US guided PRP injection (Laimujam et al., 2022; Chi-Kai et al.,2019). Precautions and advice: Prior to PRP injection patients will be informed about the following matters
10. A minimum of one week before procedure, stop using any anti-inflammatory drugs, such as Ibuprofen, Diclofenac, or Naproxen
11. Make sure to stop taking systemic steroids two weeks in advance of the procedure.
12. Refrain from using intraarticular steroid injections for at least 12 weeks prior to procedure.
13. Eat a substantial, healthy meal and make sure to stay hydrated on the day of the treatment. After the PRP injection patient will be advised about the following things:
14. If pain, ice can be applied 2-3 times a day for 10-15 minutes as needed for comfort
15. Take tab Paracetamol 1 gm twice daily for mild to moderate pain and tab Tramadol 50 mg twice daily if severe pain
16. Avoid applying heat to the injection site for the first 72 hours of post procedure.
17. After 72 hours apply warm moist compression 2-3 times daily.
18. Use functional knee brace for 8 weeks during walking.
19. Discontinue anti-inflammatory medications for at least 2 weeks of post procedure.
20. Avoid systematic steroids for 6 weeks of post procedure.
21. Avoid consumption of any alcoholic beverages for 2 days post-procedure.
22. Avoid smoking. Complications after PRP injection: (vijay et al.,2024) PRP related complications- Pain, swelling, redness, stiffness, discomfort at the injection site, post injection flare, allergic reaction Procedure related complications - Bleeding or hematoma, vasovagal syncope, infection Management of complications: (vijay et al.,2024) Reassure the patient-Most of these symptoms are self limiting and spontaneously subsided within 2-3 days. It is best to stay hydrated and drink plenty of water to help promote healing. But in serious condition I will manage the patients in following way:

• Pain, redness, swelling- ice compression, tab paracetamol
• Allergic reaction / flare- Tab paracetamol, antihistamine
• Bleeding/hematoma- Direct pressure on the bleeding point, ice application, elevation
• Vasovagal syncope- lying flat, elevate the leg, proper aeration
• Infection/septic arthritis- Immediate hospitalization, joint aspiration for diagnosis, IV antibiotics, serial joint aspiration, joint irrigation ADL instruction for both group: 0-3 days:
• Avoid prolonged standing, stairs, squatting, kneeling
• Limit weight bearing 4-14 days:
• Gradually increase walking on flat surfaces
• Use functional knee brace for 8 weeks
• Avoid twisting, pivoting, or high knee flexion activities 3-6 weeks:
• Resume cooking, laundry, and standing activities with breaks
• Light household chores allowed
• Avoid rapid direction changes or stairs often Group-B (Control group): This group will be managed in the Department of Physical Medicine and Rehabilitation, BMU, Dhaka with conventional conservative therapy including physical therapy, functional bracing, lifestyle modification. Physical therapy includes exercise program and physical modalities (ice compression or warm-moist compression). Exercise program will be started from day 4 in both groups. (Oscar et al.,2024) I will provide instructions for entire exercise program, supply necessary videos, and monitor exercise adherence through video call between follow-ups. Patient will take tab Paracetamol 1 gm twice daily for pain. Warm moist compression also be advised before exercise. If pain increased gradually and not relieved by drug, then he/she will stop exercise immediately and apply ice 2-3 times daily for 2-3 days. After pain subside start exercise again. Functional bracing also be advised for both group from 1st week. Exercise program: (Laimujam et al., 2022 Strehl et al., 2007). Phase 1(1-3 weeks): Objectives include the reduction of swelling, partial weight bearing to full weight bearing, 0-100-degree range of motion, 4+/5 quadriceps strength, and 5/5 hamstring strength. The exercise program that is included in this phase are:
• Supported bilateral calf raises
• Gentle flexion range of motion (ROM) 120 degree
• Extension range of motion to 0 degree
• Quadriceps setting
• Hip abduction and extension
• Hamstring pulleys/rubbers Phase 2 (3-8 weeks): The objectives will be full knee hyper extension, knee flexion to 130 degrees, full squat, good control and balance. Exercises include- • ROM exercise
• VMO setting
• Mini squats and lunges
• Leg press double to single
• Step-ups
• Bridges double to single
• Hip abduction and extension with Thera Band
• Single leg calf raises
• Balance and proprioceptive exercise. Phase 3 (8-16 weeks): The objectives of phase three include full range of motion, full strength and power, return to jogging, running, agility, return to restricted sports-specific drills and use of the same exercise program as in phase two with a stepped-up level of difficulty, repetitions and weight, jump, land drills, and agility drills. Each of the exercises in all phases will be done by 10 repetitions 2 to 3 times daily. Always warm-up before and cool-down/stretch after exercises.