Platelet rich plasma and anterior cruciate ligament repair: A new frontier, or a short term adjunct

Abstract

Platelet rich plasma (PRP) is an autologous blood product rich in platelets, showing promise in reducing inflammation and accelerating healing. While extensively utilized in plastic surgery, dermatology, and osteoarthritis treatment, its application in anterior cruciate ligament (ACL) injuries is limited. This article examines PRP's potential in ACL reconstruction (ACLR), exploring its history, current usage, controversies and future directions. PRP has demonstrated significant early benefits in ligamentisation and vascularisation post-ACLR, though its long-term efficacy is inconsistent. Studies suggest that PRP may serve as both an adjunct therapy in ACLR to enhance initial healing and reduce postoperative complications, and as a non-surgical alternative for small ACL tears. Despite these promising findings, outcome variability necessitates further high-quality research to optimize PRP formulations and determine its most effective applications. The exploration of PRP as a treatment modality in ACLR offers promising but varied outcomes. PRP holds considerable promise as both an adjunct and alternative to traditional ACLR. This article underscores the need for targeted research to fully realize PRP's therapeutic potential in ACL treatment, aiming to inform future studies and clinical practices. By understanding PRP's mechanisms of efficacy and identifying the most beneficial patient populations, PRP could significantly impact orthopaedics and sports medicine, improving recovery pathways and patient outcomes.

Key Words: Anterior cruciate ligament; Anterior cruciate ligament repair; Anterior cruciate ligament rupture; Platelet rich plasma; New frontier

Core Tip: Platelet rich plasma (PRP) shows promise in enhancing early healing and reducing complications in anterior cruciate ligament reconstruction, though its long-term efficacy remains inconsistent. Optimizing PRP formulations and targeted research are essential to fully realize its therapeutic potential. PRP could serve as both an adjunct and non-surgical alternative in anterior cruciate ligament treatments, potentially revolutionizing patient recovery in orthopaedics and sports medicine.

INTRODUCTION

Platelet rich plasma (PRP) is an autologous blood product with a high concentration of platelets, in a small volume of plasma[1,2]. While the mechanisms of PRP remain unclear, prevailing theories suggest that PRP activates receptors on the cell membranes of target cells, triggering the formation of high-energy phosphate bonds[3]. This process activates signalling proteins, which in turn stimulate further cellular activities, including angiogenesis and mitogenesis[3]. PRP has been shown to reduce inflammatory and proinflammatory markers, such as interleukin (IL)-1, IL-2, and tumour necrosis factor-alpha, leading to a faster and more optimal return to prior function post-injury[4]. PRP shows promise and is used in various fields, including plastic surgery, dermatology, and the treatment of osteoarthritis (OA), it is not widely used in or alongside the treatment of anterior cruciate ligament (ACL) injuries[5-7].

The ACL plays an important role in the biomechanics of gait and general function, with ACL deficient knees being shown to have decreased variability in gait, leading to greater rigidity in patients’ gait[8,9]. Injuries to the ACL are the most frequently studied orthopaedic injuries, with incidence varying with age and sex. Peak incidence is reported to be around 241 per 100000 cases in males, and 228 per 100000 cases in females, at ages 19-25 and ages 14-18, respectively[10].

Surgical repair or reconstruction of the ACL (ACLR) is on the rise, particularly among females aged 14-17, with an increase of 8.14 cases per 100000 per year[11]. While ACLR has been shown to have good outcomes, noting high rates of return to pre-injury levels of activity, there are varying rates of post-operative complications[12-14]. Treatments such as PRP have shown promise as an adjunct or alternative to ACLR[15-16].

This article highlights the potential of PRP in ACL injuries, building on the work of Soufan et al[17], who emphasize the potential of biologics such as PRP in OA. It aims to highlight the current up to date knowledge and trends and inform further high-level studies on this topic.

THE HISTORY OF PRP IN SURGERY

Mościcka and Przylipiak[18] outline the history of autologous PRP, highlighting the roles of Donné, Bizzozero and Wright in the discovery and early development of regenerative therapies[18-22]. The early 1940s brought about the use of embryonic extracts of growth factors and cytokines, promoting would healing, paving the way for regenerative medicine[23].

PRP’s modern origins are based in haematology, being used as a basic transfusion product in the 1970s to treat thrombocytopenia[24,25]. Surgical applications followed, particularly in oral and maxillofacial surgery, with adaptations into platelet-rich fibrin (PRF). PRF, alongside PRP, combined properties to form a homeostatic and anti-inflammatory surgical adjunct[2,26]. By the 1990’s, PRP was widely used in various dental and cardiac surgeries, evolving into the present day, where PRP has a vast range of applications in the surgical field[27-30]. Within the field of orthopaedics, PRP is most commonly used to treat OA, showing great promise, further applications of PRP could benefit the orthopaedic landscape[31].

CURRENT USAGE OF PRP IN ACLR

A recent meta-analysis by McRobb et al[32] highlights significant early increases in the rate of ligamentisation and vascularisation when PRP is used following ACLR, though no significant improvement was found in later stages of the healing process, with varying postoperative pain and function outcomes reported. Furthermore, PRP administered into ACL graft and tunnel intraoperatively has been shown to yield better healing characteristics compared to controls with similar outcomes found at 6 months post ACLR[33-36]. However, long-term outcomes indicate that PRP does not significantly improve traditional ACLR in terms of functional scores or graft healing[37,38]. As such while studies like Valentí Azcárate et al[38] compare PRP to a control, being used during an arthroscopic ACLR and finding that PRP significantly reduces postoperative swelling and inflammation within the first 24 hours (P < 0.05), with no differences in functional or clinical outcomes at 3 months, 6 months and 12 months. In a similar study by Komzák et al[37], a total of 40 patients underwent surgery; 20 received single-bundle hamstring reconstruction with PRP application (PRP group), and 20 underwent the same procedure without PRP (control group). PRP showed no significant benefits in graft remodelling, bone ingrowth, or functional outcomes at 3 months or 12 months postoperatively. Both groups improved over time, but no differences were observed in magnetic resonance imaging findings or functional scores (P > 0.05).

When used as an alternative to ACLR, PRP has shown similar postoperative outcomes, highlighting its potential for use in small ACL tears, thereby reducing the need for surgical intervention in certain patients[15]. PRP alone has been shown to be more effective than other alternatives, such as hyaluronic acid, for knee pathologies like OA[39]. However, studies on its role in ACLR underscore the need for further research on this topic[37].

When activated, PRP delivers growth factors, including platelet-derived growth factor, transforming growth factor-beta, vascular endothelial growth factor (VEGF), epidermal growth factor, insulin-like growth factor-I, fibroblastic growth factor, and hepatocyte growth factor (HGF) to injury sites[40-43]. These have been shown to accelerate ligament healing. While the optimal composition of PRP, specific to ligament healing, is an area of controversy, this article aims to promote further research on this topic[40].

CONTROVERSY

We found a paucity of high level of evidence works in relation to the benefits (or disadvantages and problems) of PRP in ACLR compared to ACL reconstruction alone or ACLR with the adjunct of hyaluronic acid, or even conservative measures alone[37]. Therefore, as further explained in the above sections, a lack of scientific evidence persist on the topic.

While PRP has potential in ACLR, it has varying outcomes, as per the previous sections, raising questions about its efficacy. One lens to approach this through, is cost effectiveness. One way to approach this is through cost-effectiveness. A study in the United States found the mean price for a single unilateral same-day PRP injection was $714 with a standard deviation of $144, and a mean claim of 76% efficacy[44]. PRP has a higher initial cost but significantly superior quality-adjusted life-years, proving more cost-effective compared to other treatments[45,46]. However, these figures pertain to OA treatment with PRP, reducing the generalisability of prospective results to ACL tears and ACLR[44-46]. Given the limited evidence base for studies exploring PRP use in ACLR, further research should examine its cost-effectiveness ratio. If found to be high, this could justify healthcare institutions stocking and implementing such treatment, thereby improving its availability.

The limitations surrounding PRP use in ACLR extend beyond the absence of long-term studies and highlight fundamental gaps in understanding its efficacy and mechanisms. As such, the heterogeneity of PRP formulations, including platelet concentrations and activation methods, underscores the lack of standardization in its application, potentially confounding study results and clinical outcomes[24]. Additionally, the limited sample sizes and methodological variability across studies reduce the generalizability of findings, further complicating efforts to draw definitive conclusions[47].

One could find a significant amount of studies on the most appropriate management options for ACL ruptures (both in paediatric or adult patients), but controversies and debates still exist with regards to specific surgical indications, surgical options/techniques and the use of “adjunct” treatments, such as PRP and hyaluronic acid[48-50].

FUTURE WORKS

Given the therapeutic potential of PRP, further studies should assess its efficacy across various patient populations. Hada et al[51] recently found that in active and fit patients, PRP administered six weeks post-ACL injury can expedite the return to sport. After an average of 139.5 days and 2.8 PRP sessions, all 10 included patients with ACL tears returned to their previous level of activity, highlighting its potential to be used as a non surgical option or alterative to ACLR[51]. Studies should also focus on effective characterisation of PRP.

We believe PRP should be utilized where patients have specific goals, particularly professional athletes. Long-term studies could investigate the prevalence of OA after PRP injections post-ACLR, potentially leading to improved treatment and preventative strategies for OA. Additionally, future research should focus on developing an optimal PRP composition to maximize its therapeutic efficacy. Furthermore, long-term follow up works comparing the outcomes of ACLR alone or ACLR with the adjunct of PRP or hyaluronic acid should be carried out. The use of PRP as a conservative strategy for small ACL tears should also be further explored[51].

CONCLUSION

In summary, the exploration of PRP as a treatment modality in ACLR offers promising but varied outcomes. While PRP has shown significant benefits in accelerating early ligamentisation and vascularisation post-ACLR, these advantages do not extend to long-term functional improvements or graft healing. The efficacy of PRP as an adjunct therapy in ACLR highlights its potential to enhance the initial stages of healing and reduce postoperative complications. Additionally, PRP's application in treating small ACL tears may present a viable non-surgical alternative, thereby broadening its therapeutic scope.

Despite these positive short-term outcomes, the inconsistency in long-term benefits underscores the need for further high-quality research. Future studies should focus on optimizing PRP formulations specific to ligament healing, understanding the mechanisms behind its variable efficacy, and identifying patient populations that may benefit the most from PRP therapy. The integration of PRP in ACL treatment protocols could revolutionize patient recovery pathways, but its full potential will only be realized through comprehensive and targeted research efforts.

Thus, while PRP holds considerable promise as both an adjunct and alternative to traditional ACLR, ongoing investigation is essential to establish its definitive role and to maximize its therapeutic benefits in orthopaedics and sports medicine.