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. 2025 Mar 3;13(3):23259671241312754.
doi: 10.1177/23259671241312754. eCollection 2025 Mar.

Preoperative Platelet-Rich Plasma Injections Decrease Inflammatory and Chondrodegenerative Biomarkers in Patients With Acute Anterior Cruciate Ligament Tears: A Pilot Randomized Controlled Trial

Adam W Anz  1 , Eric A Branch  1 , Steve E Jordan  1 , Roger V Ostrander 3rd  1 , Brett J Kindle  1 , James C Presley  1 , Joshua G Hackel  1 , Emily Maggi  1 , Hillary A Plummer  1
Affiliations

Preoperative Platelet-Rich Plasma Injections Decrease Inflammatory and Chondrodegenerative Biomarkers in Patients With Acute Anterior Cruciate Ligament Tears: A Pilot Randomized Controlled Trial

Adam W Anz et al. Orthop J Sports Med. .

Abstract

Background: Posttraumatic osteoarthritis occurs at an alarming rate after anterior cruciate ligament (ACL) injury and reconstruction (ACLR).

Purpose/hypothesis: The purpose of this pilot randomized controlled trial was to evaluate the preoperative effect of a 2-injection series of platelet-rich plasma (PRP) on the progression of inflammatory and chondrodegenerative biomarkers before ACLR. It was hypothesized that preoperative PRP injections would decrease the chondrotoxicity of the presurgical knee fluid.

Study design: Randomized controlled trial; Level of evidence, 1.

Methods: A total of 24 participants were randomized to either a control or an intervention group. Both groups received joint aspirations within the first 10 days after ACL injury (visit 1). In addition to joint aspiration at visit 1, the PRP group received a leukocyte-poor, nonactivated PRP injection at visit 1 and an additional PRP injection 5 to 12 days after the initial visit (visit 2). Joint fluid samples were harvested in both groups at the time of ACLR (visit 3). The joint fluid and PRP samples were subject to inflammatory and chondrodegenerative biomarker analysis for the following: interleukin (IL)-1ß, IL-10, IL-6, granulocyte-macrophage colony-stimulating factor, IL-5, interferon (IFN)-γ, tumor necrosis factor-α, IL-2, IL-4, and IL-8.

Results: The final analysis was completed on 8 participants in the control group and 8 in the intervention group. At visit 1, no significant differences were observed in cytokine concentrations between the control and intervention groups. Between visits 1 and 3, the control group demonstrated significant decreases in IL-8 (P = .007) and IFN-γ (P = .007), whereas the intervention group demonstrated significant decreases in all cytokine concentrations (P < .05) except for IL-8 (P = .08). At visit 3, similar to visit 1, no significant group differences were observed in cytokine concentrations. The PRP products in the intervention group were analyzed using complete blood counts and were consistent with defined concentrations found in leukocyte-poor PRP product.

Conclusion: Intervention with aspiration combined with a 2-injection series of leukocyte-poor PRP in the acute ACL-injured knee resulted in a significant reduction in effusion inflammatory markers, whereas the control aspiration (without PRP injections) did not show such marker reduction.

Registration: NCT04088227 (ClinicalTrials.gov identifier).

Keywords: anterior cruciate ligament; anterior cruciate ligament reconstruction; platelet-rich plasma; posttraumatic osteoarthritis.

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Conflict of interest statement

One or more of the authors has declared the following potential conflict of interest or source of funding: Funding for this study was received from the State of Florida Department of Health. A.W.A. has received education payments from Arthrex, consulting fees from Arthrex and Bioventus, nonconsulting fees from Arthrex and Smith & Nephew, and royalties from Arthrex. E.A.B. has received grant support from Arthrex; education payments from Arthrex, Smith & Nephew, and MVP Orthopedics; and hospitality payments from Stryker. S.E.J. has received education payments from CGG Medical, nonconsulting fees from Arthrex, and royalties from Arthrex. R.V.O. has received hospitality payments from CGG Medical. B.J.K. has received consulting fees from Sonex Health. J.G.H. has received consulting fees and honoraria from Tenex Health. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Figures

Figure 1.
Figure 1.
CONSORT (Consolidated Standards of Reporting Trials) flow diagram of patient inclusion in the study.
Figure 2.
Figure 2.
Overview of platelet-rich plasma (PRP) preparation.
Figure 3.
Figure 3.
Inflammatory and chondrodegenerative biomarker concentrations. GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor; V1, visit 1 (≤10 days after anterior cruciate ligament injury); V3, visit 3 (at anterior cruciate ligament reconstruction).
Figure 4.
Figure 4.
Sample size calculation for a power of 80% and type 1 error of .5% (A) n was inflated by 20% to account for loss to follow-up; power=0.8; α = 0.005 (Bonferroni correction) and (B) n was inflated by 20% to account for loss to follow-up; power = 0.8; α = 0.05.
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