Original Research

Effects of Platelet-Rich Plasma and Indomethacin on Biomechanics of Rotator Cuff Repair

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We conducted a study to determine if platelet-rich plasma (PRP) enhances the strength of rotator cuff repair (RCR) and if concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) affects PRP efficacy. We also wanted to determine the optimal centrifugation protocol for making PRP from rats.

This study used 48 rats, 14 in a centrifugation protocol and 34 in an operative protocol. Six syngeneic rats from the operative group were used as PRP blood donors; the other 28 operative rats underwent bilateral RCRs. The Autologous Conditioned Plasma system (Arthrex) was used to prepare leukocyte-poor PRP. One shoulder was randomized to an intratendinous PRP injection, and the other received normal saline. Each rat was also randomly placed on a postoperative diet, either a regular diet or an indomethacin-enhanced diet. After rats were euthanized at 3 weeks, specimens were dissected to isolate the supraspinatus tendon at its humeral attachment, which was subjected to biomechanical testing.

PRP prepared with a protocol of 5 minutes × 1300 revolutions per minute had the highest platelet index. Mean (SD) energy to failure was significantly higher (P = .03) in tendons treated with PRP, 11.7 (7.3) N-mm, than in tendons treated with saline, 8.7 (4.6) N-mm. Both groups (PRP, saline) showed no significant differences between tendons treated with NSAIDs and those not treated with NSAIDs.

Intraoperative application of PRP enhances energy to failure after RCR in rats. There were no differences in biomechanical strength with NSAID use and no interactions between PRP and NSAID use.


 

References

Take-Home Points

  • The optimal centrifugation protocol for production of rat PRP is 1300 rpm for 5 minutes.
  • PRP administration in RCR improves tendon biomechanics in a rat model.
  • Administration of NSAIDs following RCR has no significant effect on tendon biomechanical properties.
  • NSAIDs may be co-administered with PRP without reducing efficacy of PRP.
  • The role of PRP and NSAIDs in human RCR remains unclear.

Rotator cuff tears are a common source of shoulder pain and disability among older adults and athletes. Full-thickness tears alone occur in up to 30% of adults older than 60 years. 1 Surgical repair is plagued by an unpredictable rate of recurrence (range, 11%-94%). 1-10 As a result of improved suture materials, knotting patterns, and anchor designs, hardware issues are no longer the primary cause of rotator cuff repair (RCR) failures; now the principal mode of failure is biologic. 2 Animal model studies have found that, after injury and subsequent healing, the tendon–bone interface remains abnormal. 11 Rotator cuff research therefore has focused largely on biological enhancement of tendon-to-bone healing.

One means of biological augmentation is autologous platelet-rich plasma (PRP), which has supraphysiologic concentrations of platelets and their secreted growth factors. Although there is no consensus on the long-term efficacy of PRP, some studies suggest PRP accelerates healing over short and intermediate terms, which may contribute to a more rapid decrease in pain and more rapid return to normal activities. 12-18 Similarly, systemic nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used to treat musculoskeletal injuries, including rotator cuff pathology. However, NSAIDs inhibit cyclooxygenase activity, and clinical and experimental data have shown that cyclooxygenase 2 function is crucial in normal tendon-to-bone healing. 19-21

Comprehensive studies have been conducted on the efficacy of both PRP and NSAIDs, but the interaction of concurrently used PRP and NSAIDs has not been determined. As many physicians use both modalities in the treatment of soft-tissue injuries, it is important to study the potential interactions when coadministered. Prior studies in small animal models suggest NSAIDs may impair tendon-to-bone healing in RCR, but there is no evidence regarding the effect of NSAIDs on the efficacy of PRP treatment. 21

We conducted a study to determine the interaction of PRP and NSAIDs when used as adjuncts to RCR in a rat model. We hypothesized that PRP would increase the strength of RCR and that NSAIDs would interfere with the effects of PRP. A preliminary study objective was to determine an appropriate centrifugation protocol for producing PRP from rat blood, for use in this study and in future rat-based studies of PRP.

Materials and Methods

Part A: Pretesting Determination of PRP Centrifugation Protocol

Fourteen adult male Fischer rats were used in part A of this study, which was conducted to determine an appropriate PRP centrifugation protocol. Traditional PRP centrifugation protocols are established for human blood, but rat red blood cells (RBCs) and human RBCs differ in size. 22 In our preliminary study, we wanted to determine the adjusted centrifuge speed and duration for producing clinically optimal PRP from rats. Clinically optimal PRP has reduced levels of RBCs, which decrease platelet affinity. Although the role of leukocytes in PRP preparations is debated, reducing the number of white blood cells (WBCs) decreases the number of matrix metalloproteinases and reactive oxygen species that may lead to inflammation. We used the platelet index (ratio of platelets to WBCs) and the RBC count to quantify the quality of our PRP sample.

Each rat in part A was anesthetized while supine. We used the Autologous Conditioned Plasma (ACP) system (Arthrex), which requires only 1 centrifugation cycle to create PRP. About 9 mL or 10 mL of blood was obtained by cardiac aspiration using an ACP Double Syringe (Arthrex). After blood retrieval, a thoracotomy was performed to confirm each rat’s death.

Figure 1.
Each blood sample was centrifuged once under 1 of 6 different centrifugation protocols, varying in duration (minutes) and speed (revolutions per minute [rpm]) ( Figure 1 ). Initially, 12 rats were evenly divided among the 6 protocols, 2 rats per group. The spun PRP product from each rat was evaluated for RBC count, platelet count, and WBC count, and a platelet index was calculated. The 2 centrifugation protocols with the highest mean platelet index, 5 minutes × 1300 rpm and 3 minutes × 1800 rpm, were then increased in size by 1 rat each (new sample size, 3). With these 2 rats added, the highest overall platelet index and lowest RBC and WBC counts were found in the 5 minutes × 1300 rpm protocol

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