REVIEW ARTICLE
Platelet-Rich Plasma for Rotator Cuff Repair F. Alan Barber, MD, FACS
Abstract: Rotator cuff tears are a common cause of shoulder pain and disability. Because they combine both traumatic and degenerative elements, the surgical repair can be challenging. Even after surgical intervention, tendon residual defects or “retears” often develop. Risk factors for tendon “retears” include patient age, number of tendons involved, tear size, and smoking. Platelet-rich plasma (PRP) is a supraphysiological concentration of platelets, which may be able to positively augment rotator cuff tendon healing. Not all PRPs are the same and those containing higher leukocyte levels may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors from the PRP and may actually inhibit some parts of the healing response. As yet, the clinical data does not conclusively prove a benefit from PRP, but discernment is required in evaluating the published results. As different PRPs may act differently and the results may be dose dependent requiring more PRP to achieve a beneficial threshold. How success is measured (clinical outcomes vs. intact cuff tendons) and how long the patients are followed are also critical items. Currently, the PRP fibrin matrix version holds the greatest promise for improving clinical success after rotator cuff tendon repair. Key Words: platelet-rich plasma, PRP, rotator cuff tendon, arthroscopy, biological augmentation, shoulder
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onsistently achieving healing after surgery for rotator cuff tears is challenging. What can be done to improve healing in cuff repairs? The factors which adversely affect rotator cuff tendon healing include increasing age (older than 65 y), increasing the number of tendons involved, larger tear sizes, increased preoperative duration of symptoms, and the preoperative stage of fatty degeneration.1–3 There are several strategies to address these concerns: patient selection, biological augmentation, and mechanical reinforcement. The goal for tendon healing is to replicate normal biology. The normal anatomy of the rotator cuff transitions through 4 phases from tendon, fibrocartilage, calcified fibrocartilage, and bone. The ultimate goal of surgical repair is to replicate this normal fibrocartilage transition zone as much as possible. Ide et al4 demonstrated that after surgery this fibrocartilage transition zone actually becomes a fibrovascular scar.
PATIENT SELECTION Although at present, it is difficult to affect the development of a fibrovascular transition, an awareness of patient selection can lead to better repair outcomes. Age From the Plano Orthopedic Sports Medicine and Spine Center, Plano, TX. Disclosure: The author declares no conflict of interest. Reprints: F. Alan Barber, MD, FACS, Plano Orthopedic Sports Medicine and Spine Center, 5228 West Plano Parkway, Plano, TX 75093. Copyright r 2013 by Lippincott Williams & Wilkins
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makes a significant difference in healing. Boileau et al5 described in 2005 that rotator cuff repair in patients under 55 years of age is associated with a 95% healing rate. A 75% of rotator cuff tendon healing rate was observed in the age group from 55 to 64 years, and patients older than 65 years had complete healing in only 43% of the rotator cuff tendons. The size of the tear also makes a difference. Two tendon tears heal less completely than 1 tendon tear. Microvascular disease is another confounding variable especially in smokers2,6,7 and nonsteroidal anti-inflammatory drugs and steroid use can also have an impact.8
BIOLOGICAL AUGMENTATION Biological augmentation options include recombinant human BMP-12, which has been shown to increase rotator cuff tendon to bone healing strength in sheep.9,10 Fibroblast growth factor-2 helps with granulation tissue and remodeling, and there are several growth factors which while providing a more robust fibrovascular tissue formation produce poor quality scar tissue.4,9–12 In addition, numerous cytokines can positively affect tendon healing. However, a single factor therapy has several limits. Healing is a complex event. A single factor does not mimic the multiple coordinated actions of many factors normally associated with healing. Platelet-rich plasma (PRP) contains a granules, dense granules, several cytokines, and other bioactive factors. It allows the delivery of these in a physiological balance. Platelet degranulation releases growth factors and stimulates healing. However, the final growth factor concentration depends upon the amount of whole blood used, the platelet recovery efficiency, and the final volume of platelets. It should be remembered that not all PRPs are the same. The effectiveness of PRP can be influenced by what is in it and what is administered along with it to influence platelet activation. Growth factor and catabolic cytokine concentrations are influenced by the PRP cellular composition (for instance, the presence of leukocytes). It is not just the platelets that influence the clinical response to PRP.13 Platelets have been shown to increase anabolic signaling, whereas leukocytes increase catabolic signaling molecules.2,14 Some preparations contain higher levels of leukocytes. Consequently, based upon the data, a reduced leukocyte PRP seems to offer better healing without scar tissue formation.2 Leukocyte-rich preparations have been shown to have more inflammatory catabolic mediators (matrix metalloproteinase-9 and 1L-1b) that may be detrimental to tendon healing.14 Another evaluation of the in vivo effect in the healthy tendons reported greater inflammatory responses 5 days after the treatment with leukocyte-rich PRP when compared with leukocyte-poor PRP.3 This resulted in greater early tendon architecture disruption, higher vascularity, and fibrosis in the histology. At present, there are no studies that suggest what the longterm effect of leukocyte-rich preparations might be, but these short-term studies raise concerns about their use.
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How the PRP is activated can make a difference. Thrombin is often used as a platelet activator. Han et al15 have shown that PRP can stimulate chondrogenesis and osteogenesis. However, thrombin activation of the PRP triggered an immediate release of growth factors from the PRP and the result was to inhibit chondrogenesis and osteogenesis.15 In addition, inflammatory cells were present in demineralized bone matrix samples that were mixed with thrombin-activated PRP but not present in matrix mixed with PRP alone. Physically, there are 2 types of PRP. The liquid form can be injected into the area of the rotator cuff repair. However, the liquid version tends to disappear in 7 to12 hours. A solid platelet fibrin construct created using a double centrifuge spin provides a scaffold and a reservoir of growth factors. This scaffolding or matrix allows the elution of growth factors for up to 7 days. The preparation of these 2 different forms is with the use of a centrifuge. After a single spin, the elements of the blood are separated with the red cells, white cells, and plasma components separated. At this point, the PRP products, which are liquid, are simply selectively extracted from the tube for use. To create the solid matrix or membrane versions, the clear liquid component is also drawn off but then centrifuged for a second time. After the second centrifugation, the membrane is located at the bottom of the bottle and can be decanted for use. The clinical application for these different forms of PRP differs. The liquid is simply injected into the area of the repair. The platelet fibrin construct must be sutured into the interface between the tendon and the bone. This can be either at the suture line for a single row repair or between the medial and lateral rows in a double row repair. Other factors can influence the effectiveness of the PRP used. Thrombin is sometimes used to activate the PRP. It has been shown to accelerate the release of growth factors and to significantly decrease the efficacy of PRP in bone grafting.15 In addition, preparations with high leukocyte counts have also been implicated in poorer results.16 Calcium is sometimes used to form the PRPF matrix clot and seems to be more desirable in terms of a delayed release of growth factors. Finally, how or exactly where to apply the PRP and in what amount is also unclear. Data from Thomopoulos et al17,18 suggest that interposing the matrix material between the bone and tendon of the repair site may delay or impair healing. Perhaps, the greatest source of variability of the PRP product is related to the variations in harvested blood from each patient.
CLINICAL EVIDENCE In recent years, several studies have looked at the clinical response of rotator cuff healing associated with biological augmentation using various forms of PRP. Castricini et al19 recently published their clinical experience with 88 patients randomized with and without a single PRP matrix globule (Cascade; Musculoskeletal Tissue Foundation, Edison, NJ). The primary outcome measure was the Constant score6 and a power analysis was performed for that factor alone. The secondary outcome measure was the magnetic resonance imaging (MRI) reading of tendon healing performed by orthopedic surgeons associated with the study. At a mean follow-up of 20 months (range, 16 to 30 mo), the primary outcome measure (Constant score) showed no difference between the groups.
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The secondary outcome measure (MRI cuff evaluation) was based upon 78 of the 88 patients who had a postoperative MRI. They reported an overall healing rate of 94%. Four control patients without augmentation using a the single (9 mL) globule of PRP fibrin matrix had retears (10.5%), whereas only 1 retear occurred in patients receiving the PRP fibrin matrix. The concern with this analysis was that a statistical error had occurred by turning continuous data into one of the 3 categories. Arnoczky20 performed an analysis of the data presented in this article and found that using the authors’ data and comparing normal to abnormal (PRP vs. no PRP), the footprint area with the PRP was statistically better (P = 0.02), the MRI signal intensity was better (P < 0.001), but the tendon thickness was not statistically different (P = 0.09). It should be emphasized that in this study only one 9 mL PRP matrix globule was used. This may be significant. Rodeo et al21 reported 79 patients prospectively randomized into groups with and without a single PRP fibrin matrix globule (Cascade). Of the 79, 67were available for a 12-week follow-up. In the 2 groups, 35 received the PRP matrix globule and 32 served as the control. The primary outcome measure was an intact cuff versus a defect based upon an ultrasound examination at 6 and 12 weeks postsurgery. Unfortunately, they did not enroll the amount required by their own power analysis for statistical significance, and lost 12 of the 79 patients to follow-up before the 12-week interval. In addition, the repair techniques were very mixed. Twenty six single row and 42 double row repairs were performed and the repair technique was unknown for 11 patients. This trial was stopped early and they could not demonstrate a difference in outcome scores or muscle strength between the groups. Ultrasound showed no difference between the groups at 6 or 12 weeks. Interestingly, their data showed 95% healing on ultrasound at 6 weeks for tears 3 cm) demonstrated 50% healing at 6 weeks and 56% healing at 12 weeks. Concerns about this study include the use of only one 9 mL matrix globule, enrollment did not meet the power analysis requirements, and ultrasound was used to show cuff healing as an endpoint. Don Buford at the Arthroscopy Association of North America’s 2011 annual meeting reported in an instructional course lecture his experience using ultrasound to assess rotator cuff healing. He indicated that rotator cuff healing is not consistently demonstrated by ultrasound until at least 4 months after surgery. In addition, Lee and colleagues (“Comparison of the Integrity of Repaired Rotator Cuff with Ultrasonography Before and After Arthrography.” Presented at the American Academy of Orthopedic Surgeons, 2012) recently showed that postoperative ultrasound showed only an 8% retear rate as opposed to a 47% retear rate of the same patients using magnetic resonance arthrography. The principal concern about this data is the risk of a b error. If a study is not sufficiently powered, proving that a difference does not exist is not possible. The mere fact that statistical difference was not shown does not mean one does not exist. Barber et al1 reported 2 matched groups of rotator cuff repairs. Twenty were randomized to receive PRP fibrin matrix associated with rotator cuff repair and 20 without PRP fibrin matrix. This study is different from the previous r
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one; in that 2 Cascade fibrin matrix globules (18 mL) were sutured into the interval between the rotator cuff tendon and the bone. The primary outcome measure for this study was an MRI showing tear or no tear at 12 or 24 months after surgery. The average clinical follow-up was 31 months (range, 24 to 44 mo) and the power analysis was carried out, which showed that 20 per group would be sufficient. Secondary outcome measures included clinical outcome scores (Constant, Rowe, ASES, SANE, SST). MRI results indicated 70% complete healing with the PRP matrix repair and 40% complete healing in those rotator cuff repairs without PRP fibrin matrix (P = 0.03). Those patients with tears between 1 and 3 cm had 86% healing with 2 PRP fibrin matrix globules, whereas those without the 2 PRP fibrin matrix globules had only 50% healing. Clinical outcome scores did not show a statistically significant difference between groups. Weber et al11 also used a single row repair with a single PRP fibrin matrix (Cascade) in a prospective, randomized, controlled trial of rotator cuff repairs with and without PRP fibrin matrix insertion into the repair interval between the tendon and the bone. A power analysis was performed on the number required to show a statistical difference in perioperative pain measured by visual analog scale (VAS). Sixty consecutive patients were required with 30 randomized into each group. MRI examinations were also obtained between 3 and 5 months postsurgery. The authors report some technical difficulties in achieving a quality clot at the beginning of the study and it is unclear if these patients were still included in the study group. No significant difference in VAS, SST, ASES scores, or narcotic use was observed between the groups. The MRI rating system of Sugaya et al22 was used to stratify patient tendon healing into 5 categories postsurgery. All MRI scans were reviewed in a blinded manner by a fellowship-trained orthopedic surgeon in addition to the review of the operating surgeons. Only 28 of the PRPF matrix group and 24 of the control group had MRIs. On the basis of the tear or no tear results and the Sugaya categorical scores, no statistical difference was demonstrated by the addition of the single PRP fibrin matrix globule. They also concluded that the size of the tear preoperatively was the most important variable for postoperative cuff integrity. Bergeson et al3 reported a comparison of rotator cuff repairs in high-risk cuff tears (older patients, larger tears, with more fatty degeneration) and reported that the 16 patients in which PRP fibrin matrix was used did not demonstrate improved healing rates or functional outcome scores compared with a retrospective review of 21 similar patients who served as controls. The absence of a power analysis and the retrospective nature of the data collection limit the ability to conclude that no difference exists. The appropriate statement is that a difference could not be shown. Notably, the 21 patients in the control group were drawn from a pool of 38 patients who had been operated on in the year before the start of the study. Some of these 38 patients could not be contacted and the 2 patients with identified tears in the control group were only interviewed by phone. Postoperative infections occurred in 2 of the 16 PRP fibrin matrix patients but none of the previous control patients. Although there is no doubt that the 2 PRP fibrin matrix patients had infections, the fact that the control group was retrospective with incomplete data collection opens the door for some undiagnosed infections. Other studies using PRP fibrin matrix have not reported infections. r
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A recent systematic review by Chahal et al23 concluded that the use of PRP does not have an effect on overall retear rates or shoulder-specific outcomes after arthroscopic rotator cuff repair. However, there was a decrease in the rate of retearing observed among patients treated with PRP in small-size and medium-size tears. After a search of several databases, a total of 5 articles were included in their review. Three different types of PRP were used in these 5 studies. Two of the 5 used a liquid form of PRP and 3 used the Cascade fibrin matrix. Two of the Cascade studies used 2 PRP globules (18 mL) and 1 used a single globule (9 mL). Four of these studies included patients with large or at-risk tears. Even so, Forest plots illustrating the merged results from these studies indicated that 4 of the 5 studies showed that using PRP numerically reduced the overall retear rate. The overall pooled retear rates for all tears of all sizes did not achieve statistical significance. With PRP, the retear rate was 25.6% (29 of 113), whereas without the PRP the retear rate was 36.1% (43 of 119 patients). However, looking at only small-sized to medium-sized tears, the use of PRP statistically significantly reduced the cuff retear rate (7.9% with PRP and 26.8% without PRP). When the large tears were added to the calculation, a statistical benefit for PRP was not shown. The Cascade PRP fibrin matrix used in these studies has been replaced by a platelet-rich plasma fibrin membrane (PRPFM). This membrane is circular in shape and is more durable, allowing easier suturing and manipulation. A comparison of the of the older PRP fibrin matrix to the PRPFM was carried out by Visser et al.24 They found that the fiber content of the PRPFM was greater and more compact than the PRP fibrin matrix. There was a statistically significant increase (> 2-fold) in cell proliferation, increased TGF-b-1 concentration in the PRP membrane, and greater cell density on day 1 in their study. Other forms of PRP have been studied. Using a liquid form of PRP (GPS system; Biomet Biologics, Warsaw, IN), Randelli et al25 prospectively randomized single row rotator cuff repair patients into 2 groups: repair without a PRP injection (n = 27) and with a PRP injection (n = 26). This form of PRP contains autologous thrombin. The results of this study showed that the GPS PRP statistically significantly reduced postoperative pain during the first postoperative month and again at the 24-month data collection interval. Statistically significant higher outcome measure scores (Constant, strength in external rotation, UCLA, and Simple Shoulder Test) were reported at the 3-month interval for the PRP group, but not afterward. Eighty-five percent of both the study groups had postoperative MRIs at a minimum of 12 months after surgery and were assessed for retears and intact tendons. Using the MRI evaluation, patients with grade 1 (minimally retracted tendon) and grade 2 (retracted but not to the glenoid) tears had rotator cuff healing statistically significantly affected with the use of PRP. All but 1 patient in both the study groups with a severe (grade 3 retraction) cuff tear and every massive (grade 4 retraction) cuff tear demonstrated a retear regardless of treatment. When grades 1 and 2 retracted tears were evaluated, those treated with PRP (n = 16) healed better than the control group (n = 19). The number of retears in grade 1 or 2 tears was 2 (14%) in the PRP group and 6 (37%) in the control group. This was not statistically significant. Although these numbers are small, they are consistent with the PRP fibrin matrix data and suggest that PRP may be more effective in smaller cuff tears with less retraction. www.sportsmedarthro.com |
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Jo et al26 reported a nonrandomized comparison between 19 suture bridge cuff repairs with a unique form of PRP matrix and 23 without PRP. This PRP was prepared by collecting blood the day before surgery and using plateletpheresis to create in 3 separate 3 mL globules, which were stored at room temperature with agitation until the next day. At surgery, these 3 globules were threaded on a suture and placed into the interface between the tendon and the bone. At an average follow-up of 19.7 months (minimum 16 mo), no difference in clinical outcomes measures was observed. At a minimum of 9 months after surgery, the repaired tendons were assessed using MRI. Only 15 of 19 patients in the PRP group and 17 of 23 patients in the control group had the MRI. The PRP group retear rate was 26.7%, whereas the control group retear rate was 41.2% (P = 0.39). This was not significant. This type of PRP seems to be unique at this point in the literature and should not be confused with the Cascade product (a single 9 mL globule) reported by others.1,3,11,19,21
MECHANICAL REINFORCEMENT In addition to patient selection and biological augmentation, mechanical reinforcement has been used to improve rotator cuff tendon healing, especially in the larger tendon tears. Some data, which is available, suggests that a combination of mesenchymal stem cells, PRP, and dermal allografting may successfully recreate a transition zone.27 A retrospective case review of 14 patients with large or massive cuff tears (median, 4 cm; range, 2.5 to 6 cm) augmented with acellular human dermal allograft demonstrated favorable structural healing rates and statistically significantly improved functional outcomes in the near term.28 A recent prospective, multicenter, randomized control trial of patients undergoing arthroscopic 2-tendon (>3 cm) rotator cuff repairs with and without augmentation using acellular human dermal matrix reported followup at a mean of 24 months (range, 12 to 38 mo). The repair augmentation with the acellular human dermal allograft resulted in more frequent intact cuffs as determined by gadoliniumenhanced MRI and higher ASES and Constant scores.
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Intact repairs were found in 85% of the augmented group and 40% of the unaugmented group (P < 0.01).29 The use of an acellular dermal allograft to span a gap >1 cm is an FDA off-label use. However, while off label, gap jumping of cuff defects with acellular human dermal allografts has been shown to demonstrate significant improvement in pain, range of motion, and strength while subjective outcome measures (ASES and SF-12 scores) demonstrated statistically significant improvement at an average 3-year follow-up.30 This benefit has been reported by others.31
PRPFM AUGMENTATION TECHNIQUE Any rotator cuff repair must incorporate the established principals initially articulated by Gerber et al.32 The repair technique should have sufficiently high initial fixation strength, avoid the development of gap formation during the healing period, and maintain this mechanical stability until healing is complete.33 The author’s preference is to use a PRPFM to biologically enhance most rotator cuff repairs. Although cuff repairs can be performed in either the beach chair or the lateral decubitus position, our preference is the lateral decubitus position. An initial diagnostic arthroscopy is performed with a thorough assessment of the cuff tendon tear pattern. A clear understanding of the morphology of the tendon tear is required to appropriately mobilize it over the greater tuberosity and plan the repair. Mobilization of the tendon is performed as required and any appropriate margin convergence stitches placed (Fig. 1). The reattachment site on the greater tuberosity is cleared of soft tissue and abraded using a shaver on fast forward to provide a bleeding bed while preserving the cortical bone enhancing the suture anchor attachment. This process includes the placement of marrow vents (a microfracture of the greater tuberosity) to enhance healing (Fig. 2). The suture anchors are inserted at the appropriate sites to avoid placing too much tension on the repair and the sutures are passed in a routine fashion using an antegrade suture passer. For single row repairs, a shuttling suture is passed through the tendon at the level of the repair sutures before tying them. For double row repairs the medial row
FIGURE 1. The tendon is assessed for mobility both before traction is applied (A) and afterward (B). If insufficient mobility exists, it should be freed on the superior and inferior surfaces as needed (copyright F. Alan Barber, MD).
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FIGURE 2. The reattachment site on the greater tuberosity is cleared of soft tissue, abraded to provide a bleeding bed while preserving the cortical bone, and marrow vents are placed to enhance healing (copyright F. Alan Barber, MD).
Platelet-Rich Plasma for Rotator Cuff Repair
FIGURE 4. This circular membrane is folded upon itself twice until it is one quarter its original size. This triangular-shaped graft is secured using a running whip stitch of No. 2-0 Vicryl around the periphery. This creates a “pizza pie slice” and facilitates handling and insertion (copyright F. Alan Barber, MD).
sutures are tied and left long. Then the shuttling suture is passed slightly lateral to the completed medial row. The leading end of the shuttling suture is captured and drawn through the anterior portal leaving the trailing end out of the transdeltoid cannula. The PRPFM is prepared using a double spin technique. This requires drawing 18 mL of blood and produces a circular membrane of PRPFM (Fig. 3). This circular membrane is folded on itself twice until it is one quarter its original size. This triangular-shaped graft is fixed using a running whip stitch around the periphery of No. 2-0 Vicryl suture. This creates a “pizza pie slice,” which facilitates handling and insertion (Fig. 4). Two dilating knots (simple overhand knots) are tied in the trailing end of the shuttling suture, which is then passed through a metal cannula, which is itself inserted through
the rubber dam of the lateral (transdeltoid) cannula (Fig. 5). A third overhand knot is tied proximal to the previous 2 knots and used to capture the Vicryl sutures of the PRPFM graft. The shuttling suture is then drawn out the anterior portal. As the shuttle is pulled through the tendon, the dilating knots dilate the tendon tissue making subsequent passage of the suture easier. Finally the knot capturing the Vicryl sutures is pulled through the tendon. As they are advanced, these Vicryl sutures in turn pass the PRPFM graft into position in the interval between the rotator cuff tendon and the greater tuberosity (Fig. 6). The Vicryl sutures are disengaged from the shuttling suture and the shuttling suture removed out the anterior cannula. With the PRPFM graft in place, the rotator cuff repair is completed (Fig. 7). In a single row repair, the previously placed but untied knots are tied. For a double row repair,
FIGURE 3. The platelet-rich plasma fibrin membrane (PRPFM) is prepared using a double spin technique, requires 18 mL of blood, and produces a circular membrane of PRPFM (copyright F. Alan Barber, MD).
FIGURE 5. Two dilating knots (simple overhand knots) are tied in the trailing end of the shuttling suture, which is then passed through a metal cannula inserted through the rubber dam of the lateral (transdeltoid) cannula (copyright F. Alan Barber, MD).
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FIGURE 6. The knot capturing the Vicryl sutures is pulled through the tendon. As they are advanced, these Vicryl sutures in turn pass the platelet-rich plasma fibrin membrane (PRPFM) graft into position in the interval between the rotator cuff tendon and the greater tuberosity (copyright F. Alan Barber, MD).
the lateral row anchors are inserted securing the sutures from the medial row to complete the repair. No discussion of rotator cuff repair can fail to address the issue of single row versus double row repairs. Many authors advocate the superiority of the double row repair. The recent meta-analysis by DeHaan et al33 showed a strong trend toward higher failure rates in patients undergoing single row compared with double row rotator cuff repair. However, many clinical reports do not support this and the increased costs, complexity, and operating time should be considered.34–36 In addition, there is considerable biomechanical testing data, which shows that a double row repair has a time 0 strength superior to a single row repair and provides greater footprint coverage. However, most of this data studied repair constructs that are not currently consistent with clinical practice. Current double row repairs
FIGURE 8. Cho type 2: this is a failure at the musculotendinous junction (medial row, black arrow). The medial row anchor (white arrow) is visible on this view but not the lateral row anchor (copyright F. Alan Barber, MD).
are increasingly using suture bridging and transosseous equivalent techniques.37 Even more significantly, current single row and double row repairs use ultra-high molecular weight polyethylene containing sutures. In contrast, single row repairs are no longer created using a single mattress stitch and advocates of single row repairs now focus on triple-loaded anchors with UHMWPEcontaining sutures. A recent comparison of triple-loaded, single row repairs to suture bridging and classic double row repairs showed no significant advantage in ultimate time 0 strength between these types of repair.38 In addition, Cho et al39 and others40 have shown that when double row constructs fail (especially in younger patients), the failure is often at the musculotendinous junction. Holding the cuff tendon footprint fixed over a greater area lead to musculotendinous junction failure in rotator cuff muscles with less fatty degeneration or muscle atrophy. Two failure modes were identified: Cho type 1 (failure at the original repair site) and Cho type 2 (failure around the medial row). This raises special concerns as the Cho type 2 failure (musculotendinous junction tear) (Fig. 8) occurred with double row repairs in 59% of Cho’s failure cases. The percentage of the Cho type 1 retear increased with the severity of fatty degeneration or muscle atrophy suggesting that healthier tendon tissue is more likely to tear in a catastrophic Cho type 2 manner (at the musculotendinous junction). This type of failure leaves a virtually irreparable situation.
CONCLUSIONS
FIGURE 7. With the platelet-rich plasma fibrin membrane (PRPFM) graft (black arrow) in place, the rotator cuff repair is completed (copyright F. Alan Barber, MD).
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Improving success for rotator cuff tear surgery can be achieved with proper patient selection considering the established risk factors, biological augmentation, and possibly mechanical reinforcement. Risk factors for failure include patient age, number of tendons involved, tear size, and smoking. PRP may biologically augment rotator cuff r
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tendon healing. However, not all PRPs are the same and those containing higher leukocyte levels and thrombin activation may prove detrimental to tendon healing. Confusion in the clinical data does not conclusively prove a benefit from PRP and results may be dose dependent. Currently, the PRP fibrin matrix version of PRP holds the greatest promise for improving clinical success after rotator cuff tendon repair. REFERENCES 1. Barber FA, Hrnack SA, Snyder SJ, et al. Rotator cuff repair healing influenced by platelet-rich plasma construct augmentation. Arthroscopy. 2011;27:1029–1035. 2. McCarrel TM, Minas T, Fortier LA. Optimization of leukocyte concentration in platelet-rich plasma for the treatment of tendinopathy. J Bone Joint Surg Am. 2012;94(e143):1–8. 3. Bergeson AG, Tashjian RZ, Greis PE, et al. Effects of plateletrich fibrin matrix on repair integrity of at-risk rotator cuff tears. Am J Sports Med. 2012;40:286–293. 4. Ide J, Kikukawa K, Hirose J, et al. The effects of fibroblast growth factor-2 on rotator cuff reconstruction with acellular dermal matrix grafts. Arthroscopy. 2009;25:608–616. 5. Boileau P, Brassart N, Watkinson DJ, et al. Arthroscopic repair of full-thickness tears of the supraspinatus: does the tendon really heal? J Bone Joint Surg Am. 2005;87:1229–1240. 6. Constant CR, Murley AH. A clinical method of functional assessment of the shoulder. Clin Orthop Relat Res. 1987; 214:160–164. 7. Mallon WJ, Misamore G, Snead DS, et al. The impact of preoperative smoking habits on the results of rotator cuff repair. J Shoulder Elbow Surg. 2004;13:129–132. 8. Cohen DB, Kawamura S, Ehteshami JR, et al. Indomethacin and celecoxib impair rotator cuff tendon-to-bone healing. Am J Sports Med. 2006;34:362–369. 9. Rodeo SA, Potter HG, Kawamura S, et al. Biologic augmentation of rotator cuff tendon-healing with use of a mixture of osteoinductive growth factors. J Bone Joint Surg Am. 2007;89:2485–2497. 10. Rodeo SA. Biologic augmentation of rotator cuff tendon repair. J Shoulder Elbow Surg. 2007;16(suppl):S191–S197. 11. Weber SC, Kauffman JI, Parise C, et al. Platelet-rich fibrin matrix in the management of arthroscopic repair of the rotator cuff: a prospective, randomized, double-blinded study. Am J Sports Med. 2013;41:263–270. 12. Ide J, Kikukawa K, Hirose J, et al. The effect of a local application of fibroblast growth factor-2 on tendon-to-bone remodeling in rats with acute injury and repair of the supraspinatus tendon. J Shoulder Elbow Surg. 2009;18:391–398. 13. Boswell SG, Cole BJ, Sundman EA, et al. Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy. 2012;28:429–439. 14. Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39:2135–2140. 15. Han B, Woodell-May J, Ponticiello M, et al. The effect of thrombin activation of platelet-rich plasma on demineralized bone matrix osteoinductivity. J Bone Joint Surg Am. 2009;91:1459–1470. 16. Castillo TN, Pouliot MA, Kim HJ, et al. Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. Am J Sports Med. 2011;39:266–271. 17. Thomopoulos S, Williams GR, Soslowsky LJ. Tendon to bone healing: differences in biomechanical, structural, and compositional properties due to a range of activity levels. J Biomech Eng. 2003;125:106–113. 18. Thomopoulos S, Soslowsky LJ, Flanagan CL, et al. The effect of fibrin clot on healing rat supraspinatus tendon defects. J Shoulder Elbow Surg. 2002;11:239–247.
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19. Castricini R, Longo UG, De Benedetto M, et al. Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a randomized controlled trial. Am J Sports Med. 2011;39:258–265. 20. Arnoczky SP. Letter to the editor. Am J Sports Med. 2011;39:NP8. 21. Rodeo SA, Delos D, Williams RJ, et al. The effect of plateletrich fibrin matrix on rotator cuff tendon healing: a prospective, randomized clinical study. Am J Sports Med. 2012;40:1234–1241. 22. Sugaya H, Maeda K, Matsuki K, et al. Functional and structural outcome after arthroscopic full-thickness rotator cuff repair: single-row versus dual-row fixation. Arthroscopy. 2005;21:1307–1316. 23. Chahal J, Van Thiel GS, Mall N, et al. The role of plateletrich plasma in arthroscopic rotator cuff repair: a systematic review with quantitative synthesis. Arthroscopy. 2012;28: 1718–1727. 24. Visser LC, Arnoczky SP, Caballero O, et al. Platelet-rich fibrin constructs elute higher concentrations of transforming growth factor-beta1 and increase tendon cell proliferation over time when compared to blood clots: a comparative in vitro analysis. Vet Surg. 2010;39:811–817. 25. Randelli P, Arrigoni P, Ragone V, et al. Platelet rich plasma in arthroscopic rotator cuff repair: a prospective RCT study, 2-year follow-up. J Shoulder Elbow Surg. 2011;20:518–528. 26. Jo CH, Kim JE, Yoon KS, et al. Does platelet-rich plasma accelerate recovery after rotator cuff repair? A prospective cohort study. Am J Sports Med. 2011;39:2082–2090. 27. Protzman NM, Stopyra GA, Hoffman JK. Biologically enhanced healing of the human rotator cuff: 8-month postoperative histological evaluation. Orthopedics. 2013;36:38–41. 28. Agrawal V. Healing rates for challenging rotator cuff tears utilizing an acellular human dermal reinforcement graft. Int J Shoulder Surg. 2012;6:36–44. 29. Barber FA, Burns JP, Deutsch A, et al. A prospective, randomized evaluation of acellular human dermal matrix augmentation for arthroscopic rotator cuff repair. Arthroscopy. 2012;28:8–15. 30. Gupta AK, Hug K, Berkoff DJ, et al. Dermal tissue allograft for the repair of massive irreparable rotator cuff tears. Am J Sports Med. 2012;40:141–147. 31. Wong I, Burns J, Snyder S. Arthroscopic GraftJacket repair of rotator cuff tears. J Shoulder Elbow Surg. 2010;19(suppl):104–109. 32. Gerber C, Schneeberger AG, Beck M, et al. Mechanical strength of repairs of the rotator cuff. J Bone Joint Surg Br. 1994;76:371–380. 33. DeHaan AM, Axelrad TW, Kaye E, et al. Does double-row rotator cuff repair improve functional outcome of patients compared with single-row technique? A systematic review. Am J Sports Med. 2012;40:1176–1185. 34. Buess E, Waibl B, Vogel R, et al. A comparative clinical evaluation of arthroscopic single-row versus double-row supraspinatus tendon repair. Acta Orthop Belg. 2009;75:588–594. 35. Grasso A, Milano G, Salvatore M, et al. Single-row versus double-row arthroscopic rotator cuff repair: a prospective randomized clinical study. Arthroscopy. 2009;25:4–12. 36. Aydin N, Kocaoglu B, Guven O. Single-row versus double-row arthroscopic rotator cuff repair in small- to mediumsized tears. J Shoulder Elbow Surg. 2010;19:722–725. 37. Burkhart SS, Cole BJ. Bridging self-reinforcing double-row rotator cuff repair: we really are doing better. Arthroscopy. 2010;26:677–680. 38. Barber FA, Hapa O, Bynum JA. Comparative testing by cyclic loading of rotator cuff suture anchors containing multiple high-strength sutures. Arthroscopy. 2010;26(suppl):S134–S141. 39. Cho NS, Lee BG, Rhee YG. Arthroscopic rotator cuff repair using a suture bridge technique: is the repair integrity actually maintained? Am J Sports Med. 2011;39:2108–2116. 40. Voigt C, Bosse C, Vosshenrich R, et al. Arthroscopic supraspinatus tendon repair with suture-bridging technique: functional outcome and magnetic resonance imaging. Am J Sports Med. 2010;38:983–991.
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Platelet-Rich Plasma for Rotator Cuff Repair F. Alan Barber, MD, FACS
Abstract: Rotator cuff tears are a common cause of shoulder pain and disability. Because they combine both traumatic and degenerative elements, the surgical repair can be challenging. Even after surgical intervention, tendon residual defects or “retears” often develop. Risk factors for tendon “retears” include patient age, number of tendons involved, tear size, and smoking. Platelet-rich plasma (PRP) is a supraphysiological concentration of platelets, which may be able to positively augment rotator cuff tendon healing. Not all PRPs are the same and those containing higher leukocyte levels may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors from the PRP and may actually inhibit some parts of the healing response. As yet, the clinical data does not conclusively prove a benefit from PRP, but discernment is required in evaluating the published results. As different PRPs may act differently and the results may be dose dependent requiring more PRP to achieve a beneficial threshold. How success is measured (clinical outcomes vs. intact cuff tendons) and how long the patients are followed are also critical items. Currently, the PRP fibrin matrix version holds the greatest promise for improving clinical success after rotator cuff tendon repair. Key Words: platelet-rich plasma, PRP, rotator cuff tendon, arthroscopy, biological augmentation, shoulder
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onsistently achieving healing after surgery for rotator cuff tears is challenging. What can be done to improve healing in cuff repairs? The factors which adversely affect rotator cuff tendon healing include increasing age (older than 65 y), increasing the number of tendons involved, larger tear sizes, increased preoperative duration of symptoms, and the preoperative stage of fatty degeneration.1–3 There are several strategies to address these concerns: patient selection, biological augmentation, and mechanical reinforcement. The goal for tendon healing is to replicate normal biology. The normal anatomy of the rotator cuff transitions through 4 phases from tendon, fibrocartilage, calcified fibrocartilage, and bone. The ultimate goal of surgical repair is to replicate this normal fibrocartilage transition zone as much as possible. Ide et al4 demonstrated that after surgery this fibrocartilage transition zone actually becomes a fibrovascular scar.
PATIENT SELECTION Although at present, it is difficult to affect the development of a fibrovascular transition, an awareness of patient selection can lead to better repair outcomes. Age From the Plano Orthopedic Sports Medicine and Spine Center, Plano, TX. Disclosure: The author declares no conflict of interest. Reprints: F. Alan Barber, MD, FACS, Plano Orthopedic Sports Medicine and Spine Center, 5228 West Plano Parkway, Plano, TX 75093. Copyright r 2013 by Lippincott Williams & Wilkins
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makes a significant difference in healing. Boileau et al5 described in 2005 that rotator cuff repair in patients under 55 years of age is associated with a 95% healing rate. A 75% of rotator cuff tendon healing rate was observed in the age group from 55 to 64 years, and patients older than 65 years had complete healing in only 43% of the rotator cuff tendons. The size of the tear also makes a difference. Two tendon tears heal less completely than 1 tendon tear. Microvascular disease is another confounding variable especially in smokers2,6,7 and nonsteroidal anti-inflammatory drugs and steroid use can also have an impact.8
BIOLOGICAL AUGMENTATION Biological augmentation options include recombinant human BMP-12, which has been shown to increase rotator cuff tendon to bone healing strength in sheep.9,10 Fibroblast growth factor-2 helps with granulation tissue and remodeling, and there are several growth factors which while providing a more robust fibrovascular tissue formation produce poor quality scar tissue.4,9–12 In addition, numerous cytokines can positively affect tendon healing. However, a single factor therapy has several limits. Healing is a complex event. A single factor does not mimic the multiple coordinated actions of many factors normally associated with healing. Platelet-rich plasma (PRP) contains a granules, dense granules, several cytokines, and other bioactive factors. It allows the delivery of these in a physiological balance. Platelet degranulation releases growth factors and stimulates healing. However, the final growth factor concentration depends upon the amount of whole blood used, the platelet recovery efficiency, and the final volume of platelets. It should be remembered that not all PRPs are the same. The effectiveness of PRP can be influenced by what is in it and what is administered along with it to influence platelet activation. Growth factor and catabolic cytokine concentrations are influenced by the PRP cellular composition (for instance, the presence of leukocytes). It is not just the platelets that influence the clinical response to PRP.13 Platelets have been shown to increase anabolic signaling, whereas leukocytes increase catabolic signaling molecules.2,14 Some preparations contain higher levels of leukocytes. Consequently, based upon the data, a reduced leukocyte PRP seems to offer better healing without scar tissue formation.2 Leukocyte-rich preparations have been shown to have more inflammatory catabolic mediators (matrix metalloproteinase-9 and 1L-1b) that may be detrimental to tendon healing.14 Another evaluation of the in vivo effect in the healthy tendons reported greater inflammatory responses 5 days after the treatment with leukocyte-rich PRP when compared with leukocyte-poor PRP.3 This resulted in greater early tendon architecture disruption, higher vascularity, and fibrosis in the histology. At present, there are no studies that suggest what the longterm effect of leukocyte-rich preparations might be, but these short-term studies raise concerns about their use.
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How the PRP is activated can make a difference. Thrombin is often used as a platelet activator. Han et al15 have shown that PRP can stimulate chondrogenesis and osteogenesis. However, thrombin activation of the PRP triggered an immediate release of growth factors from the PRP and the result was to inhibit chondrogenesis and osteogenesis.15 In addition, inflammatory cells were present in demineralized bone matrix samples that were mixed with thrombin-activated PRP but not present in matrix mixed with PRP alone. Physically, there are 2 types of PRP. The liquid form can be injected into the area of the rotator cuff repair. However, the liquid version tends to disappear in 7 to12 hours. A solid platelet fibrin construct created using a double centrifuge spin provides a scaffold and a reservoir of growth factors. This scaffolding or matrix allows the elution of growth factors for up to 7 days. The preparation of these 2 different forms is with the use of a centrifuge. After a single spin, the elements of the blood are separated with the red cells, white cells, and plasma components separated. At this point, the PRP products, which are liquid, are simply selectively extracted from the tube for use. To create the solid matrix or membrane versions, the clear liquid component is also drawn off but then centrifuged for a second time. After the second centrifugation, the membrane is located at the bottom of the bottle and can be decanted for use. The clinical application for these different forms of PRP differs. The liquid is simply injected into the area of the repair. The platelet fibrin construct must be sutured into the interface between the tendon and the bone. This can be either at the suture line for a single row repair or between the medial and lateral rows in a double row repair. Other factors can influence the effectiveness of the PRP used. Thrombin is sometimes used to activate the PRP. It has been shown to accelerate the release of growth factors and to significantly decrease the efficacy of PRP in bone grafting.15 In addition, preparations with high leukocyte counts have also been implicated in poorer results.16 Calcium is sometimes used to form the PRPF matrix clot and seems to be more desirable in terms of a delayed release of growth factors. Finally, how or exactly where to apply the PRP and in what amount is also unclear. Data from Thomopoulos et al17,18 suggest that interposing the matrix material between the bone and tendon of the repair site may delay or impair healing. Perhaps, the greatest source of variability of the PRP product is related to the variations in harvested blood from each patient.
CLINICAL EVIDENCE In recent years, several studies have looked at the clinical response of rotator cuff healing associated with biological augmentation using various forms of PRP. Castricini et al19 recently published their clinical experience with 88 patients randomized with and without a single PRP matrix globule (Cascade; Musculoskeletal Tissue Foundation, Edison, NJ). The primary outcome measure was the Constant score6 and a power analysis was performed for that factor alone. The secondary outcome measure was the magnetic resonance imaging (MRI) reading of tendon healing performed by orthopedic surgeons associated with the study. At a mean follow-up of 20 months (range, 16 to 30 mo), the primary outcome measure (Constant score) showed no difference between the groups.
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The secondary outcome measure (MRI cuff evaluation) was based upon 78 of the 88 patients who had a postoperative MRI. They reported an overall healing rate of 94%. Four control patients without augmentation using a the single (9 mL) globule of PRP fibrin matrix had retears (10.5%), whereas only 1 retear occurred in patients receiving the PRP fibrin matrix. The concern with this analysis was that a statistical error had occurred by turning continuous data into one of the 3 categories. Arnoczky20 performed an analysis of the data presented in this article and found that using the authors’ data and comparing normal to abnormal (PRP vs. no PRP), the footprint area with the PRP was statistically better (P = 0.02), the MRI signal intensity was better (P < 0.001), but the tendon thickness was not statistically different (P = 0.09). It should be emphasized that in this study only one 9 mL PRP matrix globule was used. This may be significant. Rodeo et al21 reported 79 patients prospectively randomized into groups with and without a single PRP fibrin matrix globule (Cascade). Of the 79, 67were available for a 12-week follow-up. In the 2 groups, 35 received the PRP matrix globule and 32 served as the control. The primary outcome measure was an intact cuff versus a defect based upon an ultrasound examination at 6 and 12 weeks postsurgery. Unfortunately, they did not enroll the amount required by their own power analysis for statistical significance, and lost 12 of the 79 patients to follow-up before the 12-week interval. In addition, the repair techniques were very mixed. Twenty six single row and 42 double row repairs were performed and the repair technique was unknown for 11 patients. This trial was stopped early and they could not demonstrate a difference in outcome scores or muscle strength between the groups. Ultrasound showed no difference between the groups at 6 or 12 weeks. Interestingly, their data showed 95% healing on ultrasound at 6 weeks for tears 3 cm) demonstrated 50% healing at 6 weeks and 56% healing at 12 weeks. Concerns about this study include the use of only one 9 mL matrix globule, enrollment did not meet the power analysis requirements, and ultrasound was used to show cuff healing as an endpoint. Don Buford at the Arthroscopy Association of North America’s 2011 annual meeting reported in an instructional course lecture his experience using ultrasound to assess rotator cuff healing. He indicated that rotator cuff healing is not consistently demonstrated by ultrasound until at least 4 months after surgery. In addition, Lee and colleagues (“Comparison of the Integrity of Repaired Rotator Cuff with Ultrasonography Before and After Arthrography.” Presented at the American Academy of Orthopedic Surgeons, 2012) recently showed that postoperative ultrasound showed only an 8% retear rate as opposed to a 47% retear rate of the same patients using magnetic resonance arthrography. The principal concern about this data is the risk of a b error. If a study is not sufficiently powered, proving that a difference does not exist is not possible. The mere fact that statistical difference was not shown does not mean one does not exist. Barber et al1 reported 2 matched groups of rotator cuff repairs. Twenty were randomized to receive PRP fibrin matrix associated with rotator cuff repair and 20 without PRP fibrin matrix. This study is different from the previous r
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one; in that 2 Cascade fibrin matrix globules (18 mL) were sutured into the interval between the rotator cuff tendon and the bone. The primary outcome measure for this study was an MRI showing tear or no tear at 12 or 24 months after surgery. The average clinical follow-up was 31 months (range, 24 to 44 mo) and the power analysis was carried out, which showed that 20 per group would be sufficient. Secondary outcome measures included clinical outcome scores (Constant, Rowe, ASES, SANE, SST). MRI results indicated 70% complete healing with the PRP matrix repair and 40% complete healing in those rotator cuff repairs without PRP fibrin matrix (P = 0.03). Those patients with tears between 1 and 3 cm had 86% healing with 2 PRP fibrin matrix globules, whereas those without the 2 PRP fibrin matrix globules had only 50% healing. Clinical outcome scores did not show a statistically significant difference between groups. Weber et al11 also used a single row repair with a single PRP fibrin matrix (Cascade) in a prospective, randomized, controlled trial of rotator cuff repairs with and without PRP fibrin matrix insertion into the repair interval between the tendon and the bone. A power analysis was performed on the number required to show a statistical difference in perioperative pain measured by visual analog scale (VAS). Sixty consecutive patients were required with 30 randomized into each group. MRI examinations were also obtained between 3 and 5 months postsurgery. The authors report some technical difficulties in achieving a quality clot at the beginning of the study and it is unclear if these patients were still included in the study group. No significant difference in VAS, SST, ASES scores, or narcotic use was observed between the groups. The MRI rating system of Sugaya et al22 was used to stratify patient tendon healing into 5 categories postsurgery. All MRI scans were reviewed in a blinded manner by a fellowship-trained orthopedic surgeon in addition to the review of the operating surgeons. Only 28 of the PRPF matrix group and 24 of the control group had MRIs. On the basis of the tear or no tear results and the Sugaya categorical scores, no statistical difference was demonstrated by the addition of the single PRP fibrin matrix globule. They also concluded that the size of the tear preoperatively was the most important variable for postoperative cuff integrity. Bergeson et al3 reported a comparison of rotator cuff repairs in high-risk cuff tears (older patients, larger tears, with more fatty degeneration) and reported that the 16 patients in which PRP fibrin matrix was used did not demonstrate improved healing rates or functional outcome scores compared with a retrospective review of 21 similar patients who served as controls. The absence of a power analysis and the retrospective nature of the data collection limit the ability to conclude that no difference exists. The appropriate statement is that a difference could not be shown. Notably, the 21 patients in the control group were drawn from a pool of 38 patients who had been operated on in the year before the start of the study. Some of these 38 patients could not be contacted and the 2 patients with identified tears in the control group were only interviewed by phone. Postoperative infections occurred in 2 of the 16 PRP fibrin matrix patients but none of the previous control patients. Although there is no doubt that the 2 PRP fibrin matrix patients had infections, the fact that the control group was retrospective with incomplete data collection opens the door for some undiagnosed infections. Other studies using PRP fibrin matrix have not reported infections. r
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A recent systematic review by Chahal et al23 concluded that the use of PRP does not have an effect on overall retear rates or shoulder-specific outcomes after arthroscopic rotator cuff repair. However, there was a decrease in the rate of retearing observed among patients treated with PRP in small-size and medium-size tears. After a search of several databases, a total of 5 articles were included in their review. Three different types of PRP were used in these 5 studies. Two of the 5 used a liquid form of PRP and 3 used the Cascade fibrin matrix. Two of the Cascade studies used 2 PRP globules (18 mL) and 1 used a single globule (9 mL). Four of these studies included patients with large or at-risk tears. Even so, Forest plots illustrating the merged results from these studies indicated that 4 of the 5 studies showed that using PRP numerically reduced the overall retear rate. The overall pooled retear rates for all tears of all sizes did not achieve statistical significance. With PRP, the retear rate was 25.6% (29 of 113), whereas without the PRP the retear rate was 36.1% (43 of 119 patients). However, looking at only small-sized to medium-sized tears, the use of PRP statistically significantly reduced the cuff retear rate (7.9% with PRP and 26.8% without PRP). When the large tears were added to the calculation, a statistical benefit for PRP was not shown. The Cascade PRP fibrin matrix used in these studies has been replaced by a platelet-rich plasma fibrin membrane (PRPFM). This membrane is circular in shape and is more durable, allowing easier suturing and manipulation. A comparison of the of the older PRP fibrin matrix to the PRPFM was carried out by Visser et al.24 They found that the fiber content of the PRPFM was greater and more compact than the PRP fibrin matrix. There was a statistically significant increase (> 2-fold) in cell proliferation, increased TGF-b-1 concentration in the PRP membrane, and greater cell density on day 1 in their study. Other forms of PRP have been studied. Using a liquid form of PRP (GPS system; Biomet Biologics, Warsaw, IN), Randelli et al25 prospectively randomized single row rotator cuff repair patients into 2 groups: repair without a PRP injection (n = 27) and with a PRP injection (n = 26). This form of PRP contains autologous thrombin. The results of this study showed that the GPS PRP statistically significantly reduced postoperative pain during the first postoperative month and again at the 24-month data collection interval. Statistically significant higher outcome measure scores (Constant, strength in external rotation, UCLA, and Simple Shoulder Test) were reported at the 3-month interval for the PRP group, but not afterward. Eighty-five percent of both the study groups had postoperative MRIs at a minimum of 12 months after surgery and were assessed for retears and intact tendons. Using the MRI evaluation, patients with grade 1 (minimally retracted tendon) and grade 2 (retracted but not to the glenoid) tears had rotator cuff healing statistically significantly affected with the use of PRP. All but 1 patient in both the study groups with a severe (grade 3 retraction) cuff tear and every massive (grade 4 retraction) cuff tear demonstrated a retear regardless of treatment. When grades 1 and 2 retracted tears were evaluated, those treated with PRP (n = 16) healed better than the control group (n = 19). The number of retears in grade 1 or 2 tears was 2 (14%) in the PRP group and 6 (37%) in the control group. This was not statistically significant. Although these numbers are small, they are consistent with the PRP fibrin matrix data and suggest that PRP may be more effective in smaller cuff tears with less retraction. www.sportsmedarthro.com |
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Jo et al26 reported a nonrandomized comparison between 19 suture bridge cuff repairs with a unique form of PRP matrix and 23 without PRP. This PRP was prepared by collecting blood the day before surgery and using plateletpheresis to create in 3 separate 3 mL globules, which were stored at room temperature with agitation until the next day. At surgery, these 3 globules were threaded on a suture and placed into the interface between the tendon and the bone. At an average follow-up of 19.7 months (minimum 16 mo), no difference in clinical outcomes measures was observed. At a minimum of 9 months after surgery, the repaired tendons were assessed using MRI. Only 15 of 19 patients in the PRP group and 17 of 23 patients in the control group had the MRI. The PRP group retear rate was 26.7%, whereas the control group retear rate was 41.2% (P = 0.39). This was not significant. This type of PRP seems to be unique at this point in the literature and should not be confused with the Cascade product (a single 9 mL globule) reported by others.1,3,11,19,21
MECHANICAL REINFORCEMENT In addition to patient selection and biological augmentation, mechanical reinforcement has been used to improve rotator cuff tendon healing, especially in the larger tendon tears. Some data, which is available, suggests that a combination of mesenchymal stem cells, PRP, and dermal allografting may successfully recreate a transition zone.27 A retrospective case review of 14 patients with large or massive cuff tears (median, 4 cm; range, 2.5 to 6 cm) augmented with acellular human dermal allograft demonstrated favorable structural healing rates and statistically significantly improved functional outcomes in the near term.28 A recent prospective, multicenter, randomized control trial of patients undergoing arthroscopic 2-tendon (>3 cm) rotator cuff repairs with and without augmentation using acellular human dermal matrix reported followup at a mean of 24 months (range, 12 to 38 mo). The repair augmentation with the acellular human dermal allograft resulted in more frequent intact cuffs as determined by gadoliniumenhanced MRI and higher ASES and Constant scores.
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Intact repairs were found in 85% of the augmented group and 40% of the unaugmented group (P < 0.01).29 The use of an acellular dermal allograft to span a gap >1 cm is an FDA off-label use. However, while off label, gap jumping of cuff defects with acellular human dermal allografts has been shown to demonstrate significant improvement in pain, range of motion, and strength while subjective outcome measures (ASES and SF-12 scores) demonstrated statistically significant improvement at an average 3-year follow-up.30 This benefit has been reported by others.31
PRPFM AUGMENTATION TECHNIQUE Any rotator cuff repair must incorporate the established principals initially articulated by Gerber et al.32 The repair technique should have sufficiently high initial fixation strength, avoid the development of gap formation during the healing period, and maintain this mechanical stability until healing is complete.33 The author’s preference is to use a PRPFM to biologically enhance most rotator cuff repairs. Although cuff repairs can be performed in either the beach chair or the lateral decubitus position, our preference is the lateral decubitus position. An initial diagnostic arthroscopy is performed with a thorough assessment of the cuff tendon tear pattern. A clear understanding of the morphology of the tendon tear is required to appropriately mobilize it over the greater tuberosity and plan the repair. Mobilization of the tendon is performed as required and any appropriate margin convergence stitches placed (Fig. 1). The reattachment site on the greater tuberosity is cleared of soft tissue and abraded using a shaver on fast forward to provide a bleeding bed while preserving the cortical bone enhancing the suture anchor attachment. This process includes the placement of marrow vents (a microfracture of the greater tuberosity) to enhance healing (Fig. 2). The suture anchors are inserted at the appropriate sites to avoid placing too much tension on the repair and the sutures are passed in a routine fashion using an antegrade suture passer. For single row repairs, a shuttling suture is passed through the tendon at the level of the repair sutures before tying them. For double row repairs the medial row
FIGURE 1. The tendon is assessed for mobility both before traction is applied (A) and afterward (B). If insufficient mobility exists, it should be freed on the superior and inferior surfaces as needed (copyright F. Alan Barber, MD).
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FIGURE 2. The reattachment site on the greater tuberosity is cleared of soft tissue, abraded to provide a bleeding bed while preserving the cortical bone, and marrow vents are placed to enhance healing (copyright F. Alan Barber, MD).
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FIGURE 4. This circular membrane is folded upon itself twice until it is one quarter its original size. This triangular-shaped graft is secured using a running whip stitch of No. 2-0 Vicryl around the periphery. This creates a “pizza pie slice” and facilitates handling and insertion (copyright F. Alan Barber, MD).
sutures are tied and left long. Then the shuttling suture is passed slightly lateral to the completed medial row. The leading end of the shuttling suture is captured and drawn through the anterior portal leaving the trailing end out of the transdeltoid cannula. The PRPFM is prepared using a double spin technique. This requires drawing 18 mL of blood and produces a circular membrane of PRPFM (Fig. 3). This circular membrane is folded on itself twice until it is one quarter its original size. This triangular-shaped graft is fixed using a running whip stitch around the periphery of No. 2-0 Vicryl suture. This creates a “pizza pie slice,” which facilitates handling and insertion (Fig. 4). Two dilating knots (simple overhand knots) are tied in the trailing end of the shuttling suture, which is then passed through a metal cannula, which is itself inserted through
the rubber dam of the lateral (transdeltoid) cannula (Fig. 5). A third overhand knot is tied proximal to the previous 2 knots and used to capture the Vicryl sutures of the PRPFM graft. The shuttling suture is then drawn out the anterior portal. As the shuttle is pulled through the tendon, the dilating knots dilate the tendon tissue making subsequent passage of the suture easier. Finally the knot capturing the Vicryl sutures is pulled through the tendon. As they are advanced, these Vicryl sutures in turn pass the PRPFM graft into position in the interval between the rotator cuff tendon and the greater tuberosity (Fig. 6). The Vicryl sutures are disengaged from the shuttling suture and the shuttling suture removed out the anterior cannula. With the PRPFM graft in place, the rotator cuff repair is completed (Fig. 7). In a single row repair, the previously placed but untied knots are tied. For a double row repair,
FIGURE 3. The platelet-rich plasma fibrin membrane (PRPFM) is prepared using a double spin technique, requires 18 mL of blood, and produces a circular membrane of PRPFM (copyright F. Alan Barber, MD).
FIGURE 5. Two dilating knots (simple overhand knots) are tied in the trailing end of the shuttling suture, which is then passed through a metal cannula inserted through the rubber dam of the lateral (transdeltoid) cannula (copyright F. Alan Barber, MD).
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FIGURE 6. The knot capturing the Vicryl sutures is pulled through the tendon. As they are advanced, these Vicryl sutures in turn pass the platelet-rich plasma fibrin membrane (PRPFM) graft into position in the interval between the rotator cuff tendon and the greater tuberosity (copyright F. Alan Barber, MD).
the lateral row anchors are inserted securing the sutures from the medial row to complete the repair. No discussion of rotator cuff repair can fail to address the issue of single row versus double row repairs. Many authors advocate the superiority of the double row repair. The recent meta-analysis by DeHaan et al33 showed a strong trend toward higher failure rates in patients undergoing single row compared with double row rotator cuff repair. However, many clinical reports do not support this and the increased costs, complexity, and operating time should be considered.34–36 In addition, there is considerable biomechanical testing data, which shows that a double row repair has a time 0 strength superior to a single row repair and provides greater footprint coverage. However, most of this data studied repair constructs that are not currently consistent with clinical practice. Current double row repairs
FIGURE 8. Cho type 2: this is a failure at the musculotendinous junction (medial row, black arrow). The medial row anchor (white arrow) is visible on this view but not the lateral row anchor (copyright F. Alan Barber, MD).
are increasingly using suture bridging and transosseous equivalent techniques.37 Even more significantly, current single row and double row repairs use ultra-high molecular weight polyethylene containing sutures. In contrast, single row repairs are no longer created using a single mattress stitch and advocates of single row repairs now focus on triple-loaded anchors with UHMWPEcontaining sutures. A recent comparison of triple-loaded, single row repairs to suture bridging and classic double row repairs showed no significant advantage in ultimate time 0 strength between these types of repair.38 In addition, Cho et al39 and others40 have shown that when double row constructs fail (especially in younger patients), the failure is often at the musculotendinous junction. Holding the cuff tendon footprint fixed over a greater area lead to musculotendinous junction failure in rotator cuff muscles with less fatty degeneration or muscle atrophy. Two failure modes were identified: Cho type 1 (failure at the original repair site) and Cho type 2 (failure around the medial row). This raises special concerns as the Cho type 2 failure (musculotendinous junction tear) (Fig. 8) occurred with double row repairs in 59% of Cho’s failure cases. The percentage of the Cho type 1 retear increased with the severity of fatty degeneration or muscle atrophy suggesting that healthier tendon tissue is more likely to tear in a catastrophic Cho type 2 manner (at the musculotendinous junction). This type of failure leaves a virtually irreparable situation.
CONCLUSIONS
FIGURE 7. With the platelet-rich plasma fibrin membrane (PRPFM) graft (black arrow) in place, the rotator cuff repair is completed (copyright F. Alan Barber, MD).
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Improving success for rotator cuff tear surgery can be achieved with proper patient selection considering the established risk factors, biological augmentation, and possibly mechanical reinforcement. Risk factors for failure include patient age, number of tendons involved, tear size, and smoking. PRP may biologically augment rotator cuff r
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Sports Med Arthrosc Rev
Volume 21, Number 4, December 2013
tendon healing. However, not all PRPs are the same and those containing higher leukocyte levels and thrombin activation may prove detrimental to tendon healing. Confusion in the clinical data does not conclusively prove a benefit from PRP and results may be dose dependent. Currently, the PRP fibrin matrix version of PRP holds the greatest promise for improving clinical success after rotator cuff tendon repair. REFERENCES 1. Barber FA, Hrnack SA, Snyder SJ, et al. Rotator cuff repair healing influenced by platelet-rich plasma construct augmentation. Arthroscopy. 2011;27:1029–1035. 2. McCarrel TM, Minas T, Fortier LA. Optimization of leukocyte concentration in platelet-rich plasma for the treatment of tendinopathy. J Bone Joint Surg Am. 2012;94(e143):1–8. 3. Bergeson AG, Tashjian RZ, Greis PE, et al. Effects of plateletrich fibrin matrix on repair integrity of at-risk rotator cuff tears. Am J Sports Med. 2012;40:286–293. 4. Ide J, Kikukawa K, Hirose J, et al. The effects of fibroblast growth factor-2 on rotator cuff reconstruction with acellular dermal matrix grafts. Arthroscopy. 2009;25:608–616. 5. Boileau P, Brassart N, Watkinson DJ, et al. Arthroscopic repair of full-thickness tears of the supraspinatus: does the tendon really heal? J Bone Joint Surg Am. 2005;87:1229–1240. 6. Constant CR, Murley AH. A clinical method of functional assessment of the shoulder. Clin Orthop Relat Res. 1987; 214:160–164. 7. Mallon WJ, Misamore G, Snead DS, et al. The impact of preoperative smoking habits on the results of rotator cuff repair. J Shoulder Elbow Surg. 2004;13:129–132. 8. Cohen DB, Kawamura S, Ehteshami JR, et al. Indomethacin and celecoxib impair rotator cuff tendon-to-bone healing. Am J Sports Med. 2006;34:362–369. 9. Rodeo SA, Potter HG, Kawamura S, et al. Biologic augmentation of rotator cuff tendon-healing with use of a mixture of osteoinductive growth factors. J Bone Joint Surg Am. 2007;89:2485–2497. 10. Rodeo SA. Biologic augmentation of rotator cuff tendon repair. J Shoulder Elbow Surg. 2007;16(suppl):S191–S197. 11. Weber SC, Kauffman JI, Parise C, et al. Platelet-rich fibrin matrix in the management of arthroscopic repair of the rotator cuff: a prospective, randomized, double-blinded study. Am J Sports Med. 2013;41:263–270. 12. Ide J, Kikukawa K, Hirose J, et al. The effect of a local application of fibroblast growth factor-2 on tendon-to-bone remodeling in rats with acute injury and repair of the supraspinatus tendon. J Shoulder Elbow Surg. 2009;18:391–398. 13. Boswell SG, Cole BJ, Sundman EA, et al. Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy. 2012;28:429–439. 14. Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39:2135–2140. 15. Han B, Woodell-May J, Ponticiello M, et al. The effect of thrombin activation of platelet-rich plasma on demineralized bone matrix osteoinductivity. J Bone Joint Surg Am. 2009;91:1459–1470. 16. Castillo TN, Pouliot MA, Kim HJ, et al. Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. Am J Sports Med. 2011;39:266–271. 17. Thomopoulos S, Williams GR, Soslowsky LJ. Tendon to bone healing: differences in biomechanical, structural, and compositional properties due to a range of activity levels. J Biomech Eng. 2003;125:106–113. 18. Thomopoulos S, Soslowsky LJ, Flanagan CL, et al. The effect of fibrin clot on healing rat supraspinatus tendon defects. J Shoulder Elbow Surg. 2002;11:239–247.
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Platelet-Rich Plasma for Rotator Cuff Repair
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