Hillary J. Braun

Comparison of the Acute Inflammatory Response of Two Commercial Platelet-Rich Plasma Systems in Healthy Rabbit Tendons

Background: Numerous studies have shown platelet-rich plasma (PRP) preparations differ with respect to the inclusion of certain blood components, which may affect the host’s cellular response. Hypothesis: This study evaluated the inflammatory effect of Biomet GPS III leukocyte-rich PRP (LR-PRP) versus MTF Cascade leukocyte-poor PRP (LP-PRP) after intratendinous injection in an animal model. The authors anticipated that LR-PRP would incite a greater acute inflammatory response than LP-PRP. Study Design: Controlled laboratory study. Methods: A total of 17 skeletally mature New Zealand White rabbits were tested. In all cases, healthy patellar tendons were treated. In the control animals, one patellar tendon was injected with 2 mL autologous whole blood, and the other was injected with 2 mL sterile saline. Seven total tendons were injected with whole blood, and 7 tendons were injected with saline. In the experimental animals, one patellar tendon was injected with 2 mL LR-PRP, and the other was injected with 2 mL LP-PRP. Ten tendons were injected with LR-PRP, and 10 tendons were injected with LP-PRP. Animals were euthanized at 5 or 14 days after injection. Tendons were harvested and stained using hematoxylin and eosin and scored semi-quantitatively for total white blood cells (WBCs), mononuclear cells (macrophages and lymphocytes), polymorphonuclear cells (PMNs), vascularity, fiber structure, and fibrosis. Results: At 5 days after injection, tendons treated with LR-PRP had significantly greater overall tendon scores (6.3 ± 1.79 vs 1.8 ± 1.64, P = .012), as well as mean scores for fiber structure (1.4 ± 0.22 vs 0.50 ± 0.50, P = .012), denoting disrupted composition, total WBCs (1.1 ± 0.89 vs 0.10 ± 0.22, P = .014), mononuclear cells (macrophages and lymphocytes) (0.80 ± 0.45 vs 0.10 ± 0.22, P = .014), vascularity (1.7 ± 0.27 vs 0.80 ± 0.16, P = .008), and fibrosis (1.0 ± 0.35 vs 0.3 ± 0.45, P = .037) compared with tendons treated with LP-PRP. Otherwise, there were no significant differences in mononuclear cells (P = .590), PMN cells (P = 1.00), total WBCs (P = .811), vascularity (P = .650), or total tendon score (P = .596) in any of the treatment groups at 14 days. Conclusion: Compared with leukocyte-poor Cascade PRP, leukocyte-rich GPS III PRP causes a significantly greater acute inflammatory response at 5 days after injection. There is no significant difference in the inflammatory response or cellularity regardless of the injection type at 14 days after intratendinous injection. Clinical Relevance: Platelet-rich plasma injections are frequently prepared using commercial systems and are administered for clinical treatment of chronic tendinopathy. It is important to characterize the cellular responses elucidated by different injection preparations to further understand their effect on tissue healing and aid clinical decision making. Future investigations are necessary to apply these findings to the clinical setting.

Platelet-Rich Plasma as a Treatment for Patellar Tendinopathy A Double-Blind, Randomized Controlled Trial

Background: Previous studies have shown improvement in patellar tendinopathy symptoms after platelet-rich plasma (PRP) injections, but no randomized controlled trial has compared PRP with dry needling (DN) for this condition. Purpose: To compare clinical outcomes in patellar tendinopathy after a single ultrasound-guided, leukocyte-rich PRP injection versus DN. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 23 patients with patellar tendinopathy on examination and MRI who had failed nonoperative treatment were enrolled and randomized to receive ultrasound-guided DN alone (DN group; n = 13) or with injection of leukocyte-rich PRP (PRP group; n = 10), along with standardized eccentric exercises. Patients and the physician providing follow-up care were blinded. Participants completed patient-reported outcome surveys before and at 3, 6, 9, 12, and ≥26 weeks after treatment during follow-up visits. The primary outcome measure was the Victorian Institute of Sports Assessment (VISA) score for patellar tendinopathy at 12 weeks, and secondary measures included the visual analog scale (VAS) for pain, Tegner activity scale, Lysholm knee scale, and Short Form (SF-12) questionnaire at 12 and ≥26 weeks. Results were analyzed using 2-tailed paired and unpaired t tests. Patients who were dissatisfied at 12 weeks were allowed to cross over into a separate unblinded arm. Results: At 12 weeks after treatment, VISA scores improved by a mean ± standard deviation of 5.2 ± 12.5 points (P = .20) in the DN group (n = 12) and by 25.4 ± 23.2 points (P = .01) in the PRP group (n = 9); at ≥26 weeks, the scores improved by 33.2 ± 14.0 points (P = .001) in the DN group (n = 9) and by 28.9 ± 25.2 points (P = .01) in the PRP group (n = 7). The PRP group had improved significantly more than the DN group at 12 weeks (P = .02), but the difference between groups was not significant at ≥26 weeks (P = .66). Lysholm scores were not significantly different between groups at 12 weeks (P = .81), but the DN group had improved significantly more than the PRP group at ≥26 weeks (P = .006). At 12 weeks, 3 patients in the DN group failed treatment and subsequently crossed over into the PRP group. These patients were excluded from the primary ≥26-week analysis. There were no treatment failures in the PRP group. No adverse events were reported. Recruitment was stopped because interim analysis demonstrated statistically significant and clinically important results. Conclusion: A therapeutic regimen of standardized eccentric exercise and ultrasound-guided leukocyte-rich PRP injection with DN accelerates the recovery from patellar tendinopathy relative to exercise and ultrasound-guided DN alone, but the apparent benefit of PRP dissipates over time.

The Effect of Platelet-Rich Plasma Formulations and Blood Products on Human Synoviocytes: Implications for Intra-articular Injury and Therapy

Background: The effect of platelet-rich plasma (PRP) on chondrocytes has been studied in cell and tissue culture, but considerably less attention has been given to the effect of PRP on synoviocytes. Fibroblast-like synoviocytes (FLS) compose 80% of the normal human synovium and produce cytokines and matrix metalloproteinases that can mediate cartilage catabolism. Purpose: To compare the effects of leukocyte-rich PRP (LR-PRP), leukocyte-poor PRP (LP-PRP), red blood cell (RBC) concentrate, and platelet-poor plasma (PPP) on human FLS to determine whether leukocyte and erythrocyte concentrations of PRP formulations differentially affect the production of inflammatory mediators. Study Design: Controlled laboratory study. Methods: Peripheral blood was obtained from 4 donors and processed to create LR-PRP, LP-PRP, RBCs, and PPP. Human synoviocytes were cultured for 96 hours with the respective experimental conditions using standard laboratory conditions. Cell viability and inflammatory mediator production were then evaluated. Results: Treatment with LR-PRP resulted in significantly greater synoviocyte death (4.9% ± 3.1%) compared with LP-PRP (0.72% ± 0.70%; P = .035), phosphate-buffered saline (PBS) (0.39% ± 0.27%; P = .018), and PPP (0.26% ± 0.30%; P = .013). Synoviocytes treated with RBC concentrate demonstrated significantly greater cell death (12.5% ± 6.9%) compared with PBS (P < .001), PPP (P < .001), LP-PRP (P < .001), and LR-PRP (4.9% ± 3.1%; P < .001). Interleukin (IL)–1β content was significantly higher in cultures treated with LR-PRP (1.53 ± 0.86 pg/mL) compared with those treated with PBS (0.22 ± 0.295 pg/mL; P < .001), PPP (0.11 ± 0.179 pg/mL; P < .001), and RBCs (0.64 ± 0.58 pg/mL; P = .001). IL-6 content was also higher with LR-PRP (32,097.82 ± 22,844.300 pg/mL) treatment in all other groups (P < .001). Tumor necrosis factor–α levels were greatest in LP-PRP (9.97 ± 3.110 pg/mL), and this was significantly greater compared with all other culture conditions (P < .001). Interferon-γ levels were greatest in RBCs (64.34 ± 22.987 pg/mL) and significantly greater than all other culture conditions (P < .001). Conclusion: Treatment of synovial cells with LR-PRP and RBCs resulted in significant cell death and proinflammatory mediator production. Clinical Relevance: Clinicians should consider using leukocyte-poor, RBC-free formulations of PRP when administering intra-articularly.

Incidence and Risk Factors for Injuries to the Anterior Cruciate Ligament in National Collegiate Athletic Association Football: Data From the 2004-2005 Through 2008-2009 National Collegiate Athletic Association Injury Surveillance System

Background: Injuries to the anterior cruciate ligament (ACL) are common in athletic populations, particularly in athletes participating in football, soccer, and skiing. Purpose: The purpose of this study was to analyze the National Collegiate Athletic Association (NCAA) Injury Surveillance System (ISS) men’s football ACL injury database from the playing seasons of 2004-2005 through 2008-2009 to determine the incidence and epidemiology of complete injury to the ACL in NCAA football athletes. Study Design: Descriptive epidemiology study. Methods: The NCAA ISS men’s football database was reviewed from the 2004-2005 through 2008-2009 seasons using the specific injury code, “Anterior cruciate ligament (ACL) complete tear.” The injury rate was computed for competition and practice exposures. Ninety-five percent confidence intervals (CIs) for the incident rates were calculated using assumptions of a Poisson distribution. Pairwise, 2-sample tests of equality of proportions with a continuity correction were used to estimate the associations of risk factors such as event type, playing surface, season segment, and football subdivision. Descriptive data were also described. Results: The ACL injury rate during games (8.06 per 10,000 athlete-exposures [AEs] 95% CI, 6.80-9.42) was significantly greater than the rate during practice (0.8 per 10,000 AEs 95% CI, 0.68-0.93). Players were 10.09 (95% CI, 8.08-12.59) times more likely to sustain an ACL injury in competition when compared with practices. When practice exposures were analyzed separately, the injury rate was significantly greater during scrimmages (3.99 per 10,000 AEs 95% CI, 2.29-5.94) compared with regular practices (0.83 per 10,000 AEs 95% CI, 0.69-0.97) and walk-throughs (0 per 10,000 AEs 95% CI, 0-0.14). There was an incidence rate of 1.73 ACL injuries per 10,000 AEs (95% CI, 1.47-2.0) on artificial playing surfaces compared with a rate of 1.24 per 10,000 AEs (95% CI, 1.05-1.45) on natural grass. The rate of ACL injury on artificial surfaces is 1.39 (95% CI, 1.11-1.73) times higher than the injury rate on grass surfaces. Conclusion: Between 2004 and 2009, NCAA football players experienced a greater number of ACL injuries in games compared with practices, in scrimmages compared with regular practices, and when playing on artificial turf surfaces. This latter finding will need to be confirmed by additional studies.

The In Vitro Chondrotoxicity of Single-Dose Local Anesthetics

Background: The administration of amide-type local anesthetics to cartilaginous tissues has revealed potential chondrotoxicity. Purpose: This study evaluated whether administration of single doses of 1% lidocaine, 0.25% bupivacaine, and 0.5% ropivacaine resulted in decreased chondrocyte viability or cartilage matrix degradation in vitro. Study Design: Controlled laboratory study. Methods: Monolayer human chondrocytes and intact cartilage samples were cultured for 1 week in media. Each drug was delivered in a custom bioreactor over its clinical duration of action. A Live/Dead Viability/Cytotoxicity Assay was used to determine the ratio of dead to live cells for monolayer chondrocyte cultures compared with controls. Damage to the cartilage extracellular matrix (ECM) in en bloc cartilage samples was evaluated by analysis of DNA, glycosaminoglycan (GAG), and collagen content. Results: Chondrocytes treated for 3 hours with a single dose of 1% lidocaine exhibited significantly more cell death (7.9%) compared with control media (2.9%; P < .001). No significant difference in cell death was observed in chondrocytes treated for 6 hours with 0.25% bupivacaine (2.7%) versus controls (2.8%; P = .856) or cells treated for 12 hours in 0.5% ropivacaine (2.9%) versus controls (2.4%; P = .084). There was no significant difference in GAG expression (P = .627) or DNA-normalized GAG expression (P = .065) between the intact cartilage treatment groups; however, the DNA-normalized GAG expression was markedly lower in cartilage cultures treated with 1% lidocaine (3.36 ± 1.15) compared with those in control media (7.61 ± 3.83). Conclusion: The results of this in vitro study indicate that a single-dose administration of 1% lidocaine resulted in a significant decrease in chondrocyte viability when compared with control cultures. Clinical Relevance: Single-dose injections of 1% lidocaine may be significantly chondrotoxic, and further investigation regarding in vivo chondrotoxicity appears warranted.

The Effect of Playing Surface on Injury Rate: A Review of the Current Literature

Synthetic playing surfaces are widely used for field and court sports. Artificial turf surfaces are commonly used as an alternative to natural grass, while outdoor surfaces like clay and acrylic are also prevalent. The effect of these synthetic surfaces on injury rates has not been clearly established. The available literature is largely limited to football and soccer data and the majority of studies are short-term. Confounding variables such as climate, player position and footwear, as well as varying definitions of injury, also make it difficult to draw firm conclusions about the general effect of artificial playing surfaces on injury rates. Many peer-reviewed studies cite a higher overall rate of injury on first- and second-generation artificial turf surfaces compared with natural grass. Despite differences in injury type, the rate of injury on third-generation and natural grass surfaces appears to be comparable. It also appears that clay is significantly safer than either grass or hard court tennis surfaces, but this is a conclusion drawn with limited data. Further research investigating overall injury trends as well as sport-specific data is needed to draw more definitive conclusions regarding the effect of artificial playing surfaces on injury rates.

Prospective Correlation Between Serum Relaxin Concentration and Anterior Cruciate Ligament Tears Among Elite Collegiate Female Athletes

Background: The female anterior cruciate ligament may be more susceptible to injury than the male anterior cruciate ligament because of the gender-specific expression of receptors for relaxin, a collagenolytic hormone that promotes remodeling of the anterior cruciate ligament. Purpose: This study was undertaken to investigate whether collegiate female athletes with elevated serum relaxin concentrations (SRC) sustain anterior cruciate ligament tears at an increased rate compared with those with lower SRC. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: From 2005 to 2010, 143 Division I female athletes from 2 universities participating in sports at high risk for anterior cruciate ligament tears (basketball, lacrosse, field hockey, soccer, gymnastics, and volleyball) were recruited to participate. Questionnaires and urine luteinizing hormone (LH) tests were used to determine participants’ anterior cruciate ligament injury and menstrual history and to identify their mid-luteal phase or projected cycle days 21 to 24. Serum samples were obtained for progesterone and relaxin ELISA (enzyme-linked immunosorbent assay) analysis. Participants were monitored for anterior cruciate ligament injury over their 4-year National Collegiate Athletic Association athletic career. Results: A total of 128 participants completed the study and were eligible for data analysis. The cumulative incidence of complete anterior cruciate ligament tear over the 4-year study period was 21.9%, and varied significantly by sport (P < .001). The mean SRC for athletes with anterior cruciate ligament tears (6.0 ± 8.1 pg/mL) was significantly higher than that for those without anterior cruciate ligament tears (1.8 ± 3.4 pg/mL; P = .013). In subgroup analysis of the 46 athletes who had detectable SRC, the cumulative incidence of anterior cruciate ligament tear was 14 of 46 (30.4%); the mean SRC among athletes with anterior cruciate ligament tears (14 of 46) was 12.1 ± 7.7 pg/mL and without anterior cruciate ligament tears (32 of 46), 5.7 ± 3.6 pg/mL (P = .002). When 6.0 pg/mL was set as the SRC cutoff for screening athletes for risk of anterior cruciate ligament tear in the subgroup with detectable relaxin levels, the test had 71% sensitivity, 69% specificity, 52% positive predictive value, 88% negative predictive value, and a relative risk of 4.4. These values were significant by χ2 test (P = .003) and receiver operating characteristic analysis (P = .002). Conclusion: Elite female athletes with anterior cruciate ligament tears have higher SRC than those without tears. Those with an SRC greater than 6.0 pg/mL had over 4 times increased risk for a tear. Clinical Relevance: Females with higher serum relaxin levels may be at increased risk for anterior cruciate ligament tears. Further investigation of the clinical utility of SRC testing is warranted.

Acromioclavicular Joint Injuries in National Collegiate Athletic Association Football Data From the 2004-2005 Through 2008-2009 National Collegiate Athletic Association Injury Surveillance System

Background: Injuries to the shoulder are common in collegiate football, and injuries to the acromioclavicular (AC) joint have previously accounted for up to 41% of all shoulder injuries. Purpose: To determine the incidence and epidemiology of injury to the AC joint in National Collegiate Athletic Association (NCAA) football athletes. Study Design: Descriptive epidemiology study. Methods: The NCAA Injury Surveillance System (ISS) men’s football database was reviewed from the 2004-2009 playing seasons. The exposure data set from the same years was reviewed for the purposes of computing rates of injury per athlete exposure (AE). The injury rate (number of injuries divided by number of AEs) was computed per 10,000 AEs for competition and practice exposures. Ninety-five percent confidence intervals (95% CIs) for the incidence rates were calculated using assumptions of a Poisson distribution. Results: According to the estimates made by the NCAA ISS, a total of 748 injuries to the AC joint occurred in NCAA football players during 2,222,155 AEs, accounting for 4.49% of all injuries sustained during this 5-year surveillance period. The overall rate of injury was 3.34 per 10,000 AEs (95% CI, 3.10-3.59). Players were 11.68 (95% CI, 10.11-13.49) times more likely to sustain an injury in games than practices. Partial sprains (types I or II) accounted for 96.4% of injuries, while complete sprains (≥type III) accounted for the remaining 3.6%. The average amount of time lost per injury was 11.61 days. Complete sprains resulted in a mean time loss of 31.9 days (95% CI, 24.4-39.6) while partial injuries resulted in 11.0 days lost (95% CI, 9.6-12.3). Overall, 2.41% of injuries underwent surgical intervention, with 22.2% of complete sprains and 1.7% of partial injuries resulting in surgery. Complete sprains of the AC joint were 13.5 (95% CI, 4.63-35.26) times more likely to result in surgical intervention than partial sprains. The majority of injuries (71.93%) resulted from contact with another player and 47.09% occurred while tackling or being tackled. Of all injuries, 47.63% occurred during offensive plays, while defense accounted for 20.77%. Conclusion: AC joint injuries in NCAA football players are predominantly low-grade sprains, leading to approximately 12 days of lost competition. The few severe sprains that occurred often resulted in surgery or required approximately 5 weeks of rehabilitation.

The Effect of Intra-articular Corticosteroids on Articular Cartilage A Systematic Review

Background: Intra-articular (IA) corticosteroid therapy has been used for the treatment of inflammation and pain in the knee since the 1950s. Purpose: To review the current literature on the effects of IA corticosteroids on articular cartilage. Study Design: Systematic review. Methods: A MEDLINE and SCOPUS database search was performed, and studies were selected for basic science and clinical trial research on corticosteroids with direct outcome measures of cartilage health. Preliminary searches yielded 1929 articles, and final analysis includes 40 studies. Results: Methylprednisolone, dexamethasone, hydrocortisone, betamethasone, prednisolone, and triamcinolone were reported to display dose-dependent deleterious effects on cartilage morphology, histology, and viability in both in vitro and in vivo models. The beneficial animal in vivo effects of methylprednisolone, hydrocortisone, and triamcinolone occurred at low doses (usually <2-3 mg/dose or 8-12 mg/cumulative total dose in vivo), at which increased cell growth and recovery from damage was observed; the single human clinical trial indicated a beneficial effect of triamcinolone. However, at higher doses (>3 mg/dose or 18-24 mg/cumulative total dose in vivo), corticosteroids were associated with significant gross cartilage damage and chondrocyte toxicity. Dose and time dependency of corticosteroid chondrotoxicity was supported in the in vitro results, however, without clear dose thresholds. Conclusion: Corticosteroids have a time- and dose-dependent effect on articular cartilage, with beneficial effects occurring at low doses and durations and detrimental effects at high doses and durations. Clinically, beneficial effects are supported for IA administration, but the lowest efficacious dose should be used.

The use of PRP in ligament and meniscal healing.

Platelet-rich plasma (PRP) has become a popular treatment for acute and chronic soft tissue injuries. Although the majority of research has focused on its use in tendinopathy, PRP may have potential in meniscus and ligament healing. Some level II studies support a possible benefit for anterior cruciate ligament (ACL) allograft maturation, and preliminary animal studies point to a potential role for PRP in primary ACL repair. However, randomized controlled trials have not demonstrated a benefit of PRP for ACL tendon allograft-tunnel integration. To date, 2 studies document the use of PRP for meniscal applications, but this field is largely unexplored. With respect to ligament and meniscal applications, the current literature suggests PRP may be promising for primary ACL repair in skeletally immature patients, ACL graft maturation, and repair of meniscal tears in the avascular zone.