Scott A. Rodeo

Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog.

Our study evaluated tendon-to-bone healing in a dog model. Twenty adult mongrel dogs had a transplantation of the long digital extensor tendon into a 4.8-millimeter drill-hole in the proximal tibial metaphysis. Four dogs were killed at each of five time-periods (two, four, eight, twelve, and twenty-six weeks after the transplantation), and the histological and biomechanical characteristics of the tendon-bone interface were evaluated. Serial histological analysis revealed progressive reestablishment of collagen-fiber continuity between the bone and the tendon. A layer of cellular, fibrous tissue was noted between the tendon and the bone, along the length of the bone tunnel; this layer progressively matured and reorganized during the healing process. The collagen fibers that attached the tendon to the bone resembled Sharpey fibers. High-resolution radiographs showed remodeling of the trabecular bone that surrounded the tendon. At the two, four, and eight-week time-periods, all specimens had failed by pull-out of the tendon from the bone tunnel. The strength of the interface was noted to have significantly and progressively increased between the second and the twelfth week after the transplantation. At the twelve and twenty-six-week time-periods, all specimens had failed by pull-out of the tendon from the clamp or by mid-substance rupture of the tendon. The progressive increase in strength was correlated with the degree of bone ingrowth, mineralization, and maturation of the healing tissue, noted histologically.

Platelet-Rich Plasma From Basic Science to Clinical Applications

Platelet-rich plasma (PRP) has been utilized in surgery for 2 decades; there has been a recent interest in the use of PRP for the treatment of sports-related injuries. PRP contains growth factors and bioactive proteins that influence the healing of tendon, ligament, muscle, and bone. This article examines the basic science of PRP, and it describes the current clinical applications in sports medicine. This study reviews and evaluates the human studies that have been published in the orthopaedic surgery and sports medicine literature. The use of PRP in amateur and professional sports is reviewed, and the regulation of PRP by antidoping agencies is discussed.

The Basic Science of Articular Cartilage: Structure, Composition, and Function

Articular cartilage is the highly specialized connective tissue of diarthrodial joints. Its principal function is to provide a smooth, lubricated surface for articulation and to facilitate the transmission of loads with a low frictional coefficient (Figure 1). Articular cartilage is devoid of blood vessels, lymphatics, and nerves and is subject to a harsh biomechanical environment. Most important, articular cartilage has a limited capacity for intrinsic healing and repair. In this regard, the preservation and health of articular cartilage are paramount to joint health. Figure 1. Gross photograph of healthy articular cartilage in an adult human knee. Injury to articular cartilage is recognized as a cause of significant musculoskeletal morbidity. The unique and complex structure of articular cartilage makes treatment and repair or restoration of the defects challenging for the patient, the surgeon, and the physical therapist. The preservation of articular cartilage is highly dependent on maintaining its organized architecture.

Use of Recombinant Human Bone Morphogenetic Protein-2 to Enhance Tendon Healing in a Bone Tunnel

This study examines the hypothesis that recombinant human bone morphogenetic protein-2 can enhance bone ingrowth into a tendon graft placed into a bone tunnel. We transplanted the long digital extensor tendon into a drill hole in the proximal tibia in 65 adult mongrel dogs. We applied two different doses of the bone morphogenetic protein to the tendon-bone interface in one limb using an absorbable type I collagen sponge carrier and only the collagen sponge to the contralateral (control) limb. The healed tendon-bone attachment was evaluated at serial times between 3 days and 8 weeks using radiography, histologic examination, and biomechanical testing. At all time points, histologic and radiographic examination demonstrated more extensive bone formation around the tendon with closer apposition of new bone to the tendon in the protein-treated limb than in the paired control limb. Biomechanical testing demonstrated higher tendon pull-out strength in the protein-treated side at all time points, with a statistically significant difference between the low-dose-treated side and the control side at 2 weeks. The histologic and biomechanical data suggested superior healing at the lower protein dose. This study demonstrated that bone morphogenetic protein can accelerate the healing process when a tendon graft is transplanted into a bone tunnel.

Reliability, Validity, and Responsiveness of Four Knee Outcome Scales for Athletic Patients

Background: Many patient-based knee-rating scales are available for the evaluation of athletic patients. However, there is little information on the measurement properties of these instruments and therefore no evidence to support the use of one questionnaire rather than another. The goal of the present study was to determine the reliability, validity, and responsiveness of four knee-rating scales commonly used for the evaluation of athletic patients: the Lysholm scale, the subjective components of the Cincinnati knee-rating system, the American Academy of Orthopaedic Surgeons sports knee-rating scale, and the Activities of Daily Living scale of the Knee Outcome Survey. Methods: All patients in the study had a disorder of the knee and were active in sports (a Tegner score of 4 points). Forty-one patients who had a knee disorder that had stabilized and who were not receiving treatment were administered all four questionnaires at baseline and again at a mean of 5.2 days (range, two to fourteen days) later to test reliability. Forty-two patients were administered the scales at baseline and at a minimum of three months after treatment to test responsiveness. The responses of 133 patients at baseline were studied to test construct validity. Results: The reliability was high for all scales, with the intraclass correlation coefficient ranging from 0.88 to 0.95. As for construct validity, the correlations among the knee scales ranged from 0.70 to 0.85 and those between the knee scales and the physical component scale of the Short Form-36 (SF-36) and the patient and clinician severity ratings ranged from 0.59 to 0.77. Responsiveness, measured with the standardized response mean, ranged from 0.8 for the Cincinnati knee-rating system to 1.1 for the Activities of Daily Living scale. Conclusions: All four scales satisfied our criteria for reliability, validity, and responsiveness, and all are acceptable for use in clinical research.

Meniscal Allografts—Where Do We Stand?

Meniscal transplantation has been recommended for selected meniscus-deficient patients in an effort to forestall progressive joint degeneration. Meniscal allograft transplantation may be considered for patients with symptoms (pain and swelling) due to meniscal deficiency in an effort to prevent progressive articular cartilage degeneration. Medial meniscal transplantation may also be considered during concomitant anterior cruciate ligament reconstruction, since absence of the medial meniscus results in increased forces in the anterior cruciate ligament graft. Contraindications for meniscal transplantation include advanced articular cartilage degeneration (especially on the flexion weightbearing zone of the condyle), axial malalignment, and flattening of the femoral condyle. Patient evaluation should include standing, long-leg radiographs for assessment of the mechanical axis and magnetic resonance imaging with appropriate pulse sequences for evaluation of hyaline cartilage thickness. Fresh-frozen and cryopreserved allografts are currently the most commonly used transplantation materials. Appropriate graft sizing is critical; most tissue banks size the meniscus based on radiographic tibial plateau measurements. Early results of meniscal transplantation indicate predictable improvements in pain, swelling, and knee function; however, no long-term results are available. Poor results have been reported in patients with advanced cartilage degeneration. Objective evaluations often demonstrate some degree of degeneration of the posterior horn of the transplant. Earlier transplantation should be considered for patients with known meniscal deficiency.

The Effect of Platelet-Rich Fibrin Matrix on Rotator Cuff Tendon Healing: A Prospective, Randomized Clinical Study

Background: There is a strong need for methods to improve the biological potential of rotator cuff tendon healing. Platelet-rich fibrin matrix (PRFM) allows delivery of autologous cytokines to healing tissue, and limited evidence suggests a positive effect of platelet-rich plasma on tendon biology. Purpose: To evaluate the effect of platelet-rich fibrin matrix on rotator cuff tendon healing. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Seventy-nine patients undergoing arthroscopic rotator cuff tendon repair were randomized intraoperatively to either receive PRFM at the tendon-bone interface (n = 40) or standard repair with no PRFM (n = 39). Standardized repair techniques were used for all patients. The postoperative rehabilitation protocol was the same in both groups. The primary outcome was tendon healing evaluated by ultrasound (intact vs defect at repair site) at 6 and 12 weeks. Power Doppler ultrasound was also used to evaluate vascularity in the peribursal, peritendinous, and musculotendinous and insertion site areas of the tendon and bone anchor site. Secondary outcomes included standardized shoulder outcome scales (American Shoulder and Elbow Surgeons [ASES] and L’Insalata) and strength measurements using a handheld dynamometer. Patients and the evaluator were blinded to treatment group. All patients were evaluated at minimum 1-year follow-up. A logistic regression model was used to predict outcome (healed vs defect) based on tear severity, repair type, treatment type (PRFM or control), and platelet count. Results: Overall, there were no differences in tendon-to-bone healing between the PRFM and control groups. Complete tendon-to-bone healing (intact repair) was found in 24 of 36 (67%) in the PRFM group and 25 of 31 (81%) in the control group (P = .20). There were no significant differences in healing by ultrasound between 6 and 12 weeks. There were gradual increases in ASES and L’Insalata scores over time in both groups, but there were no differences in scores between the groups. We also found no difference in vascularity in the peribursal, peritendinous, and musculotendinous areas of the tendon between groups. There were no differences in strength between groups. Platelet count had no effect on healing. Logistic regression analysis demonstrated that PRFM was a significant predictor (P = .037) for a tendon defect at 12 weeks, with an odds ratio of 5.8. Conclusion: Platelet-rich fibrin matrix applied to the tendon-bone interface at the time of rotator cuff repair had no demonstrable effect on tendon healing, tendon vascularity, manual muscle strength, or clinical rating scales. In fact, the regression analysis suggests that PRFM may have a negative effect on healing. Further study is required to evaluate the role of PRFM in rotator cuff repair.

Application of Bone Marrow-Derived Mesenchymal Stem Cells in a Rotator Cuff Repair Model

Background Rotator cuff tendons heal to bone with interposed scar tissue, which makes repairs prone to failure. The purpose of this study was to determine if the application of bone marrow-derived mesenchymal stem cells (MSCs) can improve rotator cuff healing after repair. Hypothesis Application of MSCs to the repair site will result in superior results compared with controls on histologic and biomechanical testing. Study Design Controlled laboratory study. Methods Ninety-eight Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon; 10 rats were used for MSC harvest. Eight animals were used for cell tracking with Ad-LacZ. The remaining animals received either 10 6 MSCs in a fibrin carrier, the carrier alone, or nothing at the repair site. Animals were sacrificed at 2 and 4 weeks for histologic analysis to determine the amount of fibrocartilage formation and the collagen organization at the insertion. Biomechanical testing was also performed. Results Specimens treated with Ad-LacZ–transduced MSCs exhibited more β-galactosidase activity at the repair site compared with controls at both 2 and 4 weeks, although activity at 4 weeks was less than that at 2 weeks. There were no differences in the amount of new cartilage formation or collagen fiber organization between groups at either time point. There were also no differences in the biomechanical strength of the repairs, the cross-sectional area, peak stress to failure, or stiffness. Conclusion The addition of MSCs to the healing rotator cuff insertion site did not improve the structure, composition, or strength of the healing tendon attachment site despite evidence that they are present and metabolically active. Clinical Relevance A biologic solution to the problem of tendon-to-bone healing in the rotator cuff remains elusive. The repair site may lack the cellular and/or molecular signals necessary to induce appropriate differentiation of transplanted cells. Further studies are needed to determine if cell-based strategies need to be combined with growth and differentiation factors to be effective.

Indomethacin and Celecoxib Impair Rotator Cuff Tendon-to-Bone Healing

Background Nonsteroidal anti-inflammatory drugs are commonly prescribed after rotator cuff repair. These agents can impair bone formation, but no studies have evaluated their impact on tendon-to-bone healing. Hypothesis Traditional nonselective nonsteroidal anti-inflammatory drugs and cyclooxygenase-2–specific nonsteroidal antiinflammatory drugs interfere with tendon-to-bone healing. Study Design Controlled laboratory study. Methods One hundred eighty Sprague-Dawley rats underwent acute rotator cuff repairs. Postoperatively, 60 rats received 14 days of celecoxib, a cyclooxygenase-2–specific nonsteroidal anti-inflammatory drug; 60 received indomethacin, a traditional nonselective nonsteroidal anti-inflammatory drug; and 60 received standard rat chow. Animals were sacrificed at 2, 4, and 8 weeks and evaluated by gross inspection, biomechanical testing, histologic analysis, and polarized light microscopy to quantify collagen formation and maturation. Results Five tendons completely failed to heal (4 celecoxib, 1 indomethacin). There were significantly lower failure loads in the celecoxib and indomethacin groups compared with the control groups at 2, 4, and 8 weeks (P< .001), with no significant difference between nonsteroidal anti-inflammatory drug groups. There were significant differences in collagen organization and maturation between the controls and both nonsteroidal anti-inflammatory drug groups at 4 and 8 weeks (P< .001). Controls demonstrated progressively increasing collagen organization during the course of the study (P< .001), whereas the nonsteroidal anti-inflammatory drug groups did not. Conclusion Traditional and cyclooxygenase-2–specific nonsteroidal anti-inflammatory drugs significantly inhibited tendon-tobone healing. This inhibition appears linked to cyclooxygenase-2. Clinical Relevance If the results of this study are verified in a larger animal model, the common practice of administering nonsteroidal anti-inflammatory drugs after rotator cuff repair should be reconsidered.

Biologic augmentation of rotator cuff tendon-healing with use of a mixture of osteoinductive growth factors.

BACKGROUND Clinical studies have demonstrated a high rate of incomplete healing of rotator cuff tendon repair. Since healing of such a repair is dependent on bone ingrowth into the repaired tendon, we hypothesized that osteoinductive growth factors would improve rotator cuff tendon-healing. METHODS Seventy-two skeletally mature sheep underwent detachment of the infraspinatus tendon followed by immediate repair. The animals received one of three treatments at the tendon-bone interface: (1) an osteoinductive bone protein extract on a Type-I collagen sponge carrier, (2) the collagen sponge carrier alone, and (3) no implant. The animals were killed at six and twelve weeks, and the repaired rotator cuff was evaluated with use of magnetic resonance imaging, plain radiographs, histologic analysis, and biomechanical testing. RESULTS A gap consistently formed between the end of the repaired tendon and bone in this model, with reparative scar tissue and new bone spanning the gap. Magnetic resonance imaging showed that the volume of newly formed bone (p < 0.05) and soft tissue (p < 0.05) in the tendon-bone gap were greater in the growth factor-treated animals compared with the collagen sponge control group at both time-points. Histologic analysis showed a fibrovascular tissue in the interface between tendon and bone, with a more robust fibrocartilage zone between the bone and the tendon in the growth factor-treated animals. The repairs that were treated with the osteoinductive growth factors had significantly greater failure loads at six weeks and twelve weeks (p < 0.05); however, when the data were normalized by tissue volume, there were no differences between the groups, suggesting that the treatment with growth factor results in the formation of poor-quality scar tissue rather than true tissue regeneration. The repairs that were treated with the collagen sponge carrier alone had significantly greater stiffness than the growth factor-treated group at twelve weeks (p = 0.005). CONCLUSIONS This model tests the effects of growth factors on scar tissue formation in a gap between tendon and bone. The administration of osteoinductive growth factors resulted in greater formation of new bone, fibrocartilage, and soft tissue, with a concomitant increase in tendon attachment strength but less stiffness than repairs treated with the collagen sponge carrier alone.