Jonathan D. Packer

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.

Bone Marrow–Derived Mesenchymal Stem Cells Transduced With Scleraxis Improve Rotator Cuff Healing in a Rat Model

Background: Rotator cuffs heal through a scar tissue interface after repair that makes them prone to failure. Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is thought to direct tendon development during embryogenesis. The purpose of this study was to determine if the application of mesenchymal stem cells (MSCs) transduced with adenoviral-mediated scleraxis (Ad-Scx) could improve regeneration of the tendon-bone insertion site in a rat rotator cuff repair model. Hypothesis: Bone marrow–derived cells transduced with Scx would improve the structure of the healing tendon-bone interface and result in increased tendon attachment strength. Study Design: Controlled laboratory study. Methods: Sixty Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon. Thirty animals received MSCs in a fibrin glue carrier, and 30 received Ad-Scx-transduced MSCs. Animals were sacrificed at 2 weeks and 4 weeks and evaluated for the presence of fibrocartilage and collagen fiber organization at the insertion. Biomechanical testing was performed to determine the structural and material properties of the repaired tissue. Statistical analysis was performed with a Wilcoxon rank sum test with significance set at P = .05. Results: There were no differences between the Scx and MSC groups in terms of histologic appearance at 2 weeks. However, the Scx group had higher ultimate stress-to-failure (2.6 ± 0.9 vs 1.7 ± 0.3 MPa; P = .03) and stiffness (8.4 ± 2.9 vs 5.0 ± 1.9 N/mm; P = .01) compared with the MSC group. At 4 weeks, the Scx group had more fibrocartilage (728.7 ± 50.4 vs 342.6 ± 217.0 mm2; P = .04), higher ultimate load to failure (26.7 ± 4.6 vs 20.8 ± 4.4 N; P = .01), higher ultimate stress to failure (4.7 ± 1.3 vs 3.5 ± 1.0 MPa; P < .04), and higher stiffness values (15.3 ± 3.4 vs 9.3 ± 2.2 N/mm; P < .001) as compared with the MSC group. Conclusion: Mesenchymal stem cells genetically modified with Scx can augment rotator cuff healing at early time points. Clinical Relevance: Biologic augmentation of acutely injured rotator cuffs with Scx-transduced MSCs may improve rotator cuff tendon healing and reduce the incidence of re-tears. However, further studies are needed to determine if this remains safe and effective in larger models.

Adenoviral-mediated gene transfer of human bone morphogenetic protein-13 does not improve rotator cuff healing in a rat model.

Background: Rotator cuff tendon-to-bone healing occurs by formation of a scar tissue interface after repair, which makes it prone to failure. Bone morphogenetic protein–13 (BMP-13) has been implicated in tendon and cartilage repair, and thus may augment rotator cuff repairs. The purpose of this study was to determine if the application of mesenchymal stem cells (MSCs) transduced with BMP-13 could improve regeneration of the tendon-bone insertion site in a rat rotator cuff repair model. Hypothesis: Mesenchymal stem cells genetically modified to overexpress BMP-13 will improve rotator cuff healing based on histologic and biomechanical outcomes. Study Design: Controlled laboratory study. Methods: Sixty Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon and 10 rats were used for MSC harvest. Animals were randomized into 2 groups (30 animals/group). The experimental group received 106 MSCs transduced with adenoviral-mediated gene transfer of human BMP-13 (Ad-BMP-13). The second group received untransduced MSCs. Fifteen animals in each group were sacrificed at 2 and 4 weeks. At each time point, 12 animals were allocated for biomechanical testing, and 3 for histomorphometric analysis. Results: 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 at failure, or stiffness. Conclusion: Application of MSCs genetically modified to overexpress BMP-13 did not improve healing in a rat model of rotator cuff repair. Clinical Relevance: Further studies are needed to evaluate various growth factors and combinations of growth factors to determine the optimal factor for the biologic augmentation of rotator cuff repairs.

Meniscal allograft transplantation.

Meniscal allograft transplantation has emerged as a treatment option for selected meniscus-deficient patients to restore normal meniscal function and forestall progressive joint degeneration. Contraindications include diffuse subchondral bone exposure, axial malalignment, and instability. However, a knee may be rendered suitable for meniscus transplantation if combined with chondral resurfacing, osteotomy, and/or ligament reconstruction. Although numerous studies have reported improved clinical outcomes with meniscal allograft transplantation, high-quality studies with control groups are lacking in the literature. This article describes the current indications, graft types and sizing, surgical techniques, and a review of the literature with a focus on the role of concomitant procedures.

Functional Outcomes and Patient Satisfaction After Fasciotomy for Chronic Exertional Compartment Syndrome

Background: Patients with chronic exertional compartment syndrome who have failed nonoperative treatment are evaluated with pre-exertion and postexertion compartment pressure testing and may be treated with fasciotomy. Failure rates of up to 20% have been reported and may be related to factors such as age, sex, postexertion compartment pressures, compartment(s) released, and duration of symptoms. Hypothesis: Higher preoperative postexertion compartment pressures are correlated with higher success and patient satisfaction rates after fasciotomy. Study Design: Cohort study; Level of evidence, 3. Methods: From 1999 to 2008, patients with clinical symptoms of chronic exertional compartment syndrome with failed nonoperative management underwent standardized pre-exertion and postexertion compartment pressure measurements. Patients were then offered continued nonoperative treatment or referral to an orthopaedic surgeon for compartment release. Patients with a minimum 2-year follow-up were given a telephone questionnaire describing their pretreatment and posttreatment conditions including quality and duration of symptoms, analog pain scale, symptomatic and functional responses to treatment, and satisfaction with treatment. Medical records and operative reports were reviewed. Results: The mean follow-up period for the nonoperative treatment group (n = 27) was 5.6 years (range, 2.1-10.6) and for the operative group (n = 73) was 5.2 years (range, 2.0-11.3). The operative group had a higher success rate (81%) compared with the nonoperative group (41%) (P < .001), and the operative group had a higher patient satisfaction rate (81%) compared with the nonoperative group (56%) (P = .011). There was no significant correlation between compartment pressures and patient outcomes. Patients with combined anterior and lateral compartment releases had an increased failure rate compared with isolated anterior release (31% vs 0%, respectively; P = .035). Surgical patients who were post-college had a lower satisfaction rate (66%) compared with high school (89%) and college patients (94%) (P = .017). Conclusion: High school and college patients (age <23 years) and isolated anterior compartment release (compared with anterior/lateral release) were factors associated with improved subjective function and satisfaction after fasciotomy. We recommend the avoidance of lateral release unless symptoms or postexertion compartment pressures are clearly indicative of lateral compartment involvement.

Effect of Immediate and Delayed High-Strain Loading on Tendon-to-Bone Healing After Anterior Cruciate Ligament Reconstruction

BACKGROUND We previously demonstrated, in a rat anterior cruciate ligament (ACL) graft reconstruction model, that the delayed application of low-magnitude-strain loading resulted in improved tendon-to-bone healing compared with that observed after immediate loading and after prolonged immobilization. The purpose of this study was to determine the effect of higher levels of strain loading on tendon-to-bone healing. METHODS ACL reconstruction was carried out in a rat model in three randomly assigned groups: high-strain daily loading beginning on either (1) postoperative day one (immediate-loading group; n = 7) or (2) postoperative day four (delayed-loading group; n = 11) or (3) after prolonged immobilization (immobilized group; n = 8). Animals were killed two weeks after surgery and micro-computed tomography (micro-CT) and biomechanical testing of the bone-tendon-bone complex were carried out. RESULTS The delayed-loading group had greater tissue mineral density than either the immediate-loading or immobilized group (mean [and standard deviation], 813.0 ± 24.9 mg/mL compared with 778.4 ± 32.6 mg/mL and 784.9 ± 26.4 mg/mL, respectively; p < 0.05). There was a trend toward greater bone volume per total volume fraction in both the immobilized and the delayed-loading group compared with the immediate-loading group (0.24 ± 0.03 and 0.23 ± 0.06 compared with 0.20 ± 0.05; p = 0.06). Trabecular thickness was greater in the immobilized group compared with the immediate-loading group (106.5 ± 23.0 μm compared with 72.6 ± 10.6 μm; p < 0.01). There were no significant differences in failure load or stiffness between the immobilized group and either high-strain cyclic-loading group. CONCLUSIONS Immediate application of high-strain loading appears to have a detrimental effect on healing in this rat model. Any beneficial effects of delayed loading on the healing tendon-bone interface (after a brief period of immobilization) may be offset by the detrimental effects of excessive strain levels or by the detrimental effects of stress deprivation on the graft. CLINICAL RELEVANCE The timing and magnitude of mechanical load on a healing rat ACL reconstruction graft may have important implications for postoperative rehabilitation. Avoidance of exercises that cause high graft strain in the early postoperative period may lead to improved tendon-to-bone healing in humans.

A Novel In Vivo Joint Loading System to Investigate the Effect of Daily Mechanical Load on a Healing Anterior Cruciate Ligament Reconstruction

We designed and validated a novel knee joint fixation/distraction system to study tendon-to-bone healing in an in vivo rat model of anterior cruciate ligament (ACL) reconstruction. The system uses an external fixator to apply a cyclic distraction of the knee joint while monitoring the resultant force developed across the joint, thus providing a temporal indication of structural changes during the healing process of the bone-tendon-bone reconstruction. The validation was performed using an optical kinematic tracking system to determine the local displacement of the knee. The average system compliance was determined to be 42.4 +/- 8.8 mum/N with a coefficient of variation of 20.7%. The compliance was used to obtain a best fit correction factor which brought the total root mean square error of knee joint distraction to within 179 mum (16.1%) of the applied distraction. We performed a pilot study using 15 rats that had ACL reconstructions using a flexor digitorum longus tendon autograft and found that the animals tolerated the indwelling fixator and daily anesthesia over a 10 day loading protocol. Our knee joint fixation/distraction system provides a valuable tool to study how mechanical stimuli affect in vivo bone-tendon-bone healing.

Ibuprofen impairs capsulolabral healing in a rat model of anterior glenohumeral instability

Background Failure of glenoid labrum and capsular healing after glenohumeral dislocation can lead to persistent shoulder instability. The purpose of this study was to determine the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the healing glenoid labrum and capsule after glenohumeral dislocation in a rat model. Methods Sixty-six rats had surgically induced anterior-inferior labral tears and anterior glenohumeral dislocation. Postoperatively, the animals were assigned to either normal (n = 32) or ibuprofen drinking water (n = 31). Animals were euthanized at 2 and 4 weeks postoperatively for biomechanical testing and histologic analysis. Results The maximum load increased from 2 to 4 weeks after injury in the NSAID groups but not in the control groups. At 2 weeks, the maximum load was lower in the NSAID group compared with the control group. In a matched comparison between injured and uninjured limbs, the maximum load was significantly decreased in the injured limb of the 2-week NSAID group. At 4 weeks, the NSAID group had decreased stiffness compared with the 4-week control group. Conclusions In a new rat model of glenohumeral instability, the postinjury administration of ibuprofen resulted in decreased capsulolabral healing. A matched pair analysis of injured to uninjured limbs supported the findings of impaired healing in the NSAID-treated animals. These findings demonstrate that the use of NSAIDs after glenohumeral dislocation may impair capsulolabral healing and should be limited or avoided to optimize glenohumeral stability.

Shoulder and Elbow Arthroplasty in Younger Patients

Abstract Joint arthroplasty is common in elderly patients with arthritis. The success of joint arthroplasty in the elderly population has increased the indications for joint arthroplasty in younger patients. The success and increased indications are due to advances in technology and joint arthroplasty design and materials, as well as to bone-conserving approaches that are more applicable to younger patients. Although most joint arthroplasty procedures are for the hip and knee, the upper extremity (shoulder and elbow) is the fastest-growing segment of joint arthroplasty procedures. This article presents innovative approaches to shoulder and elbow arthroplasty that are designed to treat younger patients with arthritis of the shoulder and elbow.