The Effect of Flexor Carpi Ulnaris Pulley Design on Tendon Gliding Resistance After Flexor Digitorum Superficialis Tendon Transfer for Opposition Transfer.

PURPOSE: The flexor digitorum superficialis (FDS) tendon transfer can be used to restore opposition of the thumb. Several pulley designs have been proposed for this transfer. Gliding resistance is considered to be an important factor influencing the efficiency of the pulley design. Our purpose was to compare the gliding resistance among 4 commonly used pulleys for the FDS oppositional transfer. METHODS: Ten fresh-frozen cadaver specimens were studied. The ring FDS was used as the donor tendon. An oppositional transfer was created using 4 pulley configurations: FDS passed around the flexor carpi ulnaris (a-FCU), FDS passed through a 2.5-cm circumference distally based FCU loop (2.5-FCU), FDS passed through a 3.5-cm circumference distally based FCU loop (3.5-FCU), and FDS passed through a longitudinal split in the FCU tendon (s-FCU). The gliding resistance was measured with the thumb in radial abduction and maximum opposition. RESULTS: In abduction, the average FDS gliding resistance of a-FCU, 2.5-FCU, 3.5-FCU, and s-FCU was 0.66 N (SD, 0.14 N), 0.70 N (SD, 0.14 N), 0.68 N (SD, 0.16 N), and 0.79 N (SD, 0.15 N), respectively. The peak gliding resistance of a-FCU, 2.5-FCU, 3.5-FCU, and s-FCU was 0.75 N (SD, 0.16 N), 0.74 N (SD, 0.15 N), 0.74 N (SD, 0.15 N), and 0.86 N (SD, 0.15 N), respectively. CONCLUSIONS: The average gliding resistance of the s-FCU was found to be significantly higher than that of the a-FCU and 3.5-FCU pulleys. In opposition, there were no differences in average or peak gliding resistance among the different pulley designs. CLINICAL RELEVANCE: In this in vitro cadaveric study, the FDS split pulley produced higher gliding resistance. Consideration of the pulley configuration may improve the overall thumb function by decreasing forces needed to overcome gliding resistance.

Apoptotic Body-Rich Media from Tenocytes Enhance Proliferation and Migration of Tenocytes and Bone Marrow Stromal Cells.

The intrinsic healing following tendon injury is ideal, in which tendon progenitor cells proliferate and migrate to the injury site to directly bridge or regenerate tendon tissue. However, the mechanism determining why and how those cells are attracted to the injury site for tendon healing is not understood. Since the tenocytes near the injury site go through apoptosis or necrosis following injury, we hypothesized that secretions from injured tenocytes might have biological effects on cell proliferation and migration to enhance tendon healing. Tenocyte apoptosis was induced by 24 h cell starvation. Apoptotic body-rich media (T-ABRM) and apoptotic body-depleted media (T-ABDM) were collected from culture media after centrifuging. Tenocytes and bone marrow-derived stem cells (BMDSCs) were isolated and cultured with the following four media: (1) T-ABRM, (2) T-ABDM, (3) GDF-5, or (4) basal medium with 2% fetal calf serum (FCS). The cell activities and functions were evaluated. Both T-ABRM and T-ABDM treatments significantly stimulated the cell proliferation, migration, and extracellular matrix synthesis for both tenocytes and BMDSCs compared to the control groups (GDF-5 and basal medium). However, cell proliferation, migration, and extracellular matrix production of T-ABRM-treated cells were significantly higher than the T-ABDM, which indicates the apoptotic bodies are critical for cell activities. Our study revealed the possible mechanism of the intrinsic healing of the tendon in which apoptotic bodies, in the process of apoptosis, following tendon injury promote tenocyte and stromal cell proliferation, migration, and production. Future studies should analyze the components of the apoptotic bodies that play this role, and, thus, the targeting of therapeutics can be developed.

Carpal Tunnel Syndrome Treatment and the Subsequent Alterations in Median Nerve Transverse Mobility.

OBJECTIVES: The mobility (transverse movement) of the median nerve (MN) is decreased in patients with carpal tunnel syndrome and can be measured noninvasively by ultrasound. To date, there are few prognostic features to help predict the outcome of 2 commonly performed treatments: surgical carpal tunnel release and corticosteroid injection. This study aimed to assess the changes in nerve mobility after the intervention and to correlate this with treatment and the disease severity. METHODS: A total of 181 patients with carpal tunnel syndrome with different electrophysiologic severities were recruited and assessed by dynamic ultrasound scanning of the MN before and after treatment. The dynamic ultrasound images were collected while the patients performed finger and wrist flexion. RESULTS: For both injection and carpal tunnel release, the nerve displacement increased with wrist flexion, from a mean ± SD of 7.0 ± 2.4 to 7.9 ± 2.7 mm (P < .005). Patients who underwent surgery showed greater improvement (P < .005) in nerve mobility compared to those who underwent injection. We also observed that the increase in nerve mobility was predominantly in patients with more nerve damage at baseline. CONCLUSIONS: This study shows that the dynamic behavior of the MN changes in response to treatment and lays a foundation for future studies to assess the prognostic potential of nerve mobility measurement.

Effect of a monocyte chemoattractant protein-1 synthesis inhibitor on fibroblasts from patients with carpal tunnel syndrome.

BACKGROUND: Carpal Tunnel Syndrome (CTS) is an idiopathic fibrotic disorder. Fibrosis in the subsynovial connective tissues (SSCT) of CTS and many other fibrotic diseases is mediated by Transforming growth factor ß (TGF-ß). Recently monocyte chemoattractant protein-1 (MCP-1) a cytokine involved in cellular recruitment has been suggested to regulate TGF-ß activity. It is related to the onset of diseases which are caused by fibrosis, such as idiopathic pulmonary fibrosis, renal fibrosis, and systemic scleroderma. In this study, we evaluated the effect of the MCP-1 synthesis inhibitor, Bindarit, on primary cultures of fibroblasts from the SSCT of five CTS patients. METHODS: Fibroblasts were treated with Bindarit (10 µM, 50 µM, 100 µM, or 300 µM). Responses to inhibitors were evaluated by regulation of CTS fibrosis-associated genes, fibrosis gene array and Smad luciferase reporter assay. We also assessed the combination effect of Bindarit and SD208, a TGF-ß receptor type 1 inhibitor on TGF-ß signaling. RESULTS: Collagen type III A1 (Col3), connective tissue growth factor (CTGF), and SERPINE1 expression were significantly down-regulated by Bindarit (300 µM) compared to vehicle control. In the fibrosis array, expression of inhibin beta E chain precursor (INHBE), beta actin (ACTB), endothelin 1 (EDN1) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) were significantly down-regulated, and integrin beta-3 (ITGB3) was significantly up-regulated by Bindarit (300 µM). Smad signal transduction activation was significantly down-regulated by Bindarit (300 µM) and/or SD208 (1 µM) with TGF-ß1 compared to vehicle control with TGF-ß1. CONCLUSIONS: These results suggest that Bindarit in combination with SD208 may be beneficial as medical therapy for the SSCT fibrosis associated with CTS.

The effect of fibrin formulation on cell migration in an in vitro tendon repair model.

BACKGROUND: The purpose of this study was to determine the effect of fibrinogen concentration on cell viability and migration in a tissue culture tendon healing model. METHODS: Forty-eight canine flexor digitorum profundus tendons were randomly divided into three groups. In each group the tendons were lacerated and repaired augmented with a canine bone marrow stromal cell seeded fibrin interposition patch using either 5 mg/ml fibrinogen and 25 U/ml thrombin (physiological as a control), 40 mg/ml fibrinogen and 250 U/ml thrombin (low adhesive), or 80 mg/ml fibrinogen and 250 U/ml thrombin (high adhesive). The sutured tendons were cultured for two or four weeks. RESULTS: Failure load was not significantly different among the groups. Cell-labeling staining showed that the stromal cells migrated across the gap in the control and low adhesive groups, but there was no cell migration in the high adhesive group at two weeks. CONCLUSION: A high fibrinogen concentration in a fibrin patch or glue may impede early cell migration. LEVEL OF EVIDENCE: Not applicable because this study was a laboratory study.

Shear wave elastography of the median nerve: A mechanical study.

BACKGROUND: Shear wave elastography (SWE) shows promise in peripheral neuropathy evaluation but has potential limitations due to tissue size and heterogeneity. We tested SWE sensitivity to elasticity change and the effect of probe position in a median nerve cadaver model. METHODS: Ten specimens were used to measure median nerve elasticity under increasing loads using SWE and indentation. Measurements were compared using repeated-measures analysis of variance. RESULTS: Indentation and SWE-based longitudinal nerve elasticity increased with tensile loading (P < .01), showing a similar relationship. Acquisition in a transverse plane showed lower values compared with longitudinal measurements, mostly under higher loads (P = .03), as did postdissection elasticity (P = .02). Elasticity did not change when measured proximal to the carpal tunnel. CONCLUSIONS: Longitudinal SWE is sensitive to changes in median nerve elasticity. Measuring elasticity of peripheral nerves noninvasively could elucidate intra-neural pathology related to compression neuropathies, and proof to be of added value as a diagnostic or prognostic tool.

Ultrasound-Guided Hydrodissection With Corticosteroid Injection in the Treatment of Carpal Tunnel Syndrome: A Pilot Study.

OBJECTIVES: Corticosteroid injections can provide (temporary) relief in patients with mild to moderate carpal tunnel syndrome (CTS). Hydrodissection as part of an injection has been associated with positive clinical outcomes but data for CTS so far has been scarce. This study is designed to assess patient tolerance and secondarily provide pilot data on the added effect of hydrodissection. METHODS: Twenty CTS patients were randomized to an ultrasound-guided betamethasone injection with hydrodissection (5 mL) or without (2 mL). Patient tolerance was assessed directly after intervention and patient-reported outcome after 4 and 24 weeks. Intra-group data were compared using Wilcoxon Signed Rank and inter-group with Wilcoxon rank-sum tests. RESULTS: Tolerance and pain scores did not differ between the two groups. Symptom scores decreased in both groups, but to a lesser extent in the hydrodissection group with a mean difference of -0.8 versus -1.5 in the control group at 4 weeks (P = .02). At 6 months, this difference was no longer present (P = .81). No statistically significant differences were found between the hydrodissection and control groups in the function or pain scores at follow-up at either time point. CONCLUSION: After injection, both symptomatic and functional scores improved, but the hydrodissected group did not show additional improvement. Data presented can be used to support larger studies to assess the value of hydrodissection in CTS management.

The Turkey Digit: A New Training Model for Digit Replantation.

PURPOSE: Replant survival rates have reportedly declined over the past decade. Although this problem is multifactorial, 1 potential solution may include the development of a relevant teaching model. The development of an in vivo animal model that can be used for surgical training could enhance surgeon and resident experience and potentially improve outcomes. Here, we present a novel training model for digit replantation using turkey digits. METHODS: Six mature male Bourbon Red turkeys were included in this study. With the animal under general anesthesia, the third digit on either the left or the right foot was randomly selected and amputated. The medial and lateral digital neurovascular bundles were dissected on both sides and the digit was replanted. Perfusion was confirmed prior to skin closure. The foot was casted prior to extubating the turkeys. Turkeys were then placed in a non-weight-bearing sling. Digit status was evaluated twice daily. RESULTS: All 6 replanted digits were viable immediately after surgery and for at least 24 hours after surgery. The average digit survival was 6 days with a maximum survival of 15 days. All digits were eventually lost owing to a variety of reasons including infection and arterial thrombosis. CONCLUSIONS: The turkey digit proved to be a successful short-term animal training model for digit replantation. Future studies are needed to determine optimum standard surgical procedure and postoperative care to maximize the educational benefits of this training model. CLINICAL RELEVANCE: To establish an animal model that can simulate digital replantation.

Human Fibrosis: Is There Evidence for a Genetic Predisposition in Musculoskeletal Tissues?

BACKGROUND: Pathologic fibrosis is characterized by dysregulation of gene expression with excessive extracellular matrix production. The genetic basis for solid organ fibrosis is well described in the literature. However, there is a paucity of evidence for similar processes in the musculoskeletal (MSK) system. The purpose of this review is to provide an overview of existing evidence of genetic predisposition to pathologic fibrosis in the cardiac, pulmonary, and MSK systems, and to describe common genetic variants associated with these processes. METHODS: A comprehensive search of several databases from 2000 to 2019 was conducted using relevant keywords in the English language. Genes reported as involved in idiopathic fibrotic processes in the heart, lung, hand, shoulder, and knee were recorded by 2 independent authors. RESULTS: Among 2373 eligible studies, 52 studies investigated genetic predisposition in terms of variant analysis with the following organ system distribution: 36 pulmonary studies (69%), 15 hand studies (29%), and 1 knee study (2%). Twenty-two percent of gene variants identified were associated with both pulmonary and MSK fibrosis (ie, ADAM, HLA, CARD, EIF, TGF, WNT, and ZNF genes). Genetic variants known to be involved in the MSK tissue development or contractility properties in muscle were identified in the pulmonary fibrosis. CONCLUSION: Despite shared genetic variations in both the lung and hand, there remains limited information about genetic variants associated with fibrosis in other MSK regions. This finding establishes the necessity of further studies to elucidate the genetic determinants involved in the knee, shoulder, and other joint fibrotic pathways. LEVEL OF EVIDENCE: Level III.

Calculation of flexor pollicis longus moment arm for wrist motion in a cadaver model validates the tenodesis effect for therapy.

INTRODUCTION: Synergies of fingers and wrist motion have been incorporated into therapies for finger flexor tendon injuries to improve repair outcomes. Similar synergistic therapy strategies have not been well documented for the thumb. PURPOSE OF THE STUDY: The purpose of this study was to investigate the extent to which wrist motion enables a synergistic effect at the thumb in a cadaveric model by measuring flexor pollicis longus excursion and calculating the moment arm of this tendon at the wrist joint. STUDY DESIGN: This is a basic science research. METHODS: Eight fresh-frozen cadaveric arms were obtained from our anatomical bequest program. The proximal arm was fixed in neutral pronation/supination position, and motion of the wrist was guided through either flexion/extension or radial/ulnar deviation. Fingers were fixed in extension, thumb interphalangeal and metacarpophalangeal joints were fixed in neutral extension, and the carpometacarpal joint was fixed at 30° palmar abduction. The flexor pollicis longus tendon was exposed proximal to the wrist crease and connected to a rotary potentiometer to measure tendon excursion. Optical markers were attached to the hand to capture kinematics. Wrists were moved from a neutral position over the range of flexion and extension and then from the neutral position through the range of radial to ulnar deviation. Moment arms were calculated. RESULTS: Moment arm calculation indicated that the flexor pollicis longus acts as a wrist flexor over the entire motion range and as a weak radial deviator at ulnarly-deviated positions. CONCLUSIONS: This study provides a mechanistic rationale for passive interphalangeal joint motion in varying wrist positions when treating thumb flexor tendon injuries, with benefits seen primarily for wrist extension.

Blocking fibrotic signaling in fibroblasts from patients with carpal tunnel syndrome.

Fibrosis of the subsynovial connective tissue (SSCT) in carpal tunnel syndrome (CTS) patients is increasingly recognized as an important aspect of CTS pathophysiology. In this study, we evaluated the effect of blocking profibrotic pathways in fibroblasts from the SSCT in CTS patients. Fibroblasts were stimulated with transforming growth factor ß1 (TGF-ß1), and then treated either with a specific fibrosis pathway inhibitor targeting TGF-ß receptor type 1 (TßRI), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), or vascular endothelial growth factor receptor (VEGFR). Fibrosis array and quantitative real-time polymerase chain reaction of fibrotic genes were evaluated. Array gene expression analysis revealed significant down-regulation of multiple fibrotic genes after treatment with TßRI, PDGFR, and VEGFR inhibitors. No array fibrotic genes were significantly down-regulated with EGFR inhibition. Further gene expression analysis of known CTS fibrosis markers collagen type I A2 (Col1), collagen type III A1 (Col3), connective tissue growth factor (CTGF), and SERPINE1 showed significantly down-regulation after TßRI inhibition. In contrast, VEGFR inhibition significantly down-regulated CTGF and SERPINE1, whereas, PDGFR and EGFR inhibition significantly down-regulated Col3. Taken together the inhibition of TßRI appears to be the primary mediator of fibrotic gene expression in fibroblasts from CTS patients. TGF-ß/Smad activity was further evaluated, and as expected inhibition of Smad activity was significantly down-regulated after inhibition of TßRI, but not with PDGFR, VEGFR, or EGFR inhibition. These results indicate that local therapies specifically targeting TGF-ß signaling alone or in combination offer the potential of a novel local antifibrosis therapy for patients with CTS.

Ultrasound-guided hydrodissection decreases gliding resistance of the median nerve within the carpal tunnel.

INTRODUCTION: The aim of this study was to assess alterations in median nerve (MN) biomechanics within the carpal tunnel resulting from ultrasound-guided hydrodissection in a cadaveric model. METHODS: Twelve fresh frozen human cadaver hands were used. MN gliding resistance was measured at baseline and posthydrodissection, by pulling the nerve proximally and then returning it to the origin. Six specimens were treated with hydrodissection, and 6 were used as controls. RESULTS: In the hydrodissection group there was a significant reduction in mean peak gliding resistance of 92.9 ± 34.8 mN between baseline and immediately posthydrodissection (21.4% ± 10.5%; P = 0.001). No significant reduction between baseline and the second cycle occurred in the control group: 9.6 ± 29.8 mN (0.4% ± 5.3%; P = 0.467). DISCUSSION: Hydrodissection can decrease the gliding resistance of the MN within the carpal tunnel, at least in wrists unaffected by carpal tunnel syndrome. A clinical trial of hydrodissection seems justified. Muscle Nerve 57: 25-32, 2018.

Triamcinolone Acetonide affects TGF-ß signaling regulation of fibrosis in idiopathic carpal tunnel syndrome.

BACKGROUND: Fibroblast behavior and cell-matrix interactions of cells from normal and idiopathic carpal tunnel syndrome (CTS) subsynovial connective tissue (SSCT) with and without Triamcinolone Acetonide (TA) were compared in this study. A cell-seeded gel contraction model was applied to investigate the effect of steroid treatment on SSCT fibroblast gene expression and function. METHODS: SSCT cells were obtained from CTS patients and fresh cadavers. Cells were isolated by mechanical and collagenase digestion. Collagen gels (1 mg/ml) were prepared with SSCT cells (1 × 106/mL). A sterile Petri dish with a cloning ring in the center was prepared. The area between the ring and outer dish was filled with cell-seeded collagen solution and gelled for 1 h. The gel was released from the outer way of the petri dish to allow gel contraction. Cell seeded gels were treated with 10 M triamcinolone acetonide (TA) or vehicle (DMSO) in modified MEM. Every 4 h for 3 days the contracting gels were photographed and areas calculated. Duplicate contraction tests were performed with each specimen, and the averages were used in the analyses, which were conducted using two-factor analysis of variance in a generalized linear model framework utilizing generalized estimating equations (GEE) to account for the correlation between samples. The contraction rate was determined by the area change over time, and the decay time constant was calculated. A customized mechanical test system was used to determine gel stiffness and tensile strength. Gene expression was assessed using Human Fibrosis and Cell Motility PCR arrays. RESULTS: TA-treated gels had a significantly higher contraction rate, tensile strength and stiffness than the untreated gels. Proteinases involved in remodeling had increased expression in TA-treated gels of the patient group. Pro-fibrotic genes and ECM regulators, such as TGF-ß, collagens and integrins, were down-regulated by TA, indicating that TA may work in part by decreasing fibrotic gene expression. CONCLUSIONS: This study showed that TA affects cell-matrix interaction and suppresses fibrotic gene expression in the SSCT cells of CTS patients.

Influence of Injection Volume on Rate of Subsequent Intervention in Carpal Tunnel Syndrome Over 1-Year Follow-Up.

PURPOSE: The optimal volume and dose of corticosteroid injections for treatment of carpal tunnel syndrome (CTS) have not yet been established. It is unknown whether the volume of injectate influences the outcome of carpal tunnel injection. The purpose of this study was to assess whether there is an association between the volume of injectate and subsequent intervention in the treatment of CTS. METHODS: This study evaluated residents of Olmsted County, MN, who were treated with a corticosteroid injection for CTS between 2001 and 2010. Failure of treatment was the primary outcome, defined as a subsequent intervention: either a second injection or carpal tunnel release within 1 year of initial injection. General estimating equations logistic regression was used to assess the association between injectate volume and rate of treatment failure, adjusting for age, sex, effective dose of steroid, type of steroid injected, electrodiagnostic severity, and the presence of comorbidities such as rheumatoid arthritis, diabetes mellitus, peripheral neuropathy, and radiculopathy. RESULTS: There were 856 affected hands in 651 patients. A total of 56% (n = 484) of treated hands received subsequent treatment within 1 year. Multivariable analysis showed that a larger injectate volume was significantly associated with reduced rate of treatment failure within 1 year. Rheumatoid arthritis and ultrasound-guided procedures were also associated with a reduced rate of treatment failure, whereas severe electrodiagnostic results were associated with an increased rate of failure. CONCLUSIONS: This study showed that a larger volume of corticosteroid injection is associated with reduced odds of subsequent intervention after a single corticosteroid injection in CTS. Further research is needed to determine the optimal volume for steroid injections in the treatment of CTS. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Turkey model for flexor tendon research: in vitro comparison of human, canine, turkey, and chicken tendons.

BACKGROUND: Flexor tendon injuries are one of the most common hand injuries and remain clinically challenging for functional restoration. Canine and chicken have been the most commonly used animal models for flexor tendon-related research but possess several disadvantages. The purpose of this study was to explore a potential turkey model for flexor tendon research. METHODS: The third digit from human cadaveric hands, canine forepaws, turkey foot, and chicken foot were used for this study. Six digits in each of four species were studied in detail, comparing anatomy of the flexor apparatus, joint range of motion tendon excursion, tendon cross-sectional area, work of flexion, gliding resistance at the level of the A2 pulley, modulus of elasticity, suture retention strength, and histology across species. RESULTS: Anatomically, the third digit in the four species displayed structural similarities; however, the tendon cross-sectional area of the turkey and human were similar and larger than canine and chicken. Furthermore, the turkey digit resembles the human's finger with the lack of webbing between digits, similar vascularization, tendon excursion, work of flexion, gliding resistance, mechanical properties, and suture holding strength. More importantly, human and turkey tendons were most similar in histological appearance. CONCLUSIONS: Turkey flexor tendons have many properties that are comparable to human flexor tendons which would provide a clinically relevant, economical, nonhuman companion large animal model for flexor tendon research.

Rotator cuff repair augmentation in a rat model that combines a multilayer xenograft tendon scaffold with bone marrow stromal cells.

HYPOTHESIS: A composite of multilayer tendon slices (COMTS) seeded with bone marrow stromal cells (BMSCs) may impart mechanical and biologic augmentation effects on supraspinatus tendon repair under tension, thereby improving the healing process after surgery in rats. METHODS: Adult female Lewis rats (n = 39) underwent transection of the supraspinatus tendon and a 2-mm tendon resection at the distal end, followed by immediate repair to its bony insertion site under tension. Animals received 1 of 3 treatments at the repair site: (1) no augmentation, (2) COMTS augmentation alone, or (3) BMSC-seeded COMTS augmentation. BMSCs were labeled with a fluorescent cell marker. Animals were euthanized 6 weeks after surgery, and the extent of healing of the repaired supraspinatus tendon was evaluated with biomechanical testing and histologic analysis. RESULTS: Histologic analysis showed gap formation between the repaired tendon and bone in all specimens, regardless of treatment. Robust fibrous tissue was observed in rats with BMSC-seeded COMTS augmentation; however, fibrous tissue was scarce within the gap in rats with no augmentation or COMTS-only augmentation. Labeled transplanted BMSCs were observed throughout the repair site. Biomechanical analysis showed that the repairs augmented with BMSC-seeded COMTS had significantly greater ultimate load to failure and stiffness compared with other treatments. However, baseline (time 0) data showed that COMTS-only augmentation did not increase mechanical strength of the repair site. CONCLUSION: Although the COMTS scaffold did not increase the initial repair strength, the BMSC-seeded scaffold increased healing strength and stiffness 6 weeks after rotator cuff repair in a rat model.

PAPP-A affects tendon structure and mechanical properties.

Pregnancy-associated plasma protein-A (PAPP-A) serves to increase local insulin-like growth factor (IGF) stimulation of proliferation and differentiation in many tissues through proteolysis of inhibitory IGF-binding proteins. The purpose of this study was to investigate the effects of PAPP-A on tendon structure and mechanical properties. A total of 30 tails from 6-month-old mice were tested with 10 tails in each of following groups: PAPP-A knockout (KO), skeletal-specific PAPP-A overexpressing transgenic (Tg) and wild type (WT). Morphologically, the total tail cross-sectional area (CSA), individual tissue CSAs of bone, muscle and tendon, and fascicle diameter were measured. A fascicle pullout test was performed to assess stiffness and strength of interfascicular structures. Fascicles were mechanically characterized through low and high displacement rate uniaxial tension tests providing modulus at each rate, hysteresis area and stress relaxation ratio. The KO mice had a smaller total tail CSA (p<0.05), fascicle diameter (p<0.05), absolute tendon CSA (p<0.05), fast and slow stiffness (p<0.05 for both) and larger hysteresis area (p<0.05) compared to WT and Tg mice. On the other hand, the Tg mice had a larger fascicle diameter (p<0.05), absolute tendon CSA (p<0.05), higher interfascicular strength and stiffness (p<0.05) and lower fascicular modulus at low displacement rates (p<0.05) compared to WT and KO mice. Tg mice also had larger total tail CSA area (p<0.05) and smaller hysteresis area (p<0.05) than KO mice, and larger normalized tendon CSA (p<0.05) than WT mice. Based on these data, we conclude that PAPP-A affects fascicle structure, thereby affecting tendon phenotype.

The Effect of 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide Suture Coating on Tendon Repair Strength and Cell Viability in a Canine Model.

PURPOSE: To determine if impregnating a suture with a cross-linking agent, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), improved suture pull-out strength and cell viability. METHODS: Canine flexor digitorum profundus tendons were cut in canine zone D, and a single suture loop was placed in each end, with sutures soaked in either saline or an EDC solution with a concentration of 1%, 10%, or 50%. Suture pull-out strength, stiffness, and elongation to failure was determined by pulling the loop until failure. Cytotoxicity of the EDC treatment was evaluated by suspending treated sutures over cultured tenocytes. RESULTS: Mechanical properties for the EDC-treated side were improved over controls when treated with the 10% and 50% EDC solutions. The ratio of dead to live cells was significantly increased at all distances from the suture for the 50% EDC-treated group. CONCLUSIONS: Suture treated with a 10% EDC solution provided the best combination of mechanical reinforcement and limited toxicity. CLINICAL RELEVANCE: Sutures so treated may improve the ability of a tendon repair to sustain early mobilization.

Effect of wrist and interphalangeal thumb movement on zone T2 flexor pollicis longus tendon tension in a human cadaver model.

INTRODUCTION: Therapy after flexor pollicis longus (FPL) repair typically mimics finger flexor management, but this ignores anatomic and biomechanical features unique to the FPL. PURPOSE OF THE STUDY: We measured FPL tendon tension in zone T2 to identify biomechanically appropriate exercises for mobilizing the FPL. METHODS: Eight human cadaver hands were studied to identify motions that generated enough force to achieve FPL movement without exceeding hypothetical suture strength. RESULTS: With the carpometacarpal and metacarpophalangeal joints blocked, appropriate forces were produced for both passive interphalangeal (IP) motion with 30° wrist extension and simulated active IP flexion from 0° to 35° with the wrist in the neutral position. DISCUSSION: This work provides a biomechanical basis for safely and effectively mobilizing the zone T2 FPL tendon. CONCLUSION: Our cadaver study suggests that it is safe and effective to perform early passive and active exercise to an isolated IP joint. LEVEL OF EVIDENCE: NA.

CORR® ORS Richard A. Brand Award for Outstanding Orthopaedic Research: Engineering flexor tendon repair with lubricant, cells, and cytokines in a canine model.

BACKGROUND: Adhesions and poor healing are complications of flexor tendon repair. QUESTIONS/PURPOSES: The purpose of this study was to investigate a tissue engineering approach to improve functional outcomes after flexor tendon repair in a canine model. METHODS: Flexor digitorum profundus tendons were lacerated and repaired in 60 dogs that were followed for 10, 21, or 42 days. One randomly selected repair from either the second or fifth digit in one paw in each dog was treated with carbodiimide-derivatized hyaluronic acid, gelatin, and lubricin plus autologous bone marrow stromal cells stimulated with growth and differentiation factor 5; control repair tendons were not treated. Digits were analyzed by adhesion score, work of flexion, tendon-pulley friction, failure force, and histology. RESULTS: In the control group, 35 of 52 control tendons had adhesions, whereas 19 of 49 treated tendons had adhesions. The number of repaired tendons with adhesions in the control group was greater than the number in the treated group at all three times (p = 0.005). The normalized work of flexion in treated tendons was 0.28 (± 0.08), 0.29 (± 0.19), and 0.32 (± 0.22) N/mm/° at Day 10, Day 21, and Day 42 respectively, compared with the untreated tendons of 0.46 (± 0.19) at Day 10 (effect size, 1.5; p = 0.01), 0.77 (± 0.49) at Day 21 (effect size, 1.4; p < 0.001), and 1.17 (± 0.82) N/mm/° at Day 42 (effect size, 1.6; p < 0.001). The friction data were comparable to the work of flexion data at all times. The repaired tendon failure force in the untreated group at 42 days was 70.2 N (± 8.77), which was greater than the treated tendons 44.7 N (± 8.53) (effect size, 1.9; p < 0.001). Histologically, treated repairs had a smooth surface with intrinsic healing, whereas control repairs had surface adhesions and extrinsic healing. CONCLUSIONS: Our study provides evidence that tissue engineering coupled with restoration of tendon gliding can improve the quality of tendon healing in a large animal in vivo model. CLINICAL RELEVANCE: Tissue engineering may enhance intrinsic tendon healing and thus improve the functional outcomes of flexor tendon repair.