Andrew R. Thoreson

Effects of a Lubricin-Containing Compound on the Results of Flexor Tendon Repair in a Canine Model in Vivo

BACKGROUND Tendon surface modification with a synthetic biopolymer, carbodiimide-derivatized hyaluronic acid and gelatin with the addition of lubricin (CHL), has been shown to reduce gliding resistance after tendon repair in an in vitro model. The purpose of the study was to investigate whether CHL would reduce adhesion formation and improve digital function after flexor tendon repair in a canine model in vivo. METHODS Sixty dogs were randomly assigned to either a biopolymer-treated group (n = 30) or an untreated control group (n = 30). The second and fifth flexor digitorum profundus tendons from each dog were lacerated fully at the zone-II area and then repaired. Passive synergistic motion therapy was started on the fifth postoperative day and continued until the dogs were killed on day 10, day 21, or day 42. The repaired tendons were evaluated for adhesions, normalized work of flexion, gliding resistance, repair strength, stiffness, and histological characteristics. RESULTS The normalized work of flexion of the repaired tendons treated with CHL was significantly lower than that of the non-CHL-treated repaired tendons at all time points (p < 0.05), and the prevalence of severe adhesions was also significantly decreased in the CHL-treated tendons at day 42 (p < 0.05). However, the repair failure strength and stiffness of the CHL-treated group were also significantly reduced compared with those of the control group at days 21 and 42 (p < 0.05) and the rate of tendon rupture was significantly higher in the treated group than in the control group at day 42 (p < 0.05). CONCLUSIONS Treatment with the lubricin-containing gel CHL appears to be an effective means of decreasing postoperative flexor tendon adhesions, but it is also associated with some impairment of tendon healing. Future studies will be necessary to determine if the positive effects of CHL on adhesion formation can be maintained while reducing its adverse effect on the structural integrity of the repaired tendon.

Improvement of flexor tendon reconstruction with carbodiimide-derivatized hyaluronic acid and gelatin-modified intrasynovial allografts: Study of a primary repair failure model

BACKGROUND Tendon grafts play an important role in flexor tendon reconstruction. This study was an investigation of the effects of surface modification of allograft intrasynovial tendons with carbodiimide-derivatized hyaluronic acid and gelatin in an in vivo canine model. To mimic the actual clinical situation, a novel and clinically relevant model of a failed primary flexor tendon repair was used to evaluate the flexor tendon grafts. METHODS Twenty-eight flexor digitorum profundus tendons from the second and fifth digits of fourteen dogs were lacerated and repaired in zone II in a first-surgery phase. The dogs were allowed free active motion postoperatively. In a second phase, six weeks later, the tendons were reconstructed with use of a flexor digitorum profundus allograft. In each dog, one graft was treated with carbodiimide-derivatized hyaluronic acid and gelatin (the CHG group) and the other was treated with saline solution, as a control. The dogs were restricted from free active motion, but daily therapy was performed beginning on postoperative day 5 and continued until six weeks after the operation, when the animals were killed. The outcomes were evaluated on the basis of digit work of flexion, gliding resistance, healing at the distal attachment, graft cell viability, histological findings, and findings on scanning electron microscopy. RESULTS In the first phase, all twenty-eight repaired tendons ruptured, with scar and adhesion formation in the repair site. Six weeks after allograft reconstruction, the mean work of flexion was 0.37 and 0.94 N-mm/degree in the CHG group and the saline-solution control group, respectively; these values were significantly different (p < 0.05). The gliding resistance in the CHG group was also significantly less than that in the saline-solution control group (0.18 versus 0.28 N) (p < 0.05), but no difference between groups was observed with regard to the distal tendon-bone pullout strength. Histological analysis showed that tenocytes in the host tendon proliferated and migrated toward the acellular allograft. CONCLUSIONS This primary repair failure model was reproducible and reliable, with a uniform failure pattern, and provides an appropriate and clinically relevant animal model with which to study flexor tendon reconstruction. The surface modification of allografts with carbodiimide-derivatized hyaluronic acid and gelatin improved digital function and tendon gliding ability.

Altered median nerve deformation and transverse displacement during wrist movement in patients with carpal tunnel syndrome

RATIONALE AND OBJECTIVES Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome. Strong pinch or grip with wrist flexion has been considered a risk factor for CTS. Studying median nerve displacement during wrist movements may provide useful information about median nerve kinematic changes in patients with CTS. The purpose of this study was to evaluate the deformability and mobility of the median nerve in patients with CTS compared to healthy subjects. MATERIALS AND METHODS Dynamic ultrasound images were obtained in 20 affected wrists of 13 patients with CTS. Results were compared to complementary data obtained from both wrists of 10 healthy subjects reported in a previous study. Shape and position of initial and final median nerve were measured and analyzed for six defined wrist movements. The deformation ratios for each movement were defined as the median nerve area, perimeter, and circularity of the final position normalized by respective values assessed in the initial position. The median nerve displacement vector and magnitude were also calculated. RESULTS The deformation ratio for circularity was significantly less in patients with CTS compared to healthy subjects during wrist flexion (P < .05). The mean vector of median nerve displacement during wrist flexion was significantly different between patients with CTS and healthy subjects (P < .05). The displacement magnitude of the median nerve was found to be less in patients with CTS compared to healthy subjects during most movements, with the exception of wrist extension with fingers extended. CONCLUSIONS Patients with CTS differ from normal subjects with regard to mobility and deformability of the median nerve.

Influence of radial head prosthetic design on radiocapitellar joint contact mechanics

HYPOTHESIS Our aim was to test whether anatomically designed metallic radial head implants could better reproduce native radiocapitellar contact pressure and areas than nonanatomic implants. METHODS The distal humerus and proximal radius from 6 cadaveric upper extremities were serially tested in supination with 100 N of compression force at 4 angles of flexion (0°, 30°, 60°, and 90°). By use of a thin flexible pressure transducer, contact pressures and areas were measured for the native radial head, an anatomic implant, a nonanatomic circular monopolar implant, and a bipolar nonanatomic implant. The data (mean contact pressure and mean contact area) were modeled using a 2-factor repeated-measures analysis of variance with P ≤ .05 considered to be significant. RESULTS The mean contact areas for the prosthetic radial heads were significantly less than those seen with the intact radial heads at every angle tested (P < .01). The mean contact pressures increased significantly with all prosthetic radial head types as compared with the native head. The mean contact pressures increased by 29% with the anatomic prosthesis, 230% with the monopolar prosthesis, and 220% with the bipolar prosthesis. Peak pressures of more than 5 MPa were more commonly observed with both the monopolar and bipolar prostheses than with the anatomic or native radial heads. CONCLUSIONS The geometry of radial head implants strongly influences their contact characteristics. In a direct radius-to-capitellum axial loading experiment, an anatomically designed radial head prosthesis had lower and more evenly distributed contact pressures than the nonanatomic implants that were tested.

Effect of mechanical stimulation on bone marrow stromal cell-seeded tendon slice constructs: a potential engineered tendon patch for rotator cuff repair.

Cell-based tissue engineered tendons have potential to improve clinical outcomes following rotator cuff repair, especially in large or massive rotator cuff tears, which pose a great clinical challenge. The aim of this study was to develop a method of constructing a functional engineered tendon patch for rotator cuff repair with cyclic mechanical stimulation. Decellularized tendon slices (DTSs) were seeded with BMSCs and subjected to cyclic stretching for 1, 3, or 7 days. The mechanical properties, morphologic characteristics and tendon-related gene expression of the constructs were investigated. Viable BMSCs were observed on the DTS after 7 days. BMSCs penetrated into the DTSs and formed dense cell sheets after 7 days of mechanical stretching. Gene expression of type I collagen, decorin, and tenomodulin significantly increased in cyclically stretched BMSC-DTS constructs compared with the unstrained control group (P < 0.05). The ultimate tensile strength and stiffness of the cyclically stretched tendon constructs were similar to the unstrained control group (P > 0.05). In conclusion, mechanical stimulation of BMSC-DTS constructs upregulated expression of tendon-related proteins, promoted cell tenogenic differentiation, facilitated cell infiltration and formation of cell sheets, and retained mechanical properties. The patch could be used as a graft to enhance the surgical repair of rotator cuff tears.

Resurfacing with chemically modified hyaluronic acid and lubricin for flexor tendon reconstruction

We assessed surface coating with carbodiimide derivatized hyaluronic acid combined with lubricin (cd‐HA‐Lubricin) as a way to improve extrasynovial tendon surface quality and, consequently, the functional results in flexor tendon reconstruction, using a canine in vivo model. The second and fifth flexor digitorum profundus tendons from 14 dogs were reconstructed with autologs peroneus longus (PL) tendons 6 weeks after a failed primary repair. One digit was treated with cd‐HA‐Lubricin, and the other was treated with saline as the control. Six weeks following grafting, the digits and graft tendons were functionally and histologically evaluated. Adhesion score, normalized work of flexion, graft friction in zone II, and adhesion breaking strength at the proximal repair site in zone III were all lower in the cd‐HA‐Lubricin treated group compared to the control group. The strength at the distal tendon/bone interface was decreased in the cd‐HA‐Lubricin treated grafts compared to the control grafts. Histology showed inferior healing in the cd‐HA‐Lubricin group at both proximal and distal repair sites. However, cd‐HA‐Lubricin treatment did not result in any gap or rupture at either the proximal or distal repair sites. These results demonstrate that cd‐HA‐Lubricin can eliminate graft adhesions and improve digit function, but that treatment may have an adverse effect on tendon healing.

Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia

Abstract We report a case of chronic traumatic paraplegia in which epidural electrical stimulation (EES) of the lumbosacral spinal cord enabled (1) volitional control of task‐specific muscle activity, (2) volitional control of rhythmic muscle activity to produce steplike movements while side‐lying, (3) independent standing, and (4) while in a vertical position with body weight partially supported, voluntary control of steplike movements and rhythmic muscle activity. This is the first time that the application of EES enabled all of these tasks in the same patient within the first 2 weeks (8 stimulation sessions total) of EES therapy.

Comparison of step-cut and Pulvertaft attachment for flexor tendon graft: a biomechanics evaluation in an in vitro canine model

The purpose of this study was to compare two different methods of joining tendons of similar and dissimilar sizes between recipient and donor tendons for flexor tendon grafts. Flexor digitorum profundus (FDP) and peroneus longus (PL) canine tendons were harvested and divided into four groups. The repair technique we compared was a step-cut (SC) suture and a Pulvertaft weave (PW). FDP tendons were significantly larger in diameter than PL tendons (p < 0.05). The volume of the SC repairs using either FDP or PL tendon as a graft was significantly smaller than PW repairs (p < 0.05). The ultimate load to failure and repair stiffness in FDP graft tendons significantly increased compared with the PL graft tendons (p < 0.05). The SC suture can be used as an alternative to the PW, with similar strength and less bulk for repairs using graft tendons of similar diameter. Surgeons should be aware of the effect of graft tendon size and repair method on strength and bulk when performing flexor tendon grafts.

Temporal response of canine flexor tendon to limb suspension

Tendon disuse, or stress deprivation, frequently accompanies clinical disorders and treatments, yet the metabolism of tendons subject to stress deprivation has rarely been investigated systematically. The effects of stress deprivation on canine flexor tendon were investigated in this study. One adult canine forepaw was suspended for 21 or 42 days. Control forepaws were collected from dogs that had no intervention on their limbs and paws. The expression of collagen I and III was not significantly altered in the tendons disused for 21 days but was significantly decreased at 42 days (P < 0.03). The expression of collagen II, aggrecan, decorin, and fibronectin was significantly decreased in the tendons in the suspended limbs at 21 days (P < 0.002) and further reduced at 42 days. With stress deprivation, the expression of matrix metalloproteinase 2 (MMP2) was significantly increased (P < 0.004) at 21 and 42 days. The expression of MMP3 was significantly decreased at 21 and 42 days (P < 0.03). The expression of MMP13 was not altered with stress deprivation at 21 and 42 days. The expression of MMP14 was significantly increased at 21 days (P = 0.0015) and returned to the control level at 42 days. Tissue inhibitor of metalloproteinase 1 (TIMP1) expression was decreased after the limbs were suspended for 42 days (P = 0.0043), but not 21 days. However, TIMP2 expression was not significantly different from control at 21 or 42 days. Furthermore, the cross-sectional area of the stress-deprived tendons at 42 days was decreased compared with the control group (P < 0.01). The intervention method in this study did not result in any alteration of stiffness of the tendon. Our study demonstrated that stress deprivation decreases the anabolic process and increases the catabolic process of extracellular matrix in flexor tendon.

The mechanical properties of tail tendon fascicles from lubricin knockout, wild type and heterozygous mice

The purpose of this study was to analyze the effects of lubricin on tendon stiffness and viscoelasticity. A total of 36 mice were tested with 12 mice in each of the following groups: lubricin knock-out ⁻/⁻, heterozygous ⁺/⁻ and wild-type ⁺/⁺. A ramp test was used to determine the elastic modulus by pulling the fascicles to 2.5% strain amplitude at a rate of 0.05 mm/s. Then, followed by a relaxation test that pulled the fascicles to 5% strain amplitude at a rate of 2 mm/s. The fascicles were allowed to relax for 2 min at the maximum strain and a single-cycle relaxation ratio was used to characterize viscoelastic properties. There was no significant difference in the Youngs modulus between the three groups (p > 0.05), but the knockout mice had a significantly (p < 0.05) lower relaxation ratio than the wild type mice. Based on these data, we concluded that lubricin expression has an effect on the viscoelastic properties of tendon fascicles. The clinical significance of this finding, if any, remains to be demonstrated.