58 research outputs found
The alchemy of tendon repair: A primer for the (S)mad scientist
During vertebrate development, mesenchymal progenitors capable of forming bone, cartilage, muscle, fat, or tendon arise from either neural crest or somitic mesoderm. Transcriptional programs that specify mesenchymal cell fates are initiated and modified by paracrine cues provided by TGF-β superfamily members and mediated in part via the regulated assembly of Smad-containing multiprotein transcription factor complexes. In this issue of the JCI, Hoffmann and colleagues have identified that Smad8 activation drives tendon formation from C3H10T1/2 cells, a murine cell line that recapitulates many features of normal multipotent mesenchymal cells (see the related article beginning on page 940). Cells programmed to the tenocyte cell fate in vitro formed tenogenic grafts in vivo. These results add to the accumulating evidence that proliferating, multipotent mesenchymal progenitor cells can be programmed to yield multiple cell types — e.g., osteoblasts, myocytes, chondrocytes, and tenocytes — that may be useful in cell-based therapeutic approaches to musculoskeletal diseases
Ulnar collateral ligament injuries of the thumb: phalangeal translation during valgus stress in human cadavera
BACKGROUND: The clinical diagnosis of thumb ulnar collateral ligament disruption has been based on joint angulation during valgus stress testing. This report describes a definitive method of distinguishing between complete and partial ulnar collateral ligament injuries by quantifying translation of the proximal phalanx on the metacarpal head during valgus stress testing. METHODS: Sixty-two cadaveric thumbs underwent standardized valgus stress testing under fluoroscopy with the ulnar collateral ligament intact, following an isolated release of the proper ulnar collateral ligament, and following a combined release of both the proper and the accessory ulnar collateral ligament (complete ulnar collateral ligament release). Following complete ulnar collateral ligament release, the final thirty-seven thumbs were also analyzed after the application of a valgus force sufficient to cause 45° of valgus angulation at the metacarpophalangeal joint to model more severe soft-tissue injury. Two independent reviewers measured coronal plane joint angulation (in degrees), ulnar joint line gap formation (in millimeters), and radial translation of the proximal phalanx on the metacarpal head (in millimeters) on digital fluoroscopic images that had been randomized. RESULTS: Coronal angulation across the stressed metacarpophalangeal joint progressively increased through the stages of the testing protocol: ulnar collateral ligament intact (average [and standard deviation], 20° ± 8.1°), release of the proper ulnar collateral ligament (average, 23° ± 8.3°), and complete ulnar collateral ligament release (average, 30° ± 8.9°) (p < 0.01 for each comparison). Similarly, gap formation increased from the measurement in the intact state (5.1 ± 1.3 mm), to that following proper ulnar collateral ligament release (5.7 ± 1.5 mm), to that following complete ulnar collateral ligament release (7.2 ± 1.5 mm) (p < 0.01 for each comparison). Radial translation of the proximal phalanx on the metacarpal head did not increase after isolated release of the proper ulnar collateral ligament (1.6 ± 0.8 mm vs. 1.5 ± 0.9 mm in the intact state). There was a significant increase in translation following release of the complete ulnar collateral ligament complex (3.0 ± 0.9 mm; p < 0.01) and an additional increase after forcible angulation of the joint to 45° (4.1 ± 0.9 mm; p < 0.01). Translation 2 mm greater than that in the stressed control was 100% specific for complete disruption of the ulnar collateral ligament complex. CONCLUSIONS: While transection of the proper ulnar collateral ligament leads to an increase in metacarpophalangeal joint angulation and gapping on stress fluoroscopic evaluation, only release of both the accessory and the proper ulnar collateral ligament significantly increases translation of the proximal phalanx on the metacarpal head. CLINICAL RELEVANCE: A finding of phalangeal translation on a stress fluoroscopic image distinguishes partial from complete tears of the thumb ulnar collateral ligament
Enhanced zone II flexor tendon repair through a new half hitch loop suture configuration
This study evaluated the impact of a new half hitch loop suture configuration on flexor tendon repair mechanics. Cadaver canine flexor digitorum profundus tendons were repaired with 4- or 8-strands, 4-0 or 3-0 suture, with and without half hitch loops. An additional group underwent repair with half hitch loops but without the terminal knot. Half hitch loops improved the strength of 8-strand repairs by 21% when 4-0, and 33% when 3-0 suture was used, and caused a shift in failure mode from suture pullout to suture breakage. 8-strand repairs with half hitch loops but without a terminal knot produced equivalent mechanical properties to those without half hitch loops but with a terminal knot. 4-strand repairs were limited by the strength of the suture in all groups and, as a result, the presence of half hitch loops did not alter the mechanical properties. Overall, half hitch loops improved repair mechanics, allowing failure strength to reach the full capability of suture strength. Improving the mechanical properties of flexor tendon repair with half hitch loops has the potential to reduce the postoperative risk of gap formation and catastrophic rupture in the early postoperative period
The effect of adipose-derived stem cell sheets and CTGF on early flexor tendon healing in a canine model
Oral History interview of Curt Sawyer. Interview conducted by Robin Dunn
The effect of adipose-derived stem cell sheets and CTGF on early flexor tendon healing in a canine model
Long-term outcomes following a single corticosteroid injection for trigger finger
BACKGROUND: The outcomes of corticosteroid injection for trigger finger are well documented only with short-term follow-up. The purpose of this investigation was to determine the long-term effectiveness of a single injection and to examine predictors of success up to ten years after injection. METHODS: This case series analyzed 366 first-time corticosteroid injections in flexor tendon sheaths from January 2000 to December 2007 with a minimum follow-up duration of five years. Two hundred and forty patients (66%) were female, 161 patients (44%) had multiple trigger fingers, and eighty-eight patients (24%) had diabetes at the time of injection. The primary outcome of treatment failure was defined as subsequent injection or surgical trigger finger release of the affected digit. Medical records were reviewed, and any patients without documented failure or a return office visit in 2012 to 2013 were contacted by telephone regarding symptom recurrence and the need for additional treatment. Kaplan-Meier analyses with log-rank test and Cox regression analysis assessed the effect of baseline patient and disease characteristics on injection success. RESULTS: Forty-five percent of patients demonstrated long-term treatment success after a single injection. In the final regression model, the interaction of sex and the number of trigger fingers was the single predictor of treatment success. Exploring this association revealed a ten-year success rate of 56% for female patients presenting for the first time with a trigger finger compared with 35% in male patients presenting for the first time with a trigger finger, 39% in female patients with multiple trigger fingers, and 37% in male patients with multiple trigger fingers. Eighty-four percent of treatment failures occurred within the first two years following injection. Patient age, symptom type, and undifferentiated diabetes status were not predictive of treatment success. CONCLUSIONS: Female patients presenting with their first trigger finger have the highest rate of long-term treatment success after a single corticosteroid injection. Patients who continue to experience symptom relief two years after injection are likely to maintain long-term success. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence
Orthopaedic surgeons and the medical device industry: The threat to scientific integrity and the public trust
BMP12 induces tenogenic differentiation of adipose-derived stromal cells
<div><p>Adipose-derived stromal cells (ASCs) are pluripotent cells that have the capacity to differentiate into tendon fibroblasts (TFs). They are abundant in adults, easy to access, and are therefore an ideal cell source for tendon tissue engineering. Despite this potential, the molecular cues necessary for tenogenic differentiation of ASCs are unknown. Unlike other bone morphogenetic proteins (BMPs), BMP12, BMP13, and BMP14 have been reported to be less osteo-chondrogenic and to induce tendon rather than bone formation <i>in vivo</i>. This study investigated the effects of BMP12 and BMP14 on ASC differentiation <i>in vitro</i>. In canine ASCs, BMP12 effectively increased the expression of the tendon markers scleraxis and tenomodulin at both mRNA and protein levels. Consistent with these results, BMP12 induced scleraxis promoter driven-GFP and tenomodulin protein expression in mouse ASCs. Although BMP12 also enhanced the expression of the cartilage matrix gene aggrecan in ASCs, the resulting levels remained considerably lower than those detected in tendon fibroblasts. In addition, BMP12 reduced expression of the bone marker osteocalcin, but not the osteogenic transcription factor runx-2. BMP14 exhibited similar, but marginally less potent and selective effects, compared to BMP12. BMPs are known to signal through the canonical Smad pathway and the non-canonical mitogen-activated protein kinase (MAPK) pathway. BMP12 triggered robust phosphorylation of Smad1/5/8 but not Smad2/3 or p38 MAPK in ASCs. The effect was likely conveyed by type I receptors ALK2/3/6, as phosphorylation of Smad1/5/8 was blocked by the ALK2/3/6 inhibitor LDN-193189 but not by the ALK4/5/7 inhibitor SB-505124. Moreover, ALK6 was found to be the most abundant type I receptor in ASCs, with mRNA expression 100 to 10,000 times that of any other type I receptor. Collectively, results support the conclusion that BMP12 induces tenogenic differentiation of ASCs via the Smad1/5/8 pathway.</p> </div
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