Corticosteroid-eluting endotracheal tubes (ETTs) were developed and employed in a swine laryngotracheal injury model to maintain airway patency and provide localized drug delivery to inhibit fibrotic scarring. Polycaprolactone (PCL) fibers with or without dexamethasone were electrospun onto the ETT surface PCL-only coated ETTs and placed in native airways of 18 Yorkshire swine. Regular and dexamethasone-PCL coated ETTs were placed in airways of another 18 swine injured by inner laryngeal mucosal abrasion. All groups were evaluated after 3, 7 and 14 days (n = 3/treatment/time). Larynges were bisected and localized stiffness determined by normal indentation, then sequentially matched with histological assessment. In the native airway, tissue stiffness with PCL-only ETT placement increased significantly from 3 to 7 days (
Subfailure ligament and tendon injury remain a significant burden to global healthcare. Here, we present the use of biocompatible single‐walled carbon nanohorns (CNH) as a potential treatment for the repair of sub‐failure injury in tendons. First, in vitro exposure of CNH to human tenocytes revealed no change in collagen deposition but a significant decrease in cell metabolic activity after 14 days. Additionally, gene expression studies revealed significant downregulation of collagen Types I and III mRNA at 7 days with some recovery after 14 days of exposure. Biomechanical tests with explanted porcine digitorum tendons showed the ability of CNH suspensions to modulate tendon biomechanics, most notably elastic moduli immediately after treatment. in vivo experiments demonstrated the ability of CNH to persist in the damaged matrix of stretch‐injured Sprague Dawley rat Achilles tendon but not significantly modify tendon biomechanics after 7 days of treatment. Although these results demonstrate the early feasibility of utility of CNH as a potential modality for tendon subfailure injury, additional work is needed to further validate and ensure clinical efficacy.
more » « less- NSF-PAR ID:
- 10406200
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Biomedical Materials Research Part B: Applied Biomaterials
- Volume:
- 108
- Issue:
- 5
- ISSN:
- 1552-4973
- Page Range / eLocation ID:
- p. 1907-1914
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract p = 0.0016) and 3 to 14 days (p < 0.0001) while dexamethasone-PCL ETT placement resulted in stiffness decreasing from 7 to 14 days (p = 0.031). In the injured airway, localized stiffness at 14 days was significantly greater after regular ETT placement (23.1 ± 0.725 N/m) versus dexamethasone-PCL ETTs (17.10 ± 0.930 N/m,p < 0.0001). Dexamethasone-loaded ETTs were found to reduce laryngotracheal tissue stiffening after simulated intubation injury compared to regular ETTs, supported by a trend of reduced collagen in the basement membrane in injured swine over time. Findings suggest localized corticosteroid delivery allows for tissue stiffness control and potential use as an approach for prevention and treatment of scarring caused by intubation injury. -
Diabetes mellitus (DM) is associated with musculoskeletal complications—including tendon dysfunction and injury. Patients with DM show altered foot and ankle mechanics that have been attributed to tendon dysfunction as well as impaired recovery post-tendon injury. Despite the problem of DM-related tendon complications, treatment guidelines specific to this population of individuals are lacking. DM impairs tendon structure, function, and healing capacity in tendons throughout the body, but the Achilles tendon is of particular concern and most studied in the diabetic foot. At macroscopic levels, asymptomatic, diabetic Achilles tendons may show morphological abnormalities such as thickening, collagen disorganization, and/or calcific changes at the tendon enthesis. At smaller length scales, DM affects collagen sliding and discrete plasticity due to glycation of collagen. However, how these alterations translate to mechanical deficits observed at larger length scales is an area of continued investigation. In addition to dysfunction of the extracellular matrix, tendon cells such as tenocytes and tendon stem/progenitor cells show significant abnormalities in proliferation, apoptosis, and remodeling capacity in the presence of hyperglycemia and advanced glycation end-products, thus contributing to the disruption of tendon homeostasis and healing. Improving our understanding of the effects of DM on tendons—from molecular pathways to patients—will progress toward targeted therapies in this group at high risk of foot and ankle morbidity.more » « less
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INTRODUCTION: Quadriceps tendon autografts have experienced a rapid rise in popularity for anterior cruciate ligament (ACL) reconstruction due to advantages in graft sizing and potential improvement in biomechanics. While there is a growing body of literature on use of quadriceps tendon grafts, deeper investigation into the biomechanical properties of stitch techniques in this construct has been limited. The purpose of this study was to evaluate the performance of a novel suture needle against different conventional suture needles by comparing the biomechanical properties of two commonly used stitch methods, a whip stitch, and a locking stitch in quadriceps tendon. It was hypothesized that the new device would be capable of creating both whip stitches and locking stitches that are biomechanically equivalent to similar stitch techniques performed with conventional needle products. METHODS: This was a controlled biomechanical study. A total of 24 matched pair cadaveric knees were dissected and a total of 48 quadriceps tendons were harvested and tested. All tendon grafts were standardized to the same size. Samples were then randomized into the following groups, keeping the matched pairs together: (Group 1, n=16) consisted of Company W’s novel two-part suture needle design, (Group 2, n=16) consisted of Company A suture, and (Group 3, n=16) consisted of Company B suture. For each group, the matched pairs were categorized into subgroups to be instrumented with either a whip stitch or a locking stitch. Two fellowship-trained surgeons performed all stitching, where they each instrumented 8 tendon grafts per group. For instrumentation, the grafts were clamped to a preparation stand in accordance with the manufacturer’s recommendations for passing each suture needle. A skin marker was used to identify and mark five evenly spaced points, 0.5 cm apart, as a guide to create a 5-stitch series. For Group 1, the whip stitch as well as the locking whip stitch were performed with a novel 2-part needle. For Group 2, the whip stitch was performed with loop suture needle and the locking stitch was krackow with a curved needle. Similarly, for Group 3, the whip stitch was performed with loop suture needle and the locking stitch was krackow with a curved needle (Figure 1). Cyclical testing was performed using a servohydraulic testing machine (MTS Bionix) equipped with a 5kN load cell. A standardized length of tendon, 7 cm, was coupled to the MTS actuator by passing it through a cryoclamp cooled by dry ice to a temperature of -5°C (Figure 2). All testing samples were then pre-conditioned to normalize viscoelastic effects and testing variability through application of cyclical loading to 25-100 N for three cycles. The samples were then held at 89 N for 15 minutes. Thereafter, the samples were loaded to 50-200 N for 500 cycles at 1 Hz. If samples survived, they were ramped to failure at 20 mm/min. Displacement and force data was collected throughout testing. Metrics of interest were total elongation (mm), stiffness (N/mm), ultimate failure load (N) and failure mode. Data are presented as averages plus/minus standard deviation. A one-way analysis of variance (ANOVA) with a Tukey pairwise comparison post hoc analysis was used to evaluate differences between the various stitching methods. Statistical significance was set at P = .05. RESULTS SECTION: For the whip stitch methods, the total elongation was found to be equivalent across all methods (W: 36 ± 10 mm; A: 32 ± 18 mm; B: 33 ± 8 mm). The stiffness of Company A (103 ± 11 N/mm) method was significantly larger than Company W (64 ± 8 N/mm; p=.001), whereas stiffness of whip stitch by Company W was equivalent to Company B (80 ± 32 N/mm). The ultimate failure load was equivalent across all whip stitch methods (W: 379 ± 31 mm; A: 412 ± 103 mm; B: 438 ± 63 mm). For the locking stitch method, the total elongation (W: 26 ± 10 mm; A: 14 ± 2 mm; B: 29 ± 5 mm), stiffness (W: 75 ± 11 N/mm; A: 104 ± 23 N/mm; B: 79 ± 10 N/mm) and ultimate load (W: 343 ± 22 N; A: 369 ± 30 N; B: 438 ± 63 N) were found to be equivalent across all methods. The failure mode for all groups is in Table 1. The common mode of failure across study groups and stitch configuration was suture breakage. However, the whip stitch from Company A and Company B had varied failure modes. DISCUSSION: Products from the three manufacturers were found to produce biomechanically equivalent whip stitches and locking stitches with respect to elongation and ultimate failure load. The only significant difference observed was that the whip stitch created with Company A’s product had a higher stiffness than Company W’s product, which could have been due to differences in the suture material. In this cadaveric quadriceps tendon model, it was shown that when using Company W’s novel two-part suture needle, users were capable of creating whip stitches and locking stitches that achieved equivalent biomechanical performance compared to similar stitch techniques performed with conventional needle products. A failure mode limited solely to suture breakage for methods completed with Company W’s needle product suggest a reliable suture construct with limited tissue damage. SIGNIFICANCE/CLINICAL RELEVANCE: Having a suture needle device with the versatility to easily perform different stitching constructs may provide surgeons an advantage needed to improve clinical outcomes. The data presented illustrates a strong new suture technique that has equivalent performance when compared to conventional needle devices and has promising applications in graft preparation for ligament and tendon reconstruction.more » « less
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ABSTRACT Injuries to flexor tendons can be complicated by fibrotic adhesions, which severely impair the function of the hand. Plasminogen activator inhibitor 1 (PAI‐1/SERPINE1), a master suppressor of fibrinolysis and protease activity, is associated with adhesions. Here, we used next‐generation RNA sequencing (RNA‐Seq) to assess genome‐wide differences in messenger RNA expression due to PAI‐1 deficiency after zone II flexor tendon injury. We used the ingenuity pathway analysis to characterize molecular pathways and biological drivers associated with differentially expressed genes (DEG). Analysis of hundreds of overlapping and DEG in PAI‐1 knockout (KO) and wild‐type mice (C57Bl/6J) during tendon healing revealed common and distinct biological processes. Pathway analysis identified cell proliferation, survival, and senescence, as well as chronic inflammation as potential drivers of fibrotic healing and adhesions in injured tendons. Importantly, we identified the activation of PTEN signaling and the inhibition of FOXO1‐associated biological processes as unique transcriptional signatures of the healing tendon in the PAI‐1/Serpine1 KO mice. Further, transcriptomic differences due to the genetic deletion of PAI‐1 were mechanistically linked to PI3K/Akt/mTOR, PKC, and MAPK signaling cascades. These transcriptional observations provide novel insights into the biological roles of PAI‐1 in tendon healing and could identify therapeutic targets to achieve scar‐free regenerative healing of tendons. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:43–58, 2020
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Abstract The extracellular matrix (ECM) is the primary biomechanical environment that interacts with tendon cells (tenocytes). Stresses applied via muscle contraction during skeletal movement transfer across structural hierarchies to the tenocyte nucleus in native uninjured tendons. Alterations to ECM structural and mechanical properties due to mechanical loading and tissue healing may affect this multiscale strain transfer and stress transmission through the ECM. This study explores the interface between dynamic loading and tendon healing across multiple length scales using living tendon explants. Results show that macroscale mechanical and structural properties are inferior following high magnitude dynamic loading (fatigue) in uninjured living tendon and that these effects propagate to the microscale. Although similar macroscale mechanical effects of dynamic loading are present in healing tendon compared to uninjured tendon, the microscale properties differed greatly during early healing. Regression analysis identified several variables (collagen and nuclear disorganization, cellularity, and F-actin) that directly predict nuclear deformation under loading. Finite element modeling predicted deficits in ECM stress transmission following fatigue loading and during healing. Together, this work identifies the multiscale response of tendon to dynamic loading and healing, and provides new insight into microenvironmental features that tenocytes may experience following injury and after cell delivery therapies.
