Bioactive and Elastic Emulsion Electrospun DegraPol Tubes Delivering IGF-1 for Tendon Rupture Repair.

Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I, ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier.

Computational model predicts risk of spinal screw loosening in patients.

PURPOSE: Pedicle screw loosening is a frequent complication in lumbar spine fixation, most commonly among patients with poor bone quality. Determining patients at high risk for insufficient implant stability would allow clinicians to adapt the treatment accordingly. The aim of this study was to develop a computational model for quantitative and reliable assessment of the risk of screw loosening. METHODS: A cohort of patient vertebrae with diagnosed screw loosening was juxtaposed to a control group with stable fusion. Imaging data from the two cohorts were used to generate patient-specific biomechanical models of lumbar instrumented vertebral bodies. Single-level finite element models loading the screw in axial or caudo-cranial direction were generated. Further, multi-level models incorporating individualized joint loading were created. RESULTS: The simulation results indicate that there is no association between screw pull-out strength and the manifestation of implant loosening (p = 0.8). For patient models incorporating multiple instrumented vertebrae, CT-values and stress in the bone were significantly different between loose screws and non-loose screws (p = 0.017 and p = 0.029, for CT-values and stress, respectively). However, very high distinction (p = 0.001) and predictability (R2Pseudo = 0.358, AUC = 0.85) were achieved when considering the relationship between local bone strength and the predicted stress (loading factor). Screws surrounded by bone with a loading factor higher than 25% were likely to be loose, while the chances of screw loosening were close to 0 with a loading factor below 15%. CONCLUSION: The use of a biomechanics-based score for risk assessment of implant fixation failure might represent a paradigm shift in addressing screw loosening after spondylodesis surgery.

Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro.

(1) Background: Surgical tendon repair often leads to adhesion formation, leading to joint stiffness and a reduced range of motion. Tubular implants set around sutured tendons might help to reduce peritendinous adhesions. The lubricant hyaluronic acid (HA) is a viable option for optimizing such tubes with the goal of further enhancing the anti-adhesive effect. As the implant degrades over time and diffusion is presumed, the impact of HA on tendon cells is important to know. (2) Methods: A culture medium of rabbit Achilles tenocytes was supplemented with high-molecular-weight (HMW) HA and the growth curves of the cells were assessed. Additionally, after 3, 7 and 14 days, the gene expression of several markers was analyzed for matrix assembly, tendon differentiation, fibrosis, proliferation, matrix remodeling, pro-inflammation and resolution. (3) Results: The addition of HA decreased matrix marker genes, downregulated the fibrosis marker α-SMA for a short time and slightly increased the matrix-remodeling gene MMP-2. Of the pro-inflammatory marker genes, only IL-6 was significantly upregulated. IL-6 has to be kept in check, although IL-6 is also needed for a proper initial inflammation and efficient resolution. (4) Conclusions: The observed effects in vitro support the intended anti-adhesion effect and therefore, the use of HMW HA is promising as a biodegradable implant for tendon repair.

Focus on time: dynamic imaging reveals stretch-dependent cell relaxation and nuclear deformation.

Among the stimuli to which cells are exposed in vivo, it has been shown that tensile deformations induce specific cellular responses in musculoskeletal, cardiovascular, and stromal tissues. However, the early response of cells to sustained substrate-based stretch has remained elusive because of the short timescale at which it occurs. To measure the tensile mechanical properties of adherent cells immediately after the application of substrate deformations, we have developed a dynamic traction force microscopy method that enables subsecond temporal resolution imaging of transient subcellular events. The system employs a novel, to our knowledge, tracking approach with minimal computational overhead to compensate substrate-based, stretch-induced motion/drift of stretched single cells in real time, allowing capture of biophysical phenomena on multiple channels by fluorescent multichannel imaging on a single camera, thus avoiding the need for beam splitting with the associated loss of light. Using this tool, we have characterized the transient subcellular forces and nuclear deformations of single cells immediately after the application of equibiaxial strain. Our experiments reveal significant differences in the cell relaxation dynamics and in the intracellular propagation of force to the nuclear compartment in cells stretched at different strain rates and exposes the need for time control for the correct interpretation of dynamic cell mechanics experiments.

Cross-links in posterior pedicle screw-rod instrumentation of the spine: a systematic review on mechanical, biomechanical, numerical and clinical studies.

PURPOSE: Dorsal screw-rod instrumentations are used for a variety of spinal disorders. Cross-links (CL) can be added to such constructs, however, no clear recommendations exist. This study aims to provide an overview of the available evidence on the effectiveness of CL, potentially allowing to formulate recommendations on their use. METHODS: A systematic literature review was performed on PubMed and 37 original articles were included and grouped into mechanical, biomechanical, finite element and clinical studies. The change in range of motion (ROM) was analyzed in mechanical and biomechanical studies, ROM, stiffness and stress distribution were evaluated in finite element studies and clinical outcome parameters were analyzed in clinical studies. RESULTS: A relative consistent reduction in ROM in axial rotation with CL-augmentation was reported, while minor and less consistent effects were observed in flexion-extension and lateral bending. The use of CLs was clinical beneficial in C1/2 fusion, while the limited clinical studies on other anatomic regions show no significant benefit for CL-augmentation. CONCLUSION: While CL provides some additional axial rotation stability in most situations, lateral bending and flexion-extension are less affected. Based on clinical data, CL-augmentation can only be recommended for C1/2 instrumentations, while for other cases, further clinical studies are needed to allow for evidence-based recommendations.

Biomechanical performance of bicortical versus pericortical bone trajectory (CBT) pedicle screws.

PURPOSE: The cortical bone trajectory (CBT) is an alternative to the traditional pedicle screw trajectory (TT) in posterior spinal instrumentation, enhancing screw contact with cortical bone and therefore increasing fixation strength. Additional to the trajectory, insertion depth (pericortical vs. bicortical placement) could be a relevant factor affecting the fixation strength. However, the potential biomechanical benefit of a bicortical placement of CBT screws is unknown. Therefore, the aim of this study was to quantify the fixation strength of pericortical- versus bicortical-CBT (pCBT versus bCBT) screws in a randomized cadaveric study. METHODS: Pedicle screws were either placed pericortical or bicortical with a CBT in 20 lumbar vertebrae (2 × 20 instrumented pedicles) from four human spine cadavers by using patient-specific templates. Instrumented specimens underwent physiological cyclic loading testing (1'800'000 cycles, 10 Hz), including shear and tension loads as well as bending moments. Translational and angular displacements of the screws were quantified and compared between the two techniques. RESULTS: There was a slight decrease in translational (0.2 mm ± 0.09 vs. 0.24 mm ± 0.11) and angular displacements (0.06° ± 0.05 vs. 0.13° ± 0.11) of bCBT screws when compared with pCBT screws after 1'800'000 cycles. However, the results were non-significant (p > 0.05). CONCLUSION: The authors do not recommend placing CBT screws bicortically, as no relevant biomechanical advantage is gained while the potential risk for iatrogenic injury to structures anterior to the spine is increased.

Biomaterial surface energy-driven ligand assembly strongly regulates stem cell mechanosensitivity and fate on very soft substrates.

Although mechanisms of cell-material interaction and cellular mechanotransduction are increasingly understood, the mechanical insensitivity of mesenchymal cells to certain soft amorphous biomaterial substrates has remained largely unexplained. We reveal that surface energy-driven supramolecular ligand assembly can regulate mesenchymal stem cell (MSC) sensing of substrate mechanical compliance and subsequent cell fate. Human MSCs were cultured on collagen-coated hydrophobic polydimethylsiloxane (PDMS) and hydrophilic polyethylene-oxide-PDMS (PEO-PDMS) of a range of stiffnesses. Although cell contractility was similarly diminished on soft substrates of both types, cell spreading and osteogenic differentiation occurred only on soft PDMS and not hydrophilic PEO-PDMS (elastic modulus <1 kPa). Substrate surface energy yields distinct ligand topologies with accordingly distinct profiles of recruited transmembrane cell receptors and related focal adhesion signaling. These differences did not differentially regulate Rho-associated kinase activity, but nonetheless regulated both cell spreading and downstream differentiation.

Three-Dimensional Mapping of Shear Wave Velocity in Human Tendon: A Proof of Concept Study.

Ultrasound-based shear wave elastography (SWE) provides the means to quantify tissue mechanical properties in vivo and has proven valuable in detecting degenerative processes in tendons. Its current mode of use is for two-dimensional rendering measurements, which are highly position-dependent. We therefore propose an approach to create a volumetric reconstruction of the mechano-acoustic properties of a structure of interest based on optically tracking the ultrasound probe during free-hand measurement sweeps. In the current work, we aimed (1) to assess the technical feasibility of the three-dimensional mapping of unidirectional shear wave velocity (SWV), (2) to evaluate the possible artefacts associated with hand-held image acquisition, (3) to investigate the reproducibility of the proposed technique, and (4) to study the potential of this method in detecting local adaptations in a longitudinal study setting. Operative and technical feasibility as well as potential artefacts associated with hand-held image acquisition were studied on a synthetic phantom containing discrete targets of known mechanical properties. Measurement reproducibility was assessed based on inter-day and inter-reader scans of the patellar, Achilles, and supraspinatus tendon of ten healthy volunteers and was compared to traditional two-dimensional image acquisition. The potential of this method in detecting local adaptations was studied by testing the effect of short-term voluntary isometric loading history on SWV along the tendon long axis. The suggested approach was technically feasible and reproducible, with a moderate to very good reliability and a standard error of measurement in the range of 0.300-0.591 m/s for the three assessed tendons at the two test-retest modalities. We found a consistent variation in SWV along the longitudinal axis of each tendon, and isometric loading resulted in regional increases in SWV in the patellar and Achilles tendons. The proposed method outperforms traditional two-dimensional measurement with regards to reproducibility and may prove valuable in the objective assessment of pathological tendon changes.

Tendon explant models for physiologically relevant invitro study of tissue biology - a perspective.

Background: Tendon disorders increasingly afflict our aging society but we lack the scientific understanding to clinically address them. Clinically relevant models of tendon disease are urgently needed as established small animal models of tendinopathy fail to capture essential aspects of the disease. Two-dimensional and three-dimensional cell and tissue culture models are similarly limited, lacking many physiological extracellular matrix cues required to maintain tissue homeostasis or guide matrix remodeling. These cues reflect the biochemical and biomechanical status of the tissue, and encode information regarding the mechanical and metabolic competence of the tissue. Tendon explants overcome some of these limitations and have thus emerged as a valuable tool for the discovery and study of mechanisms associated with tendon homeostasis and pathophysiology. Tendon explants retain native cell-cell and cell-matrix connections, while allowing highly reproducible experimental control over extrinsic factors like mechanical loading and nutritional availability. In this sense tendon explant models can deliver insights that are otherwise impossible to obtain from in vivo animal or in vitro cell culture models. Purpose: In this review, we aimed to provide an overview of tissue explant models used in tendon research, with a specific focus on the value of explant culture systems for the controlled study of the tendon core tissue. We discuss their advantages, limitations and potential future utility. We include suggestions and technical recommendations for the successful use of tendon explant cultures and conclude with an outlook on how explant models may be leveraged with state-of-the-art biotechnologies to propel our understanding of tendon physiology and pathology.

Notch-inducing hydrogels reveal a perivascular switch of mesenchymal stem cell fate.

The fate of mesenchymal stem cells (MSCs) in the perivascular niche, as well as factors controlling their fate, is poorly understood. Here, we study MSCs in the perivascular microenvironment of endothelial capillaries by modifying a synthetic 3D biomimetic poly(ethylene glycol) (PEG)-hydrogel system in vitro We show that MSCs together with endothelial cells form micro-capillary networks specifically in soft PEG hydrogels. Transcriptome analysis of human MSCs isolated from engineered capillaries shows a prominent switch in extracellular matrix (ECM) production. We demonstrate that the ECM phenotypic switch of MSCs can be recapitulated in the absence of endothelial cells by functionalizing PEG hydrogels with the Notch-activator Jagged1. Moreover, transient culture of MSCs in Notch-inducing microenvironments reveals the reversibility of this ECM switch. These findings provide insight into the perivascular commitment of MSCs by use of engineered niche-mimicking synthetic hydrogels.

Dynamic knee valgus in competitive alpine skiers: Observation from youth to elite and influence of biological maturation.

Numerous studies investigated the association between dynamic knee valgus and injury risk in post-pubertal and elite athletes; however, normative reference scores for competitive alpine skiers and observations on the development process throughout and beyond athletes' growth spurt are lacking. Thus, the aim of this study was to describe the dynamic knee valgus of competitive alpine skiers during drop jump landings (DJ) and single-leg squats (SLS) with respect to sex, sportive level, and biological maturation. Thirty-seven elite and 104 youth competitive alpine skiers around the growth spurt (U15) were examined for their maximal medial knee displacement (MKD) during DJ and SLS by a marker-based 3D motion analysis evaluating dynamic knee valgus. Additionally, skiers' age, anthropometry and biological maturation were assessed. MKD of youth and elite alpine skiers during DJ was comparable and did not improve with increasing training age. Female U15 skiers (on average further matured) had significantly larger MKD values during DJ than male U15 skiers (less matured) (P < .01). Moreover, MKD during DJ was directly associated with the athlete's individual biological maturation status. MKD values obtained from DJ significantly differed from those obtained during SLS (P < .01). The gender-specific difference in MKD values during DJ and their relationship with maturity offset highlight the fundamental changes to the neuromuscular control system during the growth spurt. Thus, biological maturation needs to be considered as a confounding factor for knee valgus screening. Caution is required when evaluating MKD by using high- and low-dynamic tasks, as corresponding information can differ.

Osteosarcoma-Derived Extracellular Vesicles Induce Lung Fibroblast Reprogramming.

Tumor-secreted extracellular vesicles (EVs) have been identified as mediators of cancer-host intercellular communication and shown to support pre-metastatic niche formation by modulating stromal cells at future metastatic sites. While osteosarcoma, the most common primary malignant bone tumor in children and adolescents, has a high propensity for pulmonary metastases, the interaction of osteosarcoma cells with resident lung cells remains poorly understood. Here, we deliver foundational in vitro evidence that osteosarcoma cell-derived EVs drive myofibroblast/cancer-associated fibroblast differentiation. Human lung fibroblasts displayed increased invasive competence, in addition to increased α-smooth muscle actin expression and fibronectin production upon EV treatment. Furthermore, we demonstrate, through the use of transforming growth factor beta receptor 1 (TGFBR1) inhibitors and CRISPR-Cas9-mediated knockouts, that TGFß1 present in osteosarcoma cell-derived EVs is responsible for lung fibroblast differentiation. Overall, our study highlights osteosarcoma-derived EVs as novel regulators of lung fibroblast activation and provides mechanistic insight into how osteosarcoma cells can modulate distant cells to potentially support metastatic progression.

Fascin-1 enhances experimental osteosarcoma tumor formation and metastasis and is related to poor patient outcome.

BACKGROUND: Fascin-1, a prominent actin-bundling protein, is found to be upregulated in several human carcinomas. While it is accepted that Fascin-1 expression correlates with poor clinical outcome and decreased survival in various carcinomas, its role in sarcoma such as osteosarcoma (OS) remains unknown. In the present study, we evaluated the prognostic value and biological relevance of Fascin-1 in OS. METHODS: The correlation between Fascin-1 expression and the outcome of OS patients was determined by immunohistochemistry analysis of Fascin-1 expression in a tissue microarray of OS tissue specimens collected during primary tumor resection. To examine the effect of Fascin-1, shRNA and overexpression technology to alter Fascin-1 levels in OS cells were used in cellular assays as well as in intratibial xenograft OS models in SCID mice. RESULTS: Kaplan-Meier survival analysis of Fascin-1 expression in OS tumor specimens revealed a direct relationship between Fascin-1 expression and poor patient survival. Furthermore, overexpression of Fascin-1 in OS cells significantly increased their migratory capacity as well as the activity of the matrix metalloprotease MMP-9, known to be critical for the execution of metastasis. Finally, using relevant xenograft mouse models, orthotopic intratibial transplantation of two different OS cell lines overexpressing Fascin-1 promoted tumor growth and lung metastasis. CONCLUSIONS: Collectively, our findings demonstrate for the first time that Fascin-1 has considerable potential as a novel prognostic biomarker in OS, and suggest that targeting of Fascin-1 might be a new anti-metastatic strategy in OS patient treatment.

Ultrasound-Mediated Gene Delivery Enhances Tendon Allograft Integration in Mini-Pig Ligament Reconstruction.

Ligament injuries occur frequently, substantially hindering routine daily activities and sports participation in patients. Surgical reconstruction using autogenous or allogeneic tissues is the gold standard treatment for ligament injuries. Although surgeons routinely perform ligament reconstructions, the integrity of these reconstructions largely depends on adequate biological healing of the interface between the ligament graft and the bone. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would lead to significantly improved ligament graft integration. To test this hypothesis, an anterior cruciate ligament reconstruction procedure was performed in Yucatan mini-pigs. A collagen scaffold was implanted in the reconstruction sites to facilitate recruitment of endogenous mesenchymal stem cells. Ultrasound-mediated reporter gene delivery successfully transfected 40% of cells recruited to the reconstruction sites. When BMP-6 encoding DNA was delivered, BMP-6 expression in the reconstruction sites was significantly enhanced. Micro-computed tomography and biomechanical analyses showed that ultrasound-mediated BMP-6 gene delivery led to significantly enhanced osteointegration in all animals 8 weeks after surgery. Collectively, these findings demonstrate that ultrasound-mediated gene delivery to endogenous mesenchymal progenitor cells can effectively improve ligament reconstruction in large animals, thereby addressing a major unmet orthopedic need and offering new possibilities for translation to the clinical setting.

Biomechanical comparison of two biplanar and one monoplanar reconstruction techniques of the acromioclavicular joint.

INTRODUCTION: The purpose of this proof-of-concept study was to investigate the biomechanical performance of two surgical techniques, namely (1) the double Tight-Rope fixation with an additional acromioclavicular FiberTape fixation (DTRC) and (2) the fixation of the clavicle to the acromion and coracoid in a bipodal manner (Bipod) using a Poly-Tape and FiberTape. Both techniques intend to address vertical and horizontal instability after acromioclavicular dislocation. They were compared with the commonly used (3) double Tight-Rope (DTR) technique, which only stabilizes the clavicle to the coracoid. MATERIALS AND METHODS: The acromioclavicular joint (ACJ) of 18 composite Sawbone shoulder specimens (6 per reconstruction group) were tested for posterosuperior elongation (70N cyclical load, 1500 cycles), load-to-failure and stiffness. RESULTS: After 1500 cycles, the DTRC, Bipod and DTR group showed an elongation of 0.45 mm (SD 0.14 mm), 1.19 mm (SD 0.54 mm), and 0.46 mm (SD 0.15 mm), respectively. Although the elongation of the Bipod group was increased when compared to the other two groups (Bipod versus DTRC p = 0.008; Bipod versus DTR p = 0.006), the difference was less than 0.7 mm. The DTRC showed a higher load-to-failure of 656.1N (SD 58.1 N) compared to the Bipod [531.1 N (SD 108.2N) (p = 0.039)] and DTR group [522.8 N (SD 32.8 N) (p = 0.033)]. CONCLUSION: The DTRC and the DTR group resulted in similar low elongation, while the elongation in the Bipod technique was slightly higher. Even though this difference of 0.7 mm shows statistical significance, it most likely has no clinical relevance. When testing in posterosuperior direction, which is the clinically relevant load vector, an additional fixation of the clavicle to the acromion did not reduce elongation in this study. It is, furthermore, questionable if the benefit of an increased load-to-failure in combination with no improvement in elongation and stiffness as seen in the DTRC group outweighs the possible risks and increased costs coming with the DTRC refixation.

Can Genipin-coated Sutures Deliver a Collagen Crosslinking Agent to Improve Suture Pullout in Degenerated Tendon? An Ex Vivo Animal Study.

BACKGROUND: The suture-tendon interface is often the weakest link in tendon-to-tendon or tendon-to-bone repair. Genipin is an exogenous collagen crosslink agent derived from the gardenia fruit that can enhance suture force to failure of the tendon-suture interface. Viable methods for intraoperative clinical delivery of genipin could be of clinical utility, but to our knowledge have not yet been extensively studied. QUESTIONS/PURPOSES: The purposes of this study were (1) to evaluate whether sutures precoated with genipin can augment the suture-tendon interface to improve force to failure, stiffness, and work to failure in healthy and degenerated tendons; and (2) to determine the effect of genipin on the extent and distribution of crosslinking. METHODS: Single-stitch suture pullout tests were performed ex vivo on 25 bovine superficial digital flexor tendons. To assess effects on native tissue, one group of 12 tendons was cut in proximal and distal halves and randomized to treatment (n = 12) and control groups (n = 12) in a matched-pair design. One simple stitch with a loop with either a normal suture or genipin-coated suture was applied to tendons in both groups. To simulate a degenerative tendon condition, a second group of 13 tendons was cut in proximal and distal halves, injected with 0.2 mL of collagenase D (8 mg/mL) and incubated for 24 hours before suturing with either a genipin-coated suture (n = 13) or their matched controls (n = 13). Sutures from all groups then were loaded to failure on a universal materials testing machine 24 hours after suturing. Suture pullout force, stiffness, and work to failure were calculated from force-displacement data and compared between the groups. Additionally, fluorescence was measured to determine the degree of crosslinking quantitatively and a qualitative analysis of the distribution pattern was performed by microscopy. RESULTS: In healthy tendon pairs, the median maximum pullout force was greater with genipin-coated sutures than with control sutures (median, 42 N [range, 24-73 N] versus 29 N [range, 13-48 N]; difference of medians, 13 N; p = 0.003) with corresponding increases in the required work to failure (median, 275 mJ [range, 48-369 mJ] versus 148 mJ [range, 83-369 mJ]; difference of medians, 127 mJ; p = 0.025) but not stiffness (median, 4.1 N/mm [range, 2.3-8.1 N/mm] versus 3.3 N/mm [range, 1.1-9.6 N/mm]; difference of medians, 0.8 N/mm; p = 0.052). In degenerated tendons, median maximum pullout force was greater with genipin-coated sutures than with control sutures (median, 16 N [range, 9-36 N] versus 13 N [range, 5-28 N]; difference of medians, 3 N; p = 0.034) with no differences in work to failure (median, 75 mJ [range, 11-249 mJ] versus 53 mJ [range, 14-143 mJ]; difference of medians, 22 mJ; p = 0.636) or stiffness (median, 1.9 N/mm [range, 0.7-13.4 N/mm] versus 1.6 N/mm [range, 0.5-5.6 N/mm]; difference of medians, 0.3 N/mm; p = 0.285). Fluorescence was higher in tendons treated with genipin-coated sutures compared with the control group, whereas higher fluorescence was observed in the treated healthy compared with the degenerated tendons (difference of means -3.16; standard error 1.08; 95% confidence interval [CI], 0.97-5.34; p = 0.006/healthy genipin: mean 13.04; standard error 0.78; 95% CI, 11.47-14.62; p < 0.001/degenerated genipin: mean 9.88; SD 0.75; 95% CI, 8.34-11.40; p < 0.001). CONCLUSIONS: Genipin-coated sutures improved force to failure of a simple stitch at the tendon-suture interface in healthy and degenerated tendons in an ex vivo animal model. Fluorescence was higher in tendons treated with genipin-coated sutures compared with the control group. CLINICAL RELEVANCE: A genipin-coated suture represents a potential delivery vehicle for exogenous crosslink agents to augment suture retention properties. In vivo animal studies are the next logical step to assess safety and efficacy of the approach.

Open Meniscus Repair In Full And Partial Horizontal Meniscal Lesions : A Biomechanical Cadaver Study.

Horizontal meniscal tears are often treated by partial meniscectomy. Some clinical studies have shown successful repair. The purpose of this study was to show that axial loading causes less horizontal displacement in partial than in total horizontal lesions and that suture of those lesions prevents horizontal displacement. Forty menisci were tested : sutured partial horizontal lesions (ten), sutured total horizontal lesions (ten) and matched unsutured control groups (ten each). Samples were put in a custom made fixation device. 1000 cycles with axial loading, simulating partial weight-bearing of 15kg, were applied. Displacement was measured and construct stiffness was calculated. No suture failure or pullout occurred. Horizontal displacement was insignificantly lower in partial then in full lesions as well as in sutured samples than in the control groups. Horizontal displacement is low in both sutured and unsutured menisci in our test setting. Further studies with higher loads are required.

How High Glucose Levels Affect Tendon Homeostasis.

Among the many factors playing a role in tendon disease, unregulated biochemical reactions between glucose and the collagen extracellular matrix are coming increasingly into focus. We have shown that formation of advanced glycation end-products that cross-link the collagen extracellular matrix can drastically affect cellular level mechanical properties of the matrix, and in turn affect cell-level biomechanical stimuli during physiological loading of the tissue. We suggest that these may adversely affect tendon cell response to matrix damage, as well as the quality of the consequent repair. If such mechanical feedback loops are altered, the ability of tendon cells to maintain tissue in a functional, healthy state may be compromised. Although key foundational elements of biochemical, biomechanical, and biological understanding are now in place, the full extent of how these aspects interact, including the precise mechanisms by which advanced glycation end-products pathologically disrupt connective tissue homeostasis and damage repair, are only beginning to be adequately appreciated.

Tendon Collagen Crosslinking Offers Potential to Improve Suture Pullout in Rotator Cuff Repair: An Ex Vivo Sheep Study.

BACKGROUND: The suture-tendon interface is often the weakest link in tendon to bone repair of massive rotator cuff tears. Genipin is a low-toxicity collagen crosslinker derived from the gardenia fruit that has been shown to augment collagen tissue strength and mechanically arrest tendon-tear progression. QUESTION/PURPOSE: The purpose of the current study was to evaluate whether genipin crosslinking can sufficiently augment the suture-tendon interface to improve suture pullout strength using simple single-loop sutures and the modified Mason-Allen technique. The study also aimed to assess whether time of genipin treatment is a relevant factor in efficacy. METHODS: In an ex vivo (cadaveric) sheep rotator cuff tendon model, a total of 142 suture pullout tests were performed on 32 infraspinatus tendons. Each tendon was prepared with three single-loop stitches. Two groups were pretreated by incubation in genipin solution for either 4 hours or 24 hours. Two corresponding control groups were incubated in phosphate buffered saline for the same periods. The same test protocol was applied to tendons using modified Mason-Allen technique stitch patterns. Each suture was loaded to failure on a universal materials testing machine. Suture pullout force, stiffness, and work to failure were calculated from force-displacement data, and then compared among the groups. RESULTS: Median single-loop pullout force on tendons incubated for 24 hours in genipin yielded an approximately 30% increase in maximum pullout force for single-loop stitches with a median of 73 N (range, 56-114 N) compared with 56 N (range, 40-69 N; difference of medians = 17 N; p = 0.028), with corresponding increases in the required work to failure but not stiffness. Genipin treatment for 4 hours showed no added benefit for suture-pullout behavior (46 N, [range, 35-95 N] versus 45 N, [range, 28-63 N]; difference of medians, 1 N; p = 1). No tested genipin crosslinking conditions indicated benefit for tendons grasped using the modified Mason-Allen technique after 4 hours (162 N, [range, 143-193 N] versus 140 N, [range, 129-151 N]; difference of medians, 22 N; p = 0.114) or after 24 hours of crosslinking (172 N, [range, 42-183 N] versus 164 N [range, 151-180 N]; difference of medians, 8 N; p = 0.886). CONCLUSION: Exogenous collagen crosslinking in genipin can markedly improve resistance to pullout at the tendon-suture interface for simple stitch patterns while the modified Mason-Allen stitch showed no benefit in an ex vivo animal model. CLINICAL RELEVANCE: Tendon strength augmentation by genipin pretreatment offers the potential to improve suture retention properties. Future studies are warranted for the development of clinically viable intraoperative delivery strategies and in vivo testing for safety and efficacy.

Comparison of shear wave velocity measurements assessed with two different ultrasound systems in an ex-vivo tendon strain phantom.

OBJECTIVE: The purpose of this study is to compare the reliability of SW velocity measurements of two different ultrasound systems and their correlation with the tangent traction modulus in a non-static tendon strain model. MATERIALS AND METHODS: A bovine tendon was fixed in a custom-made stretching device. Force was applied increasing from 0 up to 18 Newton. During each strain state the tangent traction modulus was determined by the stretcher device, and SW velocity (m/s) measurements using a Siemens S3000 and a Supersonic Aixplorer US machine were done for shear modulus (kPa) calculation. RESULTS: A strong significant positive correlation was found between SW velocity assessed by the two ultrasound systems and the tangent traction modulus (r = 0.827-0.954, p < 0.001), yet all SW velocity-based calculations underestimated the reference tissue tangent modulus. Mean difference of SW velocities with the S3000 was 0.44 ± 0.3 m/s (p = 0.002) and with the Aixplorer 0.25 ± 0.3 m/s (p = 0.034). Mean difference of SW velocity between the two US-systems was 0.37 ± 0.3 m/s (p = 0.012). CONCLUSION: In conclusion, SW velocities are highly dependent on mechanical forces in the tendon tissue, but for controlled mechanical loads appear to yield reproducible and comparable measurements using different US systems.