Cell-based tissue engineered flexor tendon allograft: A canine in vivo study.

This study aimed to compare the clinically established autologous extrasynovial tendon graft to a newly developed tissue-engineered allograft (Eng-allograft) in terms of functional outcomes following flexor tendon reconstruction in a canine model. The second and fifth flexor digitorum profundus (FDP) tendons from 16 dogs were transected and repaired in Zone II. After 6 weeks of cage activity, the repaired tendons were intentionally ruptured, creating a clinically relevant model for reconstruction. The re-ruptured FDP tendons were then reconstructed using either the clinically standard autologous extrasynovial tendon graft or the Eng-allograft, which had been revitalized with autologous bone marrow-derived mesenchymal stem cells (BMSCs) and synovialized using carbodiimide derivatized synovial fluid (cd-SYN). Following 12 weeks of postoperative rehabilitation, the functional outcomes of the surgical digits were evaluated. The Eng-allograft group exhibited improved digital function, including lower digit work of flexion and reduced adhesion status, while maintaining similar tendon gliding resistance compared to the autograft group. However, the failure load of both the distal and proximal host/graft conjunctions in the Eng-allograft group was significantly lower than that of the autograft group with higher graft rupture at the host-graft junction. In conclusion, the decellularized allogenic intrasynovial tendon, when revitalized BMSCs and synovialized with cd-SYN, demonstrates positive effects on digital function improvement and adhesion reduction. However, the healing at both proximal and distal graft/host junctions is far lower than the autograft. Further research is needed to enhance the healing capacity of allograft conjunctions, aiming to achieve a comparable level of healing seen with autografts.

Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon.

Background: Prevention of adhesion formation following flexor tendon repair is essential for restoration of normal finger function. Although many medications have been studied in the experimental setting to prevent adhesions, clinical application is limited due to the complexity of application and delivery in clinical translation. Methods: In this study, optimal dosages of gelatin and pentamidine were validated by gelatin concentration test. Following cell viability, cell migration, live and dead cell, and cell adhesion assay of the Turkey tenocytes, a model of Turkey tendon repair was established to evaluate the effectiveness of the Pentamidine-Gelatin sheet. Results: Pentamidine carried with gelatin, a Food and drug administration (FDA) approved material for drug delivery, showed good dynamic release, biocompatibility, and degradation. The optimal dose of pentamidine (25ug) was determined in the in vivo study using tenocyte viability, migration, and cell adhesion assays. Further biochemical analyses demonstrated that this positive effect may be due to pentamidine downregulating the Wnt signaling pathway without affecting collagen expression. Conclusions: We tested a FDA-approved antibiotic, pentamidine, for reducing adhesion formation after flexor tendon repair in both in vitro and in vivo using a novel turkey animal model. Compared with the non-pentamidine treatment group, pentamidine treated turkeys had significantly reduced adhesions and improved digit function after six weeks of tendon healing. The translational potential of this article: This study for the first time showed that a common clinical drug, pentamidine, has a potential for clinical application to reduce tendon adhesions and improve tendon gliding function without interfering with tendon healing.

Flexible self-supporting inorganic nanofiber membrane-reinforced solid-state electrolyte for dendrite-free lithium metal batteries.

Compounding of suitable fillers with PEO-based polymers is the key to forming high-performance electrolytes with robust network structures and homogeneous Li+-transport channels. In this work, we innovatively and efficiently prepared Al2O3 nanofibers and deposited an aqueous dispersion of Al2O3 into a membrane via vacuum filtration to construct a nanofiber membrane with a three-dimensional (3D) network structure as the backbone of a PEO-based solid-state electrolyte. The supporting effect of the nanofiber network structure improved the mechanical properties of the reinforced composite solid-state electrolyte and its ability to inhibit the growth of Li dendrites. Meanwhile, interconnected nanofibers in the PEO-based electrolyte and the strong Lewis acid-base interactions between the chemical groups on the surface of the inorganic filler and the ionic species in the PEO matrix provided facilitated pathways for Li+ transport and regulated the uniform deposition of Li+. Moreover, the interaction between Al2O3 and lithium salts as well as the PEO polymer increased free Li+ concentration and maintained its stable electrochemical properties. Hence, assembled Li/Li symmetric cells achieved a cycle life of more than 2000 h. LFP/Li and NMC811/Li cells provided high discharge specific capacities of up to 146.9 mA h g-1 (0.5C and 50 °C) and 166.9 mA h g-1 (0.25C and 50 °C), respectively. The prepared flexible self-supporting 3D nanofiber network structure construction can provide a simple and efficient new strategy for the exploitation of high-performance solid-state electrolytes.

Relationship Between the Changes of Tendon Elastic Moduli With Ultrasound Shear Wave Elastography and Mechanical Compression Test.

OBJECTIVE: The purpose of this study was to investigate the consistency of the changes in the elastic modulus measured with ultrasound shear wave elastography (SWE) with changes measured through mechanical testing using tendons that were artificially altered by chemical modifications. METHODS: Thirty-six canine flexor digitorum profundus tendons were used for this experiment. To mimic tendon mechanical property changes induced by tendinopathy conditions, tendons were treated with collagenase to soften the tissue by collagen digestion or with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) to stiffen the tissues through chemical crosslinking. Tendons were randomly assigned to one of three groups: immersion in phosphate-buffered saline (PBS) as a control group (n = 12), collagenase treatment (n = 12) or EDC treatment (n = 12). Immediately following SWE measurement of each tendon, mechanical compression testing was performed as a gold standard to validate the SWE measurement. Both tests were conducted before and after treatment. RESULTS: The compressive modulus and SWE shear modulus significantly decreased after collagenase treatment. Conversely, both moduli significantly increased after EDC treatment. There was no significant difference in either modulus before or after PBS treatment. As a result of a regression analysis with the percentage change of the compressive modulus as the dependent variable and SWE shear modulus as the independent variable, the best-fit regression was found to be an exponential function and the coefficient of determination was 0.687. CONCLUSION: The changes in the compressive moduli and SWE shear moduli in tendons induced by chemical treatments were correlated by approximately 70%.

In Vivo Ultrasound Shear Wave Elastography Assessment of Acute Compartment Syndrome in a Turkey Model.

OBJECTIVE: The aim of the work described here was to evaluate the objectivity and reproducibility of non-invasive intra-compartment pressure (ICP) measurement using ultrasound shear wave elastography (SWE) in a turkey model in vivo and to determine the biological and histologic changes in acute compartment syndrome (ACS). METHODS: Twenty-four turkeys were randomly divided into four groups based on the duration and fasciotomy of ACS created by infusion of up to 50 mm Hg in the tibialis muscle: group 1, ACS 2 h; group 2, ACS 4 h; group 3, ACS 2 h + fasciotomy 2 h; group 4, ACS 4 h + fasciotomy 2 h. For each turkey, the contralateral limb was considered the control. Time-synchronized measures of SWE and ICP from each leg were collected. Then turkeys were euthanized for histology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) examination. RESULTS: All models created reproducible increases in ICP and SWE, which had a strong linear relationship (r = 0.802, p < 0.0001) during phase 1. SWE remained stable (50.86 ± 9.64 kPa) when ICP remained at 50.28 ± 2.17 mm Hg in phase 2. After fasciotomy, SWE declined stepwise and then normalized (r = 0.737, p < 0.0001). Histologically, the myofiber diameter of group 2 (82.31 ± 22.92 µm) and group 4 (90.90 ± 20.48 µm) decreased significantly (p < 0.01) compared with that of the control group (103.1 ± 20.39 µm); the interstitial space of all groups increased significantly (p < 0.01). Multifocal muscle damage revealed neutrophilic infiltration, degeneration, hemorrhage and necrosis, especially in group 4. Quantitative RT-PCR verified that interleukin-6 and heparin-binding EGF-like growth factor were significantly increased in group 4. CONCLUSION: SWE provided sensitive measurements correlating to ICP in a clinically relevant ACS animal model. Once ACS time was exceeded, progression to irreversible necrosis continued spontaneously, even after fasciotomy. SWE may help surgeons in the early detection, monitoring, prognosis and decision making on fasciotomy for ACS.

Anterolateral Acromioplasty Reduces Gliding Resistance Between the Supraspinatus Tendon and the Coracoacromial Arch in a Cadaveric Model.

Purpose: To investigate the gliding resistance dynamics between the supraspinatus (SSP) tendon and the coracoacromial arch, both before and after subacromial decompression (anterolateral acromioplasty) and acromion resection (acromionectomy). Methods: Using 4 fresh-frozen cadaveric shoulders, acromion shapes were classified (2 type I and 2 type III according to Bigliani). Subacromial bursa and coracoacromial ligament maintenance replicated physiologic sliding conditions. Gliding resistance was measured during glenohumeral abduction (0° to 60°) in internal rotation (IR) and external rotation (ER). Peak gliding resistance between the SSP tendon and the coracoacromial arch was determined and compared between intact, anterolateral acromioplasty, and acromionectomy. Results: Peak SSP gliding resistance during abduction in an intact shoulder was significantly higher in IR than in ER (4.1 vs 2.1 N, P < .001). The mean peak SSP gliding resistance during 0° to 60° glenohumeral abduction in IR in the intact condition was significantly higher compared with the subacromial decompression condition (4.1 vs 2.8 N, P = .021) and with the acromionectomy condition (4.1 vs 0.9 N, P < .001). During 0° to 60° glenohumeral abduction in ER, mean peak SSP gliding resistance in the intact condition was not significantly different compared with the subacromial decompression condition (2.1 vs 2.0 N, P = .999). The 2 specimens with a hooked (i.e. type III) acromion showed significantly higher mean peak SSP gliding resistance during glenohumeral abduction in IR and ER when compared with the 2 specimens with a flat (i.e. type I) acromion (IR: 5.8 vs 3.0 N, P = .006; ER: 2.8 vs 1.4 N, P = .001). Conclusions: In this cadaveric study, peak gliding resistance between the SSP tendon and the coracoacromial arch during combined abduction and IR was significantly reduced after anterolateral acromioplasty and was significantly higher in specimens with a hooked acromion. Clinical Relevance: The clinical benefit of subacromial decompression remains unclear. This study suggests that anterolateral acromioplasty might reduce supraspinatus gliding resistance in those with a hooked acromion and in the typical "impingement" position.

Gene expression of Postn and FGF7 in canine chordae tendineae and their effects on flexor tenocyte biology.

Chordae tendineae, referred to as heart tendinous cords, act as tendons connecting the papillary muscles to the valves in the heart. Their role is analogous to tendons in the musculoskeletal system. Despite being exposed to millions of cyclic tensile stretches over a human's lifetime, chordae tendineae rarely suffer from overuse injuries. On the other hand, musculoskeletal tendinopathy is very common and remains challenging in clinical treatment. The objective of this study was to investigate the mechanism behind the remarkable durability and resistance to overuse injuries of chordae tendineae, as well as to explore their effects on flexor tenocyte biology. The messenger RNA expression profiles of chordae tendineae were analyzed using RNA sequencing and verified by quantitative reverse transcription polymerase chain reaction  and immunohistochemistry. Interestingly, we found that periostin (Postn) and fibroblast growth factor 7 (FGF7) were expressed at significantly higher levels in chordae tendineae, compared to flexor tendons. We further treated flexor tenocytes in vitro with periostin and FGF7 to examine their effects on the proliferation, migration, apoptosis, and tendon-related gene expression of flexor tenocytes. The results displayed enhanced cell proliferation ability at an early stage and an antiapoptotic effect on tenocytes, while treated with periostin and/or FGF7 proteins. Furthermore, there was a trend of promoted tenocyte migration capability. These findings indicated that Postn and FGF7 may represent novel cytokines to target flexor tendon healing. Clinical significance: The preliminary discovery leads to a novel idea for treating tendinopathy in the musculoskeletal system using specific molecules identified from chordae tendineae.

Paediatric trigger fingers: a 47-year experience.

Paediatric trigger finger is rare compared to adult trigger finger or paediatric trigger thumb, and the aetiology is unclear. Proposed causes include local trauma, anatomical anomalies and systemic conditions. The aim of the present study was to detail the anatomical causes of surgically treated paediatric trigger fingers and provide an operative algorithm based on the anatomical findings. A total of 76 trigger fingers in 38 patients were identified retrospectively at our institution between 1975 and 2022. In total, 41 fingers in 26 patients had anatomical variations. A nodular thickening on the tendon, similar to Notta's nodule in trigger thumbs, was the most common anatomical cause. Abnormal decussation of the flexor digitorum superficialis tendon was the second most common variation. The recurrence rate was significantly lower after resection of one slip of the flexor digitorum superficialis tendon compared to other surgical techniques in these patients. We recommend that surgeons assess for possible anatomical variation during surgery for the trigger finger.Level of evidence: IV.

A Ready-to-Use Purified Exosome Product for Volumetric Muscle Loss and Functional Recovery.

Large skeletal muscle defects owing to trauma or following tumor extirpation can result in substantial functional impairment. Purified exosomes are now available clinically and have been used for wound healing. The objective of this study was to evaluate the regenerative capacity of commercially available exosomes on an animal model of volumetric muscle loss (VML) and its potential translation to human muscle injury. An established VML rat model was used. In the in vitro experiment, rat myoblasts were isolated and cocultured with 5% purified exosome product (PEP) to validate uptake. Myoblast proliferation and migration was evaluated with increasing concentrations of PEP (2.5%, 5%, and 10%) in comparison with control media (F10) and myoblast growth medium (MGM). In the in vivo experiment, a lateral gastrocnemius-VML defect was made in the rat hindlimb. Animals were randomized into four experimental groups; defects were treated with surgery alone, fibrin sealant, fibrin sealant and PEP, or platelet-rich plasma (PRP). The groups were further randomized into four recovery time points (14, 28, 45, or 90 days). The isometric tetanic force (ITF), which was measured as a percentage of force compared with normal limb, was used for functional evaluation. Florescence microscopy confirmed that 5% PEP demonstrated cellular uptake ∼8-12 h. Compared with the control, myoblasts showed faster proliferation with PEP irrespective of concentration. PEP concentrations of 2.5% and 5% promoted myoblast migration faster compared with the control (<0.05). At 90 days postop, both the PEP and fibrin sealant and PRP groups showed greater ITF compared with control and fibrin sealant alone (<0.05). At 45 days postop, PEP with fibrin sealant had greater cellularity compared with control (<0.05). At 90 days postop, both PEP with fibrin sealant and the PRP-treated groups had greater cellularity compared with fibrin sealant and control (<0.05). PEP promoted myoblast proliferation and migration. When delivered to a wound with a fibrin sealant, PEP allowed for muscle regeneration producing greater functional recovery and more cellularity in vivo compared with untreated animals. PEP may promote muscle regeneration in cases of VML; further research is warranted to evaluate PEP for the treatment of clinical muscle defects.

Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how).

Several tendon and ligament animal models were presented at the 2022 Orthopaedic Research Society Tendon Section Conference held at the University of Pennsylvania, May 5 to 7, 2022. A key objective of the breakout sessions at this meeting was to develop guidelines for the field, including for preclinical tendon and ligament animal models. This review summarizes the perspectives of experts for eight surgical small and large animal models of rotator cuff tear, flexor tendon transection, anterior cruciate ligament tear, and Achilles tendon injury using the framework: "Why, Who, What, Where, When, and How" (5W1H). A notable conclusion is that the perfect tendon model does not exist; there is no single gold standard animal model that represents the totality of tendon and ligament disease. Each model has advantages and disadvantages and should be carefully considered in light of the specific research question. There are also circumstances when an animal model is not the best approach. The wide variety of tendon and ligament pathologies necessitates choices between small and large animal models, different anatomic sites, and a range of factors associated with each model during the planning phase. Attendees agreed on some guiding principles including: providing clear justification for the model selected, providing animal model details at publication, encouraging sharing of protocols and expertise, improving training of research personnel, and considering greater collaboration with veterinarians. A clear path for translating from animal models to clinical practice was also considered as a critical next step for accelerating progress in the tendon and ligament field.

Improving Mechanical Properties of Tendon Allograft through Rehydration Strategies: An In Vitro Study.

Allogenic tendons grafts sourced from intrasynovial tendons are often used for tendon reconstruction. Processing is achieved through repetitive freeze-thaw cycles followed by lyophilization. Soaking the lyophilized tendon in saline (0.9%) for 24 h is the standard practice for rehydration. However, data supporting saline rehydration over the use of other hydrating solutions are scant. The purpose of the current study was to compare the effects of different rehydration solutions on biomechanical properties of lyophilized tendon allograft. A total of 36 canine flexor digitorum profundus tendons were collected, five freeze-thaw cycles followed by lyophilization were performed for processing, and then divided into three groups rehydrated with either saline solution (0.9%), phosphate-buffered saline (PBS), or minimum essential medium (MEM). Flexural stiffness, tensile stiffness, and gliding friction were evaluated before and after allograft processing. The flexural moduli in both fibrous and fibrocartilaginous regions of the tendons were measured. After lyophilization and reconstitution, the flexural moduli of both the fibrocartilaginous and non-fibrocartilaginous regions of the tendons increase significantly in the saline and MEM groups (p < 0.05). Compared to the saline and MEM groups, the flexural moduli of the fibrocartilaginous and non-fibrocartilaginous regions of tendons rehydrated with PBS are significantly lower (p < 0.05). Tensile moduli of rehydrated tendons are significantly lower than those of fresh tendons for all groups (p < 0.05). The gliding friction of rehydrated tendons is significantly higher than that of fresh tendons in all groups (p < 0.05). There is no significant difference in either tensile moduli or gliding friction between tendons treated with different rehydration solutions. These results demonstrate that allograft reconstitution can be optimized through careful selection of hydrating solution and that PBS could be a better choice as the impact on flexural properties is lower.

The Effect of Pulling Angle on Rotator Cuff Mechanical Properties in a Canine In Vitro Model.

The objective of this study was to examine the effect of pulling angle on time-zero mechanical properties of intact infraspinatus tendon or infraspinatus tendon repaired with the modified Mason-Allen technique in a canine model in vitro. Thirty-six canine shoulder samples were used. Twenty intact samples were randomly allocated into functional pull (135°) and anatomic pull (70°) groups (n = 10 per group). The remaining sixteen infraspinatus tendons were transected from the insertion and repaired using the modified Mason-Allen technique before being randomly allocated into functional pull or anatomic pull groups (n = 8 per group). Load to failure testing was performed on all specimens. The ultimate failure load and ultimate stress of the functional pulled intact tendons were significantly lower compared with anatomic pulled tendons (1310.2 ± 167.6 N vs. 1687.4 ± 228.2 N, p = 0.0005: 55.6 ± 8.4 MPa vs. 67.1 ± 13.3 MPa, p = 0.0334). For the tendons repaired with the modified Mason-Allen technique, no significant differences were observed in ultimate failure load, ultimate stress or stiffness between functional pull and anatomic pull groups. The variance of pulling angle had a significant influence on the biomechanical properties of the rotator cuff tendon in a canine shoulder model in vitro. Load to failure of the intact infraspinatus tendon was lower at the functional pulling position compared to the anatomic pulling position. This result indicates that uneven load distribution across tendon fibers under functional pull may predispose the tendon to tear. However, this mechanical character is not presented after rotator cuff repair using the modified Mason-Allen technique.

Enhancing Functional Recovery after Segmental Nerve Defect Using Nerve Allograft Treated with Plasma-Derived Exosome.

BACKGROUND: Nerve injuries can result in detrimental functional outcomes. Currently, autologous nerve graft offers the best outcome for segmental peripheral nerve injury. Allografts are alternatives, but do not have comparable results. This study evaluated whether plasma-derived exosome can improve nerve regeneration and functional recovery when combined with decellularized nerve allografts. METHODS: The effect of exosomes on Schwann cell proliferation and migration were evaluated. A rat model of sciatic nerve repair was used to evaluate the effect on nerve regeneration and functional recovery. A fibrin sealant was used as the scaffold for exosome. Eighty-four Lewis rats were divided into autograft, allograft, and allograft with exosome groups. Gene expression of nerve regeneration factors was analyzed on postoperative day 7. At 12 and 16 weeks, rats were subjected to maximum isometric tetanic force and compound muscle action potential. Nerve specimens were then analyzed by means of histology and immunohistochemistry. RESULTS: Exosomes were readily taken up by Schwann cells that resulted in improved Schwann cell viability and migration. The treated allograft group had functional recovery (compound muscle action potential, isometric tetanic force) comparable to that of the autograft group. Similar results were observed in gene expression analysis of nerve regenerating factors. Histologic analysis showed no statistically significant differences between treated allograft and autograft groups in terms of axonal density, fascicular area, and myelin sheath thickness. CONCLUSIONS: Plasma-derived exosome treatment of decellularized nerve allograft may provide comparable clinical outcomes to that of an autograft. This can be a promising strategy in the future as an alternative for segmental peripheral nerve repair. CLINICAL RELEVANCE STATEMENT: Off-the-shelf exosomes may improve recovery in nerve allografts.

Carbodiimide-Derivatized Synovial Fluid for Tendon Graft Coating Improves Long-Term Functional Outcomes of Flexor Tendon Reconstruction.

BACKGROUND: Flexor digitorum profundus (FDP) tendon injury is common in hand trauma, and flexor tendon reconstruction is one of the most challenging procedures in hand surgery because of severe adhesion that exceeds 25% and hinders hand function. The surface properties of a graft from extrasynovial tendons are inferior to those of the native intrasynovial FDP tendons, which has been reported as one of the major causations. Improved surface gliding ability of the extrasynovial graft is needed. Thus, this study used carbodiimide-derivatized synovial fluid and gelatin (cd-SF-gel) to modify the surface of the graft, thus improving functional outcomes using a dog in vivo model. METHODS: Forty FDP tendons from the second and fifth digits of 20 adult women underwent reconstruction with a peroneus longus (PL) autograft after creation of a tendon repair failure model for 6 weeks. Graft tendons were either coated with cd-SF-gel ( n = 20) or not. Animals were euthanized 24 weeks after reconstruction, and digits were collected after the animals were euthanized for biomechanical and histologic analyses. RESULTS: Adhesion score (cd-SF-gel, 3.15 ± 1.53; control, 5 ± 1.26; P < 0.00017), normalized work of flexion (cd-SF-gel, 0.47 ± 0.28 N-mm/degree; control, 1.4 ± 1.45 N-mm/degree; P < 0.014), and distal interphalangeal joint motion (cd-SF-gel, 17.63 ± 6.77 degrees; control, 7.07 ± 12.99 degrees; P < 0.0015) in treated grafts all showed significant differences compared with nontreated grafts. However, there was no significant difference in repair conjunction strength between the two groups. CONCLUSION: Autograft tendon surface modification with cd-SF-gel improves tendon gliding ability, reduces adhesion formation, and enhances digit function without interfering with graft-host healing. CLINICAL RELEVANCE STATEMENT: The authors demonstrate a clinically relevant and translational technology by using the patient's own synovial fluid to "synovialize" an autologous extrasynovial tendon graft to improve functional outcomes following flexor tendon reconstruction.

Purified exosome product enhances chondrocyte survival and regeneration by modulating inflammation and promoting chondrogenesis.

Aim: This study was to detect the effects of purified exosome product (PEP) on C28/I2 cells and chondrocytes derived from osteoarthritis patients. Materials & methods: Cell viability and apoptosis assays were used to detect the effect of PEP on cells. qRT-PCR and cell fluorescence assays were used to investigate the potential mechanism of PEP on cell chondrogenesis. Results: PEP was internalized by cells at a fast rate and enhanced cellular proliferation and migration while attenuating apoptosis. These findings reflect the fact that PEP can increase the expression of PCNA and reduce the expression of CASP3/7/9 and BAX. Conclusion: This study suggests an innovative strategy for chondrogenesis that could be applied to osteoarthritis repair in the future.

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.

Development and validation of a novel model based on hand knob score and white matter injury on MRI to predict hand function in children with cerebral palsy.

Background: Childhood hand function is considered to be one of the strongest predictors of the ability to participate in daily activities as children with cerebral palsy (CP) reach adulthood. The manual ability classification system (MACS) is currently the most widely used for grading hand function in children with CP. However, the MACS method is subjective and may be affected by the raters' experience. Hand knob is an important control center for hand movement. Therefor this study aimed to develop and validate an objective model for hand function estimation in children with CP and visualize it as a nomogram. Methods: A total of 70 Children (2-12 years old) with CP underwent magnetic resonance imaging (MRI) scanning, MACS assessment. According to MACS, children with CP were divided into mild impairment group (grade I-III) and severe impairment group (grade IV-V). Hand function prediction models based on (I) hand knob score, (II) clinical features, and (III) the combination of clinical features and hand knob score were developed and validated separately. The models were subjected to stepwise regression according to the maximum likelihood method, and the Akaike information criterion was used to select the best model. Model discrimination was assessed using receiver operating characteristic (ROC) and calibration curves. The nomogram was finally built according to the best model. Results: The area under the curve (AUC) of the hand knob score model in the training set was 0.752, the clinical features model was 0.819, and the hand knob score and clinical features combined model was 0.880. The AUC of the hand knob score model in the validation set was 0.765, the clinical features model was 0.782, and the combined model was 0.894. The best model was the hand knob score-clinical features combined model, and the nomogram finally incorporated two assessment items: the hand knob score and white matter injury. The estimated probability of hand function injury degree of the combined model displayed good agreement with the actual occurrence probability. Conclusions: The hand knob score-clinical features combined model can be used to preliminarily assess the degree of hand impairment in children with CP, with good calibration.

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.

The Effects of the TSOL Knot on the Repair Strength and Gliding Resistance Following Flexor Tendon Repair.

BACKGROUND: The stability of a suture knot construct has been realized as an important parameter that affects the strength of flexor tendon repairs. A novel 2-strand-overhand-locking (TSOL) knot, which is not commonly used in the clinical setting, recently was reported to increase repair strength and to decrease tendon gliding resistance in a 2-strand repair technique. The purpose of the present study was to investigate the effect of the TSOL knot on tendon repair strength and gliding resistance compared with a typical surgical knot in both 2-strand and 4-strand repair techniques using an in vitro turkey flexor tendon model. METHODS: Sixty flexor digitorum profundus tendons from the long digit of the turkey foot were divided evenly into 4 groups and repaired with the following techniques: (1) a 2-strand modified Pennington repair with a square knot, (2) a 2-strand modified Pennington repair with a TSOL knot, (3) a 4-strand grasping cruciate repair with a square knot, and (4) a 4-strand grasping cruciate repair with a TSOL knot. Repaired tendons were tested for failure mode, gliding resistance, and repair strength at failure. RESULTS: The repair strength and stiffness of the 4-strand repairs were significantly higher than those of the 2-strand repairs, regardless of knot type (p < 0.05). The repair strength at failure of the TSOL knot was significantly greater than that of the square knot in 2-strand repairs (p < 0.05) but not in 4-strand repairs. The gliding resistance of the TSOL knot was significantly decreased compared with that of the square knot in both 2-strand and 4-stand repairs (p < 0.05). With regard to failure mode, the TSOL knot was less likely to fail due to knot unravelling. CONCLUSIONS: In this in vitro biomechanical study involving the use of turkey flexor tendons to compare gliding resistance and repair strength characteristics for knot-inside 2 and 4-strand repairs, the TSOL knot was associated with decreased repaired tendon gliding resistance, regardless of the number of strands used. Although the TSOL knot also increased the repair strength, the difference was only significant when 2-strand repairs were used. The results of our study support the use of the TSOL knot in the clinical setting of flexor tendon repair using 2 or 4-strand, knot-inside methods. CLINICAL RELEVANCE: In surgical repair of flexor tendons, there is substantial interest in maximizing strength while minimizing friction. This study shows the potential utility of the TSOL knot to increase repair strength while decreasing gliding resistance, particularly in 2-strand repairs.

Translational therapy from preclinical animal models for muscle degeneration after rotator cuff injury.

Chronic rotator cuff tears are debilitating diseases which significantly affect patients' quality of life and pose substantial financial burden to the society. The intraoperative reparability of injured tendon and postoperative probability of tendon retear are highly associated with the quality of torn muscles, specifically, the severity of muscle atrophy and fatty infiltration. Animal models that reproduce the characteristic muscle pathology after rotator cuff injury have been developed and used to provide insight into the underlying biology and pathophysiology. In this review, we briefly summarize the current information obtained from preclinical animal studies regarding the degenerative change of cuff muscle subsequent to tendon release and/or suprascapular nerve denervation. Importantly, we focus on the potential translational therapeutic targets or agents for the prevention or reversal of muscle atrophy and fatty infiltration. While further studies are warranted to assess the safety and efficacy of novel therapies derived from these preclinical animal research, we believe that their clinical translation for the treatment of rotator cuff disorders is on the horizon. The Translational potential of this article: Novel therapeutic strategies described in this review from preclinical animal studies hold a great translational potential for preventing or reversing rotator cuff muscle pathology, while further assessments on their safety and efficacy are warranted.