Fluffy hybrid nanoadjuvants for reversing the imbalance of osteoclastic and osteogenic niches in osteoporosis.

Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their low bioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. This calls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybrid structures with bioactive components and stable fluffy topological morphology by cross-linking calcium and phosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequent grafting of -PEG-DAsp8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealed that these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecular mechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that small-dose AL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivo results restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as the consequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant with peculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well as bone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies for other bone diseases.

Decellularization-Based Modification Strategy for Bioactive Xenografts Promoting Tendon Repair.

Xenografts have emerged as a promising option for severe tendon defects treatment. However, despite undergoing decellularization, concerns still remain regarding the immunogenicity of xenografts. Because certain components within the extracellular matrix also possess immunogenicity. In this study, a novel strategy of post-decellularization modification aimed at preserving the endogenous capacity of cells on collagen synthesis to mask antigenic epitopes in extracellular matrix is proposed. To implement this strategy, a human-derived rosiglitazone-loaded decellularized extracellular matrix (R-dECM) is developed. R-dECM can release rosiglitazone for over 7 days in vitro. By suppressing M1 macrophage polarization, R-dECM protects the migration and collagen synthesis abilities of tendon-derived stem cells (TDSCs), while also stabilizing the phenotype of M2 macrophages in vitro. RNA sequencing reveals R-dECM can mitigate the detrimental crosstalk between TDSCs and inflammatory cells. When applied to a rat patellar tendon defect model, R-dECM effectively inhibits early inflammation, preventing chronic inflammation. Its duration of function far exceeds the release time of rosiglitazone, implying the establishment of immune evasion, confirming the effectiveness of the proposed strategy. And R-dECM demonstrates superior tendon repair outcomes compared to dECM. Thus, this study provides a novel bioactive scaffold with the potential to enhance the long-term clinical outcomes of xenogeneic tendon grafts.

Durable Immunomodulatory Nanofiber Niche for the Functional Remodeling of Cardiovascular Tissue.

Functional remodeling and prolonged anti-inflammatory responses are both vital for repairing damage in the cardiovascular system. Although these aspects have each been studied extensively alone, attempts to fabricate scaffolds that combine these effects have seen limited success. In this study, we synthesized salvianic acid A (SA, danshensu) blocked biodegradable polyurethane (PCHU-D) and enclosed it within electrospun nanofibers to synthesize a durable immunomodulatory nanofiber niche (DINN), which provided sustained SA release during inflammation. Given its excellent processability, mechanical properties, and shape memory function, we developed two variants of the DINN as vascular scaffolds and heart patches. Both these variants exhibited outstanding therapeutic effects in in vivo experiments. The DINN was expertly designed such that it gradually decomposes along with SA release, substantially facilitating cellular infiltration and tissue remodeling. Therefore, the DINN effectively inhibited the migration and chemotaxis of inflammatory cells, while also increasing the expression of angiogenic genes. As a result, it promoted the recovery of myocardial function after myocardial infarction and induced rapid reendothelialization following arterial orthotopic transplantation repair. These excellent characteristics indicate that the DINN holds great potential as a multifunctional agent for repairing cardiovascular tissues.

Bi-lineage inducible and immunoregulatory electrospun fibers scaffolds for synchronous regeneration of tendon-to-bone interface.

Facilitating regeneration of the tendon-to-bone interface can reduce the risk of postoperative retear after rotator cuff repair. Unfortunately, undesirable inflammatory responses following injury, difficulties in fibrocartilage regeneration, and bone loss in the surrounding area are major contributors to suboptimal tendon-bone healing. Thus, the development of biomaterials capable of regulating macrophage polarization to a favorable phenotype and promoting the synchronous regeneration of the tendon-to-bone interface is currently a top priority. Here, strontium-doped mesoporous bioglass nanoparticles (Sr-MBG) were synthesized through a modulated sol-gel method and Bi-lineage Inducible and Immunoregulatory Electrospun Fibers Scaffolds (BIIEFS) containing Sr-MBG were fabricated. The BIIEFS were biocompatible, showed sustained release of multiple types of bioactive ions, enhanced osteogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs), and facilitated macrophage polarization towards the M2 phenotype in vitro. The implantation of BIIEFS at the torn rotator cuff resulted in greater numbers of M2 macrophages and the synchronous regeneration of tendon, fibrocartilage, and bone at the tendon-to-bone interface, leading to a significant improvement in the biomechanical strength of the supraspinatus tendon-humerus complexes. Our research offers a feasible strategy to fabricate immunoregulatory and multi-lineage inducible electrospun fibers scaffolds incorporating bioglass nanoparticles for the regeneration of soft-to-hard tissue interfaces.

Increased Expression of Adipokines in Patients With Frozen Shoulder.

BACKGROUND: Adipokines represent a spectrum of bioactive molecules that could modulate fibroblastic and inflammatory processes. The role of adipokines in the pathogenesis of frozen shoulder (FS), a common musculoskeletal disorder characterized by chronic inflammation, remains obscure. PURPOSE: To evaluate whether adipokines contribute to the pathogenic mechanisms of FS and to evaluate any potential correlation of adipokines with patients' symptoms. STUDY DESIGN: Controlled laboratory study. METHODS: Shoulder capsule specimens were obtained from 10 patients with FS and 10 patients with shoulder instability (control group). The specimens were dyed using hematoxylin and eosin and immunohistochemically assessed with antibodies targeting adipokines, collagen I, collagen III, and tumor necrosis factor α. Immunoreactivity was graded from "no" to "strong" in a blinded manner. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) analysis was conducted. Before the surgery, patient-reported frequency of pain, severity of pain, stiffness, and shoulder range of motion were documented. RESULTS: In comparison with the control group, patients with FS had significantly greater pain frequency, pain severity, and stiffness and more limited shoulder range of motion (P < .001). Hematoxylin and eosin- and Masson trichrome-stained samples from the FS group displayed hypercellularity and increased collagen fibers. Immunohistochemistry and RT-qPCR analyses indicated that expression of adipokines was significantly increased in FS capsules compared with the control group. The expression of collagen I, collagen III, and tumor necrosis factor α was also increased in FS capsules. No significant correlation was noted between adipokine expression and patient-reported outcomes in the control group, whereas in patients with FS, adiponectin expression was correlated with pain frequency (r = 0.78; P = .01) and stiffness (r = 0.73; P = .02). Visfatin was also correlated with pain frequency (r = 0.70; P = .02). CONCLUSION/CLINICAL RELEVANCE: This study indicated a potential role for adipokines in the pathogenesis of FS and demonstrated a correlation between adipokine expression and patients' pain and stiffness.

Arthroscopic Dynamic Anterior Stabilization Using Either Long Head of the Biceps or Conjoined Tendon Transfer for Anterior Shoulder Instability Results in a Similarly Low Recurrence Rate.

PURPOSE: To compare the clinical outcomes of arthroscopic dynamic anterior stabilization (DAS) between transferring the long head of the biceps (DAS-LHB) and the conjoined tendon (DAS-CT) for anterior shoulder instability with <15% glenoid bone loss. METHODS: From January 2016 to May 2019, a total of 63 patients who underwent DAS for recurrent anterior shoulder dislocation with <15% glenoid bone loss were included, comprising 33 patients in DAS-LHB group and 30 patients in DAS-CT group. Clinical outcomes were assessed preoperatively and at a minimum 3-year follow-up, including patient-reported outcomes, range of motion, and return to sports (RTS). Postoperative recurrent instability (including dislocation, subluxation, and subjective instability with a positive apprehension test), revisions and complications also were recorded. RESULTS: No significant demographic characteristics difference was detected between the DAS-LHB (26.3 ± 7.9 years) and DAS-CT groups (26.0 ± 6.7 years). At the latest follow-up, there were no significant differences between the 2 groups in functional scores: Oxford Shoulder Instability Score (14.8 ± 2.8 vs 15.2 ± 3.6), Rowe score (95.9 ± 6.5 vs 93.2 ± 10.2), visual analog scale for pain (0.8 ± 1.2 vs 0.7 ± 1.7), and American Shoulder and Elbow Surgeons (95 ± 8.8 vs 95.2 ± 9.1) (all P > .218). No significant difference was detected between groups in the rates of RTS (90.1% vs 86.7%, P = .700) and RTS at previous level (78.7% vs 73.3%, P = .258), respectively. No recurrent dislocation occurred in either group. One patient felt occasional subluxation in the DAS-LHB group, and one was positive for the apprehension test in each group. One patient presented with postoperative shoulder stiffness and underwent a secondary arthroscopic debridement in the DAS-CT group. CONCLUSIONS: Comparable rates of recurrence, complication, return to sports, and subjective shoulder function were observed between DAS-LHB and DAS-CT groups. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic trial.

Intraoperative Ultrasound Guided Robotic Pancreatic Enucleation, Does a Distance of 3mm Still Matters?

Background: A minimal distance of 3 mm to main pancreatic duct (MPD) was generally considered to be necessary for pancreatic enucleation (PE). This study was designed to report the safety and feasibility of PE for tumors located in 3 mm to MPD Under the intraoperative ultrasound (IOUS) guidance.Methods: The data of patients who received IOUS guided robotic PE from January 2018 to May 2019 in the second department of hepato-pancreato-biliary surgery were reviewed in this study. According to the distance to MPD (less than 3 mm or not), patients were divided in 2 groups, and the short-term operative outcomes were compared.Statistics: Students' t-test and Mann-Whitney U test were used for comparing continuous variables, and Chi-squared test was used for comparing categorical variables.Results: And a total of 56 patients were analyzed, and a minimal distance less than 3 mm between the tumor and pancreatic duct measured by IOUS was found in 12 patients. The tumors and MPD were clearly revealed intraoperatively in all the cases. The operative duration was significantly longer in patients with tumors located in 3 mm from MPD (143.25 ± 40.89 min vs 107.14 ± 37.73 min, t = 2.756, P=.014). There was no significant difference between the rate of post-operative pancreatic fistula and other complications in the different groups (χ2 =.924, P=.48).Discussion and conclusion: robotic PE could be safely performed under IOUS guidance for benign or low-grade malignant tumors located less than 3 mm to the MPD.

Rotator cuff tear reaching the superior half portion of the humeral head causes shoulder abduction malfunction.

PURPOSE: To examine the biomechanical properties governing posterosuperior rotator cuff (RC) tear progression and dynamic shoulder abduction function, in the absence of excess loading. METHODS: Twelve freshly frozen cadaveric shoulders were evaluated via an established dynamic shoulder abduction stimulator. The shoulder abduction functions were primarily evaluated using subacromial contact pressure (SACP) during an abduction procedure, and subsequent middle deltoid force (MDF) under 5 conditions: (1) intact, (2) anterior 1/3 posterosuperior rotator cuff (PSRC) tear, (3) anterior 2/3 PSRC tear, (4) entire PSRC tear, and (5) global RC tear (tear involving the entire superior RC). RESULTS: No obvious differences were observed in the peak MDF required for abduction, and in the peak SACP among the four PSRC tear statuses (49.8 ± 9.2 N, 0.39 ± 0.05 mPa [1/3 PSRC tear]; 49.3 ± 6.8 N, 0.40 ± 0.06 mPa [2/3 PSRC tear]; 51.6 ± 7.0 N, 0.44 ± 0.08 mPa [entire PSRC tear]), as well as intact statuses (48.3 ± 9.8 N, 0.40 ± 0.05 mPa). However, significant elevations in the peak MDF and peak SACP levels were observed among the four PSRC tear statuses and global RC tear (68.1 ± 9.3 N; 4.12 ± 1.50 mPa, P < 0.01). CONCLUSION: In the absence of excess loading, the biomechanical function of the shoulder was not impaired by a simple PSRC tear. However, once the tear size reached the half superior portion of the humeral head, the humeral head migrated to the surface of the subacromion, and this action markedly decreased shoulder abduction function.

Clinical and Radiological Outcomes in Patients With Anterior Shoulder Instability and Glenoid Bone Loss after Arthroscopic Free Bone Block Combined With Dynamic Anterior Stabilization.

BACKGROUND: As an alternative to the Latarjet procedure, the arthroscopic free bone block (FBB) procedure combined with dynamic anterior stabilization (DAS) has been recently proposed to provide both glenoid augmentation and a tendon sling effect for treating anterior shoulder instability (ASI) with glenoid bone loss. PURPOSE: To evaluate the clinical and radiological outcomes of FBB-DAS for ASI with glenoid bone loss. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients who underwent arthroscopic FBB-DAS for ASI with >15% glenoid bone loss between February 2017 and March 2020 were screened and enrolled in this study. Clinical outcome measures were assessed preoperatively and at a minimum 2-year follow-up, including recurrence, complications, shoulder functional scores, range of motion, and return to sports. Postoperative computed tomography and magnetic resonance imaging were also performed. RESULTS: Of a total of 65 patients with a mean follow-up of 46.1 ± 13.1 months, no patients experienced a recurrent dislocation or subluxation postoperatively, while 2 had a positive anterior apprehension test (3.1%). Additionally, 2 patients (3.1%) experienced complications of hematoma and shoulder stiffness, respectively. The mean visual analog scale score, American Shoulder and Elbow Surgeons score, Rowe score, and Oxford Shoulder Instability Score all improved significantly from 3.2 ± 2.4, 75.0 ± 18.9, 43.6 ± 27.3, and 33.8 ± 9.0 preoperatively to 1.3 ± 0.8, 95.1 ± 8.0, 95.5 ± 7.8, and 14.8 ± 3.5 at final follow-up, respectively (all P < .001). No difference was detected in range of motion except for 8.1° and 7.5° external rotation limitations in adduction and abduction, respectively. There were 62 patients (95.4%) who returned to sports, and 54 patients (83.1%) returned to the preinjury level. The transferred biceps tendon was intact in all 59 patients who completed radiological examination at the latest follow-up. Good bone healing was achieved in 98.3% of patients, and the glenoid bone defect decreased from 18.1% to 4.9%. Osseous and labral glenoids were significantly enlarged in width and depth on the latest magnetic resonance imaging (all P < .001). CONCLUSION: Arthroscopic FBB-DAS provided satisfactory clinical and radiological outcomes for ASI with glenoid bone loss. Despite slight external rotation restrictions, it achieved low recurrence and complication rates, excellent shoulder functional scores, a high return-to-sports rate, and favorable graft healing and remodeling.

Regulating Macrophages through Immunomodulatory Biomaterials Is a Promising Strategy for Promoting Tendon-Bone Healing.

The tendon-to-bone interface is a special structure connecting the tendon and bone and is crucial for mechanical load transfer between dissimilar tissues. After an injury, fibrous scar tissues replace the native tendon-to-bone interface, creating a weak spot that needs to endure extra loading, significantly decreasing the mechanical properties of the motor system. Macrophages play a critical role in tendon-bone healing and can be divided into various phenotypes, according to their inducing stimuli and function. During the early stages of tendon-bone healing, M1 macrophages are predominant, while during the later stages, M2 macrophages replace the M1 macrophages. The two macrophage phenotypes play a significant, yet distinct, role in tendon-bone healing. Growing evidence shows that regulating the macrophage phenotypes is able to promote tendon-bone healing. This review aims to summarize the impact of different macrophages on tendon-bone healing and the current immunomodulatory biomaterials for regulating macrophages, which are used to promote tendon-bone healing. Although macrophages are a promising target for tendon-bone healing, the challenges and limitations of macrophages in tendon-bone healing research are discussed, along with directions for further research.

Relationship between the progression of posterosuperior rotator cuff tear size and shoulder abduction function: A cadaveric study via dynamic shoulder simulator.

Posterosuperior rotator cuff tear (PSRCT) is one of the most common shoulder disorders in elderly people's daily life; however, the biomechanical relationship between PSRCT and shoulder abduction function is still controversial. In this study, a total of twelve freshly frozen cadaveric shoulders were included and tested in five conditions: intact rotator cuff, 1/3 PSRCT, 2/3 PSRCT, entire PSRCT, and global RCT. In each condition, extra load (0%, 45%, and 90% failure load) was sequentially added to the distal humerus, and the function of the remaining rotator cuff was mainly evaluated via the middle deltoid force (MDF) required for abduction. It is found that the peak MDF is required for abduction did not differ among the three PSRCT conditions (1/3 PSRCT: 29.30 ± 5.03 N, p = 0.96; 2/3 PSRCT: 29.13 ± 9.09 N, p = 0.98; entire PSRCT: 28.85 ± 7.12 N, p = 0.90) and the intact condition (29.18 ± 4.99 N). However, the peak MDF significantly differed between the global RCT (76.27 ± 4.94 N, p < 0.01) and all PSRCT and intact conditions. Under 45% failure load, the MDF of the entire PSRCT and global tear conditions were significantly increased compared with another status. With the 90% failure load, only the 1/3 PSRCT condition maintained the same shoulder function as the intact rotator cuff. These biomechanical testing jointly suggested that the weight-bearing ability of the shoulder significantly decreased as PSRCT progressed.

Animal Models of Rotator Cuff Injury and Repair: A Systematic Review.

There are a large number of animal studies on rotator cuff injury and repair, but a lack of detailed research and evaluation on the animal models. This systematic review aims to provide a framework for animal studies and repair patches for rotator cuff injury. Four hundred nine animal studies were included, of which the most common animal model of rotator cuff injury is rat (53.56%), the most common site of rotator cuff injury is the supraspinatus tendon (62.10%), and the most common injury type (degree) is acute tear (full thickness) (48.41%). The most common research purpose is to evaluate the repair effect of the patch (24.94%), followed by the observation of pathophysiological changes after rotator cuff injury (20.87%). Among the five types of repair patch materials including nondegradable and degradable synthetic materials, autologous and allogeneic tissues, and naturally derived biomaterial, the last one is the mostly used (52.74%). For different animal models, the rodent models (rat and mouse) are the most commonly used and probably the most suitable species for preliminary studies of rotator cuff injury; the rabbit, canine, sheep, and goat models are more suitable for biomechanical performance testing, rehabilitation training, and validation of surgical methods; and the nonhuman primate models (monkey and baboon) are the closest to human, but it is more difficult to carry out the animal studies on them because of ethical issues, high feeding cost, and management difficulties.

Exploring the spatial disparity of home-dwelling time patterns in the USA during the COVID-19 pandemic via Bayesian inference.

In this study, we aim to reveal hidden patterns and confounders associated with policy implementation and adherence by investigating the home-dwelling stages from a data-driven perspective via Bayesian inference with weakly informative priors and by examining how home-dwelling stages in the USA varied geographically, using fine-grained, spatial-explicit home-dwelling time records from a multi-scale perspective. At the U.S. national level, two changepoints are identified, with the former corresponding to March 22, 2020 (9 days after the White House declared the National Emergency on March 13) and the latter corresponding to May 17, 2020. Inspections at U.S. state and county level reveal notable spatial disparity in home-dwelling stage-related variables. A pilot study in the Atlanta Metropolitan area at the Census Tract level reveals that the self-quarantine duration and increase in home-dwelling time are strongly correlated with the median household income, echoing existing efforts that document the economic inequity exposed by the U.S. stay-at-home orders. To our best knowledge, our work marks a pioneering effort to explore multi-scale home-dwelling patterns in the USA from a purely data-driven perspective and in a statistically robust manner.

Bankart Repair With Transferred Long Head of the Biceps Provides Better Biomechanical Effect Than Conjoined Tendon Transfer in Anterior Shoulder Instability With 20% Glenoid Defect.

PURPOSE: To examine the biomechanical differences between labral repair with transferred conjoined tendon and transferred long head of the biceps tendon (LHBT) for anterior shoulder instability with 20% bone loss. METHODS: Twelve cadaveric shoulders were tested in sequent 5 conditions: intact, 20% glenoid defect, Bankart repair, Bankart repair with transferred conjoined tendon (dynamic conjoined tendon sling, DCS), and with transferred LHBT (dynamic LHBT sling, DLS) at 60° of glenohumeral abduction and 60° of external rotation. The physiological glenohumeral joint load was created by forces applied to the rotator cuff, conjoined tendon, and LHBT. The glenohumeral compression force and range of motion were recorded before anteroinferior force application. The anterior, inferior, and total translations were measured with 20, 30, 40, and 50 N of anteroinferior force, respectively. RESULTS: Anteroinferior glenoid defect led to significant increase of humerus translation and decrease of glenohumeral compression force. DLS provided better resistance effect in both anterior-posterior and superior-inferior directions than DCS under high loading condition (40 N, P =.03; 50 N, P <.01). Both DCS and DLS procedures could further restore glenohumeral compression force with Bankart repair (Bankart repair: 32.1 ± 4.0 N; DCS: 36.7 ± 3.2 N, P < .01; DLS: 35.8 ± 3.6 N, P =.03). No range of motion restrictions were observed relative to the normal shoulder. CONCLUSIONS: Both the DLS and DCS techniques could reduce the anterior-inferior translation and partially restore the glenohumeral stability in anterior shoulder instability with 20% anteroinferior glenoid defect compared with Bankart repair. Under greater loading conditions, DLS provides better stability than DCS. CLINICAL RELEVANCE: Shoulder stability can be restored by DLS and DCS with low load. With greater shoulder stability requirements, DLS might be a better option than DCS for anterior shoulder instability with 20% bone loss.

Crimped nanofiber scaffold mimicking tendon-to-bone interface for fatty-infiltrated massive rotator cuff repair.

Electrospun fibers, with proven ability to promote tissue regeneration, are widely being explored for rotator cuff repairing. However, without post treatment, the microstructure of the electrospun scaffold is vastly different from that of natural extracellular matrix (ECM). Moreover, during mechanical loading, the nanofibers slip that hampers the proliferation and differentiation of migrating stem cells. Here, electrospun nanofiber scaffolds, with crimped nanofibers and welded joints to biomimic the intricate natural microstructure of tendon-to-bone insertion, were prepared using poly(ester-urethane)urea and gelatin via electrospinning and double crosslinking by a multi-bonding network densification strategy. The crimped nanofiber scaffold (CNS) features bionic tensile stress and induces chondrogenic differentiation, laying credible basis for in vivo experimentation. After repairing a rabbit massive rotator cuff tear using a CNS for 3 months, the continuous translational tendon-to-bone interface was fully regenerated, and fatty infiltration was simultaneously inhibited. Instead of micro-CT, µCT was employed to visualize the integrity and intricateness of the three-dimensional microstructure of the CNS-induced-healed tendon-to-bone interface at an ultra-high resolution of less than 1 µm. This study sheds light on the correlation between nanofiber post treatment and massive rotator cuff repair and provides a general strategy for crimped nanofiber preparation and tendon-to-bone interface imaging characterization.

A regeneration process-matching scaffold with appropriate dynamic mechanical properties and spatial adaptability for ligament reconstruction.

Ligament regeneration is a complicated process that requires dynamic mechanical properties and allowable space to regulate collagen remodeling. Poor strength and limited space of currently available grafts hinder tissue regeneration, yielding a disappointing success rate in ligament reconstruction. Matching the scaffold retreat rate with the mechanical and spatial properties of the regeneration process remains challenging. Herein, a scaffold matching the regeneration process was designed via regulating the trajectories of fibers with different degradation rates to provide dynamic mechanical properties and spatial adaptability for collagen infiltration. This core-shell structured scaffold exhibited biomimetic fiber orientation, having tri-phasic mechanical behavior and excellent strength. Besides, by the sequential material degradation, the available space of the scaffold increased from day 6 and remained stable on day 24, consistent with the proliferation and deposition phase of the native ligament regeneration process. Furthermore, mature collagen infiltration and increased bone integration in vivo confirmed the promotion of tissue regeneration by the adaptive space, maintaining an excellent failure load of 67.65% of the native ligament at 16 weeks. This study proved the synergistic effects of dynamic strength and adaptive space. The scaffold matching the regeneration process is expected to open new approaches in ligament reconstruction.

Dynamic Double-Sling Augmentation Prevents Anteroinferior Translation for Recurrent Anteroinferior Shoulder Dislocation With 20% Glenoid Bone Loss: A Cadaveric Biomechanical Study.

PURPOSE: To biomechanically compare the dynamic double-sling with single-sling augmentation using the conjoined tendon (CT) with 20% of an anteroinferior glenoid bone defect under the high loads in shoulders. METHODS: With the shoulder in 60° of glenohumeral abduction and 60° of external rotation, the 12 shoulders stability was tested sequentially in 5 conditions: intact, 20% glenoid bone loss, Bankart repair, single-sling augmentation with the CT, and double-sling augmentation with both the CT and long head of the biceps tendon (LHBT). The anteroinferior humeral head (HH) translation force of 20N, 30N, 40N, 50N, or 60N was applied to determine the shoulder stability in each condition. RESULTS: The total HH translation over 8.77 mm represented the anteroinferior shoulder instability (95% confidence interval of bone defect: 7.76-8.77 mm). A significant increase in anteroinferior HH translation was demonstrated after the creation of 20% glenoid bone defect under the 20N translational force (10.52 ± 0.71 mm). Structural failure after the Bankart repair and the single-sling augmentation under the 30N (9.84 ± 1.25 mm) and 40N (9.59 ± 0.66 mm) translational forces, respectively, were observed. The double-sling augmentation effectively prevented the anteroinferior HH translation under the translational force of less than 40N, and only half of the augmentation structure (8.25 ± 1.66 mm) had failed under the 50N translational forces. CONCLUSION: In the absence of any Hill-Sachs lesion and when tested at 60° abduction and external rotation in shoulders with 20% glenoid bone defects, at time-zero, the double-sling augmentation strategy could effectively prevent anteroinferior translation when compared with the Bankart repair or the single-sling augmentation technique under all magnitudes of the translational force in biomechanical simulation. Nevertheless, none of the constructs restored the HH translation to the normal intact state. CLINICAL RELEVANCE: Double-sling augmentation technique may represent a reliable option for preventing anteroinferior translation.

Evaluation of patches for rotator cuff repair: A systematic review and meta-analysis based on animal studies.

Based on the published animal studies, we systematically evaluated the outcomes of various materials for rotator cuff repair in animal models and the potentials of their clinical translation. 74 animal studies were finally included, of which naturally derived biomaterials were applied the most widely (50.0%), rats were the most commonly used animal model (47.0%), and autologous tissue demonstrated the best outcomes in all animal models. The biomechanical properties of naturally derived biomaterials (maximum failure load: WMD 18.68 [95%CI 7.71-29.66]; P = 0.001, and stiffness: WMD 1.30 [95%CI 0.01-2.60]; P = 0.048) was statistically significant in the rabbit model. The rabbit model showed better outcomes even though the injury was severer compared with the rat model.

Emerging geo-data sources to reveal human mobility dynamics during COVID-19 pandemic: opportunities and challenges.

Effectively monitoring the dynamics of human mobility is of great importance in urban management, especially during the COVID-19 pandemic. Traditionally, the human mobility data is collected by roadside sensors, which have limited spatial coverage and are insufficient in large-scale studies. With the maturing of mobile sensing and Internet of Things (IoT) technologies, various crowdsourced data sources are emerging, paving the way for monitoring and characterizing human mobility during the pandemic. This paper presents the authors' opinions on three types of emerging mobility data sources, including mobile device data, social media data, and connected vehicle data. We first introduce each data source's main features and summarize their current applications within the context of tracking mobility dynamics during the COVID-19 pandemic. Then, we discuss the challenges associated with using these data sources. Based on the authors' research experience, we argue that data uncertainty, big data processing problems, data privacy, and theory-guided data analytics are the most common challenges in using these emerging mobility data sources. Last, we share experiences and opinions on potential solutions to address these challenges and possible research directions associated with acquiring, discovering, managing, and analyzing big mobility data.

Acceleration of ligamentization and osseointegration processes after anterior cruciate ligament reconstruction with autologous tissue-engineered polyethylene terephthalate graft.

BACKGROUND: Despite the advantages of excellent mechanical properties for rapid return to sports and early rehabilitation after anterior cruciate ligament (ACL) reconstruction with polyethylene terephthalate (PET) artificial ligament, the graft failure rate during long-term follow-up is relatively high due to poor graft-host incorporation. The purpose of the present study was to investigate the effect of autologous tissue-engineered PET (ATE-PET) grafts on osseointegration and ligamentization after ACL reconstruction. METHODS: Forty-eight New Zealand white rabbits were randomly divided into PET group (n=24) and ATE-PET group (n=24). In the ATE-PET group, the rabbits initially underwent subcutaneous implantation of the PET ligament. Two weeks later, unilateral ipsilateral ACL reconstruction was performed using an ATE-PET graft. In the PET group, the rabbits underwent ACL reconstruction using PET grafts as controls. Macroscopic observation, micro-computed tomography, histological and immunofluorescent staining, and biomechanical tests were conducted to evaluate the effects at 4 and 12 weeks postoperatively. RESULTS: The ATE-PET graft was highly pre-vascularized with myofibroblast aggregation after two weeks of subcutaneous implantation. With regard to the intraosseous part of the graft, the ATE-PET group had significantly higher bone mineral density and bone volume/total volume ratio at 12 weeks. Histologically, the width of the interface between the graft and bone was smaller. Regarding the intra-articular part, thicker tissue coverage with a glossy appearance was observed in the ATE-PET group at 12 weeks on macroscopic observation. Histological staining also showed more collagen fibers grew in the grafts with fewer inflammatory reactions of the ATE-PET group at both 4 and 12 weeks. Immunofluorescently, both α-SMA-positive vessels and α-SMA-positive myofibroblasts were found to be significantly greater around the graft in the ATE-PET group at 4 weeks and markedly declined at 12 weeks. Moreover, the ATE-PET group presented significantly greater failure load and stiffness than the PET group at 12 weeks (53.7±5.4 vs. 42.5±4.5 N, P<0.01; 12.9±3.0 vs. 9.8±1.3 N/mm, P=0.04). CONCLUSIONS: The ATE-PET artificial ligament with pre-vascularization and myofibroblast aggregation could effectively accelerate intra-articular graft ligamentization and intraosseous graft osseointegration, thus enhancing the biomechanical properties after ACL reconstruction in a rabbit model.