Tailored Water-Soluble Covalent Organic Cages for Encapsulation of Pyrene and Information Encryption.

Forming pyridine salts to construct covalent organic cages is an effective strategy for constructing covalent cage compounds. Covalent organic cages based on pyridine salt structures are prone to form water-soluble supramolecular compounds. Herein, we designed and synthesized a triangular prism-shaped hexagonal cage with a larger cavity and relatively flexible conformation. The supramolecular cage structure was also applied to the encapsulation of pyrene and information encryption.

A Dual-Targeted Metal-Organic Framework Based Nanoplatform for the Treatment of Rheumatoid Arthritis by Restoring the Macrophage Niche.

Inflammatory infiltration and bone destruction are important pathological features of rheumatoid arthritis (RA), which originate from the disturbed niche of macrophages. Here, we identified a niche-disrupting process in RA: due to overactivation of complement, the barrier function of VSIg4+ lining macrophages is disrupted and mediates inflammatory infiltration within the joint, thereby activating excessive osteoclastogenesis and bone resorption. However, complement antagonists have poor biological applications due to superphysiologic dose requirements and inadequate effects on bone resorption. Therefore, we developed a dual-targeted therapeutic nanoplatform based on the MOF framework to achieve bone-targeted delivery of the complement inhibitor CRIg-CD59 and pH-responsive sustained release. The surface-mineralized zoledronic acid (ZA) of ZIF8@CRIg-CD59@HA@ZA targets the skeletal acidic microenvironment in RA, and the sustained release of CRIg-CD59 can recognize and prevent the complement membrane attack complex (MAC) from forming on the surface of healthy cells. Importantly, ZA can inhibit osteoclast-mediated bone resorption, and CRIg-CD59 can promote the repair of the VSIg4+ lining macrophage barrier to achieve sequential niche remodeling. This combination therapy is expected to treat RA by reversing the core pathological process, circumventing the pitfalls of traditional therapy.

Micron-resolution Imaging of Cortical Bone under 14 T Ultrahigh Magnetic Field.

Compact, mineralized cortical bone tissues are often concealed on magnetic resonance (MR) images. Recent development of MR instruments and pulse techniques has yielded significant advances in acquiring anatomical and physiological information from cortical bone despite its poor 1 H signals. This work demonstrates the first MR research on cortical bones under an ultrahigh magnetic field of 14 T. The 1 H signals of different mammalian species exhibit multi-exponential decays of three characteristic T2 or T2 * values: 0.1-0.5 ms, 1-4 ms, and 4-8 ms. Systematic sample comparisons attribute these T2 /T2 * value ranges to collagen-bound water, pore water, and lipids, respectively. Ultrashort echo time (UTE) imaging under 14 T yielded spatial resolutions of 20-80 microns, which resolves the 3D anatomy of the Haversian canals. The T2 * relaxation characteristics further allow spatial classifications of collagen, pore water and lipids in human specimens. The study achieves a record of the spatial resolution for MR imaging in bone and shows that ultrahigh-field MR has the unique ability to differentiate the soft and organic compartments in bone tissues.

The deubiquitinase UCHL1 negatively controls osteoclastogenesis by regulating TAZ/NFATC1 signalling.

The ubiquitin‒proteasome system (UPS) plays a key role in maintaining protein homeostasis and bone remodelling. However, the role of deubiquitinating enzymes (DUBs) in bone resorption is still not well defined. Here, we identified the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) as a negative regulator of osteoclastogenesis by using the GEO database, proteomic analysis, and RNAi. Osteoclast-specific UCHL1 conditional knockout mice exhibited a severe osteoporosis phenotype in an ovariectomized model. Mechanistically, UCHL1 deubiquitinated and stabilized the transcriptional coactivator with PDZ-binding motif (TAZ) at the K46 residue, thereby inhibiting osteoclastogenesis. The TAZ protein underwent K48-linked polyubiquitination, which was degraded by UCHL1. As a substrate of UCHL1, TAZ regulates NFATC1 through a nontranscriptional coactivator function by competing with calcineurin A (CNA) for binding to NFATC1, which inhibits NFATC1 dephosphorylation and nuclear transport to impede osteoclastogenesis. Moreover, overexpression of UCHL1 locally alleviated acute and chronic bone loss. These findings suggest that activating UCHL1 may serve as a novel therapeutic approach targeting bone loss in various bone pathological states.

Netrin-1 mediates nerve innervation and angiogenesis leading to discogenic pain.

Objective: Discogenic low back pain (LBP) is associated with nociceptive nerve fibers that grow into degenerated intervertebral discs (IVD) but the etiopathogenesis of disease is not fully understood. The purpose of this study was to clarify the role of Netrin-1 in causing discogenic LBP. Methods: The level of nociceptive nerve innervation was examined in disc degenerative patients and rat needle-punctured models by immunohistochemistry. Nucleus pulposus (NP) cells were isolated from IVD tissues of rats and induced degeneration by interleukin-1ß (IL-1ß) or tumor necrosis factor α (TNFα). The candidate genes related to neuron outgrowth and migration were selected by Next-generation sequencing (NGS). CRISPR/Cas9 was used to knockdown Netrin-1 in NP cells. The impact of Netrin-1 on nerve innervation were evaluated with P2X2、NF200 staining and microfluidics assay. Meanwhile the CD31 staining and transwell assay were used to evaluate the impact of Netrin-1 in angiogenesis. The proteins and RNA extracted from NP cells related to catabolism and anabolism were examined by western blot assay and RT-qPCR experiment. ChIP and luciferase experiments were used to assess the intracellular transcriptional regulation of Netrin-1. Further, a needle-punctured rat model followed by histomorphometry and immunofluorescence histochemistry was used to explore the potential effect of Netrin-1 on LBP in vivo. Results: The level of nerve innervation was increased in severe disc degenerative patients while the expression of Netrin-1 was upregulated. The supernatants of NP cells stimulated with IL-1ß or TNFα containing more Netrin-1 could promote axon growth and vascular endothelial cells migration. Knocking down Netrin-1 or overexpressing transcription factor TCF3 as a negative regulator of Netrin-1 attenuated this effect. The needle-punctured rat model brought significant spinal hypersensitivity, nerve innervation and angiogenesis, nevertheless knocking down Netrin-1 effectively prevented disc degeneration-induced adverse impacts. Conclusion: Discogenic LBP was induced by Netrin-1, which mediated nerve innervation and angiogenesis in disc degeneration. Knocking down Netrin-1 by CRISPR/Cas9 or negatively regulating Netrin1 by transcription factor TCF3 could alleviate spinal hypersensitivity. The translational potential of this article: This study on Netrin-1 could provide a new target and theoretical basis for the prevention and treatment for discogenic back pain.

Porcine epidemic diarrhea virus 3CLpro causes apoptosis and collapse of mitochondrial membrane potential requiring its protease activity and signaling through MAVS.

Porcine epidemic diarrhea (PED) is a highly contagious and virulent intestinal infectious disease characterized by diarrhea, vomiting and dehydration. Although PEDV-induced apoptosis has been characterized in vitro and vivo, the functional proteins related to this event and the mechanism still need further research. Here, we firstly demonstrated that PEDV epidemic strain JS2013 could trigger apoptosis in a dose- and time-dependent manner. Then, PEDV 3CLpro was further identified as a crucial inducer of PEDV-triggered apoptosis. In addition, using site-directed mutagenesis to disrupt the protease activity of 3CLpro by His41 and Cys144 mutations, we found that 3CLpro-induced apoptosis and mitochondrial damage significantly reduced, suggesting that the protease activity of 3CLpro was essential for apoptosis and mitochondrial damage. Furthermore, PEDV 3CLpro could synergistically promote MAVS-mediated apoptosis and MAVS was involved in the signaling pathway of 3CLpro-induced apoptosis, but no direct interaction between PEDV 3CLpro and MAVS was detected by immunoprecipitation assays. Our findings provide important insights into the role of 3CLpro in the pathogenicity of PEDV.

Multiplex array analysis of serum cytokines offers minimal predictive value for cognitive function in the subacute phase after stroke.

Objective: The effects of inflammation on post-stroke cognitive function are still unclear. This study investigated the correlation between the Th17-related cytokines in peripheral blood and post-stroke cognitive function after ischemic stroke in the subacute phase. Design: A retrospective cohort study. Setting: Academic acute inpatient rehabilitation facility. Participants: One hundred and fourteen patients with first ischemic stroke were categorized as the poor cognitive recovery group (n = 58) or good cognitive recovery group (n = 56) based on their cognitive MRFS efficiency. Interventions: All subjects received routine physical, occupational, and speech-language pathology therapy. Main outcome measures: Serum cytokines/chemokine (IL-1 ß, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-17E, IL-17F, IL-21, IL-22, IL-23, IL-27, IL-28A, IL-31, IL-33, GM-CSF, IFN-γ, MIP-3 α, TNF-α, and TNF-ß) levels were measured in duplicate using Human Th17 magnetic bead panel and multiplex array analysis (Luminex-200 system). The primary functional outcome was a gain in functional independence measure (FIM) cognitive subscore at discharge. The secondary outcome measures were FIM total score at discharge, length of stay in the hospital, and discharge destination. Cognitive Montebello Rehabilitation Factor Score (MRFS) and cognitive MRFS efficiency were calculated. Demographic and clinical characteristics were obtained from the medical record. Results: The good cognitive recovery group had an interesting trend of higher IL-13 than the poor cognitive recovery group (good cognitive recovery group 257.82 ± 268.76 vs. poor cognitive recovery group 191.67 ± 201.82, p = 0.049, unit: pg/ml). However, Pearson's correlation analysis showed no significant correlation between cytokine levels and gain of cognition, cognitive MRFS, or cognitive MRFS efficiency. Receiver operating characteristic (ROC) analysis of cytokines also suggested a low accuracy of prediction as a predictor for post-stroke cognitive recovery improvement. Conclusion: Our preliminary findings suggested that the level of serum cytokines had minimal predictive value for the recovery of cognitive function during the subacute inpatient rehabilitation after stroke.

Surface Modification with NGF-Loaded Chitosan/Heparin Nanoparticles for Improving Biocompatibility of Cardiovascular Stent.

Late thrombosis and restenosis remain major challenges to the safety of drug-eluting stents. Biofunctional modification to endow the surface with selective anticoagulation and promote endothelium regeneration has become a hotpot recently. In this study, chitosan and heparin were found to form three-dimensional nanoparticles by spontaneous electrostatic interaction. Based on the specific binding properties between heparin and nerve growth factor (NGF), a new type of NGF-loaded heparin/chitosan nanoparticles was constructed for surface modification. The results of material characterization show that the nanoparticles are successfully immobilized on the surface of the material. In vitro blood compatibility and endothelial cell compatibility assay showed that the modified surface could selectively inhibit platelet adhesion and smooth muscle cell overproliferation, while accelerating endothelialization via promoting endothelial cell proliferation and enhancing endothelial progenitor cell mobilization.

Clinical effectiveness of ultrasound guided subacromial-subdeltoid bursa injection of botulinum toxin type A in hemiplegic shoulder pain: A retrospective cohort study.

Hemiplegic shoulder pain (HSP), which occurs in most patients with hemiplegia, causes considerable distress and worsens outcomes in rehabilitation. Although they have received the treatments such as anti-inflammatory drugs or physical therapy, many of the individuals remain suffering from shoulder pain 6 months after acute stroke event. In this retrospective study, we evaluated the effectiveness of ultrasound guided subacromial-subdeltoid (SASD) bursa injections with botulinum toxin type A (BoNT/A) compared to steroids for refractory HSP.The data were collected retrospectively by reviewing the patient's medical records and pain questionnaires in our rehabilitation center. In total, 38 patients who received ultrasound guided SASD bursa injection (BoNT/A group, n = 18; corticosteroid group, n = 20) were included. The pain visual analog scale (VAS) score at rest and during arm passive abduction, Fugl-Meyer score of upper limbs (F-M score) were evaluated before, 2, 4, 8, and 12 weeks after injection.Both 2 groups obtained a significant improvement of VAS score at rest or during arms passive abduction compared to baseline score (within group compare, P < .05). There were no significant differences of pain score improvement between two groups at week 2, 4, 8, and 12 after injection either at rest or during passive arm abduction (between 2 groups compare, P > .05). There were also no differences in results of the post treatment F-M score between 2 groups (between 2 groups compare, P > .05). Similarly, during the follow-up period no collateral effects were reported after BoNT/A injection.SASD bursa BoNT/A injection can substantially reduce the pain as corticosteroid in patients with HSP. BoNT/A injection could be a useful strategy for replacing steroids as a treatment for refractory HSP especially in the patients who cannot tolerate the steroids injection.

Targeted Metabolomic Profiling Reveals Association Between Altered Amino Acids and Poor Functional Recovery After Stroke.

Amino acids have been shown to be among the most important metabolites to be altered following stroke; however, they are a double-edged sword with regard to regulating hemostasis. In this study, we conducted a targeted metabolomic study to examine the association between serum levels of amino acids and functional recovery after stroke. Three hundred and fifty-one patients with stroke admitted to an acute rehabilitation hospital were screened, and 106 patients were selected based on inclusion and exclusion criteria. Recruited patients were stratified using Montebello Rehabilitation Factor Score (MRFS) efficiency. We selected the top (n = 20, 19%) and bottom (n = 20, 19%) of MRFS efficiency for metabolomic analysis. A total of 21 serum amino acids levels were measured using ultra high performance liquid chromatography and mass spectrometry. The normalized data were analyzed by multivariate approaches, and the selected potential biomarkers were combined in different combinations for prediction of stroke functional recovery. The results demonstrated that there were significant differences in leucine-isoleucine, proline, threonine, glutamic acid, and arginine levels between good and poor recovery groups. In the training (0.952) and test (0.835) sets, metabolite biomarker panels composed of proline, glutamic acid, and arginine had the highest sensitivity and specificity in distinguishing good recovery from poor. In particular, arginine was present in the top 10 combinations of the average area under the receiver operating characteristic curve (AUC) test set. Our findings suggest that amino acids related to energy metabolism and excitotoxicity may play an important role in functional recovery after stroke. Therefore, the level of serum arginine has predictive value for the recovery rate after stroke.

Enhanced Effect of Tendon Stem/Progenitor Cells Combined With Tendon-Derived Decellularized Extracellular Matrix on Tendon Regeneration.

Decellularized extracellular matrices have been clinically used for tendon regeneration. However, only a few systematic studies have compared tendon stem/progenitor cells to mesenchymal stromal cells on the tendon-derived decellularized matrix. In the present study, we prepared extracellular matrix derived from porcine tendons and seeded with tendon stem/progenitor cells, embryonic stem cell-derived mesenchymal stromal cells or without stem cells. Then we implanted the mixture (composed of stem cells and scaffold) into the defect of a rat Achilles tendon. Next, 4 weeks post-surgery the regenerated tendon tissue was collected. Histological staining, immunohistochemistry, determination of collagen content, transmission electron microscopy, and biomechanical testing were performed to evaluate the tendon structure and biomechanical properties. Our study collectively demonstrated that decellularized extracellular matrix derived from porcine tendons significantly promoted the regeneration of injured tendons when combined with tendon stem/progenitor cells or embryonic stem cell-mesenchymal stromal cells. Compared to embryonic stem cell-mesenchymal stromal cells, tendon stem/progenitor cells combined with decellularized matrix showed more improvement in the structural and biomechanical properties of regenerated tendons in vivo. These findings suggest a promising strategy for functional tendon tissue regeneration and further studies are warranted to develop a functional tendon tissue regeneration utilizing tendon stem/progenitor cells integrated with a tendon-derived decellularized matrix.

Cytotoxicity of local anesthetics on rabbit adipose-derived mesenchymal stem cells during early chondrogenic differentiation.

Local anesthetics (LAs) are commonly used to provide peri-operative pain control in the peripheral joints. In the field of regenerative medicine, adipose-derived mesenchymal stem cells (ADMSCs) are gaining attention as a cellular source for repair and regeneration in degenerative diseases. However, previous studies have demonstrated that the commonly used drugs lidocaine, ropivacaine, bupivacaine and mepivacaine may be toxic to human chondrocytes, which has raised concerns over whether they exert similar negative effects on ADMSCs during early chondrogenic differentiation. In the present in vitro study, the cytotoxicity of different LAs to ADMSCs was determined during early chondrogenic differentiation. At concentrations similar to those after physiological dilution once injected into the degenerative tissues, LAs (1% lidocaine, 0.5% bupivacaine, 0.5% ropivacaine or 2% mepivacaine) and PBS (control group) were incubated with rabbit ADMSCs (rADMSCs) for 60 min. Following further culture for 3 or 7 days, the cell viability, apoptosis and morphological alterations of chondrogenic differentiation were measured by determining the mitochondrial activity, by flow cytometric analysis, Safranine Fast Green double staining and reverse transcription-quantitative polymerase chain reaction of chondrogenesis-associated genes. The results indicated that the mitochondrial activity in rADMSC was decreased and the apoptotic rate was increased, following treatment with LAs (P<0.05). Lidocaine (1%) was less cytotoxic to rADMSCs during early chondrogenesis compared with other LAs. The expression levels of chondrogenesis-associated markers, including collagen I, collagen III and sex-determining region Y box 9 were all decreased at day 3 following exposure to LAs compared with the control group (P<0.05). The expression levels of these chondrogenesis-associated genes began to increase on day 7 following exposure but remained lower compared with the control group (P<0.05). Of note, 2% mepivacaine and 1% lidocaine exhibited a less pronounced negative effect on chondrogenesis-associated gene expression compared with other LAs. Therefore, the present study concluded that LAs are cytotoxic to rADMSCs during early chondrogenesis. Attention should be paid to the different types of LA selected in conjunction with ADMSC injection therapy.

Cell-Based Therapies for Lumbar Discogenic Low Back Pain: Systematic Review and Single-Arm Meta-analysis.

STUDY DESIGN: A systematic review and single-arm meta-analysis of clinical trials. OBJECTIVE: To assess the efficacy of mesenchymal stem cells or chondrocyte in patients with discogenic low back pain. SUMMARY OF BACKGROUND DATA: There is no previous review evaluated the efficacy of mesenchymal stem cell or chondrocyte therapy in adults with discogenic low back pain. METHODS: A comprehensive literature search was conducted on PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO, and Web of Science from database inception through on September 10th, 2015. We included clinical trials that evaluated stem cells or chondrocyte-based therapy in patients with discogenic back pain. The primary outcomes of interest were pain score and Oswestry Disability Index (ODI). We performed random-effects model meta-analyses to assess net changes in the same outcome variables. Heterogeneity between studies was estimated by I statistic. RESULTS: The initial search identified 1393 articles, of which 6 studies were eligible for this review. The pooled mean difference in pain score from baseline to follow-up points was 44.2 points decreased (95% CI: -61.8 to -26.5, P < 0.001, I  = 99.4%). Meanwhile, the pooled mean difference in ODI from baseline to follow-up points was 32.2 points decreased (95% CI: -41.6 to -22.9, P < 0.001, I  = 99.5%). No related adverse effects were reported by the included studies. CONCLUSION: Cell-based therapy is for patients who have discogenic low back pain associated with improved pain relief and ODI. More stringently designed randomized double-blind clinical trials with appropriately determined sample sizes will be needed to confirm its clinical efficacy and safety. LEVEL OF EVIDENCE: 4.

Intra-articular injections of botulinum toxin a for refractory joint pain: a systematic review and meta-analysis.

OBJECTIVE: To assess the benefit of intra-articular injection of Botulinum toxin A (BoNT-A) for chronic refractory joint pain regardless of joint or pathology. DATA SOURCES: The search was performed on Ovid MEDLINE(R) In-Process and Other Non-Indexed Citations, Ovid MEDLINE(R), Ovid EMBASE, Web of Science, and Scopus inception through Week 12, 2016. Trial selection: Clinical randomized controlled trials that evaluated BoNT-A intra-articular injection in patients with refractory joint pain were included. DATA EXTRACTION: Two independent reviewers conducted data extraction. RESULTS: A total of 6 out of 284 records were included. The analysis indicated that a statistically significant decreased pain score was found in BoNT-A therapy group than control group with WMD=1.10 (95% CI: 0.35 to 1.85; P<0.001; I2=95%); WMD=0.7 (95% CI: 0.09 to 1.32; P=0.02; I2=0%) at week 4, and 8 after injection, respectively. WOMAC score was also significant decreased in BoNT-A therapy group than control group with WMD=4.71 (95% CI: 2.76 to 6.67; P<0.001; I2=0%); WMD=3.67 (95% CI: 1.08 to 6.26; P=0.006; I2=27%) at week 4 and12 after injection, respectively. There was no difference in adverse event between BoNT-A therapy group and control group with OR=1.25 (95% CI: 0.88 to 1.78; P=0.47; I2=0%). CONCLUSION: As compared with conventional therapy, BoNT-A intra-articular injection have beneficial effects with improved pain score and WOMAC score in adult patients with refractory joint pain.

Effectiveness of Ultrasound-Guided Versus Fluoroscopy or Computed Tomography Scanning Guidance in Lumbar Facet Joint Injections in Adults With Facet Joint Syndrome: A Meta-Analysis of Controlled Trials.

OBJECTIVE: To review the literature and assess the comparative effectiveness of ultrasound-guided (USG) versus computed tomography (CT)-/fluoroscopy-guided lumbar facet joint injections in adults. DATA SOURCES: PubMed, Ovid MEDLINE, Ovid Embase, EBSCO, and Web of Science. STUDY SELECTION: Randomized or nonrandomized controlled trials comparing the clinical effectiveness between USG and CT-/fluoroscopy-guided injection techniques in patients with facet syndrome were included. DATA EXTRACTION: Two reviewers independently screened abstracts and full texts. The results of the mean procedure duration, decreased pain score, and Modified Oswestry Disability score after treatment were extracted and presented in the form of mean ± SD. DATA SYNTHESIS: There were 103 records screened; 3 studies were included, with a total of 202 adults with facet joint pain. There was no statistically significant difference between the 2 groups in pain score and Modified Oswestry Disability score after injection (weighted mean difference [WMD], .07; 95% confidence interval [CI], -.51 to .65; P=.80; I(2)=78%; WMD, -.55; 95% CI, -1.31 to .22; P=.16; I(2)=0%, respectively). There was also no statistically significant difference in the mean procedure duration between the 2 groups (standardized mean difference [SMD], .97; 95% CI, -1.01 to 2.94; P=.34; I(2)=97%). CONCLUSIONS: This review suggested that no significant differences in pain and functional improvement were noted between the USG and CT-/fluoroscopy-guided techniques in facet joint injection. USG injection is feasible and minimizes exposure of radiation to patients and practitioners in the lumbar facet joint injection process.

Electrospun scaffolds for multiple tissues regeneration in vivo through topography dependent induction of lineage specific differentiation.

Physical topographic cues from various substrata have been shown to exert profound effects on the growth and differentiation of stem cells due to their niche-mimicking features. However, the biological function of different topographic materials utilized as bio-scaffolds in vivo have not been rigorously characterized. This study investigated the divergent differentiation pathways of mesenchymal stem cells (MSCs) and neo-tissue formation trigged by aligned and randomly-oriented fibrous scaffolds, both in vitro and in vivo. The aligned group was observed to form more mature tendon-like tissue in the Achilles tendon injury model, as evidenced by histological scoring and collagen I immunohistochemical staining data. In contrast, the randomly-oriented group exhibited much chondrogenesis and subsequent bone tissue formation through ossification. Additionally, X-ray imaging and osteocalcin immunohistochemical staining also demonstrated that osteogenesis in vivo is driven by randomly oriented topography. Furthermore, MSCs on the aligned substrate exhibited tenocyte-like morphology and enhanced tenogenic differentiation compared to cells grown on randomly-oriented scaffold. qRT-PCR analysis of osteogenic marker genes and alkaline phosphatase (ALP) staining demonstrated that MSCs cultured on randomly-oriented fiber scaffolds displayed enhanced osteogenic differentiation compared with cells cultured on aligned fiber scaffolds. Finally, it was demonstrated that cytoskeletal tension release abrogated the divergent differentiation pathways on different substrate topography. Collectively, these findings illustrate the relationship between topographic cues of the scaffold and their inductive role in tissue regeneration; thus providing an insight into future development of smart functionalized bio-scaffold design and its application in tissue engineering.

The effect of decellularized matrices on human tendon stem/progenitor cell differentiation and tendon repair.

It is reported that decellularized collagen matrices derived from dermal skin and bone have been clinically used for tendon repair. However, the varying biological and physical properties of matrices originating from different tissues may influence the differentiation of tendon stem cells, which has not been systematically evaluated. In this study, the effects of collagenous matrices derived from different tissues (tendon, bone and dermis) on the cell differentiation of human tendon stem/progenitor cells (hTSPCs) were investigated, in the context of tendon repair. It was found that all three matrices supported the adhesion and proliferation of hTSPCs despite differences in topography. Interestingly, tendon-derived decellularized matrix promoted the tendinous phenotype in hTSPCs and inhibited their osteogenesis, even under osteogenic induction conditions, through modulation of the teno- and osteolineage-specific transcription factors Scleraxis and Runx2. Bone-derived decellularized matrix robustly induced osteogenic differentiation of hTSPCs, whereas dermal skin-derived collagen matrix had no apparent effect on hTSPC differentiation. Based on the specific biological function of the tendon-derived decellularized matrix, a tissue-engineered tendon comprising TSPCs and tendon-derived matrix was successfully fabricated for Achilles tendon reconstruction. Implantation of this cell-scaffold construct led to a more mature structure (histology score: 4.08 ± 0.61 vs. 8.51 ± 1.66), larger collagen fibrils (52.2 ± 1.6 nm vs. 47.5 ± 2.8 nm) and stronger mechanical properties (stiffness: 21.68 ± 7.1 Nm m(-1) vs.13.2 ± 5.9 Nm m(-1)) of repaired tendons compared to the control group. The results suggest that stem cells promote the rate of repair of Achilles tendon in the presence of a tendinous matrix. This study thus highlights the potential of decellularized matrix for future tissue engineering applications, as well as developing a practical strategy for functional tendon regeneration by utilizing TSPCs combined with tendon-derived decellularized matrix.