Publications by authors named "Hongbin Lu"

128 Publications

A Remote Sensor System Based on TDLAS Technique for Ammonia Leakage Monitoring.

Sensors (Basel) 2021 Apr 2;21(7). Epub 2021 Apr 2.

State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, 2699 Qianjin Street, Changchun 130012, China.

The development of an efficient, portable, real-time, and high-precision ammonia (NH) remote sensor system is of great significance for environmental protection and citizens' health. We developed a NH remote sensor system based on tunable diode laser absorption spectroscopy (TDLAS) technique to measure the NH leakage. In order to eliminate the interference of water vapor on NH detection, the wavelength-locked wavelength modulation spectroscopy technique was adopted to stabilize the output wavelength of the laser at 6612.7 cm, which significantly increased the sampling frequency of the sensor system. To solve the problem in that the light intensity received by the detector keeps changing, the signal processing technique was adopted. The practical application results proved that the signal processing technique had a satisfactory suppression effect on the signal fluctuation caused by distance changing. Using Allan deviation analysis, we determined the stability and limit of detection (LoD). The system could reach a LoD of 16.6 ppm·m at an average time of 2.8 s, and a LoD of 0.5 ppm·m at an optimum averaging time of 778.4 s. Finally, the measurement result of simulated ammonia leakage verified that the ammonia remote sensor system could meet the need for ammonia leakage detection in the industrial production process.
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http://dx.doi.org/10.3390/s21072448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036584PMC
April 2021

A biomechanical comparison of a mesh suture to a polyblend suture in a porcine tendon model.

Ann Transl Med 2021 Mar;9(6):450

Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.

Background: The suture-tendon interface turned out to be the weak point of a repaired rotator cuff. A double rip-stop (DRS) technique was developed to enhance the strength of the suture-tendon interface. The first aim of this study was to compare the suture-tendon interface strength between mesh suture and the No. 2 FiberWire (FW), which is commonly used in the clinic. The second aim was to compare the biomechanical properties of rotator cuff repair between mesh suture and No. 2 FiberWire using a typical suture-bridge (SB) and DRS techniques.

Methods: Eighteen porcine subscapularis tendon (SST) was randomly assigned to the Mesh-tendon group and FiberWire-tendon group. A single suture loop was passed through the SST with a Mesh suture or FiberWire. Thirty-two infraspinatus tendons (ISTs) were randomly assigned to four groups: SB-Mesh group: SB technique with Mesh suture, SB-FW group: SB technique with FiberWire, DRS-Mesh group: DRS technique with Mesh suture, and DRS-FW group: DRS technique with FiberWire. All repaired specimens were underwent failure testing. Failure modes, load to create a 3-mm gap, failure load, and stiffness were compared.

Results: There were no significant differences between the Mesh-tendon group and FiberWire-tendon group regarding the failure load, stiffness, and ultimate stress. When the same technique was used, the rotator cuff repaired with a mesh suture had the similar load to create a 3-mm gap, failure load, and stiffness compared with FiberWire. When the same suture was used, the DRS technique had a significantly higher load to create a 3-mm gap formation and failure load compared with the SB technique.

Conclusions: The repair failure strength and stiffness using the mesh suture were similar to the FiberWire suture regardless of the repair techniques. However, the repair strength in the DRS technique was significantly stronger than the SB technique when the same suture material was used.
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http://dx.doi.org/10.21037/atm-20-1065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039690PMC
March 2021

Adipose-Derived Stromal Cell-Sheets Sandwiched, Book-Shaped Acellular Dermal Matrix Capable of Sustained Release of Basic Fibroblast Growth Factor Promote Diabetic Wound Healing.

Front Cell Dev Biol 2021 25;9:646967. Epub 2021 Mar 25.

The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.

The management of diabetic wounds is a therapeutic challenge in clinical settings. Current tissue engineering strategies for diabetic wound healing are insufficient, owing to the lack of an appropriate scaffold that can load a large number of stem cells and induce the interaction of stem cells to form granulation tissue. Herein we fabricated a book-shaped decellularized dermal matrix (BDDM), which shows a high resemblance to native dermal tissue in terms of its histology, microstructure, and ingredients, is non-cytotoxic and low-immunogenic, and allows adipose-derived stromal cell (ASC) attachment and proliferation. Then, a collagen-binding domain (CBD) capable of binding collagen was fused into basic fibroblast growth factor (bFGF) to synthetize a recombinant growth factor (termed as CBD-bFGF). After that, CBD-bFGF was tethered onto the collagen fibers of BDDM to improve its endothelial inducibility. Finally, a functional scaffold (CBD-bFGF/BDDM) was fabricated. and experiments demonstrated that CBD-bFGF/BDDM can release tethered bFGF with a sustained release profile, steadily inducing the interaction of stem cells down to endothelial differentiation. ASCs were cultured to form a cell sheet and then sandwiched by CBD-bFGF/BDDM, thus enlarging the number of stem cells loaded into the scaffold. Using a rat model, the ASC sheets sandwiched with CBD-bFGF/BDDM (ASCs/CBD-bFGF/BDDM) were capable of enhancing the formation of granulation tissue, promoting angiogenesis, and facilitating collagen deposition and remodeling. Therefore, the findings of this study demonstrate that ASCs/CBD-bFGF/BDDM could be applicable for diabetic wound healing.
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http://dx.doi.org/10.3389/fcell.2021.646967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027315PMC
March 2021

A Novel Graphene Quantum Dot-Based mRNA Delivery Platform.

ChemistryOpen 2021 Apr 7. Epub 2021 Apr 7.

Department of Microtechnology and Nanoscience, Chalmers University of Technology, 9 Kemivägen, Gothenborg, 412 96, Sweden.

During the last decades, there has been growing interest in using therapeutic messager RNA (mRNA) together with drug delivery systems. Naked, unformulated mRNA is, however, unable to cross the cell membrane and is susceptible to degradation. Here we use graphene quantum dots (GQDs) functionalized with polyethyleneimine (PEI) as a novel mRNA delivery system. Our results show that these modified GQDs can be used to deliver intact and functional mRNA to Huh-7 hepatocarcinoma cells at low doses and, that the GQDs are not toxic, although cellular toxicity is a problem for these first-generation modified particles. Functionalized GQDs represent a potentially interesting delivery system that is easy to manufacture, stable and effective.
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http://dx.doi.org/10.1002/open.202000200DOI Listing
April 2021

Cell-Free Book-Shaped Decellularized Tendon Matrix Graft Capable of Controlled Release of BMP-12 to Improve Tendon Healing in a Rat Model.

Am J Sports Med 2021 04 5;49(5):1333-1347. Epub 2021 Mar 5.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Background: Achilles tendon (AT) defects often occur in traumatic and chronic injuries. Currently, no graft can satisfactorily regenerate parallel tendinous tissue at the defect site to completely restore AT function.

Purpose: To develop a cell-free functional graft by tethering bone morphogenetic protein 12 (BMP-12) on a book-shaped decellularized tendon matrix (BDTM) and to determine whether this graft is more beneficial for AT defect healing than an autograft.

Study Design: Controlled laboratory study.

Methods: Canine patellar tendon was sectioned into a book shape and decellularized to fabricate a BDTM. The collagen-binding domain (CBD) was fused into the N-terminus of BMP-12 to synthesize a recombinant BMP-12 (CBD-BMP-12), which was tethered to the BDTM to prepare a cell-free functional graft (CBD-BMP-12/BDTM). After its tensile resistance, tenogenic inducibility, and BMP-12 release dynamics were evaluated, the efficacy of the graft for tendon regeneration was determined in a rat model. A total of 140 mature male Sprague-Dawley rats underwent AT tenotomy. The defect was reconstructed with reversed AT (autograft group), native BMP-12 tethered to an intact decellularized tendon matrix (IDTM; NAT-BMP-12/IDTM group), native BMP-12 tethered to a BDTM (NAT-BMP-12/BDTM group), CBD-BMP-12 tethered on an IDTM (CBD-BMP-12/IDTM group), and CBD-BMP-12 tethered on a BDTM (CBD-BMP-12/BDTM group). The rats were sacrificed 4 or 8 weeks after surgery to harvest AT specimens. Six specimens from each group at each time point were used for histological evaluation; the remaining 8 specimens were used for biomechanical testing.

Results: In vitro CBD-BMP-12/BDTM was noncytotoxic, showed high biomimetics with native tendons, was suitable for cell adhesion and growth, and had superior tenogenic inducibility. In vivo the defective AT in the CBD-BMP-12/BDTM group regenerated more naturally than in the other groups, as indicated by more spindle-shaped fibroblasts embedded in a matrix of parallel fibers. The biomechanical properties of the regenerated AT in the CBD-BMP-12/BDTM group also increased more significantly than in the other groups.

Conclusion: CBD-BMP-12/BDTM is more beneficial than autograft for healing AT defects in a rat model.

Clinical Relevance: The findings of this study demonstrate that CBD-BMP-12/BDTM can serve as a practical graft for reconstructing AT defects.
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http://dx.doi.org/10.1177/0363546521994555DOI Listing
April 2021

Characterization of the distributions of collagen and PGs content in the decellularized book-shaped enthesis scaffolds by SR-FTIR.

BMC Musculoskelet Disord 2021 Mar 1;22(1):235. Epub 2021 Mar 1.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Background: Bone-tendon interface (enthesis) plays a pivotal role in relaxing load transfer between otherwise structurally and functionally distinct tissue types. Currently, decellularized extracellular matrix (DEM) from enthesis provide a natural three-dimensional scaffold with tissue-specific orientations of extracellular matrix molecules for enthesis regeneration, however, the distributions of collagen and PGs content in the decellularized book-shaped enthesis scaffolds from rabbit rotator cuff by SR-FTIR have not been reported.

Methods: Native enthesis tissues (NET) harvested from rabbit rotator cuff were sectioned into cuboid (about 30 mm × 1.2 mm × 10 mm) for decalcification. The decellularized book-shaped enthesis scaffolds and intrinsic ultrastructure were evaluated by histological staining and scanning electron microscopy (SEM), respectively. The distributions of collagen and PGs content in the decellularized book-shaped enthesis scaffolds from rabbit rotator cuff were also measured innovatively by SR-FTIR.

Results: The decellularized book-shaped enthesis scaffolds from rabbit rotator cuff were successfully obtained. Histomorphology and SEM evaluated the effect of decellularization and the structure of extracellular matrix during decellularization. After mechanical testing, the failure load in the NET group showed significantly higher than that in the DEM group (P < 0.05). Meanwhile, the stiffness of the DEM group was significantly lower than the NET group. Furthermore, the distributions of collagen and PGs content in the decellularized book-shaped enthesis scaffolds were decreased obviously after decellularization by SR-FTIR quantitative analysis.

Conclusion: SR-FTIR was applied innovatively to characterize the histological morphology of native enthesis tissues from rabbit rotator cuff. Moreover, this technology can be applied for quantitative mapping of the distribution of collagen and PGs content in the decellularized book-shaped enthesis scaffolds.
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http://dx.doi.org/10.1186/s12891-021-04106-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923620PMC
March 2021

Two-dimensional quasi-nanosheets enabled by coordination-driving deposition and sequential etching.

Nanoscale 2021 Mar 24;13(9):4758-4766. Epub 2021 Feb 24.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Collaborative Innovation Center of Polymers and Polymer Composites, Fudan University, 2005 Songhu Road, Shanghai 200438, China.

Transition-metal compounds are attractive for catalysis and other fields but generally suffer from aggregating propensity, circuitous diffusion pathways and limited reaction activities. Two-dimensional (2D) quasi-nanosheets composed of nano-sized crystals with precisely controlled stoichiometric features can readily overcome these problems. We here construct a variety of interconnected 2D holey arrays composed of single-crystal nitrogen-doped nanoparticles through a coordination-driving deposition and sequential etching (CDSE) strategy, independent of the phases and stoichiometries of target crystals. The strong coordination between the empty orbits of metal ions and n-orbits of pyridine nitrogen in conjugated carbon nitride (CN) confines the growth of metal species in 2D form. Meanwhile, the eighteen-membered-rings of CN coupled with metal ions can be thermally etched preferentially as a result of weakened N[double bond, length as m-dash]C bonds caused by forming the TiO-N configuration. The as-obtained metal oxide quasi-nanosheets and their phosphatized counterparts show impressive activities in photocatalysis and electrocatalysis owing to the synergetic effect of geometric and compositional features. Our CDSE strategy offers a versatile platform, with which to explore the properties and functions of hierarchical architectures.
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http://dx.doi.org/10.1039/d0nr08620gDOI Listing
March 2021

The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model.

Am J Sports Med 2021 03 16;49(4):909-917. Epub 2021 Feb 16.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Background: How to improve rotator cuff healing remains a challenge. Little is known about the effect of the parasympathetic transmitter acetylcholine (ACh) and the acetylcholinesterase inhibitor pyridostigmine (PYR), both of which have anti-inflammatory properties, in the healing process of rotator cuff injury.

Hypothesis: ACh and PYR could enhance bone-tendon interface healing in a murine model of rotator cuff repair.

Study Design: Controlled laboratory study.

Methods: A total of 160 C57BL/6 mice underwent unilateral rotator cuff repair surgery. Fibrin gel (FG) was used as a drug carrier. The mice were randomly assigned to 4 groups with 40 mice per group: FG group (received FG alone), 10 M ACh group (received FG containing 10 M ACh), 10 M ACh group (received FG containing 10 M ACh), and PYR group (received FG containing 25 µg of PYR). Ten mice in each group were euthanized at 2, 4, 8, and 12 weeks postoperatively. Histologic, immunohistochemical, and biomechanical evaluations were performed for analysis.

Results: Histologically, fibrocartilage-like tissue was shown at the repaired site. The proteoglycan content of the 10 M ACh group was significantly increased compared with the FG group at 4 weeks. M2 macrophages were identified at the repaired site for all groups at 2 and 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the FG group, but a number of M2 macrophages were retained at the repaired sites in the ACh and PYR groups. Biomechanically, failure load and stiffness of the ACh and PYR groups were significantly higher than those of the FG group at 4 weeks. The stiffness of the ACh and PYR groups was significantly increased compared with the FG group at 8 weeks ( < .001 for all). At 12 weeks, most of the healing properties of the ACh and PYR groups were not significantly different compared with the FG group.

Conclusion: ACh and PYR enhanced the early stage of bone-tendon insertion healing after rotator cuff repair.

Clinical Relevance: These findings imply that ACh and PYR could serve as potential therapeutic strategies for rotator cuff healing.
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http://dx.doi.org/10.1177/0363546520988680DOI Listing
March 2021

Performance and bacterial community dynamics of hydroponically grown Iris pseudacorus L. during the treatment of antibiotic-enriched wastewater at low/normal temperature.

Ecotoxicol Environ Saf 2021 Apr 11;213:111997. Epub 2021 Feb 11.

College of Life Science, Cangzhou Normal University, Cangzhou 061001, PR China.

Antibiotics are widely detected in the water environment, posing a serious threat to the health of humans and animals. The effect of levofloxacin (LOFL) on pollutant removal and the difference in the influence mechanisms at normal and low temperatures in constructed wetlands are worth discussing. A hydroponic culture experiment was designed with Iris pseudacorus L. at low and normal temperatures. LOFL (0-100 µg/L) was added to the systems. The results indicated that the removal of pollutants was affected most by temperature, followed by LOFL concentration. At the same concentration of LOFL, the pollutant removal rate was significantly higher at normal temperature than at low temperature. Low concentrations of LOFL promoted the degradation of pollutants except TN under normal-temperature conditions. Compared with the results at low temperature, the bacterial community richness was higher and the diversity of bacterial communities was lower under normal-temperature conditions. The genera and the function of bacteria were greatly affected by antibiotic concentration, temperature and test time. A series of microorganisms resistant to antibiotics and low temperature were identified in this study. The results will provide valuable information and a reference for our understanding of the ecological effects of LOFL.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111997DOI Listing
April 2021

Acceleration of Bone-Tendon Interface Healing by Low-Intensity Pulsed Ultrasound Is Mediated by Macrophages.

Phys Ther 2021 Feb 9. Epub 2021 Feb 9.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.

Objective: Low-intensity pulsed ultrasound (LIPUS) has been proven to facilitate bone-tendon interface (BTI) healing and regulate some inflammatory cytokines. However, the role of macrophages, a key type of inflammatory cell, during treatment remains unknown. This study aimed to investigate the role of macrophages in the treatment of BTI injury with LIPUS in a rotator cuff tear animal model.

Methods: In this experimental and comparative study, a total of 160 C57BL/6 mature male mice that underwent supraspinatus tendon detachment and repair were randomly assigned to 4 groups: daily ultrasonic treatment and liposomal clodronate (LIPUS+LC), daily ultrasonic treatment and liposomes (LIPUS), daily mock sonication and liposomal clodronate (LC), and daily mock sonication and liposomes (control). LIPUS treatment was initiated immediately postoperatively and continued daily until the end of the experimental period.

Results: The failure load and stiffness of the supraspinatus tendon-humerus junction were significantly higher in the LIPUS group than in the other groups at postoperative weeks 2 and 4, whereas those in the LIPUS+LC and LC groups were lower than those in the control group at postoperative week 4. The LIPUS, LIPUS+LC, and LC groups exhibited significantly more fibrocartilage than the control group at 2 weeks. Only the LIPUS group had more fibrocartilage than the control group at 4 weeks. Micro-computed tomography results indicated that LIPUS treatment could improve the bone quality of the attachment site after both 2 and 4 weeks. When macrophages were depleted by LC, the bone quality-promoting effect of LIPUS treatment was significantly reduced.

Conclusions: The enhancement of BTI healing by LIPUS might be mediated by macrophages.

Impact: In our study, LIPUS treatment appeared to accelerate BTI healing, which was associated with macrophages based on our murine rotator cuff repair model. The expressions of macrophage under LIPUS treatment may offer a potential mechanism to explain BTI healing and the effects of LIPUS on BTI healing.
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http://dx.doi.org/10.1093/ptj/pzab055DOI Listing
February 2021

UTX/KDM6A deletion promotes the recovery of spinal cord injury by epigenetically triggering intrinsic neural regeneration.

Mol Ther Methods Clin Dev 2021 Mar 10;20:337-349. Epub 2020 Dec 10.

Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha 410008, China.

Interrupted axons that fail to regenerate mainly cause poor recovery after spinal cord injury (SCI). How neurons epigenetically respond to injury determines the intrinsic growth ability of axons. However, the mechanism underlying epigenetic regulation of axonal regeneration post-SCI remains largely unknown. In this study, we elucidated the role of the epigenetic regulatory network involving ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX)/microRNA-24 (miR-24)/NeuroD1 in axonal regeneration and functional recovery in mice following SCI. Our results showed that UTX was significantly increased post-SCI and repressed axonal regeneration . However, downregulation of UTX remarkably promoted axonal regeneration. Furthermore, miR-24 was increased post-SCI and positively regulated by UTX. miR-24 also inhibited axonal regeneration. Chromatin immunoprecipitation (ChIP) indicated that UTX binds to the miR-24 promoter and regulates miR-24 expression. Genome sequencing and bioinformatics analysis suggested that NeuroD1 is a potential downstream target of UTX/miR-24. A dual-luciferase reporter assay indicated that miR-24 binds to NeuroD1; moreover, it represses axonal regeneration by negatively regulating the expression of NeuroD1 via modulation of microtubule stability. UTX deletion prominently promoted axonal regeneration and improved functional recovery post-SCI, and silencing NeuroD1 restored UTX function. Our findings indicate that UTX could be a potential target in SCI.
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http://dx.doi.org/10.1016/j.omtm.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820127PMC
March 2021

Effect of book-shaped acellular tendon scaffold with bone marrow mesenchymal stem cells sheets on bone-tendon interface healing.

J Orthop Translat 2021 Jan 24;26:162-170. Epub 2020 Mar 24.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.

Background: Tissue engineering has exhibited great effect on treatment for bone-tendon interface (BTI) injury. The aim of this study was to evaluate the effect of a book-shaped acellular tendon scaffold (ATS) with bone marrow mesenchymal stem cells sheets (MSCS) for BTI injury repair.

Methods: ATS was designed based on the shape of "book", decellularization effect was evaluated by Hematoxylin and eosin (H&E), 4', 6-diamidino-2-phenylindole (DAPI) and scanning electron microscopy (SEM), then bone marrow mesenchymal stem cells (MSCs) were cultured on ATS to assess the differentiation inductivity of ATS. A rabbit right partial patellotomy model was established, and MSCS seeded on ATS were implanted into the lesion site. The patella-patellar tendon (PPT) at 2, 4, 8 or 16 weeks post-operation were obtained for histological, biomechanical and immunofluorescence analysis.

Results: H&E, DAPI and SEM results confirmed the efficiency of decellularization of ATS, and their in vitro tenogenic and chondrogenic ability were successfully identified. In vivo results showed increased macrophage polarization toward the M2 phenotype, IL-10 expression, regenerated bone and fibrocartilage at the patella-patellar tendon interface of animals received MSCS modified ATS implantation. In addition, the level of tensile strength was also the highest in MSCS modified ATS implantation group.

Conclusion: This study suggests that ATS combined with MSCS performed therapeutic effects on promoting the regeneration of cartilage layer and enhancing the healing quality of patella-patellar tendon interface.

The Translational Potential Of This Article: This study showed the good biocompatibility of the ATS, as well as the great efficacy of ATS with MSCS on tendon to bone healing. The results meant that the novel book-shaped ATS with MSCS may have a great potential for clinical application.
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http://dx.doi.org/10.1016/j.jot.2020.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773951PMC
January 2021

Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis.

Stem Cell Res Ther 2021 Jan 7;12(1):20. Epub 2021 Jan 7.

Department of Spine Surgery and Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China.

Background: Spinal cord injury is a devastating clinical condition for which there are currently no effective therapeutic options. In the present study, we aim to investigate if the effect of an administered injection of exosomes derived from human urine stem cell (USC-Exo) embedded in hydrogel could improve the spinal cord functional recovery after injury and the underlying mechanism.

Methods: Exosomes were isolated from USC and identified by transmission electron microscopy (TEM) and Western blot. Functional assays in vitro were performed to assess the effects of USC-Exo on tube formation and migration, as well as their regulatory role in the PI3K/AKT signaling pathway activation. A locally administered injection of exosome embedded in hydrogel was used for SCI treatment. The effects of USC-Exo on functional recovery and the role of the candidate protein ANGPTL3 harboring in USC-Exo for promoting angiogenesis in SCI model were assessed.

Results: In the current study, we demonstrate that a locally administered injection of USC-Exo embedded in hydrogel can pass the spinal cord blood-brain barrier and deliver ANGPTL3 to the injured spinal cord region. In addition, the administration of human USC-Exo could enhance spinal cord neurological functional recovery by promoting angiogenesis. The results of mechanistic studies revealed that ANGPTL3 is enriched in USC-Exo and is required for their ability to promote angiogenesis. Functional studies further confirmed that the effects of USC-Exo on angiogenesis are mediated by the PI3K/AKT signaling pathway.

Conclusion: Collectively, our results indicate that USC-Exo serve as a crucial regulator of angiogenesis by delivering ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.
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http://dx.doi.org/10.1186/s13287-020-02078-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791988PMC
January 2021

A combinatorial method to visualize the neuronal network in the mouse spinal cord: combination of a modified Golgi-Cox method and synchrotron radiation micro-computed tomography.

Histochem Cell Biol 2021 Apr 4;155(4):477-489. Epub 2021 Jan 4.

Department of Spine Surgery, Xiangya Hospital, Central South University, Xiangya Road No. 87, Changsha, 410008, Hunan, People's Republic of China.

Exploring the three-dimensional (3D) morphology of neurons is essential to understanding spinal cord function and associated diseases comprehensively. However, 3D imaging of the neuronal network in the broad region of the spinal cord at cellular resolution remains a challenge in the field of neuroscience. In this study, to obtain high-resolution 3D imaging of a detailed neuronal network in the mass of the spinal cord, the combination of synchrotron radiation micro-computed tomography (SRμCT) and the Golgi-cox staining were used. We optimized the Golgi-Cox method (GCM) and developed a modified GCM (M-GCM), which improved background staining, reduced the number of artefacts, and diminished the impact of incomplete vasculature compared to the current GCM. Moreover, we achieved high-resolution 3D imaging of the detailed neuronal network in the spinal cord through the combination of SRμCT and M-GCM. Our results showed that the M-GCM increased the contrast between the neuronal structure and its surrounding extracellular matrix. Compared to the GCM, the M-GCM also diminished the impact of the artefacts and incomplete vasculature on the 3D image. Additionally, the 3D neuronal architecture was successfully quantified using a combination of SRμCT and M-GCM. The SRμCT was shown to be a valuable non-destructive tool for 3D visualization of the neuronal network in the broad 3D region of the spinal cord. Such a combinatorial method will, therefore, transform the presentation of Golgi staining from 2 to 3D, providing significant improvements in the 3D rendering of the neuronal network.
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http://dx.doi.org/10.1007/s00418-020-01949-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062354PMC
April 2021

Designing a novel vacuum aspiration system to decellularize large-size enthesis with preservation of physicochemical and biological properties.

Ann Transl Med 2020 Nov;8(21):1364

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Background: Functional and rapid enthesis regeneration remains a challenge after arthroscopic rotator cuff (RC) repair. Tissue-engineering a large-size biomimetic scaffold may be an adjuvant strategy to improve this clinical dilemma. Herein, we developed an optimized protocol to decellularize large-size enthesis as scaffolds for augmenting RC tear.

Methods: A novel vacuum aspiration system (VAS) was set up, which can provide a negative pressure to suck out cellular substances from tissue blocks without using chemical detergents. Large-size enthesis tissue specimens were harvested from canine infraspinatus tendon (IT) insertion, and then decellularized with an optimized protocol [freeze-thaw processing followed by nuclease digestion and phosphate buffer saline (PBS) rinsing in the custom-designed VAS], or a conventional protocol (freeze-thaw processing followed by nuclease digestion and PBS rinsing), thus fabricating two kinds of acellular enthesis matrix (AEM), namely C-AEM and O-AEM. After that, the C-AEM and O-AEM were comparatively evaluated from the aspect of their physicochemical and biological properties.

Results: Physiochemically, the O-AEM preserved the morphologies, ingredients, and tensile properties much better than the C-AEM. Biologically, studies demonstrated that both C-AEM and O-AEM show no cytotoxicity and low immunogenicity, which could promote stem cells attachment and proliferation. Interestingly, O-AEM showed better region-specific inducibility on the interacted stem cell down osteogenic, chondrogenic and tenogenic lineages compared with C-AEM. Additionally, using a canine IT repair model, the injured enthesis patched with O-AEM showed a significant improvement compared with the injured enthesis patched with C-AEM or direct suture histologically.

Conclusions: The proposed VAS may help us fabricate large-size AEM with good physicochemical and biological properties, and this AEM may have potential clinical applications in patching large/massive RC tear.
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http://dx.doi.org/10.21037/atm-20-3661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723548PMC
November 2020

Isolation and Characterization of Multipotent Canine Urine-Derived Stem Cells.

Stem Cells Int 2020 30;2020:8894449. Epub 2020 Sep 30.

Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008.

Current cell-based therapies on musculoskeletal tissue regeneration were mostly determined in rodent models. However, a direct translation of those promising cell-based therapies to humans exists a significant hurdle. For solving this problem, canine has been developed as a new large animal model to bridge the gap from rodents to humans. In this study, we reported the isolation and characterization of urine-derived stem cells (USCs) from mature healthy beagle dogs. The isolated cells showed fibroblast-like morphology and had good clonogenicity and proliferation. Meanwhile, these cells positively expressed multiple markers of MSCs (CD29, CD44, CD90, and CD73), but negatively expressed for hematopoietic antigens (CD11b, CD34, and CD45). Additionally, after induction culturing, the isolated cells can be differentiated into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. The successful isolation and verification of USCs from canine were useful for studying cell-based therapies and developing new treatments for musculoskeletal injuries using the preclinical canine model.
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http://dx.doi.org/10.1155/2020/8894449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545436PMC
September 2020

Treadmill running initiation times and bone-tendon interface repair in a murine rotator cuff repair model.

J Orthop Res 2020 Sep 16. Epub 2020 Sep 16.

Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, People's Republic of China.

Postoperative exercise has been demonstrated to be beneficial for bone-tendon interface (BTI) healing, yet the debate regarding the optimal time to initiate exercise after tendon enthesis repair is ongoing. This study aimed to evaluate the initiation times for exercise after enthesis repair. A total of 192 C57BL/6 mice underwent acute supraspinatus tendon injury repair. The animals were then randomly assigned to four groups: free cage activity after repair (control group); treadmill running started on postoperative day 2 (2-day delayed group); treadmill running started on postoperative day 7 (7-day delayed group), and treadmill running started on postoperative day 14 (14-day delayed group). Mice were euthanized at 4 and 8 weeks postoperatively, and histological, biomechanical, and bone morphometric tests were performed. Higher failure loads and bone volume fractions were found for the 7-day delayed group and the 14-day delayed group at 4 weeks postoperatively. The 7-day delayed group had better biomechanical properties and higher bone volume fractions than the 2-day delayed group at 4 weeks postoperatively. Histologically, the 7-day delayed group exhibited lower modified tendon-to-bone maturity scores than the control group and the 2-day delayed group at 4 and 8 weeks postoperatively. Quantitative reverse-transcription polymerase chain reaction results showed that the 7-day delayed group had higher expressions of chondrogenic- and osteogenic-related genes. Statement of clinical significance: Postoperative treadmill running initiated on postoperative day 7 had a more prominent effect on BTI healing than other treatment regimens in this study and could accelerate BTI healing and rotator cuff repair.
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http://dx.doi.org/10.1002/jor.24863DOI Listing
September 2020

Periosteum progenitors could stimulate bone regeneration in aged murine bone defect model.

J Cell Mol Med 2020 10 15;24(20):12199-12210. Epub 2020 Sep 15.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Periosteal stem cells are critical for bone regeneration, while the numbers will decrease with age. This study focused on whether Prx1 cell, a kind of periosteal stem cell, could stimulate bone regeneration in aged mice. Four weeks and 12 months old Prx1CreER-GFP; Rosa26 mice were used to reveal the degree of Prx1 cells participating in the femoral fracture healing procedure. One week, 8 weeks, 12 and 24 months old Prx1CreER-GFP mice were used to analyse the real-time distribution of Prx1 cells. Twelve months old C57BL/6 male mice (n = 96) were used to create the bone defect model and, respectively, received hydrogel, hydrogel with Prx1 mesenchymal stem cells and hydrogel with Prx1 cells. H&E staining, Synchrotron radiation-microcomputed tomography and mechanical test were used to analyse the healing results. The results showed that tdTomato cells were involved in bone regeneration, especially in young mice. At the same time, GFP cells decreased significantly with age. The Prx1 cells group could significantly improve bone regeneration in the murine bone defect model via directly differentiating into osteoblasts and had better osteogenic differentiation ability than Prx1 mesenchymal stem cells. Our finding revealed that the quantity of Prx1 cells might account for decreased bone regeneration ability in aged mice, and transplantation of Prx1 cells could improve bone regeneration at the bone defect site.
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http://dx.doi.org/10.1111/jcmm.15891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579685PMC
October 2020

Bacterial response to formaldehyde in an MFC toxicity sensor.

Enzyme Microb Technol 2020 Oct 20;140:109565. Epub 2020 Apr 20.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, PR China; Research Center of Environmental Pollution Control Engineering Technology, Chinese Research Academy of Environmental Sciences, Beijing, 100012, PR China. Electronic address:

Microbial fuel cells (MFCs) have been extensively studied as toxicity sensors. MFCs have potential as toxicity sensors because when their anodes are exposed to toxic substances or the concentration of the target is changed, the voltage generated by certain microorganisms with active electrical activity attached to the anode changes. However, the underlying reasons behind this phenomenon have not been deeply explored. Therefore, the activity of anodic microorganisms during voltage drops in MFCs under formaldehyde (FA) stress was studied. The composition of the microbial community structure with similar active voltage drops under different concentrations of FA was investigated. The results showed that under exposure to high concentrations (169.20 mg/L) of FA, the voltage changes in MFCs could be divided into five stages. With prolonged exposure to FA, the ratio of live/dead bacteria decreased from 4.78 to 0.65. This result indicated that voltage drops may be caused by FA causing cell membrane rupture. Analysis of the microbial community structure under treatments including inoculation and three concentrations of FA revealed that Geobacter and other electrogenic bacteria were effectively enriched in the MFCs. Low-concentration and long-term exposure to FA had a greater impact on microbial communities than high-concentration and short-term exposure. Pseudomonas and Acidovorax were more significantly affected by FA than Flavobacterium and Geobacter. This study explains the reason for the voltage drop of MFCs after exposure to toxic substances from the perspective of the microorganisms.
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http://dx.doi.org/10.1016/j.enzmictec.2020.109565DOI Listing
October 2020

3D-Printed Extracellular Matrix/Polyethylene Glycol Diacrylate Hydrogel Incorporating the Anti-inflammatory Phytomolecule Honokiol for Regeneration of Osteochondral Defects.

Am J Sports Med 2020 09 7;48(11):2808-2818. Epub 2020 Aug 7.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Background: Osteoarthritis is the leading cause of disability worldwide; cartilage degeneration and defects are the central features. Significant progress in tissue engineering holds promise to regenerate damaged cartilage tissue. However, a formidable challenge is to develop a 3-dimensional (3D) tissue construct that can regulate local immune environment to facilitate the intrinsic osteochondral regeneration.

Purpose: To evaluate efficacy of a 3D-printed decellularized cartilage extracellular matrix (ECM) and polyethylene glycol diacrylate (PEGDA) integrated novel scaffold (PEGDA/ECM) together with the natural compound honokiol (Hon) for regenerating osteochondral defect.

Study Design: Controlled laboratory study.

Methods: We used a stereolithography-based 3D printer for PEGDA/ECM bioprinting. A total of 36 Sprague-Dawley rats with cylindrical osteochondral defect in the trochlear groove of the femur were randomly assigned into 3 different treatments: no scaffold implantation (Defect group), 3D printed PEGDA/ECM scaffold alone (PEGDA/ECM group), or Hon suspended in a 3D-printed PEGDA/ECM scaffold (PEGDA/ECM/Hon group). 12 rats that underwent only medial parapatellar incision surgery were used as normal controls. The femur specimens were postoperatively harvested at 4 and 8 weeks for gross, micro-CT, and histological evaluations. The efficacy of PEGDA/ECM/Hon scaffold on the release of proinflammatory cytokines from the macrophages stimulated by lipopolysaccharide (LPS) was evaluated in-vitro.

Results: In vitro results determined that PEGDA/ECM/Hon scaffold could suppress the release of proinflammatory cytokines from macrophages that were stimulated by LPS. Macroscopic images showed that the PEGDA/ECM/Hon group had significantly higher ICRS scoring than that of defect and PEGDA/ECM groups. Micro-CT evaluation demonstrated that much more bony tissue was formed in the defect sites implanted with the PEGDA/ECM scaffold or PEGDA/ECM/Hon scaffold compared with the untreated defects. Histological analysis showed that the PEGDA/ECM/Hon group had a significant enhancement in osteochondral regeneration at 4 and 8 weeks after surgery in comparison with the ECM/PEGDA or defect group.

Conclusion: This study demonstrated that 3D printing of PEGDA/ECM hydrogel incorporating the anti-inflammatory phytomolecule honokiol could provide a promising scaffold for osteochondral defect repair.
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http://dx.doi.org/10.1177/0363546520941842DOI Listing
September 2020

Shape-controlled synthesis of planar PtPb nanoplates for highly efficient methanol electro-oxidation reaction.

Chem Commun (Camb) 2020 Aug;56(64):9138-9141

School of Chemistry and Chemical Engineering, Nantong University, 9 Seyuan Road, Nantong, 226019, Jiangsu, P. R. China.

In this work, novel insights into the influence of different nanocrystal structures on the electrocatalytic oxidation of methanol are reported. Herein, we have successfully prepared high-yield PtPb nanoplates in the diethylene glycol (DEG) solvent. The as-obtained PtPb nanoplates with a large surface area of the (102) facet show higher MOR activity and superior durability in alkaline electrolyte compared with both zero-dimensional PtPb nanoparticles and commercial Pt/C. Further chronoamperometric (CA) measurements and discrete Fourier transform (DFT) calculations indicate that the PtPb nanoplates possess much better operation durability and CO tolerance due to the negative adsorption energy of the (102) facet.
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http://dx.doi.org/10.1039/d0cc03704dDOI Listing
August 2020

A quick start method for microbial fuel cells.

Chemosphere 2020 Nov 15;259:127323. Epub 2020 Jun 15.

School of Chemical and Environmental Engineering, China University of Mining and Technology (Beijing), Beijing, 100083, PR China.

Microbial fuel cells (MFCs) have great potential to detect toxicity early. Study of toxicity sensors based on MFCs requires a large number of stable MFCs. However, the start-up time of MFCs is generally long, which limits research progress. In this study, a first-stage preculture based on H-type MFCs (first culture) and a second-stage preculture based on multistage MFC reactor series culture (second culture) were used in combination with preculture MFCs. The goal of obtaining an MFC with stable performance in only one day was achieved. The obtained MFC could be stable for 33 h and rapidly regenerated with replacement of the anode substrate. The start-up time was shortened because after the first culture and the secondary culture, the protein content attached to the electrode reached 1.2864 ± 0.0174 mg/cm and 2.22 ± 0.12 mg/cm, respectively. Bacteria that generate electricity, such as Geobacter, were effectively enriched. This study may improve the development efficiency of MFC toxicity sensors.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127323DOI Listing
November 2020

Enhanced Polysulfide Regulation Porous Catalytic VO/VC Heterostructures Derived from Metal-Organic Frameworks toward High-Performance Li-S Batteries.

ACS Nano 2020 Jul 24;14(7):8495-8507. Epub 2020 Jun 24.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Collaborative Innovation Center of Polymers and Polymer Composites, Fudan University, Shanghai 200438, China.

The development of Li-S batteries is largely impeded by the complicated shuttle effect of lithium polysulfides (LiPSs) and sluggish reaction kinetics. In addition, the low mass loading/utilization of sulfur is another key factor that makes Li-S batteries difficult to commercialize. Here, a porous catalytic VO/VC@carbon composite derived from MIL-47 (V) featuring heterostructures is reported to be an efficient polysulfide regulator in Li-S batteries, achieving a substantial increase in sulfur loading while still effectively suppressing the shuttle effect and enhancing kinetics. Systematic mechanism analyses suggest that the LiPSs strongly adsorbed on the VO surface can be rapidly transferred to the VC surface through the built-in interface for subsequent reversible conversion by an efficient catalytic effect, realizing enhanced regulation of LiPSs from capture to conversion. In addition, the porous structure provides sufficient sulfur storage space, enabling the heterostructures to exert full efficacy with a high sulfur loading. Thus, this S-VO/VC@carbon@graphene cathode exhibits prominent rate performance (587.6 mAh g at 5 C) and a long lifespan (1000 cycles, 0.017% decay per cycle). It can still deliver superior electrochemical performance even with a sulfur loading of 8.1 mg cm. These heterostructures can be further applied in pouch cells and produce stable output at different folding angles (0-180°). More crucially, the cells could retain 4.3 mAh cm even after 150 cycles, which is higher than that of commercial lithium-ion batteries (LIBs). This strategy for solving the shuttle effect under high sulfur loading provides a promising solution for the further development of high-performance Li-S batteries.
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http://dx.doi.org/10.1021/acsnano.0c02762DOI Listing
July 2020

SRμCT Reveals 3D Microstructural Alterations of the Vascular and Neuronal Network in a Rat Model of Chronic Compressive Thoracic Spinal Cord Injury.

Aging Dis 2020 May 9;11(3):603-617. Epub 2020 May 9.

1Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China.

The complex pathology of chronic thoracic spinal cord compression involves vascular and neuroarchitectural repair processes that are still largely unknown. In this study, we used synchrotron radiation microtomography (SRμCT) to quantitatively characterize the 3D temporal-spatial changes in the vascular and neuronal network after chronic thoracic spinal cord compression in order to obtain further insights into the pathogenesis of this disease and to elucidate its underlying mechanisms. Direct 3D characterization of the spinal cord microvasculature and neural microstructure of the thoracic spinal cord was successfully reconstructed. The significant reduction in vasculature and degeneration of neurons in the thoracic spinal cord visualized via SRμCT after chronic compression were consistent with the changes detected by immunofluorescence staining. The 3D morphological measurements revealed significant reductions of neurovascular parameters in the thoracic spinal cord after 1 month of compression and became even worse after 6 months without relief of compression. In addition, the distinct 3D morphological twist and the decrease in branches of the central sulcal artery after chronic compression vividly displayed that these could be the potential triggers leading to blood flow reduction and neural deficits of the thoracic spinal cord. Our findings propose a novel methodology for the 3D analysis of neurovascular repair in chronic spinal cord compression, both qualitatively and quantitatively. The results indicated that compression simultaneously caused vascular dysfunction and neuronal network impairment, which should be acknowledged as concurrent events after chronic thoracic spinal cord injury. Combining neuroprotection with vasoprotection may provide promising therapeutic targets for chronic thoracic spinal cord compression.
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http://dx.doi.org/10.14336/AD.2019.0529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220295PMC
May 2020

Extracting drug-drug interactions from texts with BioBERT and multiple entity-aware attentions.

J Biomed Inform 2020 06 23;106:103451. Epub 2020 May 23.

School of Computer Science and Technology, Dalian University of Technology, 116024 Dalian, China. Electronic address:

Drug-drug interactions (DDIs) extraction is one of the important tasks in the field of biomedical relation extraction, which plays an important role in the field of pharmacovigilance. Previous neural network based models have achieved good performance in DDIs extraction. However, most of the previous models did not make good use of the information of drug entity names, which can help to judge the relation between drugs. This is mainly because drug names are often very complex, leading to the fact that neural network models cannot understand their semantics directly. To address this issue, we propose a DDIs extraction model using multiple entity-aware attentions with various entity information. We use an output-modified bidirectional transformer (BioBERT) and a bidirectional gated recurrent unit layer (BiGRU) to obtain the vector representation of sentences. The vectors of drug description documents encoded by Doc2Vec are used as drug description information, which is an external knowledge to our model. Then we construct three different kinds of entity-aware attentions to get the sentence representations with entity information weighted, including attentions using the drug description information. The outputs of attention layers are concatenated and fed into a multi-layer perception layer. Finally, we get the result by a softmax classifier. The F-score is used to evaluate our model, which is also adopted by most previous DDIs extraction models. We evaluate our proposed model on the DDIExtraction 2013 corpus, which is the benchmark corpus of this domain, and achieves the state-of-the-art result (80.9% in F-score).
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http://dx.doi.org/10.1016/j.jbi.2020.103451DOI Listing
June 2020

Highly Oriented Graphite Aerogel Fabricated by Confined Liquid-Phase Expansion for Anisotropically Thermally Conductive Epoxy Composites.

ACS Appl Mater Interfaces 2020 Jun 2;12(24):27476-27484. Epub 2020 Jun 2.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Collaborative Innovation Center of Polymers and Polymer Composites, Fudan University, 2005 Songhu Road, Shanghai 200438, P. R. China.

Graphene-based thermally conductive polymer composites are of great importance for the removal of the excess heat generated by electronic devices. However, due to the orientation of graphene sheets in the polymer matrix, the through-plane thermal conductivity of polymer/graphene composites remains far from satisfactory. We here demonstrate a confined liquid-phase expansion strategy to fabricate highly oriented confined expanded graphite (CEG) aerogels. After being incorporated into epoxy resin (EP), the resulting EP/CEG composites exhibit a high through-plane thermal conductivity (4.14 ± 0.21 W m K) at a quite low filler loading of 1.75 wt % (0.91 vol %), nearly 10 times higher than that of neat EP resin and 7.5 times higher than the in-plane thermal conductivity of the composite, indicating that the CEG aerogel has a high through-plane thermal conductivity enhancement efficiency that outperforms those of many graphite/graphene-based fillers. The facile preparation method holds great industrial application potential in fabricating anisotropic thermally conductive polymer composites.
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http://dx.doi.org/10.1021/acsami.0c02151DOI Listing
June 2020

Functional decellularized fibrocartilaginous matrix graft for rotator cuff enthesis regeneration: A novel technique to avoid in-vitro loading of cells.

Biomaterials 2020 08 17;250:119996. Epub 2020 Apr 17.

Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China. Electronic address:

Rapid and functional enthesis regeneration after rotator cuff tear (RCT) remains a challenge in clinic. Current tissue-engineering strategies for solving this challenge are focused on developing grafts with the mode of in-vitro loading cells on a scaffold. However, this mode is complicated and time-inefficient, moreover the preservation of this graft outside a cell incubator is highly inconvenient, thus limiting their clinical application. Developing a cell-free graft with chemotaxis to recruit postoperative injected cells may be a promising approach to solve these problems. Herein, we prepared a recombinant SDF-1α (termed as C-SDF-1α) capable of binding collagen and chemotaxis, which were then tethered on the collagen fibers of book-shaped decellularized fibrocartilage matrix (BDFM) to fabricate this cell-free graft (C-SDF-1α/BDFM). This C-SDF-1α/BDFM is noncytotoxicity and low-immunogenicity, allows synovium-derived mesenchymal stem cells (SMSCs) attachment and proliferation, and shows superior chondrogenic inducibility. More importantly, C-SDF-1α/BDFM released the tethered SDF-1α with a sustained release profile in-vitro and in-vivo, thus steadily recruiting chemokine (C-X-C motif) receptor 4 positive (CXCR4) cells. Rats with RCT were repaired acutely with C-SDF-1α/BDFM together with postoperative CXCR4SMSCs injection (C-SDF-1α/BDFM + CXCR4SMSCs), BDFM in-vitro pre-loaded CXCR4SMSCs (BDFM/CXCR4SMSCs), or direct suture only (CTL). At postoperative 14-day, compared with BDFM/CXCR4SMSCs, C-SDF-1α/BDFM + CXCR4SMSCs showed a little more CXCR4SMSCs at the healing site. At postoperative week 4 or 8, rats treated with C-SDF-1α/BDFM + CXCR4SMSCs presented a similar RC healing quality as BDFM/CXCR4SMSCs, both of which were significantly better than the CTL. Collectively, compared with conventional BDFM/CXCR4SMSCs, C-SDF-1α/BDFM, as a cell-free graft with chemotaxis, could recruit postoperative injected CXCR4cells into the healing site to participating RC healing, thus avoiding the complex process of in-vitro loading cells on a scaffold and necessitating immense care for the graft outside cell incubator, making it very convenient for clinical application.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119996DOI Listing
August 2020

Sustained release of collagen-affinity SDF-1α from book-shaped acellular fibrocartilage scaffold enhanced bone-tendon healing in a rabbit model.

J Orthop Res 2020 Apr 10. Epub 2020 Apr 10.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Rapid and functional bone-tendon (B-T) healing remains a difficulty in clinical practice. Tissue engineering has emerged as a promising strategy to address this problem. However, the majority of tissue engineering scaffolds are loaded with stem cells to enhance the regenerability in B-T healing, which is complicated and inconvenient for clinical application. Accordingly, developing a cell-free scaffold with chemotactic function and chondrogenic inducibility may be an effective approach. In this study, a collagen affinity peptide derived from the A3 domain of von Willebrand factor (a hemostasis factor) was fused into the C-terminal of a stromal cell-derived factor-1α (SDF-1α) to synthesize a recombinant SDF-1α capable of binding collagen and chemotactic activity. The recombinant SDF-1α was then tethered on the collagen fibers of a book-shaped acellular fibrocartilage scaffold (BAFS), thus fabricating a novel scaffold (C-SDF-1α/BAFS) with chemotactic function and chondrogenic inducibility. In vitro tests determined that this scaffold was noncytotoxic and biomimetic, could attract stem cells migrating to the scaffold using sustainably released C-SDF-1α, and inducedthe interacting stem cells down the chondrogenic lineage. In vivo, the C-SDF-1α/BAFS significantly enhanced the B-T healing in a rabbit partial patellectomy model, as shown by the larger cartilaginous metaplasia region, better fibrocartilage regeneration, additional bone formation, and improved biomechanical properties. Therefore, the findings of the study demonstrate that the C-SDF-1α/BAFS could potentially be applied for B-T healing.
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http://dx.doi.org/10.1002/jor.24687DOI Listing
April 2020

Treadmill exercise facilitated rotator cuff healing is coupled with regulating periphery neuropeptides expression in a murine model.

J Orthop Res 2021 03 9;39(3):680-692. Epub 2020 Apr 9.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Postoperative exercise has been found able to accelerate bone-tendon (B-T) healing. In this study, we systematically compared tendon-to-bone healing in mice subjected to postoperative treadmill exercise and free cage recovery in a murine rotator cuff repair model. Specifically, C57BL/6 mice underwent unilateral supraspinatus tendon (SST) detachment and repair were randomly allocated into treadmill group and control group. Treadmill group received daily treadmill running initiated from postoperative day 7 while the control group was allowed free cage activity. Mice were euthanized at postoperative 4 and 8 weeks for synchrotron radiation micro-computed tomography (SR-μCT), histology and biomechanical tests to investigate the effect of treadmill running on B-T healing. The results indicated that treadmill running initiated at day 7 postoperatively was able to accelerate B-T healing, as evidenced by better tendon-to-bone maturation and increased mechanical property. Recent studies show that peripheral neuropeptides are closely associated with musculoskeletal tissue repair. We furtherly conducted quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining to investigate the temporal-spatial expression of calcitonin gene-related peptide (CGRP), substance P (SP), and peripheral neuropeptide Y (NPY) to verify whether they are related to rotator cuff healing. Our results show increased expression of CGRP, SP, and NPY at the healing site under the effect of mechanical stimulation. In conclusion, delayed postoperative exercise with moderate strength appears to accelerate the early phase of B-T healing, a process that may prove to be linked to increased expression of periphery neuropeptides known to play a role in tissue healing.
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http://dx.doi.org/10.1002/jor.24678DOI Listing
March 2021

Structure and ingredient-based biomimetic scaffolds combining with autologous bone marrow-derived mesenchymal stem cell sheets for bone-tendon healing.

Biomaterials 2020 05 18;241:119837. Epub 2020 Feb 18.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, People's Republic of China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, People's Republic of China. Electronic address:

Tendon attaches to bone across a robust fibrocartilaginous tissue termed the bone-tendon interface (BTI), commonly injured in the field of sports medicine and orthopedics with poor prognosis. So far, there is still a lack of effective clinical interventions to achieve functional healing post BTI injury. However, tissue-engineering may be a promising treatment strategy. In this study, a gradient book-type triphasic (bone-fibrocartilage-tendon) scaffold is fabricated based on the heterogeneous structure and ingredient of BTI. After decellularization, the scaffold exhibits no residual cells, while the characteristic extracellular matrix of the original bone, fibrocartilage and tendon is well preserved. Meanwhile, the bone, fibrocartilage and tendon regions of the acellular scaffold are superior in osteogenic, chondrogenic and tenogenic inducibility, respectively. Furthermore, autologous bone marrow mesenchymal stem cell (BMSC) sheets (CS) combined with the acellular scaffolds is transplanted into the lesion site of a rabbit BTI injury model to investigate the therapeutic effects. Our results show that the CS modified scaffold not only successfully achieves triple biomimetic of BTI in structure, ingredient and cell distribution, but also effectively accelerates bone-tendon (B-T) healing. In general, this work demonstrates book-type acellular triphasic scaffold combined with autologous BMSCs sheets is a promising graft for repairing BTI injury.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119837DOI Listing
May 2020