Adipose Triglyceride Lipase Deficiency Aggravates Angiotensin II-Induced Atrial Fibrillation by Reducing Peroxisome Proliferator-Activated Receptor α Activation in Mice.

Atrial fibrillation (AF) is a main risk factor for cerebrovascular diseases but lacks precision therapy. Adipose triglyceride lipase (ATGL) is a key enzyme involved in the intracellular degradation of triacylglycerol and plays an important role in lipid and energy metabolism. However, the role of ATGL in the regulation of AF remains unclear. In this study, AF was induced by infusion of angiotensin II (Ang II, 2000 ng/kg/min) for 3 weeks in male ATGL knockout (KO) mice and age-matched C57BL/6 wild-type mice. The atrial volume was measured by echocardiography. Atrial fibrosis, inflammatory cells, and superoxide production were detected by histologic examinations. The results showed that ATGL expression was significantly downregulated in the atrial tissue of the Ang II-infused mice. Moreover, Ang II-induced increase in the inducibility and duration of AF, atrial dilation, fibrosis, inflammation, and oxidative stress in wild-type mice were markedly accelerated in ATGL KO mice; however, these effects were dramatically reversed in the ATGL KO mice administered with peroxisome proliferator-activated receptor (PPAR)-α agonist clofibric acid. Mechanistically, Ang II downregulated ATGL expression and inhibited PPAR-α activity, activated multiple signaling pathways (inhibiting kappa B kinase α/ß-nuclear factor-κB, nicotinamide adenine dinucleotide phosphate oxidase, and transforming growth factor-ß1/SMAD2/3) and reducing Kv1.5, Cx40, and Cx43 expression, thereby contributing to atrial structural and electrical remodeling and subsequent AF. In summary, our results indicate that ATGL KO enhances AF inducibility, possibly through inhibiting PPAR-α activation and suggest that activating ATGL might be a new therapeutic option for treating hypertensive AF.

Bilayered scaffold with 3D printed stiff subchondral bony compartment to provide constant mechanical support for long-term cartilage regeneration.

BACKGROUND/OBJECTIVE: We seek to figure out the effect of stable and powerful mechanical microenvironment provided by Ti alloy as a part of subchondral bone scaffold on long-term cartilage regeneration.Methods: we developed a bilayered osteochondral scaffold based on the assumption that a stiff subchondral bony compartment would provide stable mechanical support for cartilage regeneration and enhance subchondral bone regeneration. The subchondral bony compartment was prepared from 3D printed Ti alloy, and the cartilage compartment was created from a freeze-dried collagen sponge, which was reinforced by poly-lactic-co-glycolic acid (PLGA). RESULTS: In vitro evaluations confirmed the biocompatibility of the scaffold materials, while in vivo evaluations demonstrated that the mechanical support provided by 3D printed Ti alloy layer plays an important role in the long-term regeneration of cartilage by accelerating osteochondral formation and its integration with the adjacent host tissue in osteochondral defect model at rabbit femoral trochlea after 24 weeks. CONCLUSION: Mechanical support provided by 3D printing Ti alloy promotes cartilage regeneration by promoting subchondral bone regeneration and providing mechanical support platform for cartilage synergistically. TRANSLATIONAL POTENTIAL STATEMENT: The raw materials used in our double-layer osteochondral scaffolds are all FDA approved materials for clinical use. 3D printed titanium alloy scaffolds can promote bone regeneration and provide mechanical support for cartilage regeneration, which is very suitable for clinical scenes of osteochondral defects. In fact, we are conducting clinical trials based on our scaffolds. We believe that in the near future, the scaffold we designed and developed can be formally applied in clinical practice.

A novel tissue engineered nerve graft constructed with autologous vein and nerve microtissue repairs a long-segment sciatic nerve defect.

Veins are easy to obtain, have low immunogenicity, and induce a relatively weak inflammatory response. Therefore, veins have the potential to be used as conduits for nerve regeneration. However, because of the presence of venous valves and the great elasticity of the venous wall, the vein is not conducive to nerve regeneration. In this study, a novel tissue engineered nerve graft was constructed by combining normal dissected nerve microtissue with an autologous vein graft for repairing 10-mm peripheral nerve defects in rats. Compared with rats given the vein graft alone, rats given the tissue engineered nerve graft had an improved sciatic static index, and a higher amplitude and shorter latency of compound muscle action potentials. Furthermore, rats implanted with the microtissue graft had a higher density and thickness of myelinated nerve fibers and reduced gastrocnemius muscle atrophy compared with rats implanted with the vein alone. However, the tissue engineered nerve graft had a lower ability to repair the defect than autogenous nerve transplantation. In summary, although the tissue engineered nerve graft constructed with autologous vein and nerve microtissue is not as effective as autologous nerve transplantation for repairing long-segment sciatic nerve defects, it may nonetheless have therapeutic potential for the clinical repair of long sciatic nerve defects. This study was approved by the Experimental Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2016-x9-07) on September 7, 2016.

A fully biodegradable and self-electrified device for neuroregenerative medicine.

Peripheral nerve regeneration remains one of the greatest challenges in regenerative medicine. Deprivation of sensory and/or motor functions often occurs with severe injuries even treated by the most advanced microsurgical intervention. Although electrical stimulation represents an essential nonpharmacological therapy that proved to be beneficial for nerve regeneration, the postoperative delivery at surgical sites remains daunting. Here, a fully biodegradable, self-electrified, and miniaturized device composed of dissolvable galvanic cells on a biodegradable scaffold is achieved, which can offer both structural guidance and electrical cues for peripheral nerve regeneration. The electroactive device can provide sustained electrical stimuli beyond intraoperative window, which can promote calcium activity, repopulation of Schwann cells, and neurotrophic factors. Successful motor functional recovery is accomplished with the electroactive device in behaving rodent models. The presented materials options and device schemes provide important insights into self-powered electronic medicine that can be critical for various types of tissue regeneration and functional restoration.

Construction of Microunits by Adipose-Derived Mesenchymal Stem Cells Laden with Porous Microcryogels for Repairing an Acute Achilles Tendon Rupture in a Rat Model.

OBJECTIVE: Tissue engineering approaches seem to be an attractive therapy for tendon rupture. Novel injectable porous gelatin microcryogels (GMs) can promote cell attachment and proliferation, thus facilitating the repair potential for target tissue regeneration. The research objectives of this study were to assess the efficacy of tissue-like microunits constructed by multiple GMs laden with adipose-derived mesenchymal stem cells (ASCs) in accelerated tendon regeneration in a rat model. METHODS: Through a series of experiments, such as isolation and identification of ASCs, scanning electron microscopy, mercury intrusion porosimetry (MIP), laser scanning confocal microscopy and the CCK-8 test, the biocompatibility of GMs was evaluated. In an in vivo study, 64 rat right transected Achilles tendons were randomly divided into four groups: the ASCs+GMs group (microunits aggregated by multiple ASC-laden GMs injected into the gap), the ASCs group (ASCs injected into the gap), the GMs group (GMs injected into the gap) and the blank defect group (non-treated). At 2 and 4 weeks postoperatively, the healing tissue was harvested to evaluate the gross observation and scoring, biomechanical testing, histological staining and quantitative scoring. Gait analysis was performed over time. The 64 rats were randomly assigned into 4 groups: (1) micro-unit group (ASCs+GMs) containing ASC (105)-loaded 120 GMs in 60 µL DMEM; (2) cell control group (ASCs) containing 106 ASCs in 60 µL DMEM; (3) GM control group (GMs) containing 120 blank GMs in 60 µL DMEM; (4) blank defect group (Defect) containing 60 µL DMEM, which were injected into the defect sites. All animals were sacrificed at 2 and 4 weeks postsurgery (Table 1). RESULTS: In an in vitro study, GMs (from 126 µm to 348 µm) showed good porosities and a three-dimensional void structure with a good interpore connectivity of the micropores and exhibited excellent biocompatibility with ASCs. As the culture time elapsed, the extracellular matrix (ECM) secreted by ASCs encased the GMs, bound multiple microspheres together, and then formed active tendon tissue-engineering microunits. In animal experiments, the ASCs+GMs group and the ASCs group showed stimulatory effects on Achilles tendon healing. Moreover, the ASCs+GMs group was the best at improving the macroscopic appearance, histological morphology, Achilles functional index (AFI), and biomechanical properties of repair tissue without causing adverse immune reactions. CONCLUSION: Porous GMs were conducive to promoting cell proliferation and facilitating ECM secretion. The ASCs-GMs matrices showed an obvious therapeutic efficiency for Achilles tendon rupture in rats.

Platelet-Rich Plasma Therapy in the Treatment of Diseases Associated with Orthopedic Injuries.

Platelet-rich plasma (PRP) is an autologous platelet concentrate prepared from the whole blood that is activated to release growth factors (GFs) and cytokines and has been shown to have the potential capacity to reduce inflammation and improve tissue anabolism for regeneration. The use of PRP provides a potential for repair due to its abundant GFs and cytokines, which are key in initiating and modulating regenerative microenvironments for soft and hard tissues. Among outpatients, orthopedic injuries are common and include bone defects, ligament injury, enthesopathy, musculoskeletal injury, peripheral nerve injury, chronic nonhealing wounds, articular cartilage lesions, and osteoarthritis, which are caused by trauma, sport-related or other types of trauma, or tumor resection. Surgical intervention is often required to treat these injuries. However, for numerous reasons regarding limited regeneration capacity and insufficient blood supply of the defect region, these treatments commonly result in unsatisfactory outcomes, and follow-up treatment is challenging. The aim of the present review is to explore future research in the field of PRP therapy in the treatment of diseases associated with orthopedic injuries. Impact statement In recent years, platelet-rich plasma (PRP) has become widely used in the treatment of diseases associated with orthopedic injuries, and the results of numerous studies are encouraging. Due to diseases associated with orthopedic injuries being common in clinics, as a conservative treatment, more and more doctors and patients are more likely to accept PRP. Importantly, PRP is a biological product of autologous blood that is obtained by a centrifugation procedure to enrich platelets from whole blood, resulting in few complications, such as negligible immunogenicity from an autologous source, and it is also simple to produce through an efficient and cost-effective method in a sterile environment. However, the applicability, advantages, and disadvantages of PRP therapy have not yet been fully elucidated. The aim of the present review is to explore future research in the field of PRP therapy in the treatment of diseases associated with orthopedic injuries, as well as to provide references for clinics.

Facile and scalable synthesis of α-Fe2O3/γ-Fe2O3/Fe/C nanocomposite as advanced anode materials for lithium/sodium ion batteries.

To develop low-cost advanced anode materials for lithium/sodium ion batteries, the chemical reaction equilibrium of Fe(NO3)3 and glucose in hot aqueous solution is creatively used to fabricate a new α-Fe2O3/γ-Fe2O3/Fe/C nanocomposite with the primary particle sizes concentrated at 25-80 nm. As anodes for lithium ion batteries, it exhibits a discharge capacity of ∼878 mAh g-1 after 200 cycles at a current density of 200 mA g-1. Moreover, even after 1000 cycles at a current density of 3200 mA g-1, the discharge capacity is as high as ∼532 mAh g-1, with a capacity retention of over than 100% against that of the second cycle. As anodes for sodium ion batteries, the nanocomposite displays a stable discharge capacity of ∼400 mAh g-1 at a current density of 100 mA g-1 and no obvious capacity degradation happens after 200 cycles. During cycling, the α-Fe2O3/γ-Fe2O3/Fe/C nanocomposite electrodes shows high structural stability and relatively faster reaction kinetics, which should be responsible for its excellent electrochemical performance. This work provides a facile and scalable route to synthesize high-performance and low-cost Fe2O3-based nanocomposite for the secondary batteries.