Naringenin reduces oxidative stress and necroptosis, apoptosis, and pyroptosis in random-pattern skin flaps by enhancing autophagy.

BACKGROUND: Random skin flap grafting is one of the most commonly used techniques in plastic and orthopedic surgery. However, necrosis resulting from ischemia and ischemia-reperfusion injury in the distal part of the flap can severely limit the clinical application of the flap. Studies have revealed that naringenin reduces pyroptosis, apoptosis, and necroptosis, inhibits oxidative stress, and promotes autophagy. In this study, the effects of Naringenin on flap viability and its underlying mechanism were evaluated. METHODS: Mice with random skin flaps were randomly allocated to control, Naringenin, and Naringenin + 3-methyladenine groups. On postoperative day 7, flap tissues were collected to estimate angiogenesis, necroptosis, apoptosis, pyroptosis, oxidative stress, and autophagy via hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. RESULTS: The results revealed that naringenin promoted the viability of the random flaps as well as angiogenesis, while inhibiting oxidative stress and decreasing pyroptosis, apoptosis, and necroptosis. These effects were reversed by the autophagy inhibitor 3-methyladenine. CONCLUSIONS: The findings indicated that naringenin treatment could promote flap survival by inhibiting pyroptosis, apoptosis, necroptosis, and alleviating oxidative stress, caused by the activation of autophagy.

Preferentially Biodegradable Gypsum Fibers Endowing Invisible Microporous Structures and Enhancing Osteogenic Capability of Calcium Phosphate Cements.

It is known that hydroxyapatite-type calcium phosphate cement (CPC) shows appreciable self-curing properties, but the phase transformation products often lead to slow biodegradation and disappointing osteogenic responses. Herein, we developed an innovative strategy to endow invisible micropore networks, which could tune the microstructures and biodegradation of α-tricalcium phosphate (α-TCP)-based CPC by gypsum fibers, and the osteogenic capability of the composite cements could be enhanced in vivo. The gypsum fibers were prepared via extruding the gypsum powder/carboxylated chitosan (CC) slurry through a 22G nozzle (410 µm in diameter) and collecting with a calcium salt solution. Then, the CPCs were prepared by mixing the α-TCP powder with gypsum fibers (0-24 wt %) and an aqueous solution to form self-curing cements. The physicochemical characterizations showed that injectability was decreased with an increase in the fiber contents. The µCT reconstruction demonstrated that the gypsum fiber could be distributed in the CPC substrate and produce long-range micropore architectures. In particular, incorporation of gypsum fibers would tune the ion release, produce tunnel-like pore networks in vitro, and promote new bone tissue regeneration in rabbit femoral bone defects in vivo. Appropriate gypsum fibers (16 and 24 wt %) could enhance bone defect repair and cement biodegradation. These results demonstrate that the highly biodegradable cement fibers could mediate the microstructures of conventional CPC biomaterials, and such a bicomponent composite strategy may be beneficial for expanding clinical CPC-based applications.

Intra-articular delivery of geraniol encapsulated by pH/redox-responsive nanogel ameliorates osteoarthritis by regulating oxidative stress and inflammation.

Osteoarthritis (OA) remains a challenging condition due to limited drug bioavailability within the avascular and dense cartilage matrix. This study introduces a pH/redox-responsive nanogel for enhanced delivery of geraniol in OA therapy. We investigated geraniol's role in preventing chondrocyte matrix degradation and designed a pH/redox-responsive nanogel as a delivery platform. Our methods included Western blot, histological staining, and immunohistochemistry. Geraniol treatment reduced Keap1 expression while elevating Nrf2 and HO-1 levels, effectively inhibiting cartilage matrix degradation. The pH/redox-responsive nanogel further enhanced geraniol's therapeutic impact. Our study demonstrates that geraniol encapsulated within a pH/redox-responsive nanogel mitigates OA by regulating oxidative stress and inflammation. This innovative approach holds potential as an effective OA therapeutic strategy.

The design of strut/TPMS-based pore geometries in bioceramic scaffolds guiding osteogenesis and angiogenesis in bone regeneration.

The pore morphology design of bioceramic scaffolds plays a substantial role in the induction of bone regeneration. Specifically, the effects of different scaffold pore geometry designs on angiogenesis and new bone regeneration remain unclear. Therefore, we fabricated Mg/Sr co-doped wollastonite bioceramic (MS-CSi) scaffolds with three different pore geometries (gyroid, cylindrical, and cubic) and compared their effects on osteogenesis and angiogenesis in vitro and in vivo. The MS-CSi scaffolds were fabricated by digital light processing (DLP) printing technology. The pore structure, mechanical properties, and degradation rate of the scaffolds were investigated. Cell proliferation on the scaffolds was evaluated using CCK-8 assays while angiogenesis was assessed using Transwell migration assays, tube formation assays, and immunofluorescence staining. The underlying mechanism was explored by western blotting. Osteogenic ability of scaffolds was evaluated by alkaline phosphatase (ALP) staining, western blotting, and qRT-PCR. Subsequently, a rabbit femoral defect model was prepared to compare differences in the scaffolds in osteogenesis and angiogenesis in vivo. Cell culture experiments showed that the gyroid pore scaffold downregulated YAP/TAZ phosphorylation and enhanced YAP/TAZ nuclear translocation, thereby promoting proliferation, migration, tube formation, and high expression of CD31 in human umbilical vein endothelial cells (HUVECs) while strut-based (cubic and cylindrical pore) scaffolds promoted osteogenic differentiation in bone marrow mesenchymal stem cells and upregulation of osteogenesis-related genes. The gyroid pore scaffolds were observed to facilitate early angiogenesis in the femoral-defect model rabbits while the strut-based scaffolds promoted the formation of new bone tissue. Our study indicated that the pore geometries and pore curvature characteristics of bioceramic scaffolds can be precisely tuned for enhancing both osteogenesis and angiogenesis. These results may provide new ideas for the design of bioceramic scaffolds for bone regeneration.

Pinocembrin alleviates pyroptosis and apoptosis through ROS elimination in random skin flaps via activation of SIRT3.

Random skin flap grafting is the most common skin grafting technique in reconstructive surgery. Despite progress in techniques, the incidence of distal flap necrosis still exceeds 3%, which limits its use in clinical practice. Current methods for treating distal flap necrosis are still lacking. Pinocembrin (Pino) can inhibit reactive oxygen species (ROS) and cell death in a variety of diseases, such as cardiovascular diseases, but the role of Pino in random flaps has not been explored. Therefore, we explore how Pino can enhance flap survival and its specific upstream mechanisms via macroscopic examination, Doppler, immunohistochemistry, and western blot. The results suggested that Pino can enhance the viability of random flaps by inhibiting ROS, pyroptosis and apoptosis. The above effects were reversed by co-administration of Pino with adeno-associated virus-silencing information regulator 2 homolog 3 (SIRT3) shRNA, proving the beneficial effect of Pino on the flaps relied on SIRT3. In addition, we also found that Pino up-regulates SIRT3 expression by activating the AMP-activated protein kinase (AMPK) pathway. This study proved that Pino can improve random flap viability by eliminating ROS, and ROS-induced cell death through the activation of SIRT3, which are triggered by the AMPK/PGC-1α signaling pathway.

Correction: Core-shell bioceramic fiber-derived biphasic granules with adjustable core compositions for tuning bone regeneration efficacy.

Correction for 'Core-shell bioceramic fiber-derived biphasic granules with adjustable core compositions for tuning bone regeneration efficacy' by Zhaonan Bao et al., J. Mater. Chem. B, 2023, 11, 2417-2430, https://doi.org/10.1039/D3TB90052E.

Bioceramic scaffolds with triply periodic minimal surface architectures guide early-stage bone regeneration.

The pore architecture of porous scaffolds is a critical factor in osteogenesis, but it is a challenge to precisely configure strut-based scaffolds because of the inevitable filament corner and pore geometry deformation. This study provides a pore architecture tailoring strategy in which a series of Mg-doped wollastonite scaffolds with fully interconnected pore networks and curved pore architectures called triply periodic minimal surfaces (TPMS), which are similar to cancellous bone, are fabricated by a digital light processing technique. The sheet-TPMS pore geometries (s-Diamond, s-Gyroid) contribute to a 3‒4-fold higher initial compressive strength and 20%-40% faster Mg-ion-release rate compared to the other-TPMS scaffolds, including Diamond, Gyroid, and the Schoen's I-graph-Wrapped Package (IWP) in vitro. However, we found that Gyroid and Diamond pore scaffolds can significantly induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Analyses of rabbit experiments in vivo show that the regeneration of bone tissue in the sheet-TPMS pore geometry is delayed; on the other hand, Diamond and Gyroid pore scaffolds show notable neo-bone tissue in the center pore regions during the early stages (3-5 weeks) and the bone tissue uniformly fills the whole porous network after 7 weeks. Collectively, the design methods in this study provide an important perspective for optimizing the pore architecture design of bioceramic scaffolds to accelerate the rate of osteogenesis and promote the clinical translation of bioceramic scaffolds in the repair of bone defects.

Core-shell bioceramic fiber-derived biphasic granules with adjustable core compositions for tuning bone regeneration efficacy.

Silicate-based biomaterials-clinically applied fillers and promising candidates-can act as a highly biocompatible substrate for osteostimulative osteogenic cell growth in vitro and in vivo. These biomaterials have been proven to exhibit a variety of conventional morphologies in bone repair, including scaffolds, granules, coatings and cement pastes. Herein, we aim to develop a series of novel bioceramic fiber-derived granules with core-shell structures which have a hardystonite (HT) shell layer and changeable core components-that is, the chemical compositions of a core layer can be tuned to include a wide range of silicate candidates (e.g., wollastonite (CSi)) with doping of functional ions (e.g., Mg, P, and Sr). Meanwhile, it is versatile to control the biodegradation and bioactive ion release sufficiently for stimulating new bone growth after implantation. Our method employs rapidly gelling ultralong core-shell CSi@HT fibers derived from different polymer hydrosol-loaded inorganic powder slurries through the coaxially aligned bilayer nozzles, followed by cutting and sintering treatments. It was demonstrated that the nonstoichiometric CSi core component could contribute to faster bio-dissolution and biologically active ion release in tris buffer in vitro. The rabbit femoral bone defect repair experiments in vivo indicated that core-shell bioceramic granules with an 8% P-doped CSi-core could significantly stimulate osteogenic potential favorable for bone repair. It is worth concluding that such a tunable component distribution strategy in fiber-type bioceramic implants may develop new-generation composite biomaterials endowed with time-dependent biodegradation and high osteostimulative activities for a range of bone repair applications in situ.

Treatment of postoperative non-union with internal fixation loosening of Garden IV femoral neck fracture with teriparatide in a young adult: A case report.

Background: Postoperative non-union of femoral neck fracture often needs secondary operation. We report a case of a postoperative non-union of femoral neck fracture treated with teriparatide. Case presentation: A young male patient with Garden IV femoral neck fracture who showed no obvious signs of healing 3 months after percutaneous hollow nail fixation in which the fracture line was enlarged and the hollow nail was withdrawn. Bone non-union healed after 6 months of continuous subcutaneous injection of teriparatide at a dosage of 20 mg/day after the patient refused a secondary surgery. As far as we know, there have been no relevant reports on this type of fracture yet. Conclusions: Teriparatide is expected to be beneficial in treating young patients with a displaced femoral neck fracture who have difficulty in healing from non-union and who are keen on avoiding secondary surgery.

A new injectable quick hardening anti-collapse bone cement allows for improving biodegradation and bone repair.

The development of injectable cement-like biomaterials via a minimally invasive approach has always attracted considerable clinical interest for modern bone regeneration and repair. Although α-tricalcium phosphate (α-TCP) powders may readily react with water to form hydraulic calcium-deficient hydroxyapatite (CDHA) cement, its long setting time, poor anti-collapse properties, and low biodegradability are suboptimal for a variety of clinical applications. This study aimed to develop new injectable α-TCP-based bone cements via strontium doping, α-calcium sulfate hemihydrate (CSH) addition and liquid phase optimization. A combination of citric acid and chitosan was identified to facilitate the injectable and anti-washout properties, enabling higher resistance to structure collapse. Furthermore, CSH addition (5 %-15 %) was favorable for shortening the setting time (5-20 min) and maintaining the compressive strength (10-14 MPa) during incubation in an aqueous buffer medium. These α-TCP-based composites could also accelerate the biodegradation rate and new bone regeneration in rabbit lateral femoral bone defect models in vivo. Our studies demonstrate that foreign ion doping, secondary phase addition and liquid medium optimization could synergistically improve the physicochemical properties and biological performance of α-TCP-based bone cements, which will be promising biomaterials for repairing bone defects in situations of trauma and diseased bone.

Integrating pore architectures to evaluate vascularization efficacy in silicate-based bioceramic scaffolds.

Pore architecture in bioceramic scaffolds plays an important role in facilitating vascularization efficiency during bone repair or orbital reconstruction. Many investigations have explored this relationship but lack integrating pore architectural features in a scaffold, hindering optimization of architectural parameters (geometry, size and curvature) to improve vascularization and consequently clinical outcomes. To address this challenge, we have developed an integrating design strategy to fabricate different pore architectures (cube, gyroid and hexagon) with different pore dimensions (∼350, 500 and 650 µm) in the silicate-based bioceramic scaffolds via digital light processing technique. The sintered scaffolds maintained high-fidelity pore architectures similar to the printing model. The hexagon- and gyroid-pore scaffolds exhibited the highest and lowest compressive strength (from 15 to 55 MPa), respectively, but the cube-pore scaffolds showed appreciable elastic modulus. Moreover, the gyroid-pore architecture contributed on a faster ion dissolution and mass decay in vitro. It is interesting that both µCT and histological analyses indicate vascularization efficiency was challenged even in the 650-µm pore region of hexagon-pore scaffolds within 2 weeks in rabbit models, but the gyroid-pore constructs indicated appreciable blood vessel networks even in the 350-µm pore region at 2 weeks and high-density blood vessels were uniformly invaded in the 500- and 650-µm pore at 4 weeks. Angiogenesis was facilitated in the cube-pore scaffolds in comparison with the hexagon-pore ones within 4 weeks. These studies demonstrate that the continuous pore wall curvature feature in gyroid-pore architecture is an important implication for biodegradation, vascular cell migration and vessel ingrowth in porous bioceramic scaffolds.

Rational design of nonstoichiometric bioceramic scaffolds via digital light processing: tuning chemical composition and pore geometry evaluation.

Bioactive ceramics are promising candidates as 3D porous substrates for bone repair in bone regenerative medicine. However, they are often inefficient in clinical applications due to mismatching mechanical properties and compromised biological performances. Herein, the additional Sr dopant is hypothesized to readily adjust the mechanical and biodegradable properties of the dilute Mg-doped wollastonite bioceramic scaffolds with different pore geometries (cylindrical-, cubic-, gyroid-) by ceramic stereolithography. The results indicate that the compressive strength of Mg/Sr co-doped bioceramic scaffolds could be tuned simultaneously by the Sr dopant and pore geometry. The cylindrical-pore scaffolds exhibit strength decay with increasing Sr content, whereas the gyroid-pore scaffolds show increasing strength and Young's modulus as the Sr concentration is increased from 0 to 5%. The ion release could also be adjusted by pore geometry in Tris buffer, and the high Sr content may trigger a faster scaffold bio-dissolution. These results demonstrate that the mechanical strengths of the bioceramic scaffolds can be controlled from the point at which their porous structures are designed. Moreover, scaffold bio-dissolution can be tuned by pore geometry and doping foreign ions. It is reasonable to consider the nonstoichiometric bioceramic scaffolds are promising for bone regeneration, especially when dealing with pathological bone defects.

Bone tissue regeneration: The role of finely tuned pore architecture of bioactive scaffolds before clinical translation.

Spatial dimension of pores and interconnection in macroporous scaffolds is of particular importance in facilitating endogenous cell migration and bone tissue ingrowth. However, it is still a challenge to widely tune structure parameters of scaffolds by conventional methods because of inevitable pore geometrical deformation and poor pore interconnectivity. Here, the long-term in vivo biological performances of nonstoichiometric bioceramic scaffolds with different pore dimensions were assessed in critical-size femoral bone defect model. The 6% Mg-substituted wollastonite (CSi-Mg6) powders were prepared via wet-chemical precipitation and the scaffolds elaborately printed by ceramic stereolithography, displaying designed constant pore strut and tailorable pore height (200, 320, 450, 600 µm), were investigated thoroughly in the bone regeneration process. Together with detailed structural stability and mechanical properties were collaboratively outlined. Both µCT and histological analyses indicated that bone tissue ingrowth was retarded in 200 µm scaffolds in the whole stage (2-16 weeks) but the 320 µm scaffolds showed appreciable bone tissue in the center of porous constructs at 6-10 weeks and matured bone tissue were uniformly invaded in the whole pore networks at 16 weeks. Interestingly, the neo-tissue ingrowth was facilitated in the 450 µm and 600 µm scaffolds after 2 weeks and higher extent of bone regeneration and remodeling at the later stage. These new findings provide critical information on how engineered porous architecture impact bone regeneration in vivo. Simultaneously, this study shows important implications for optimizing the porous scaffolds design by advanced additive manufacture technique to match the clinical translation with high performance.

Hypoxia inducible factor-1 (HIF-1α) reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.

BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation. RESULTS: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1ß, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy. CONCLUSIONS: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.

Seasonal variation and correlation analysis of vitamin D and parathyroid hormone in Hangzhou, Southeast China.

This study aimed to describe the 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) status of Southeast Chinese individuals influenced by season. The secondary aim was to determine the cutoff for sufficient 25(OH)D in a four-season region. From January 2011 to June 2014, a total of 17 646 individuals were evaluated in our study. The serum levels of PTH were detected simultaneously in 5579 cases. A total of 25(OH)D and intact PTH were measured by the electrochemiluminescent immunoassay. The distribution of the concentration, prevalence and seasonal variability of 25(OH)D and PTH were studied. The mean 25(OH)D concentration in our study was 43.00(30.40) nmol/L. The prevalence of insufficiency (25(OH)D < 50 nmol/L) was 62.87% and that of deficiency (<30 nmol/L) was 28.54%. Mean serum 25(OH)D levels revealed a limited sinusoidal profile throughout the year and were significantly higher in Autumn. On the other hand, PTH levels showed an opposite response to seasonal effects relative to 25(OH)D. Age, BMI and daylight were not significantly correlated with 25(OH)D and serum PTH reached a plateau at higher values of serum 25(OH)D of 42.86 nmol/L. This study demonstrated that Vitamin D insufficiency is highly prevalent in Southeast China. The concentration of 25(OH)D in the male group was generally higher than that in the female group. Seasonal variation was an important aspect of 25(OH)D and PTH concentration. This study revealed that the optimal serum threshold of 25(OH)D for bone health should be between 40 and 50 nmol/L for Southeast Chinese individuals.

Modification of pore-wall in direct ink writing wollastonite scaffolds favorable for tuning biodegradation and mechanical stability and enhancing osteogenic capability.

Surface chemistry and mechanical stability determine the osteogenic capability of bone implants. The development of high-strength bioactive scaffolds for in-situ repair of large bone defects is challenging because of the lack of satisfying biomaterials. In this study, highly bioactive Ca-silicate (CSi) bioceramic scaffolds were fabricated by additive manufacturing and then modified for pore-wall reinforcement. Pure CSi scaffolds were fabricated using a direct ink writing technique, and the pore-wall was modified with 0%, 6%, or 10% Mg-doped CSi slurry (CSi, CSi-Mg6, or CSi-Mg10) through electrostatic interaction. Modified CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds with over 60% porosity demonstrated an appreciable compressive strength beyond 20 MPa, which was ~2-fold higher than that of pure CSi scaffolds. CSi-Mg6 and CSi-Mg10 coating layers were specifically favorable for retarding bio-dissolution and mechanical decay of scaffolds in vitro. In-vivo investigation of critical-size femoral bone defects repair revealed that CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds displayed limited biodegradation, accelerated new bone ingrowth (4-12 weeks), and elicited a suitable mechanical response. In contrast, CSi scaffolds exhibited fast biodegradation and retarded new bone regeneration after 8 weeks. Thus, tailoring of the chemical composition of pore-wall struts of CSi scaffolds is beneficial for enhancing the biomechanical properties and bone repair efficacy.

Effect of Foreign Ion Substitution and Micropore Tuning in Robocasting Single-Phase Bioceramic Scaffolds on the Physicochemical Property and Vascularization.

The inorganic powder slurry extrusion printing technique known as robocasting is an interesting method to fabricate complex porous architectures whereby feedstocks containing organic binders and powders are printed and the resulting scaffolds are subjected to sintering. A major limiting factor of this technique is the simultaneous tailoring of vascularization efficacy and osteogenic activity, usually done by adding the secondary phase in the organic slurry before the writing step. Mechanical mixing of biphasic powders is required to avoid compromising the biological performance and physical defects caused by significantly different physicochemical properties. This study addresses this issue by developing a selective ion doping and microstructure tuning for the production of bioceramic scaffolds with a binozzle robocasting process. Different metal ions (Sr2+, Mg2+) were doped into wollastonite (CaSiO3; CSi) powders considering the mechanical stability and bioactive enhancement of the bioceramic scaffolds. Subsequently, the Mg-doped CSi slurries were used as shell-nozzle feedstocks added with 5, 10, and 15 µm diameter polystyrene microbeads that allowed shell-layer micropore production in pore struts during sintering. Finally, the most promising pore-strut microstructures and mechanical evolution of scaffolds were evaluated, and especially the enhanced fibrovascularization potential was confirmed in dorsal muscle embedding model in rabbits. This study may open an avenue to designing multiproperty-tuned macro- and microporous bioceramics for bone regenerative medicine, especially in challenging bone defect conditions.

Hypoxia inducible factor-1 (HIF-1α) reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723

BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation. RESULTS: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1ß, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy. CONCLUSIONS: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.

Core-Shell Biphasic Microspheres with Tunable Density of Shell Micropores Providing Tailorable Bone Regeneration.

IMPACT STATEMENT: We have developed the new core-shell bioceramic CSi-Sr4@CaP-px microspheres with tuning porous shell layer so that the biodegradation of both CSi-Sr4 core and CaP shell is readily adjusted synergistically. This is for the first time, to the best of our knowledge, that the bioceramic scaffolds concerning gradient distribution and microstructure-tailoring design is available for tailoring biodegradation and ion release (bioactivity) to optimizing osteogenesis. Furthermore, it is possibly helpful to develop new bioactive scaffold system for time-dependent tailoring bioactivity and microporous structure to significantly enhance bone regeneration and repair applications, especially in some non-load-bearing arbitrary 3D anatomical bone and teeth defects.

Knockdown of miR-372 Inhibits Nerve Cell Apoptosis Induced by Spinal Cord Ischemia/Reperfusion Injury via Enhancing Autophagy by Up-regulating Beclin-1.

To investigate the role of miR-372/Beclin-1 on nerve cell apoptosis induced by spinal cord ischemia/reperfusion injury (SCII). We established in vivo and in vitro SCII model. MiR-372 and Beclin-1 expressions in spinal cord tissues of SCII rats and SCII nerve cells were measured. The cell apoptosis was detected by flow cytometry. MiR-372 inhibitor was used to reduce miR-372 expression. Dual luciferase reporter assay was used to confirm the interaction between miR-372 and Beclin-1. MiR-372 expression in spinal cord tissues of SCII rats and SCII nerve cells was increased, while Beclin-1 expression was decreased. Knockdown of miR-372 could inhibit SCII nerve cell apoptosis. In addition, MiR-372 could negatively regulate Beclin-1 expression. Autophagy inhibitor could inhibit autophagy to promote the apoptosis of SCII nerve cells through decreasing Beclin-1, while interference of miR-372 changed the effect of autophagy inhibitor. Interference of miR-372 could reduce nerve cell apoptosis in SCII via increasing autophagy by up-regulating Beclin-1.