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Dao-Yu Zhu,1,* Bin Lu,2,* Jun-Hui Yin,1 Qin-Fei Ke,2 He Xu,2 Chang-Qing Zhang,1 Ya-Ping Guo,2 You-Shui Gao1,3 1Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China; 2The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China; 3Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA 6009, Australia *These authors contributed equally to this work Background: Biomaterial-induced osteogenesis is mainly related to hierarchically porous structures and bioactive components. Rare earth elements are well known to promote osteogenesis and stimulate bone repair; however, the underlying biological effects of gadolinium (Gd) element on bone regeneration are not yet known. Methods: In this study, we successfully fabricated gadolinium-doped bioglass (Gd-BG) scaffolds by combining hollow mesoporous Gd-BG microspheres with chitosan and evaluated in vitro effects and underlying mechanisms with Cell Counting Kit-8, scanning electron microscopy, alkaline phosphatase, Alizarin red staining, and polymerase chain reaction. Cranial defect model of rats was constructed to evaluate their in vivo effects. Results: The results indicated that Gd-BG scaffolds could promote the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Mechanistically, the Akt/GSK3β signaling pathway was activated by the Gd-BG scaffolds. The enhancing effect of Gd-BG scaffolds on the osteogenic differentiation of hBMSCs was inhibited by the addition of LY294002, an inhibitor of Akt. Moreover, the in vivo cranial defect model of rats indicated that the Gd-BG scaffolds could effectively promote bone regeneration. Conclusion: Both in vitro and in vivo results suggested that Gd-BG scaffolds have promising applications in bone tissue engineering. Keywords: bone scaffold, gadolinium, Akt/GSK3β pathway, bone regeneration

Diabetic complications with high-glucose status (HGS) cause the dysregulated autophagy and excessive apoptosis of multiple-type cells, leading to the difficulty in wound self-healing. Herein, we firstly developed fiber-reinforced gelatin (GEL)/β-cyclodextrin (β-CD) therapeutic hydrogels by the modification of platelet-rich plasma exosomes (PRP-EXOs). The GEL fibers that were uniformly dispersed within the GEL/β-CD hydrogels remarkably enhanced the compression strengths and viscoelasticity. The PRP-EXOs were encapsulated in the hydrogels via the covalent crosslinking between the PRP-EXOs and genipin. The diabetic rat models demonstrated that the GEL/β-CD hydrogels and PRP-EXOs cooperatively promoted diabetic wound healing. On the one hand, the GEL/β-CD hydrogels provided the biocompatible microenvironments and active components for cell adhesion, proliferation and skin tissue regeneration. On the other hand, the PRP-EXOs in the therapeutic hydrogels significantly activated the autophagy and inhibited the apoptosis of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs). The activation of autophagy and inhibition of apoptosis in HUVECs and HSFs induced the blood vessel creation, collagen formation and re-epithelialization. Taken together, this work proved that the incorporation of PRP-EXOs in a wound dressing was an effective strategy to regulate autophagy and apoptosis, and provide a novel therapeutic platform for diabetic wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Autogenous bone grafting has long been considered the gold standard for treating critical bone defects. However, its use is plagued by numerous drawbacks, such as limited supply, donor site morbidity, and restricted use for giant-sized defects. For this reason, there is an increasing need for effective bone substitutes to treat these defects. Mollusk nacre is a natural structure with outstanding mechanical property due to its notable "brick-and-mortar" architecture. Inspired by the nacre architecture, our team designed and fabricated a nacre-mimetic cerium-doped layered nano-hydroxyapatite/chitosan layered composite scaffold (CeHA/CS). Hydroxyapatite can provide a certain strength to the material like a brick. And as a polymer material, chitosan can slow down the force when the material is impacted, like an adhesive. As seen in natural nacre, the combination of these inorganic and organic components results in remarkable tensile strength and fracture toughness. Cerium ions have been demonstrated exceptional anti-osteoclastogenesis capabilities. Our scaffold featured a distinct layered HA/CS composite structure with intervals ranging from 50 to 200 μm, which provided a conducive environment for human bone marrow mesenchymal stem cell (hBMSC) adhesion and proliferation, allowing for in situ growth of newly formed bone tissue. In vitro, Western-blot and qPCR analyses showed that the CeHA/CS layered composite scaffolds significantly promoted the osteogenic process by upregulating the expressions of osteogenic-related genes such as RUNX2, OCN, and COL1, while inhibiting osteoclast differentiation, as indicated by reduced TRAP-positive osteoclasts and decreased bone resorption. In vivo, calvarial defects in rats demonstrated that the layered CeHA/CS scaffolds significantly accelerated bone regeneration at the defect site, and immunofluorescence indicated a lowered RANKL/OPG ratio. Overall, our results demonstrate that CeHA/CS scaffolds offer a promising platform for bone regeneration in critical defect management, as they promote osteogenesis and inhibit osteoclast activation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Herein, we developed a multimodal antibacterial nanoplatform via synergism effect including knife-effect, photothermal, photocatalytic induced reactive oxygen species (ROS), and Cu 2+ inherent attribute. Typically, 0.8-TC/Cu-NS possesses higher photothermal property with the higher photothermal conversion efficiency of 24% and the moderate temperature up to 97 °C. Meanwhile, 0.8-TC/Cu-NS exhibits the more active ROS, 1 O 2 and ·O 2 - . Hence, 0.8-TC/Cu-NS possesses best antibacterial properties against S. aureus and E. coli in vitro with efficiency of 99.94%/99.97% under near-infrared (NIR) light, respectively. In the therapeutic practical use for wound healing of Kunming mice, this system exhibits outstanding curing capacity and good biocompatibility. Based on the electron configuration measurement and density functional theory (DFT) simulation, it is confirmed that the electrons on CB of Cu-TCPP flow fleetingly to MXene trough the interface, with redistribution of charge and band upward bending over Cu-TCPP. As a result, the self-assembled 2D/2D interfacial Schottky junction have made great favor to accelerate photogenerated charges mobility, hamper charge recombination, and increases the photothermal/photocatalytic activity. This work gives us a hint to mostly design the multimodal synergistic nanoplatform under NIR light in biological applications without drug resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In situ regeneration of large-segment bone defects is a difficult clinical problem. Here, we innovatively developed magnetically oriented micro-cellulose fibres using nano-hydroxyapatite/chitosan (CEF/Fe 3 O 4 /HA/CS) and loaded an NFκB pathway inhibitor on the surface of magnetically oriented cellulose fibres (CEF/Fe 3 O 4 /HA/CS/PQQ) prepared as a layered bioscaffold. CEF/Fe 3 O 4 /HA/CS/PQQ was constructed by layering HA/CS sheets. Nano-hydroxyapatite was deposited on the surface of cellulose fibres, then the magnetic nanoparticles on the cellulose fibres were aligned on the surface of chitosan under a magnetic field. Oriented cellulose fibres enhanced the compressive properties of the scaffold, with an average maximum compressive strength of 1.63 ​MPa. The CEF/Fe 3 O 4 /HA/CS/PQQ layered scaffold was filled into the body, and the acute inflammatory response (IL-1β and TNF-α) was suppressed through the early sustained release of PQQ. The CEF/Fe 3 O 4 /HA/CS/PQQ-layered scaffold further inhibited the osteoclasts differentiation. It was further found that the nano-hydroxyapatite on the surface of oriented cellulose fibres promoted the formation and migration of new blood vessels, accelerated the processing of collagen-I fibres to cartilage, and endochondral ossification. Hence, the development of the CEF/Fe 3 O 4 /HA/CS/PQQ layered scaffold with oriented fibres guides bone growth direction and pro-osteogenesis activity and provides a novel strategy for the in situ regeneration of large segmental bone defects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

Osteoporotic bone defects result from an imbalance in bone homeostasis, excessive osteoclast activity, and the weakening of osteogenic mineralization, resulting in impaired bone regeneration. Herein, inspired by the hierarchical structures of mollusk nacre, nacre exhibits outstanding high-strength mechanical properties, which are in part due to its delicate layered structure. SrFe 12 O 19 nanoparticles and nano-layered double hydroxide (LDH) were incorporated into a bioactive chitosan (CS) matrix to form multifunctional layered nano-SrFe 12 O 19 -LDH/CS scaffolds. The compressive stress value of the internal ordered layer structure matches the trabecular bone (0.18 ​MPa). The as-released Mg 2+ ions from the nano-LDH can inhibit bone resorption in osteoclasts by inhibiting the NFκB signaling pathway. At the same time, the as-released Sr 2+ ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP-2/SMAD signaling pathway. In vivo, the Mg 2+ ions released from the SrFe 12 O 19 -LDH/CS scaffolds inhibited the release of pro-inflammatory factors (IL-1β and TNF-α), while the as-released Sr 2+ ions promoted osteoblastic proliferation and the mineralization of osteoblasts inside the layered SrFe 12 O 19 -LDH/CS scaffolds. Immunofluorescence for OPG, RANKL, and CD31, showed that stable vasculature could be formed inside the layered SrFe 12 O 19 -LDH/CS scaffolds. Hence, this study on multifunctional SrFe 12 O 19 -LDH/CS scaffolds clarifies the regulatory mechanism of osteoporotic bone regeneration and is expected to provide a theoretical basis for the research, development, and clinical application of this scaffold on osteoporotic bone defects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Natural polymer hydrogels are widely used as wound dressings, but they do not have enough bioactivity to accelerate angiogenesis and re-epithelialization. Herein, a therapeutic system was firstly constructed in which endothelin-1 (ET-1), as an endogenous vasoconstrictor peptide, was embedded in a photo-crosslinking gelatin methacryloyl (GelMA) hydrogel for full-thickness wound healing. The multifunctional GelMA-ET-1 hydrogels contained the arginine-glycine-aspartate (RGD) motifs of gelatin that provided adhesive sites for cell proliferation and migration. The ET-1 was wrapped within the network of crosslinked GelMA hydrogels via intermolecular hydrogen bonding interactions, effectively avoiding oxidization by atmospheric oxygen and in vivo enzymatic biodegradation. Notably, the ET-1 in the functional hydrogels significantly promoted the proliferation, migration and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The full-thickness skin defect model of rats further revealed that the GelMA-ET-1 hydrogels significantly accelerated new blood vessel formation, collagen deposition and re-epithelialization. After 14 days, the full-thickness skin defects almost closed and were filled with the newly formed tissue. Hence, the photo-crosslinking GelMA-ET-1 hydrogels functionalized with ET-1 can be employed as a promising therapeutic system for wound healing.

Background: Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects., Methods: Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration., Results: Graphene oxide (GO) nanoparticles, hydrated CePO 4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO 4 /CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO 4 /CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce 3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce 3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration., Conclusion: The multifunctional CePO 4 /CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

Electret melt-blown nonwovens are widely used for air purification due to their low pressure drop and high filtration efficiency. However, the charge stability could be affected by the ambient temperature and humidity, reducing the filtration efficiency, resulting in the electret melt blown filter not providing effective protection. Herein, we used corona charge to prepare electret melt-blown nonwovens and systematically studied the effects of different temperature and humidity on the structure, morphology, filtration performance, and surface potential within 24 h. The effect of treatment temperature and humidity on pressure drop was minimal because the fiber morphology and web structure of melt-blown nonwovens were not damaged. When the treatment temperature was lower than 70 °C, the effect on the filtration efficiency of the sample was small, but when the temperature increased to 90 or 110 °C, the filtration efficiency decreased significantly with the increase of the treatment time, and the surface potential also declined similarly. In conclusion, high temperatures will lead to charge escape and reduce the electrostatic adsorption effect. Furthermore, at the same temperature, increasing relative humidity can accelerate the charge release and make the filtration efficiency drop more. After the sample was treated at 110 °C and 90% relative humidity for 24 h, the filtration efficiency decreased from 95.49% to 38.16% at a flow rate of 14.16 cm s -1 , and the surface potential dropped to the lowest value of -1.01 kV. This result shows that all links of electret melt-blown filter material from raw material to final use should be avoided in high temperature and high humidity conditions to ensure the protection effect.

Background: Spinal cord injury (SCI) triggers the primary mechanical injury and secondary inflammation-mediated injury. Neuroinflammation-mediated insult causes secondary and extensive neurological damage after SCI. Microglia play a pivotal role in the initiation and progression of post-SCI neuroinflammation., Methods: To elucidate the significance of LRCH1 to microglial functions, we applied lentivirus-induced LRCH1 knockdown in primary microglia culture and tested the role of LRCH1 in microglia-mediated inflammatory reaction both in vitro and in a rat SCI model., Results: We found that LRCH1 was downregulated in microglia after traumatic SCI. LRCH1 knockdown increased the production of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 after in vitro priming with lipopolysaccharide and adenosine triphosphate. Furthermore, LRCH1 knockdown promoted the priming-induced microglial polarization towards the pro-inflammatory inducible nitric oxide synthase (iNOS)-expressing microglia. LRCH1 knockdown also enhanced microglia-mediated N27 neuron death after priming. Further analysis revealed that LRCH1 knockdown increased priming-induced activation of p38 mitogen-activated protein kinase (MAPK) and Erk1/2 signaling, which are crucial to the inflammatory response of microglia. When LRCH1-knockdown microglia were adoptively injected into rat spinal cords, they enhanced post-SCI production of pro-inflammatory cytokines, increased SCI-induced recruitment of leukocytes, aggravated SCI-induced tissue damage and neuronal death, and worsened the locomotor function., Conclusion: Our study reveals for the first time that LRCH1 serves as a negative regulator of microglia-mediated neuroinflammation after SCI and provides clues for developing novel therapeutic approaches against SCI.

Design and fabrication of novel adsorbents to remove heavy metal ions in continuous-flow wastewater remained a great challenge. Inspired by the hierarchical architecture and biomineralization process of nacre, we firstly constructed hydroxyapatite/chitosan (HA/CH) layered composites. The brick-and-mortar characteristics of HA/CH layered composites improved their flexure strengths up to 3.08 MPa so that the hierarchical architectures could not be destroyed even under high-pressure drop. HA/CH layered composites had the hierarchical microstructures analogous to plate towers, facilitating the separation of adsorbents from water. The interlaminar macropores in the layered composites contributed to the transfer of continuous-flow wastewater. The Pb(II), Cd(II) and Hg(II) ions in wastewater showed similar adsorption trends, and their adsorption amounts arrived at 295.96, 192.37 and 127.38 mg g -1 after 6 days, respectively. Among the above heavy metal ions, the HA/CH layered composites possessed the best Pb(II) adsorption ability due to forming lead hydroxyapatite rods and CH-Pb complexes. The Pb(II) adsorption performances of HA/CH layered composites matched well with Elovich equation, pseudo-first-order and pseudo-second-order kinetics models, revealing the heterogeneous chemisorption mechanism at adsorbent/wastewater interfaces. Therefore, the nacre-like HA/CH layered composites with appropriate mechanical property and excellent adsorption capacity are a novel platform for heavy metal removal in continuous-flow wastewater., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chitosan (CTS) and mesoporous calcium silicate (MCS) have been developed for bone defect healing; however, their bone regeneration capacity still does not satisfy the patients with bone diseases. Gadolinium (Gd) is accumulated in human bones, and plays a beneficial role in regulating cell performance and bone regeneration. We firstly constructed Gd-doped MCS/CTS (Gd-MCS/CTS) scaffolds by a lyophilization technology. The interconnected arrangement of CTS films lead to forming macropores by using ice crystals as templates during the lyophilization procedure, and the Gd-MCS nanoparticles dispersed uniformly on the macropore walls. The biocompatible chemical components and hierarchical pores facilitated the attachment and spreading of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Interestingly, the Gd dopants in the scaffolds effectively activated the Wnt/β-catenin signaling pathway, resulting in excellent cell proliferation and osteogenic differentiation capacities. The osteogenic-related genes such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and collagen type1 (COL-1) were remarkably up-regulated by Gd-MCS scaffolds as compared with MCS scaffolds, and their expression levels increased in a positive correlation with Gd doping amounts. Moreover, in vivo rat cranial defect tests further confirmed that Gd-MCS/CTS scaffolds significantly stimulated collagen deposition and new bone formation. The exciting finding suggested the beneficial effects of Gd 3+ ions on osteogenic differentiation and new bone regeneration, and Gd-MCS/CTS scaffolds can be employed as a novel platform for bone defect healing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bioglass scaffolds have great application potentials in orthopedics, and Ursolic acid (UA) can effectively promote in vivo new bone formation. Herein, we for the first time developed the mesoporous bioglass/chitosan porous scaffolds loaded with UA (MBG/CS/UA) for enhanced bone regeneration. The MBG microspheres with particle sizes of ~300 nm and pore sizes of ~3.9 nm were uniformly dispersed on the CS films. The mesoporous structure within the MBG microspheres and the hydrogen bonding between the scaffolds and UA drugs made the MBG/CS/UA scaffolds have controlled drug release performances. The as-released UA drugs from the scaffolds increased remarkably the alkaline phosphatase activity, osteogenic differentiation related gene type I collagen, runt-related transcription factor 2 expression, and osteoblast-associated protein expression. Moreover, the results of micro-CT images, histomorphological observations demonstrated that the MBG/CS/UA scaffolds improved new bone formation ability. Therefore, the MBG/CS/UA porous scaffolds can be used as novel bone tissue engineering materials., (Copyright © 2018. Published by Elsevier Inc.)

Hierarchically porous structures and bioactive compositions of artificial biomaterials play a positive role in bone defect healing and new bone regeneration. Herein, cerium oxide nanoparticles-modified bioglass (Ce-BG) scaffolds were firstly constructed by the incorporation of hollow mesoporous Ce-BG microspheres in CTS via a freeze-drying technology. The interconnected macropores in Ce-BG scaffolds facilitated the in-growth of bone cells/tissues from material surfaces into the interiors, while the hollow cores and mesopore shells in Ce-BG microspheres provides more active sites for bone mineralization. The cerium oxide nanoparticles in the scaffolds rapidly promoted the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs), as confirmed by the up-regulation of osteogenesis-related markers such as OCN, ALP and COL-1. The enhanced osteoinductivity of Ce-BG scaffolds was mainly related to the activated ERK pathway, and it was blocked by adding a selective ERK1/2 inhibitor (SCH772984). In vivo rat cranial defect models revealed that Ce-BG scaffolds accelerated collagen deposition, osteoblast formation and bone regeneration as compared to BG scaffolds. The exciting results demonstrated that the synergistic effects between hierarchically porous structures and cerium oxide nanoparticles contributed to osteogenic ability, and hollow mesoporous Ce-BG scaffolds would be a novel platform for bone regeneration.

Trace rare earth elements such as lanthanum (La) regulated effectively bone tissue performances; however, the underlying mechanism remains unknown. In order to accelerate bone defects especially in patients with osteoporosis or other metabolic diseases, we firstly constructed lanthanum-doped mesoporous calcium silicate/chitosan (La-MCS/CTS) scaffolds by freeze-drying technology. During the freeze-drying procedure, three-dimensional macropores were produced within the La-MCS/CTS scaffolds by using ice crystals as templates, and the La-MCS nanoparticles were distributed on the macropore walls. The hierarchically porous structures and biocompatible components contributed to the adhesion, spreading and proliferation of rat bone marrow-derived mesenchymal stem cells (rBMSCs), and accelerated the in-growth of new bone tissues. Particularly, the La3+ ions in the bone scaffolds remarkably induced the osteogenic differentiation of rBMSCs via the activation of the TGF signal pathway. A critical-sized calvarial-defect rat model further revealed that the La-MCS/CTS scaffolds significantly promoted new bone regeneration as compared with pure MCS/CTS scaffolds. In conclusion, the La-MCS/CTS scaffold showed the prominent ability in osteogenesis and bone regeneration, which showed its application potential for bone defect therapy.

The surgical resection of melanoma may cause skin wounds, and the remaining melanoma cells bring a great risk of tumor recurrence. To overcome the above problem, we for the first time constructed lanthanum-doped chitosan (La-CS) hydrogels with excellent wound healing and antitumor functions. The La element was uniformly dispersed within whole hydrogels, and part of La 3+ ions reacted with CS to form La-CS complex. The complexation interaction between La 3+ ions and CS significantly improve the La 3+ release performances of La-CS hydrogels. The as-released La 3+ ions from the composite hydrogels selectively inhibited the proliferation of B-16 melanoma cells, but showed lower toxic side effects to L929 skin fibroblast cells. Moreover, the La 3+ ions triggered the apoptosis of B-16 cells through Bcl-2/Bax pathway, as confirmed by the Annexin Vand PI double staining, flow cytometry, and Western blot results. The in vivo tumor models of C57 mice revealed that the La-CS hydrogels had more significant relapse-inhibition effects on B-16 melanoma cells than the pure CS hydrogels. At the same time, the in vivo wound healing was accelerated by the multifunctional hydrogels. The exciting finding provides a critical and promising strategy in the construction of La-doped hydrogels for oncotherapy.

For effectively treating tumor related-bone defects, design and fabrication of multifunctional biomaterials still remain a great challenge. Herein, we firstly fabricated magnetic SrFe 12 O 19 nanoparticles modified-mesoporous bioglass (BG)/chitosan (CS) porous scaffold (MBCS) with excellent bone regeneration and antitumor function. The as-produced magnetic field from MBCS promoted the expression levels of osteogenic-related genes (OCN, COL1, Runx2 and ALP) and the new bone regeneration by activated BMP-2/Smad/Runx2 pathway. Moreover, the SrFe 12 O 19 nanoparticles in MBCS improved the photothermal conversion property. Under the irradiation of near-infrared (NIR) laser, the elevated temperatures of tumors co-cultured with MBCS triggered tumor apoptosis and ablation. As compared with the pure scaffold group, MBCS/NIR group possessed the excellent antitumor efficacy against osteosarcoma via the hyperthermia ablation. Therefore, the multifunctional MBCS with excellent bone regeneration and photothermal therapy functions has a great application for treating the tumor-related bone defects., (Copyright © 2018. Published by Elsevier Inc.)

Oral or intravenous chemotherapy is an important strategy to treat metastatic cancer, but it may cause systemic toxicity for healthy tissue. Herein, we for the first time fabricated mesoporous ZSM-5 zeolites/chitosan core-shell nanodisks loaded with doxorubicin (ZSM-5/CS/DOX) as drug delivery systems against osteosarcoma. The mesoporous ZSM-5 zeolites exhibited disk-like shapes with thicknesses of 100nm and diameters of 300nm, and the mesopores with pore sizes of 3.75nm were originated from desilication treatment. The pH-responsive ZSM-5/CS/DOX nanodisks possessed a great drug loading efficiency of 97.7%, and their controlled release trends of DOX were fitted well with the Korsmeyer-Peppas model. The DOX could be efficiently released the ZSM-5/CS/DOX nanodisks after cellular endocytosis and induced cancer cells apoptosis. Moreover, the pH-responsive drug carriers led to efficient tumor inhibition with low side effects, especially cardiac toxicity, as confirmed by pharmacokinetic study, serological examination and H&E staining assays. Therefore, the ZSM-5/CS/DOX nanodisks are a promising pH-responsive drug carrier for targeted cancer therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The spinal cord injury (SCI) is a detrimental neurological disease involving the primary mechanical injury and secondary inflammatory damage. Curtailing the detrimental neuroinflammation would be beneficial for spinal cord function recovery. Microglia reside in the spinal cord and actively participate in the onset, progression and perhaps resolution of post-SCI neuroinflammation. In the current study, we tested the effects of methylene blue on microglia both in vitro and in a rat SCI model. We found that methylene blue inhibited the protein levels of IL-1β and IL-18 rather than their mRNA levels in activated microglia. Further investigation indicated that methylene blue deceased the activation of NLRP3 inflammasome and NLRC4 inflammasome in microglia in vitro . Moreover, in the rat SCI model, the similar effect of methylene blue on post-SCI microglia was also observed, except that the activation of NLRC4 inflammasome was not seen. The inhibition of microglia NLRP3 inflammasome was associated with down-regulation of intracellular reactive oxygen species (ROS). The administration of methylene blue mitigated the overall post-SCI neuroinflammation, demonstrated by decreased pro-inflammatory cytokine production and leukocyte infiltrates. Consequently, the neuronal apoptosis was partially inhibited and the hind limb locomotor function was ameliorated by methylene blue treatment. Our research highlights the role of methylene blue in inhibiting post-SCI neuroinflammation, and suggests that methylene blue might be used for SCI therapy.

The toxic risks and adverse effects of anticancer drugs on healthy tissues limit their wide clinical application. Herein, we for the first time fabricated hollow mesoporous ZSM-5/chitosan ellipsoids loaded with doxorubicin (HM-ZSM-5/CS/DOX) as pH-responsive drug delivery systems against osteosarcoma. The HM-ZSM-5 ellipsoids including a hollow core and a mesoporous shell could efficiently load DOX drugs with a loading efficiency of 95.8%. The CS layer was uniformly distributed on the HM-ZSM-5 ellipsoids that contributed to the pH-responsive release of DOX drugs. The controlled DOX release kinetics from the HM-ZSM-5/CS/DOX ellipsoids was fitted well with the Korsmeyer-Peppas model. The HM-ZSM-5/CS/DOX ellipsoids exhibited good biocompatibility due to the low DOX release rate in the neutral media that simulated healthy tissues or blood. Moreover, the cellular uptake of the HM-ZSM-5/CS/DOX ellipsoids took place in tumor cells, and the quick release of DOX significantly promoted the apoptosis of MG63 cells. The levels of MDA, LDH and CK markers for the HM-ZSM-5/CS/DOX group were lower than those for the free DOX group, suggesting no systemic toxicity to the heart. Therefore, the HM-ZSM-5/CS/DOX ellipsoids as novel pH-responsive drug delivery systems can effectively treat osteosarcoma without systemic toxicity.

For effectively treating bone defects, the design of novel therapeutic scaffolds is an important strategy for enhancing stem cell osteogenic differentiation and new bone formation. Herein, we, for the first time, fabricated SC79-loaded ZSM-5/chitosan (ZSM-5/CS/SC79) porous scaffolds via the freeze-drying synthesis of ZSM-5/CS porous scaffolds followed by loading SC79 drug molecules. The ZSM-5/CS scaffolds possessed a three-dimensional (3D) interconnected porous structure, and the nanostructured ZSM-5 ellipsoids were uniformly dispersed on the CS films. The ZSM-5/CS/SC79 scaffolds had appropriate drug loading-release properties due to the hierarchically porous structures of ZSM-5 zeolites and the hydrogen bonding between the CS and SC97. In vitro cell tests demonstrated that both the ZSM-5/CS and ZSM-5/CS/SC79 scaffolds could promote the adhesion, spreading and proliferation of human bone mesenchymal stem cells (hBMSCs). Interestingly, the SC97 released from the scaffolds not only promoted the proliferation of hBMSCs, but also enhanced the osteogenic differentiation. As compared with the ZSM-5/CS control group, the ZSM-5/CS/SC79 scaffolds promoted the ALP activity of hBMSCs, improved the mRNA relative expression levels of osteocalcin (OCN), bone morphogenetic protein-2 (BMP-2) and alkaline phosphatise (ALP), and increased the protein level of β-catenin. The enhanced proliferation and osteogenic differentiation of hBMSCs contributed to the upregulation of Akt kinase by an activated Wnt/β-catenin signaling pathway. Moreover, in vivo animal tests indicated that SC79 released from the ZSM-5/CS/SC79 scaffolds promoted the new bone regeneration without systemic side effects in cranial defects. Therefore, ZSM-5/CS/SC79 scaffolds as novel and promising therapeutic scaffolds have promising applications in defined local bone regeneration.

The low quantum efficiency and limited adsorption efficiency of TiO 2 makes it only fit for the removal of VOCs with low concentrations. Herein, we for the first time fabricated nanostructured TiO 2 /activated carbon fiber felt (TiO 2 /ACFF) porous composites by the in situ deposition of TiO 2 microspheres on the carbon fibers in ACFF. Interestingly, the TiO 2 microspheres exhibit hierarchical nanostructures constructed by nanocrystals as building blocks. The TiO 2 /ACFF porous composites possess excellent adsorption and photodegradation properties for toluene because of the synergetic effects between the nanostructured TiO 2 and ACFF. The adsorption efficiencies of the TiO 2 /ACFF porous composites reach approximately 98% at the toluene concentration (<1150ppm) and approximately 77% even at the high concentration of 6900ppm. Moreover, the ACFF in the TiO 2 /ACFF porous composites significantly enhances photocatalytic property for toluene by hindering the recombination of electron-hole pairs, reducing the TiO 2 band gap energy (E g ) to 2.95eV and accelerating toluene adsorption. At the toluene concentrations of 230ppm and 460ppm, the photocatalytic oxidation efficiency of toluene into CO 2 arrives at 100% and 81.5%, respectively. Therefore, the TiO 2 /ACFF porous composites with synergetic adsorption and photocatalytic activities have great potentials for toluene removal., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Poor bone formation remains a key risk factor associated with acellular scaffolds that occurs in some bone defects, particularly in patients with metabolic bone disorders and local osteoporosis. We herein fabricated for the first time layered double hydroxide-chitosan porous scaffolds loaded with PFTα (LDH-CS-PFTα scaffolds) as therapeutic bone scaffolds for the controlled release of PFTα to enhance stem cell osteogenic differentiation and bone regeneration. The LDH-CS scaffolds had three-dimensional interconnected macropores, and plate-like LDH nanoparticles were uniformly dispersed within or on the CS films. The LDH-CS scaffolds exhibited appropriate PFTα drug delivery due to hydrogen bonding among LDH, CS and PFTα. In vitro functional studies demonstrated that the PFTα molecules exhibited potent ability to induce osteogenesis of hBMSCs via the GSK3β/β-catenin pathway, and the LDH-CS-PFTα scaffolds significantly enhanced the osteogenic differentiation of hBMSCs. In vivo studies revealed significantly increased repair and regeneration of bone tissue in cranial defect model rats compared to control rats at 12 weeks post-implantation. In conclusion, the LDH-CS-PFTα scaffolds exhibited excellent osteogenic differentiation and bone regeneration capability and hold great potential for applications in defined local bone regeneration.

Bone repair materials for the effective treatment of bone defects should simultaneously possess excellent biocompatibility and promote osteogenic differentiation. Herein, we prepared pifithrin-α-loaded layered double hydroxide/chitosan (PFTα-LDH-CS) nanohybrid composites for the first time according to the following steps: (i) the immersion of LDH nanoplates and PFTα in a CS solution; and (ii) the self-assembly synthesis of PFTα-LDH-CS nanohybrid composites after the pH value of the mixed solution was adjusted to 7.4. Interestingly, the LDH nanoplates with a thickness of ∼20 nm and width of ∼300 nm agglomerated together into flower-like shapes by self-assembly, and the CS was dispersed around the LDH nanoplates. The mesopores with the pore size of 3.95 nm among the LDH nanoplates served as channels for loading PFTα. Moreover, the CS around the LDH nanoplates increased the drug loading efficiency and drug sustained release property compared with the pure LDH nanoplates. The in vitro tests demonstrated that the human bone marrow-derived mesenchymal stem cells (hBMSCs) had good adhesion, spreading and proliferating on the LDH-CS and PFTα-LDH-CS, suggesting that both samples had the desired cytocompatibility. Note that the PFTα released from the PFTα-LDH-CS rapidly improved the cell proliferation, ALP activity, ECM mineralization and protein level of the Runt-related transcription factor 2 (RUNX2) and β-catenin. The enhanced osteogenic differentiation of hBMSCs on the PFTα-LDH-CS may be attributed to the PFTα released from the abovementioned nanohybrid composites, which resulted in the accumulation of β-catenin and activation of the β-catenin-mediated transcription activity in the cell nucleus. Therefore, the PFTα-LDH-CS nanohybrid composites with excellent cytocompatibility and enhanced osteoinductivity have great applications for novel bone repair materials.

There is a need to find better strategies to promote wound healing, especially of chronic wounds, which remain a challenge. We found that synovium mesenchymal stem cells (SMSCs) have the ability to strongly promote cell proliferation of fibroblasts; however, they are ineffective at promoting angiogenesis. Using gene overexpression technology, we overexpressed microRNA-126-3p (miR-126-3p) and transferred the angiogenic ability of endothelial progenitor cells to SMSCs, promoting angiogenesis. We tested a therapeutic strategy involving controlled-release exosomes derived from miR-126-3p-overexpressing SMSCs combined with chitosan. Our in vitro results showed that exosomes derived from miR-126-3p-overexpressing SMSCs (SMSC-126-Exos) stimulated the proliferation of human dermal fibroblasts and human dermal microvascular endothelial cells (HMEC-1) in a dose-dependent manner. Furthermore, SMSC-126-Exos also promoted migration and tube formation of HMEC-1. Testing this system in a diabetic rat model, we found that this approach resulted in accelerated re-epithelialization, activated angiogenesis, and promotion of collagen maturity in vivo. These data provide the first evidence of the potential of SMSC-126-Exos in treating cutaneous wounds and indicate that modifying the cells-for example, by gene overexpression-and using the exosomes derived from these modified cells provides a potential drug delivery system and could have infinite possibilities for future therapy. Stem Cells Translational Medicine 2017;6:736-747., (© 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

The properties of bone scaffolds, including biocompatibility, osteoinductivity and antibacterial activity, are of great importance for reconstruction of large bone defects and prevention of implant-associated infections. Herein, we develop an Ag-loaded strontium hydroxyapatite (SrHAP)/chitosan (CS) porous scaffold (Ag-SrHAP/CS) according to the following steps: (i) freeze-drying fabrication of a SrHAP/CS porous scaffold; and (ii) deposition of Ag nanoparticles on the above scaffold. In addition, HAP/CS and Ag-HAP/CS porous scaffolds are prepared under the same conditions without doping Sr element. All the HAP/CS, Ag-HAP/CS, SrHAP/CS and Ag-SrHAP/CS porous scaffolds provide a friendly environment for the adhesion, spreading and proliferation of human bone marrow mesenchymal stem cells (hBMSCs). The three-dimensional (3D) interconnected macropores with a pore size of 100-400 μm allow the spreading of hBMSCs throughout the whole scaffolds. Interestingly, the Sr ions and Ag ions released from the Ag-SrHAP/CS porous scaffolds significantly enhance their osteoinductivity and antibacterial activity, respectively. The Sr element in the SrHAP/CS and Ag-SrHAP/CS porous scaffolds increase the alkaline phosphatase (ALP) activity of hBMSCs, extracellular matrix (ECM) mineralization, and the expression levels of osteogenic-related genes BMP-2 and COL-I. Moreover, the Ag ions released from the Ag-HAP/CS and Ag-SrHAP/CS scaffolds can effectively inhibit the growth and attachment of Staphylococcus aureus (S. aureus, ATCC 25923). In conclusion, the Ag-SrHAP/CS porous scaffold possesses excellent biocompatibility, osteoinductivity and antibacterial activity, so it has great potential for application in bone tissue engineering to repair bone defects and avoid infections.

The exploration of an effective diabetic chronic wound healing process still remains a great challenge. Herein, we used gene overexpression technology to obtain synovial mesenchymal stem cells (SMSCs) and the miR-126-3p highly expressed SMSCs (SMSCs-126). The exosomes derived from miR-126-3p overexpressed SMSCs (SMSCs-126-Exos) with a particle size of 85 nm were encapsulated in hydroxyapatite/chitosan (HAP-CS) composite hydrogels (HAP-CS-SMSCs-126-Exos) as wound dressings. The SMSCs-126-Exos, CS and low-crystallinity HAP nanorods with a length of 200 nm and a diameter of 50 nm are uniformly dispersed within the whole composite hydrogel. The HAP-CS-SMSCs-126-Exos possess the controlled release property of SMSCs-126-Exos for at least 6 days. The released SMSCs-126-Exos nanoparticles stimulate the proliferation and migration of human dermal fibroblasts and human dermal microvascular endothelial cells (HMEC-1). At the same time, the migration and capillary-network formation of HMEC-1 are promoted through the activation of MAPK/ERK and PI3K/AKT. In vivo tests demonstrate that the HAP-CS-SMSCs-126-Exos successfully promote wound surface re-epithelialization, accelerate angiogenesis, and expedite collagen maturity due to the presence of HAP, CS and SMSCs-126-Exos. Therefore, the HAP-CS-SMSCs-126-Exos possess great potential application for diabetic chronic wound healing, and especially provide the possibility of using exosomes derived from modified cells as a new approach to bring wonderful functionality and controllability in future chronic wound therapy.

Hydroxyapatite (HA) crystals exhibit rod-like shape with c-axis orientation and plate-like shape with a(b)-axis orientation in vertebrate bones and tooth enamel surfaces, respectively. Herein, we report the synthesis of HA coatings with the oriented nanorod arrays (RHACs) and HA coatings with oriented nanoplate arrays (PHACs) by using bioglass coatings as sacrificial templates. After soaking in simulated body fluid (SBF) at 120°C, the bioglass coatings are hydrothermally converted into the HA coatings via a dissolution-precipitation reaction. If the Ca/P ratios in SBF are 2.50 and 1.25, the HA crystals on the coatings are oriented nanorod arrays and oriented nanoplate arrays, respectively. Moreover, the bioglass coatings are treated with SBF at 37°C, plate-like HA coatings with a low crystallinity (SHACs) are prepared. As compared with the Ti6Al4V and SHACs, the human bone marrow stromal cells (hBMSCs) on the RHACs and PHACs have better cell adhesion, spreading, proliferation and osteogenic differentiation because of their moderately hydrophilic surfaces and similar chemical composition, morphology and crystal orientation to human hard tissues. Notably, the morphologies of HA crystals have no obvious effects on cytocompatibility and osteogenic differentiation. Hence, the HA coatings with oriented nanoplate arrays or oriented nanorod arrays have a great potential for orthopedic applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Understanding the mechanisms underlying neuronal death in spinal cord injury (SCI) and developing novel therapeutic approaches for SCI-induced damage are critical for functional recovery. Here we investigated the role of heme oxygenase-1 (HO-1) in neuroprotection after SCI., Methods: Adeno-associated virus expressing HO-1 was prepared and injected into rat spinal cords before SCI model was performed. HO-1 expression, inflammasome activation, and the presence of inflammatory cytokines were determined by quantitative polymerase chain reaction, immunohistological staining, immunoblot, and immunoprecipitation. Neuronal apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling. The hindlimb locomotor function was evaluated for extent of neurologic damage. In an in vitro model, hydrogen peroxide was used to induce similar inflammasome activation in cultured primary spinal cord neurons, followed by evaluation of above parameters with or without transduction of HO-1-expressing adeno-associated virus., Results: Endogenous HO-1 expression was found in spinal cord neurons after SCI in vivo, in association with the expression of Nod-like receptor protein 1 (NLRP1) and the formation of NLRP1 inflammasomes. Administration of HO-1-expressing adeno-associated virus effectively decreased expression of NLRP1, therefore alleviating NLRP1 inflammasome-induced neuronal death and improving functional recovery. In the in vitro model, exogenous HO-1 expression protected neurons from hydrogen peroxide-induced neuronal death by inhibiting NLRP1 expression. In addition, HO-1 inhibited expression of activating transcription factor 4 (ATF4), which is a transcription factor regulating NLRP1 expression., Conclusions: HO-1 protects spinal cord neurons after SCI through inhibiting NLRP1 inflammasome formation.

Background . To explore influence of continuous illumination, luzindole, and Tamoxifen on incidence of scoliosis model of rats. Methods . Thirty-two one-month-old female rats were rendered into bipedal rats. The bipedal rats were divided into 4 groups: group A by intraperitoneal injection of luzindole and continuous illumination; group B by intraperitoneal injection of luzindole only; group C by intraperitoneal injection of luzindole and oral administration of Tamoxifen; and group D by intraperitoneal injection of equivalent saline. Radiographs were taken at 8th week and 16th week, and incidence and the Cobb angles of scoliosis were calculated. At 16th week, all rats were sacrificed. Before the sacrifice, the levels of calmodulin were measured in each group. Results . At 8th week, scoliosis occurred in groups A and B, with an incidence of 75% and 12.5%, respectively, while rats in group C or D had no scoliosis. At 16th week, scoliosis incidences in groups A and B were 57% and 62.5%, respectively. No scoliosis occurred in group C or D. Calmodulin in platelets in group B was significantly different, compared with groups A and D. There was no significant difference in calmodulin in platelets in groups B and C. Conclusion . By intraperitoneal injection of luzindole in bipedal rats, scoliosis rat models could be successfully made. Under light, incidence of scoliosis may be increased at an early period but it is reversible. Tamoxifen can suppress natural process of scoliosis., Competing Interests: All authors have no conflict of interests in this study.

An ideal scaffold for bone tissue engineering should have interconnected porous structure, good biocompatibility, and mechanical properties well-matched with natural bones. Collagen is the key component in the extracellular matrix (ECM) of natural bones, and plays an important role in bone regeneration. The biological activity of collagen has promoted it to be an advantageous biomaterial for bone tissue engineering; however, the mechanical properties of these scaffolds are insufficient and the porous structures are not stable in the wet state. An effective strategy to solve this problem is to fabricate a hybrid scaffold of biologically derived and synthetic material, which have the necessary bioactivity and mechanical stability needed for bone synthesis. In this work, a three-dimensional macroporous bone scaffold based on collagen (CO) fiber and bioglass (BG) is fabricated by a slurry-dipping technique, and its relevant mechanical and biological properties are evaluated. The CO/BG scaffold is interconnected with a porosity of 81 ± 4.6% and pore size of 40-200 μm. Compared with CO scaffold, water absorption value of CO/BG scaffold decreases greatly from 889% to 52%, which significantly alleviates the swelling behavior of collagen and improves the stability of scaffold structure. The CO/BG scaffold has a compression strength of 5.8 ± 1.6 MPa and an elastic modulus of 0.35 ± 0.01 Gpa, which are well-matched with the mechanical properties of trabecular bones. In vitro cell assays demonstrate that the CO/BG scaffold has good biocompatibility to facilitate the spreading and proliferation of human bone marrow stromal cells. Hence, the CO/BG scaffold is promising for bone tissue engineering application., (© 2014 Wiley Periodicals, Inc.)

The fabrication of bone scaffolds with interconnected porous structure, adequate mechanical properties, excellent biocompatibility and osteoinductivity presents a great challenge. Herein, a hybrid nanostructured hydroxyapatite-chitosan (HA-CS) composite scaffold has been fabricated according to the following steps: (i) the deposition of brushite-CS on a CS fibre porous scaffold by a dip-coating method; and (ii) the formation of a hybrid nanostructured HA-CS composite scaffold by the in situ conversion of brushite to HA using a bioinspired mineralization process. The hybrid HA-CS composite scaffold possesses three-dimensional (3D) interconnected pores with pore sizes of 30-80 μm. The HA rods with a length of ∼200 nm and width of ∼50 nm are perpendicularly oriented to the CS fibres. Interestingly, the abovementioned HA rods are composed of many smaller nanorods with a length of ∼40 nm and width of ∼10 nm oriented along the c-axis. The hybrid nanostructured HA-CS composite scaffold exhibits good mechanical properties with a compression strength of 9.41 ± 1.63 MPa and an elastic modulus of 0.17 ± 0.02 GPa, which are well-matched to those of trabecular bone. The influences of the hybrid HA-CS composite scaffold on cells have been investigated using human bone marrow stem cells (hBMSCs) as cell model and the CS fibre porous scaffold as the control sample. The hybrid HA-CS composite scaffold not only supports the adhesion and proliferation of hBMSCs, but also improves the osteoinductivity. The alkaline phosphatase activity and mineralization deposition on the hybrid HA-CS composite scaffold are higher than those on the CS fibre porous scaffold. Moreover, the hybrid HA-CS composite scaffold can promote the formation of new bone in rat calvarial defects as compared with the CS fibre porous scaffold. The excellent biocompatibility, osteoinductivity and mechanical properties suggest that the hybrid nanostructured HA-CS composite scaffold has great potential for bone tissue engineering.

To determine the neuronal connections in the periaqueductal gray (PAG) is important for studying modulation of neuronal activity of PAG to influence sympathetic responses. We had characterized projections from the left kidney to the midbrain PAG in adult male melanocortin-4 receptor (MC4R)-green fluorescent protein (GFP) transgenic mice by using retrograde tracing techniques of pseudorabies virus (PRV)-614 for direct visualization under two-photon immunofluorescence microscope. We found that injections of PRV-614 into the kidney resulted in retrograde infection of neurons in the ventrolateral sub-areas of PAG, and PRV-614/MC4R-GFP double-labeled neurons were detected in the ventrolateral sub-areas of PAG. These results indicated that a subpopulation of ventrolateral PAG neurons innervating renal tissues expressed MC4R, suggesting that deep brain stimulation of the ventrolateral PAG may influence renal function by melanocortinergic pathway.

Hydroxyapatite (HA) is the main inorganic constituent of natural bones and teeth with c-axis orientation and a(b)-axis orientation, respectively. Designing HA coatings (HACs) with specific orientation and morphology is an important strategy to improve their biological properties. Herein, we report, for the first time, the hydrothermal synthesis of HACs with oriented nanoplate arrays according to the following steps: (i) deposition of brushite/chitosan coatings (BCCs) on Ti6Al4V substrates; and (ii) transformation of HACs with oriented nanoplate arrays from BCCs after hydrothermal treatment with alkaline solutions. After soaking the BCCs in a NaOH solution under hydrothermal conditions, the Ca 2+ and PO 4 3- ions are released from the coatings because of the dissolution reaction of brushite, and they react with OH - ions to form HA nanoplates. Interestingly, these HA nanoplates with a preferential c-plane orientation are perpendicular to the coating surfaces. Hydrothermal reaction time and Ca/P ratio of BCCs have great effects on the morphologies of HA nanoplates. On increasing the reaction time from 3 h to 3 days or decreasing the Ca/P ratio from 2.0 to 1.0, the widths (or lengths) of HA nanoplates increase gradually. Simulated body fluid immersion (SBF) tests reveal that the HACs with oriented nanoplate arrays can promote the formation of apatite on the surfaces, suggesting their good in vitro bioactivity. Moreover, human bone marrow stromal cells (hBMSCs) have been used as cell models to investigate cytocompatibility of the HACs. The hBMSCs on the HACs have better cell adhesion, spreading, proliferation and osteogenic differentiation than those on Ti6Al4V substrates because the HACs are similar to the minerals of human hard tissues in chemical composition, morphology and crystallographic orientation. Therefore, HACs with oriented nanoplate arrays have great potential for use as implants of human hard tissues.

Bone defects caused by trauma and disease have become urgent problems. Three-dimensional (3D) porous scaffolds for bone tissue engineering should ideally have an interconnected porous structure, good biocompatibility and mechanical properties similar to those of natural bones. In the present study, a chitosan/bioglass (CS/BG) 3D porous scaffold was constructed by initially preparing a CS fibre 3D porous scaffold by needle-punching, and then depositing BG on the scaffold by dip-coating. The CS/BG 3D porous scaffold had an interconnected porous structure, with a porosity of 77.52% and a pore size around 50 μm. Water absorption values of the CS fibre 3D porous scaffold and the corresponding CS/BG scaffold were 570% and 59%, respectively. The BG present in the latter significantly decreased the swelling of the CS fibres, thus improving the stability of the scaffolds. The CS/BG 3D porous scaffold possessed good mechanical properties, with a compression strength of 7.68 ± 0.38 MPa and an elastic modulus of 0.46 ± 0.02 GPa, which are well-matched to those of trabecular bone. In vitro cell assay results demonstrated that the CS/BG 3D porous scaffold had good biocompatibility, which facilitates the spreading and proliferation of human bone marrow stromal cells (hBMSCs). The CS/BG 3D porous scaffold is thus a suitable material for bone tissue engineering.

The aim of this study is to investigate cross-linked gelatin-chitosan nanofibers produced by means of electrospinning. Gelatin and chitosan nanofibers were electrospun and then cross-linked by glutaraldehyde (GTA) vapor at room temperature. Scanning electron microscopy (SEM) images showed that the cross-linked mats could keep their nanofibrous structure after being soaked in deionized water at 37° C. The cross-linking mechanism was discussed based on FT-IR results. The two main mechanisms of cross-linking for chitosan and gelatin-chitosan complex are Schiff base reaction and acetalization reaction. For gelatin, the mechanism of cross-linking was Schiff base reaction. The mechanical properties of nanofibrous mats were improved after cross-linking. The biocompatibility of electrospun nanofibrous mats after cross-linking was investigated by the viability of porcine iliac endothelial cells (PIECs). The morphologies of PIECs on the cross-linked nanofibrous mats were observed by SEM. In addition, proliferation of PIECs was tested with the method of methylthiazol tetrazolium (MTT) assay. The results indicate that gelatin-chitosan nanofibrous mats could be a promising candidate for tissue-engineering scaffolds.