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Challenges of repairing injuries and damage to the cartilage still remain in orthopedics. The characteristics of cartilage structure, especially avascular, make it a limited capacity of self-renewal. Articular cartilage defect or damage result from various causes will lead to degenerative osteoarthritis (OA). Surgical treatment and non-surgical treatment can temporarily alleviate symptoms to some extent but can't fundamentally restore the normal structure and function of cartilage, and therefore give rise to progressive degeneration. Autologous or allogeneic cartilage transplantation has been employed to the treatment of osteoarthritis for years. Nevertheless, the major deficiency of cartilage grafting is the inability and insufficiency to repair large cartilage defect. Implants are also unable to integrate with native tissue well. Adipose-derived stem cells (ASCs) can be easily isolated from subcutaneous fat tissues and harvest as intact cell sheets containing extracellular matrix (ECM), intercellular connect, ion channel, growth factor receptors, nexin and other important cell surface proteins by means of temperature-responsive culture dish (TCD). A cell sheet can provide a large amount of extracellular matrix, fibronectin, and cells contributing to the integration of cartilage. Decellularized extracellular matrix (DECM) of cartilage debris with excellent cell affinity and signal transduction is capable of driving cartilage homeostasis and regeneration. Appropriate decellularization process would remove cellular remnants of cartilage debris, keep the mechanical properties, and avoid the adverse immune response of allografts effectively. Micro-porous cartilage debris conduces to cell migration and angiogenesis. The cell-round shape of adipose-derived stem cells cultured in the three-dimensional (3D) system provided by hydrogel is more susceptible to chondrogenic stimulation and prevents it from fibroblast-like phenotypic conversion. We hypothesize that adipose-derived stem cell sheet encapsulated construct of micro-porous decellularized cartilage debris and hydrogel can effectively promote regeneration of cartilage defect. The construct of decellularized cartilage debris and hydrogel provide a favorable microenvironment for stem cells. Adipose-derived stem cells sheet supply fibronectin, collagen, and cells contributing to integration and regeneration of cartilage restore. Moreover, the constructs can be shaped and fabricated according to the configuration of target defect, especially in osteoarthritis, which is promising for clinical application. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to investigate the efficacy of the delayed fat flap on viability and longevity of grafted fat in an animal model. Sixty New Zealand rabbits were used for the long-term study. In each animal, a U-shaped fat flap was raised randomly in the inguinal region on one leg and then resutured in place to delay the flap for ischaemic pretreatment. The contralateral inguinal region was left untreated as a matched control. At 12h after the delaying operation, vascular endothelial growth factor (VEGF) expression in the fat from both groups of 10 rabbits was assessed. At 3 weeks, fat grafts from both the pretreated and control inguinal regions were transferred into a pocket that had been created on each side of the dorsal midline of the rabbit. Ten rabbits were sacrificed at intervals of 1, 3, 6, 9 and 12 months after transplantation for gross and histomorphometric analysis. Results showed that VEGF protein level in the pretreated fat flaps was significantly higher than that in the controls at 12h after the delaying operation. The number of vessels was increased in pretreated groups at 1 month, but no significant difference observed between two groups at 3 months. Histomorphometric analysis showed that the capillary density of the fat grafts was significantly higher in the pretreated group than that in controls at 1 and 3 months, respectively (P <0.01). There was no statistical difference in fat graft size and weight between the pretreated and control groups at 1 and 3 months after transplantation (P >0.05). However, the fat grafts in control groups disappeared after 6 months, and those in the pretreated groups were still maintained up to 12 months. This study demonstrated that the pretreatment of fat tissues with ischaemia insult could be advantageous for their viability and longevity. These results encourage further studies on potential clinical application of this new and simple technique to enable long lasting results. [Copyright &y& Elsevier]

Abstract: A biphasic layer with a Zn-containing β-tricalcium phosphate (ZnTCP) phase and a fluoridated hydroxyapatite (FHA) phase on titanium alloy substrate was prepared by the sol–gel technique. Scanning electron microscopy and energy-dispersive X-ray analysis results showed the ZnTCP/FHA layer to have a heterogeneous surface with microscaled gibbous structures originating from ZnTCP particle agglomeration. This layer had a slow and sustained Zn release behavior. The scratch test result of the ZnTCP/FHA layer was 489±4mN, indicating good interface bonding between the layer and substrate. The ZnTCP/FHA layer supported cell growth, and showed a statistically significant increase in cell viability in comparison with another biphasic layer (TCP/FHA) without Zn. This work demonstrates that the present biphasic ZnTCP/FHA layer has the potential to play a significant role in enhancing bone growth when used as the outermost part of bioactive coatings on metallic implants. [Copyright &y& Elsevier]

Abstract: Fluoridated hydroxyapatite (FHA) coatings were deposited onto Ti6Al4V substrates by sol–gel dip-coating method. X-ray photoelectron spectroscopy results showed that fluoride ions were successfully incorporated into the hydroxyapatite (HA) lattice structure. The dissolution behavior in Tris-buffered physiological saline indicated that all fluoridated HA coatings had lower solubility than that of the pure HA coating. The lowest solubility was obtained at fluoride ion concentrations of 0.8–1.1M. In vitro cell responses were evaluated with human osteosarcoma MG63 cells in terms of cell morphology, proliferation and differentiation (alkaline phosphatase activity and osteocalcin level). For all coatings tested, similar cell morphologies and good cell viability were observed. Coatings fluoridated to 0.8–1.1 had a stronger stimulating effect on cell proliferation and differentiation activities. The influences on cell phenotypes were attributed mainly to a combined ion effect of Ca, P and F released from the coating during dissolution. For the best dissolution resistance and cell activities, it is recommended that the molar level of fluoride ion be from 0.8 to 1.1, such that the coating takes the form of Ca10(PO4)6(OH)1.2–0.9F0.8–1.1. [Copyright &y& Elsevier]

Focuses on digital image scrambling. Transformation of a scrambled digital image to divert the true meaning of image; Classification of methods on scrambling of digital images; Encryption of the original image.

Abstract: The restoration of the degenerated articular cartilage in patients with osteoarthritis (OA) is still a challenge for researchers and clinicians. Drug interventions and surgical treatments have been widely attempted for cartilage regeneration in OA. However, the results were largely unsatisfactory. Autologous chondrocyte implantation (ACI) or matrix-induced autologous chondrocyte implantation (MACI) offers potential for the regeneration of cartilage over the long-term. However, due to the limitations and disadvantages of ACI, alternative therapies for cartilage regeneration are in need. The availability of large quantities of mesenchymal stem cells (MSCs) and the multilineage differentiation, especially their chondrogenic differentiation property, have made MSCs the most promising cell source for cartilage regeneration. In addition, MSCs have been shown the ability to undergo site-specific differentiation. MSCs can be obtained as MSC sheets using the temperature-responsive culture dish method. The MSC sheet can provide amounts of cells and extracellular matrix, which might provide the continuity between the implant and host cartilage, thus improving integrative cartilage repair. Moreover, OA is associated with progressive and often severe inflammation. MSCs not only have the ability to contribute structurally to tissue repair, but also possess potent immunomodulatory and anti-inflammatory effects. Taken together, these properties make MSC sheet promising candidate for cartilage repair in OA. We hypothesize that MSC sheet encapsulated cartilage debris can efficiently promote cartilage repair in OA patients. Chondrocytes can be obtained and cultured from small cartilage debris in vitro. Therefore, the chondrocytes may grow from the debris in cartilage defect and improve cartilage regeneration. MSC sheet provide amounts of cells, ECM and protein for cartilage regeneration and integration, and may play some roles of periosteum. The operation of MSC sheet encapsulated cartilage debris for cartilage repair is simple and practical. Moreover, the cell sheet/cartilage debris constructs can be easily shaped based on the size and shape of cartilage defects. The new method might have great potential in treating cartilage defects clinically, especially for OA patients. [Copyright &y& Elsevier]

Abstract: A novel amorphous calcium phosphate (ACP)/poly(l-lactic acid) (PLLA) material, which can experience morphological variations in the microstructure is supposed to be a suitable candidate as scaffold for cartilage tissue-engineering. The purpose of this study was to evaluate the efficacy of this scaffold combined with basic fibroblast growth factor (bFGF) to repair articular cartilage defects in a rabbit model. Forty-two osteochondral defects created in the femoral condyles were (a) left untreated, (b) treated by PLLA combined with bFGF, or (c) ACP/PLLA loaded with bFGF. The treatment of PLLA incorporated with bFGF improved defect filling compared with that left untreated, while the regenerated tissue was mainly fibrocartilage and showed little bone formation with only a small amount of collagen type II (Col II) and no aggrecan gene message measured. When implanted with ACP/PLLA and bFGF, most of the defects were filled with a well-established layer of cartilage tissue with abundance of cartilaginous extracellular matrix accumulation observed. Positive immunohistochemical staining of Col II was observed. High levels of Col II and aggrecan message were also detected by RT-PCR. These results indicate the feasibility of using the combination of ACP/PLLA with bFGF for cartilage repair. [Copyright &y& Elsevier]

• Natural polysaccharides from G. lucidum inhibit osteosarcoma in vivo and in vitro. • Immuneregulation on PD-L1 expression through STAT3 phosphorylation blockade. • PD-L1 downregulation via pho-STAT3 blockade verified by activator rescue assay. • Allograft osteosarcoma model for in vivo immune study. • Assay on main organs to prove safety and monoclonal antibody related side-effects remission. Osteosarcoma is a malignant musculoskeletal tumor with early metastasis and a poor prognosis, especially in adolescents. Ganoderma lucidum (Leyss. Ex Fr.) Karst (G. lucidum), a traditional East Asian medicine, has been reported to play a critical role in antitumor and immunomodulatory activity. The aim of this study was to investigate the effects and molecular mechanisms of water extract of sporoderm-broken spores of G. lucidum (BSGWE) on osteosarcoma PD-L1 (programmed cell death-ligand 1) transcriptional regulation, efficacy enhancement, and side effect remission. The antitumor effects on cell proliferation of BSGWE in osteosarcoma cells were detected by apoptosis flow cytometry, and the migration ability of HOS and K7M2 cells were evaluated by cell scratch assay. Potential signaling regulation of PD-L1 was detected by western blotting. To confirm the signaling pathway of BSGWE-related PD-L1 downregulation, a pho-STAT3 turnover experiment was carried out. Colivelin was administered as a pho-STAT3 activator to rescue the BSGWE-induced PD-L1 inhibition. To further study in vivo signaling, in a Balb/c osteosarcoma allograft model, tumor volume was measured using an in vivo bioluminescence imaging system. The body weight curve and tumor volume curve were analyzed to reveal the remission effects of BSGWE on PD-L1 antibody-related body weight loss and its immunomodulatory effects on the osteosarcoma and spleen. The PD-L1 expression level and expression of related transcription-factor pho-STAT3 in tumor cells and spleens were assessed by IHC analysis. BSGWE suppressed the proliferation and migration of osteosarcoma cells in vitro via induction of apoptosis. In addition, BSGWE downregulated PD-L1 expression and related STAT3 (signal transducers and activators of transcription) phosphorylation levels in a dose-dependent manner. Western blotting and qRT-PCR assay revealed that BSGWE downregulated PD-L1 expression by inhibiting STAT3 phosphorylation. A turnover experiment showed that colivelin administration could rescue PD-L1 inhibition via pho-STAT3 activation. BSGWE not only downregulated PD-L1 expression via the STAT3 pathway in an allograft Balb/c mouse model, but also relieved complications including weight loss and spleen atrophy in a mouse monoclonal antibody therapy model on the basis of its traditional advantages in immune enhancement. BSGWE downregulated PD-L1 expression via pho-STAT3 inhibition of protein and RNA levels. BSGWE enhanced PD-L1 antibody efficacy via phosphorylated STAT3 downregulation in vitro and in vivo. BSGWE also relieved complications of weight loss and spleen atrophy in a murine allograft osteosarcoma immune checkpoint blockade therapy model. [ABSTRACT FROM AUTHOR]

Excessive activation of osteoclast activity is responsible for many bone diseases, such as osteoporosis, rheumatoid arthritis, periprosthetic osteolysis, and periodontitis. Natural compounds that inhibit osteoclast formation and/or function have therapeutic potential for treating these diseases. Catalpol, a bioactive iridoid extracted from a traditional herbal medicine Rehmannia glutinosa , exhibits various pharmacological properties, including anti-inflammatory, antioxidant, antidiabetic, and antitumor effects. However, its effects on osteoclast formation and function remain unknown. In the present study, we showed that catalpol inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption, as well as the expression of osteoclast-related marker genes. The investigation of molecular mechanisms showed that catalpol upregulated phosphatase and tensin homolog (PTEN) activity by reducing its ubiquitination and degradation, subsequently suppressing RANKL-induced NF-κB and AKT signaling pathways, leading to an inhibition on NFATc1 induction. Furthermore, catalpol protected mice against inflammation- and ovariectomy-induced bone loss by inhibiting osteoclast activity in vivo. These results suggest that catalpol might be developed as a promising candidate for treating osteoclast-related bone diseases. [ABSTRACT FROM AUTHOR]