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Jing-Hua Yang,1 Zuohui Zhao,2 Wanting Niu,3 Han-Pil Choi,3 Kazem M Azadzoi4 1Department of Surgery, Boston University School of Medicine and Proteomics Laboratory, VA Boston Healthcare System, Boston, MA, USA; 2Department of Urology, Boston University School of Medicine, Boston, MA, USA; 3Research Department, VA Boston Healthcare System, Boston, MA, USA; 4Departments of Urology and Pathology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USACorrespondence: Kazem M Azadzoi, VA Boston Healthcare System, Building 1A, Room 317 (151), 150 South Huntington Avenue, Boston, MA, 02130, USA, Tel +1 857-364-5602, Email kazadzoi@bu.eduPurpose: Growing evidence suggests that ischemia provokes detrusor overactivity and degenerative responses in the bladder. Underlying mechanisms appear to involve modification of smooth muscle contractile rudiments by hypoxia, redox, cellular stress and cell survival signaling. Downstream pathways of cellular stress and stress response molecules eliciting bladder dysfunction in ischemia remain largely elusive. Our goal was to define the role of double stranded RNA (dsRNA), a stress response molecule provoked by redox, in ischemia mediated bladder dysfunction.Methods: A rat model of pelvic ischemia along with a cell culture hypoxia model were used to investigate the expression levels, functional consequences, structural aspects, and regulatory mechanisms of dsRNA in the bladder. Gene and protein expression were examined by reverse transcription polymerase chain reaction (RT-PCR), dot blot, and Western blotting, respectively. Tissue structure and function were assessed using histological staining and organ bath. Regulatory mechanisms were analyzed in cultured bladder smooth muscle cells.Results: The data presented here provide the first evidence of the formation of dsRNA in the overactive bladder. dsRNA is a cellular stress response molecule that sensitizes smooth muscle and regulates inflammatory and degenerative rejoinders. Our data suggest that the production of dsRNA in the bladder is provoked by ischemia. Formation of dsRNA appears to augment bladder smooth muscle contractions and provoke fibrotic and apoptotic responses. Downstream actions of dsRNA in the bladder may involve upregulation of dsRNA-activated protein kinase R (PKR) and caspase-3, the executioner of apoptosis.Conclusion: Activation of dsRNA/PKR pathway may play a role in sensitization of bladder smooth muscle cells to contractile stimuli, whereas dsRNA and caspase-3 crosstalk appear to modulate cellular stress and instigate degenerative responses in bladder ischemia. These observations suggest the role of dsRNA in bladder dysfunction and may open new perspectives to overcome overactive smooth muscle contractions and structural damage in the bladder.Keywords: bladder, ischemia, overactivity, dsRNA, contraction, degeneration

The treatment of a variety of defects in bony sites could benefit from mitogenic stimulation of osteoprogenitor cells, including endogenous bone marrow-derived mesenchymal stem cells (bMSCs), and from provision of such cells with a matrix permissive of their migration, proliferation, and osteogenic differentiation. That such MSC stimulation could result from treatment with noninvasive (extracorporeal) shock waves (ESWs), and the matrix delivered by injection could enable this therapeutic approach to be employed for applications in which preformed scaffolds and growth factor therapy are difficult to deploy. The objectives of the present study were to investigate focused ESWs for their effects on proliferation, migration, and osteogenic differentiation in an injectable gelatin (Gtn) matrix capable of undergoing covalent cross-linking in vivo. Gtn was conjugated with hydroxyphenyl propionic acid (HPA) in order to enable it to be covalently cross-linked with minute amounts of horseradish peroxidase and hydrogen peroxide. The results demonstrated that 500 shocks of 0.4-mJ/mm2 energy flux density resulted in a twofold greater proliferation of bMSCs in the Gtn-HPA matrix after 14 days, compared with bMSCs grown with supplementation with platelet-derived growth factor (PDGF)-BB, a known mitogen for bMSCs. Moreover, SW treatment enhanced substantially osteogenic differentiation of bMSCs. The Gtn-HPA gel was permissive of MSC migration under the chemotactic influence of the growth factor, PDGF-BB, incorporated into and released by the gel. ESW treatment had no effect on the motility of the MSCs. The findings of the study warrant further investigation of this combined treatment modality for select bony defects.

Background and Purpose: Although VEGF 165 (vascular endothelial growth factor-165) is able to enhance both angiogenesis and neurogenesis, it also increases vascular permeability through the blood-brain barrier. Heparan sulfate (HS) sugars play important roles in regulating VEGF bioactivity in the pericellular compartment. Here we asked whether an affinity-purified VEGF 165 -binding HS (HS7) could augment endogenous VEGF activity during stroke recovery without affecting blood-brain barrier function. Methods: Both rat brain endothelial cell line 4 and primary rat neural progenitor cells were used to evaluate the potential angiogenic and neurogenic effects of HS7 in vitro. For in vivo experiments, male Sprague-Dawley rats were subjected to 100 minutes of transient focal cerebral ischemia, then treated after 4 days with either PBS or HS7. One week later, infarct volume, behavioral sequelae, immunohistochemical markers of angiogenesis and neural stem cell proliferation were assessed. Results: HS7 significantly enhanced VEGF 165 -mediated angiogenesis in rat brain endothelial cell line 4 brain endothelial cells, and increased the proliferation and differentiation of primary neural progenitor cells, both via the VEGFR2 (vascular endothelial growth factor receptor 2) pathway. Intracerebroventricular injection of HS7 improved neurological outcome in ischemic rats without changing infarct volumes. Immunostaining of the compromised cerebrum demonstrated increases in collagen IV/Ki67 and nestin/Ki67 after HS7 exposure, consistent with its ability to promote angiogenesis and neurogenesis, without compromising blood-brain barrier integrity. Conclusions: A VEGF-activating glycosaminoglycan sugar, by itself, is able to enhance endogenous VEGF 165 activity during the post-ischemic recovery phase of stroke.

The concept of the neurovascular unit emphasizes the importance of cell-cell signaling between neural, glial, and vascular compartments. In neurogenesis, for example, brain endothelial cells play a key role by supplying trophic support to neural progenitors. Here, we describe a surprising phenomenon where brain endothelial cells may release trans-differentiation signals that convert astrocytes into neural progenitor cells in male mice after stroke. After oxygen-glucose deprivation, brain endothelial cells release microvesicles containing pro-neural factor Ascl1 that enter into astrocytes to induce their trans-differentiation into neural progenitors. In mouse models of focal cerebral ischemia, Ascl1 is upregulated in endothelium prior to astrocytic conversion into neural progenitor cells. Injecting brain endothelial-derived microvesicles amplifies the process of astrocyte trans-differentiation. Endothelial-specific overexpression of Ascl1 increases the local conversion of astrocytes into neural progenitors and improves behavioral recovery. Our findings describe an unexpected vascular-regulated mechanism of neuroplasticity that may open up therapeutic opportunities for improving outcomes after stroke.

Yiran Yan,1,* Yan Chen,2,* Zhongxun Liu,1 Feiyan Cai,3 Wanting Niu,4,5 Liming Song,1 Haifeng Liang,1 Zhiwen Su,1 Bo Yu,1 Fei Yan6 1Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China; 2Department of Ultrasonic Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China; 3Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China; 4VA Boston Healthcare System, Boston, MA, 02130, USA; 5Department of Orthopedics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA; 6CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei YanShenzhen Institutes of Advance Technology, Chinese Academy of Science, 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen, Guangdong, 518055, People’s Republic of ChinaTel +86 755 86392284Fax +86 755 96382299Email fei.yan@siat.ac.cnBo YuDepartment of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye Avenue, Haizhu District, Guangzhou, Guangdong, 510280, People’s Republic of ChinaTel +86 20 67282573Fax +86 20 61643010Email gzyubo@163.comBackground: Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Owing to the presence of blood–brain barrier (BBB), conventional pharmaceutical agents are difficult to the diseased nuclei and exert their action to inhibit or delay the progress of PD. Recent literatures have demonstrated that curcumin shows the great potential to treat PD. However, its applications are still difficult in vivo due to its poor druggability and low bioavailability through the BBB.Methods: Melt-crystallization methods were used to improve the solubility of curcumin, and curcumin-loaded lipid-PLGA nanobubbles (Cur-NBs) were fabricated through encapsulating the curcumin into the cavity of lipid-PLGA nanobubbles. The bubble size, zeta potentials, ultrasound imaging capability and drug encapsulation efficiency of the Cur-NBs were characterized by a series of analytical methods. Low-intensity focused ultrasound (LIFU) combined with Cur-NB was used to open the BBB to facilitate curcumin delivery into the deep brain of PD mice, followed by behavioral evaluation for the treatment efficacy.Results: The solubility of curcumin was improved by melt-crystallization methods, with 2627-fold higher than pure curcumin. The resulting Cur-NBs have a nanoscale size about 400 nm and show excellent contrast imaging performance. Curcumin drugs encapsulated into Cur-NBs could be effectively released when Cur-NBs were irradiated by LIFU at the optimized acoustic pressure, achieving 30% cumulative release rate within 6 h. Importantly, Cur-NBs combined with LIFU can open the BBB and locally deliver the curcumin into the deep-seated brain nuclei, significantly enhancing efficacy of curcumin in the Parkinson C57BL/6J mice model in comparison with only Cur-NBs and LIFU groups.Conclusion: In this work, we greatly improved the solubility of curcumin and developed Cur-NBs for brain delivery of curcumin against PD through combining with LIFU-mediating BBB. Cur-NBs provide a platform for these potential drugs which are difficult to cross the BBB to treat PD disease or other central nervous system (CNS) diseases.Keywords: nanobubbles, blood–brain barrier, low-intensity focus ultrasound, curcumin, Parkinson’s disease

Wear particles-induced inflammatory osteolysis, a major factor of aseptic loosening affects the long-term survival of orthopedic prostheses. Increasing observations have demonstrated that osteocytes, making up over 95% of all the bone cells, is involved in wear particle-induced periprosthetic osteolysis, but its mechanism remains unclear. In the present study, we embedded micro-sized tricalcium phosphate (TCP) particles (30 mg) under the periosteum around the middle suture of the mouse calvaria to establish a calvarial osteolysis model and investigated the biological effects of the particles on calvaria osteocytes in vivo. Results showed that TCP particles induced pyroptosis and activated the NLRP3 inflammasome in calvaria osteocytes, which was confirmed by obvious increases in empty lacunae, protein expressions of speck-like protein containing CARD (ASC), NOD-like receptor protein 3 (NLRP3), cleaved caspase-1 (Casp-1 p20) and cleaved gasdermin D (GSDMD-N), and resulted in elevated ratios of Casp-1 p20/Casp-1 and interleukin (IL)-1β/pro-IL-1β. Simultaneously, TCP particles enhanced serum levels of lactate dehydrogenase (LDH) and IL-1β. Furthermore, the pyroptotic effect was reversed by the Casp-1 inhibitor VX765 or the NLRP3 inhibitor MCC950. In addition, TCP particles increased the levels of intracellular reactive oxygen species (ROS) and malonaldehyde (MDA), whereas decreased the antioxidant enzyme nuclear factor E2-related factor 2 (Nrf2) level, leading to oxidative stress in calvaria osteocytes; the ROS scavenger N-acetylcysteine (NAC) attenuated these effects of pyroptotic death and the NLPR3 activation triggered by TCP particles. Collectively, our data suggested that TCP particles promote pyroptotic death of calvaria osteocytes through the ROS/NLRP3/Caspase-1 signaling axis, contributing to osteoclastogenesis and periprosthetic osteolysis.

Laparoscopic partial nephrectomy and robot-assisted partial nephrectomy are attracting increased attention from urologists. They can achieve the same effect of oncology control as radical nephrectomy; moreover, they can offer better preservation of renal function, thus obtaining long-term living benefits. The indications are also expanding, making it possible for larger and more difficult tumors. Laparoscopic partial nephrectomy and robot-assisted partial nephrectomy can be performed by transperitoneal and retroperitoneal approaches, with their individual advantages and limitations. In addition, the renal tumor scoring systems have been widely used and studied in laparoscopic partial nephrectomy and robot-assisted partial nephrectomy. In ­order to better preserve renal function, the zero-ischemia technique is widely used. The application of intraoperative imaging technology provides convenience and greater benefits. Besides, whether minimal invasive partial nephrectomy can be performed without stop antiplatelet treatment is still disputed. Clinicians perform substantial exploration and practice to achieve the “trifecta” of surgery: complete resection of the tumor, maximum protection of renal function, and no complications.

We reviewed nanotoxicity and regulatory aspects of nanoengineering and nanomaterials in musculoskeletal regeneration. The chapter includes host response, biocompatibility, safety, and processing environment. Acute immune response, chronic immune response, and activation of immune cells were introduced in host response. Physiochemical parameters of nanomaterials impacting the biocompatibility including particle size and surface charge, shape and conjugation, protein corona, and activation of coagulation were summarized. We also introduced cell-biomaterial interaction and methods to determine the biocompatibility. To assess the safety of nanoparticles (NP), physicochemical parameters, biodegradation, incubation condition, toxicity species, assay methods of toxicity, and toxicity mechanisms are considered. Furthermore, we illustrated the safety of carbon nanotubes, fullerenes, graphene, and metallic nanoparticles that are used widely. In addition, tissue engineering, micro- and nanofabrication technology, stem-cell engineering, and 3-D environment were illustrated in processing environment.

Musculoskeletal system belongs to the movement system, which is composed of bone, joint, and skeletal muscle. It is the main part of the body and plays the role of supporting the body, protecting the important organs, and moving. In this chapter, we will understand the composition of musculoskeletal system, the characteristics of musculoskeletal system injuries and diseases (including work-related musculoskeletal diseases, arthritis, and degenerative disc disease), and the failure cases of orthopedic implants. Learning the occurrence and pathophysiology of musculoskeletal system and the existing treatment schemes, problems, and challenges will provide a more comprehensive perspective for the renewal of clinical treatment.

Objective: Volatile anesthetic such as isoflurane causes widespread neurodegeneration in the developing animal brains and also induces cognitive impairments. Paeonol is a plant-derived phenolic com...

Epileptic seizures are the main clinical manifestation of low-grade astrocytoma. Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. Until now, the role of VGSCs and the relationships between calmodulin (CaM)/CaM-dependent protein kinase II (CaMKII) and VGSCs in low-grade astrocytoma have not been demonstrated. In our study, the protein expression of NaV1.3, NaV1.6 and CaM was significantly increased in the tumor compared to control tissue, while the level of p-CaMKII/CaMKII was significantly decreased in the tumor group as determined by Western Blotting and immunohistochemistry. Furthermore, double-labeling immunofluorescence results showed that NaV1.3/NaV1.6 and CaM co-localization was significantly increased in the tumor group compared to control tissue. This study represents the first evidence of the abnormal changes in VGSCs subtypes and CaM/CaMKII pathway in human brain low-grade astrocytoma, providing new potential targets for molecular therapies of this disease.

// Ming Li 1 , Ying Wang 2, 3 , Liang Cheng 4 , Wanting Niu 5 , Guoan Zhao 6 , Jithin K. Raju 7 , Jun Huo 1 , Bin Wu 1 , Bo Yin 1 , Yongsheng Song 1 and Renge Bu 1 1 Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China 2 Department of Nuclear Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China 3 Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA 4 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA 5 Department of Orthopedics, Brigham and Women’s Hospital, VA Boston Healthcare System, Harvard Medical School, Boston, Massachusetts 02115, USA 6 School of Network Education, Beijing University of Posts and Telecommunications, Hebei, Beijing 100088, P.R. China 7 Department of Clinical Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China Correspondence to: Renge Bu, email: burg@sj-hospital.org Keywords: renal cell carcinoma, lncRNA, diagnosis, prognosis, therapy Received: November 18, 2016 Accepted: March 20, 2017 Published: April 12, 2017 ABSTRACT Renal cell carcinoma is one of the most common malignancy in adults, its prognosis is poor in an advanced stage and early detection is difficult due to the lack of molecular biomarkers. The identification of novel biomarkers for RCC is an urgent and meaningful project. Long non-coding RNA (lncRNA) is transcribed from genomic regions with a minimum length of 200 bases and limited protein-coding potential. Recently, lncRNAs have been greatly studied in a variety of cancer types. They participate in a wide variety of biological processes including cancer biology. In this review, we provide a new insight of the profiling of lncRNAs in RCC and their roles in renal carcinogenesis, with an emphasize on their potential in diagnosis, prognosis and potential roles in RCC therapy.

Background Mangiferin (MF) was reported to possess anti-inflammatory activity. This investigation tried to probe into the underlying mechanism of MF in osteoarthritis. Methods ATDC5 cells were pretreated with series concentrations of MF (0.1, 1, 5, 10, 15, 20 μM) for 2 h and then were exposed to lipopolysaccharide (LPS) (5 μg/ml) for 12 h to construct the inflammatory injury model. The cell viability, productions of pro-inflammatory cytokines and enzymes were respectively measured by employing CCK-8 assay, western blot, ELISA, and quantitative reverse-transcription (qRT)-PCR. miR-181a expression was altered by employing cell transfection. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) method was employed for detection of reactive oxygen species (ROS) generation. Dual luciferase activity assay was conducted for analyzing the relationship between miR-181a and PTEN. The underlying mechanism was determined by employing western blot. Results High doses of MF treatment (15 and 20 μM) noticeably induced inflammatory injury exhibiting as increased the productions of pro-inflammatory cytokines, enzymes and ROS, activated NF-κB pathway and deactivated PTEN/PI3K/AKT pathway in ATDC5 cells. Besides, MF treatment notably remitted LPS-induced inflammatory injury through deactivation of NF-κB pathway and activation of PTEN/PI3K/AKT pathway. PTEN was a target of miR-181a. Inhibition of miR-181a remarkably reversed MF-triggered impacts on ATDC5 cells. Conclusion MF attenuated LPS-induced inflammatory damage through miR-181a/PTEN axis and thereby inhibiting NF-κB pathway and activating PI3K/AKT pathway.

Biomaterials provide novel platforms to deliver stem cell and growth factor therapies for central nervous system (CNS) repair. The majority of these approaches have focused on the promotion of neural progenitor cells and neurogenesis. However, it is now increasingly recognized that glial responses are critical for recovery in the entire neurovascular unit. In this study, we investigated the cellular effects of epidermal growth factor (EGF) containing hydrogels on primary astrocyte cultures. Both EGF alone and EGF‐hydrogel equally promoted astrocyte proliferation, but EGF‐hydrogels further enhanced astrocyte activation, as evidenced by a significantly elevated Glial fibrillary acidic protein (GFAP) gene expression. Thereafter, conditioned media from astrocytes activated by EGF‐hydrogel protected neurons against injury and promoted synaptic plasticity after oxygen–glucose deprivation. Taken together, these findings suggest that EGF‐hydrogels can shift astrocytes into neuro‐supportive phenotypes. Consistent with this idea, quantitative‐polymerase chain reaction (qPCR) demonstrated that EGF‐hydrogels shifted astrocytes in part by downregulating potentially negative A1‐like genes (Fbln5 and Rt1‐S3) and upregulating potentially beneficial A2‐like genes (Clcf1, Tgm1, and Ptgs2). Further studies are warranted to explore the idea of using biomaterials to modify astrocyte behavior and thus indirectly augment neuroprotection and neuroplasticity in the context of stem cell and growth factor therapies for the CNS. stem cells translational medicine 2019;8:1242&1248, Biomaterials provide novel platforms to deliver stem cell and growth factor therapies for central nervous system repair. Our data suggest that epidermal growth factor‐containing hydrogels can shift astrocytes into potentially beneficial A2‐like phenotypes that may augment neuroprotection and neuroplasticity during the recovery phase after brain injury.

The purpose of this study was to evaluate the histologic features of the caprine labrum, with emphasis on the chondrolabral junction, with the goal of informing the feasibility of the goat as an animal model. The left hip joint of six adolescent Spanish goats (Capra pyrenaica) was harvested and subjected to anatomical and histological assessments. Human acetabular and femoral head samples, collected during total hip arthroplasty, served as comparison samples. The caprine labrum was found to consist of mostly type I collagen with uniform crimp, with an average crimp length of 20.8 µm. Upon histological assessment, acetabular articular chondrocytes were found to express substance-P, especially near or in the chondrolabral junction. And the majority of nonvascular cells expressed α-smooth muscle actin (SMA), with no notable elastin and laminin expression. Human labrum demonstrated similar staining patterns. Overall, the goat hip was found to be homologous to the human hip, demonstrating potential as a useful animal model for future studies. This is the first report of a crimped collagen structure in the labrum. Crimped type I collagen at the chondrolabral junction imparts an extension-recovery property which allows for toleration of stress without permanent deformation, underlying the importance of its preservation during surgery. The high expression of substance-P reflects the degree to which the labrum is innervated. Finally, the expression of α-SMA with contractile characteristics could indicate the potential for chondrocyte (i.e., myochondrocytes) modeling of the extracellular matrix. Statement of Clinical Significance: Establishment of a large animal model and deeper knowledge of the histological composition of the hip joint will enhance our study of the acetabular labrum, including repair techniques. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1070-1080, 2020.

Background This study investigated the efficacy of extracorporeal shock wave (ESW) application in stimulating dermal thickness, vascularity, and collagen synthesis of facial skin in a large animal model. Materials and methods The facial skin of the maxillary and mandibular areas of goats (n = 6 per group) was treated with ESWs of different intensities (0.15 and 0.45 mJ/mm2; 1000 pulses). After 4 d, histology and immunohistochemistry were used to evaluate the following: dermal thickness, total number and abundance of microvessels, amount of type 1 collagen, and α-smooth muscle actin expression. Results Dermal thickness, number and abundance of microvessels, and collagen synthesis increased after ESW application at both intensities (each P Conclusions A single-session application of focused low-energy ESWs to facial skin can increase dermal thickness by stimulating collagen production and local microcirculation. These findings commend the technique for future investigation for pretreatment of local or microvascular skin flaps to enhance tissue healing.

Supplementary_Data for In Situ Cross-linking Hydrogel as a Vehicle for Retinal Progenitor Cell Transplantation by Jeayoung Park, Petr Baranov, Aybike Aydin, Hany Abdelgawad, Deepti Singh, Wanting Niu, Motoichi Kurisawa, Myron Spector, and Michael J. Young in Cell Transplantation

Background In the ultrahigh molecular weight polyethylene (UHMWPE) prosthetic environment, fibroblasts affected by wear particles have the capacity of osteogenesis to reduce osteolysis. We aimed to assess the effects of macrophages on the osteogenic capability of fibroblasts treated with UHMWPE wear particles. Methods The effect of different concentrations of UHMWPE (0, 0.01, 0.1, and 1 mg/ml, respectively) on macrophage proliferation were validated by MTT assay to determine the optimum one. The fibroblasts viability was further determined in the co-culture system of UHMWPE particles and macrophage supernatants. The experiment was designed as seven groups: (A) fibroblasts only; (B) fibroblasts + 1 mg/ml UHMWPE particles; and (C1–C5) fibroblasts + 1/16, 1/8, 1/4, 1/2, and 1/1 supernatants of macrophage cultures stimulated by 1 mg/ml UHMWPE particles vs. fibroblast complete media, respectively. Alizarin red staining was used to detect calcium accumulation. The expression levels of osteogenic proteins were detected by Western blot and ELISA, including alkaline phosphatase (ALP) and osteocalcin (OCN). Results The concentration of 0.1 mg/ml was considered as the optimum concentration for macrophage proliferation due to the survival rate and was highest among the four concentrations. Fibroblast viability was better in the group of fibroblasts + 1/16 ratio of macrophage supernatants stimulated by 1 mg/ml of UHMWPE particles than the other groups (1:8, 1:4, 1:2, 1:1). ALP and OCN expressions were significantly decreased in the group of fibroblasts + 1/4, 1/2, and 1/1 supernatants stimulated by 1 mg/ml of UHMWPE particles compared with other groups (1/8, 1/16) and the group of fibroblasts + 1 mg/ml UHMWPE (p

Epileptic seizures are the main clinical manifestation of low-grade astrocytoma. Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. Until now, the role of VGSCs and the relationships between calmodulin (CaM)/CaM-dependent protein kinase II (CaMKII) and VGSCs in low-grade astrocytoma have not been demonstrated. In our study, the protein expression of Na

A chitosan-based microsphere delivery system has been fabricated for controlled release of alendronate (AL). The present study aimed to incorporate the chitosan/hydroxyapatite microspheres-loaded with AL (CH/nHA-AL) into poly(L-lactic acid)/nanohydroxyapatite (PLLA/nHA) matrix to prepare a novel microspheres-scaffold hybrid system (CM-ALs) for drug delivery and bone tissue engineering application. The characteristics of CM-ALs scaffolds containing 10% and 20% CH/nHA-AL were evaluated in vitro, including surface morphology and porosity, mechanical properties, drug release, degradation, and osteogenic differentiation. The in vivo bone repair for large segmental radius defects (1.5 cm) in a rabbit model was evaluated by radiography and histology. In vitro study showed more sustained drug release of CM-AL-containing scaffolds than these of CM/nHA-AL and PLLA/nHA/AL scaffolds, and the mechanical and degradation properties of CM-ALs (10%) scaffolds were comparable to that of PLLA/nHA control. The osteogenic differentiation of adipose-derived stem cells (ASCs) was significantly enhanced as indicated by increased alkaline phosphates (ALP) activity and calcium deposition. In vivo study further showed better performance of CM-ALs (10%) scaffolds with complete repair of large-sized bone defects within 8 weeks. A microspheres-scaffold-based release system containing AL-encapsulated chitosan microspheres was successfully fabricated in this study. Our results suggested the promising application of CM-ALs (10%) scaffolds for drug delivery and bone tissue engineering.

Nanogels have attracted much attention in the recent decades due to the combined properties of nanotechnology and cross-linking gel-like materials. These nanogels show great biocompatibility and biodegradability both in vitro and in vivo studies and have been widely used into biomedical science in terms of imaging, diagnostics, drug delivery, tissue engineering, biosensors, etc. The physicochemical properties (sizes, shapes, charges, and surface chemistries) can be easily tuned, which offer nanogels many advantages as nanocarrier for delivery of small molecules, proteins, genes, and other therapies. Incorporation of nanoparticles with a scaffold or hydrogel provides the ability to manipulate nanoscale parameters of scaffold for the development of 3D printing technology in the field of tissue engineering. In addition, these nanogels can sense and respond to environmental stimuli such as temperature, pH, light, mechanical stress, electric, magnetic field and glucose concentration. The special properties and simultaneously possesses characteristic of hydrogel and nanoparticle system make them potential candidates for sensory elements of biosensor.

Nanomaterials are honored as new materials of the 21st century. Compared with traditional organic dyes, quantum dots (QDs) have attracted extensive research interest due to their excellent fluorescent characteristics. In this research, the mercaptopropionic acid capped QDs were linked with monoclonal antibodies via EDC/NHS as immunofluorescent probes to detect the antigens in serum. The bioactivity and the titer of antibodies in the fluorescent probes were analysed with the method of enzyme linked immunosorbent assay. At last, the feature of human serum autofluorescence was analysed and then the emission wavelength range and the concentration of QDs needed in serological immunoassay were decided.

Spinal Cord Injury (SCI) results in the permanent functional impairment, leading to monoplegia, paraplegia or tetraplegia with tremendous social and economic burden. The intrinsic repair mechanism has been proven to be insufficient. The complex pathophysiology after injury imposes enormous challenging to functional recovery, given the most advanced medical intervention nowadays. Therefore, the development of effective therapeutic strategy for spinal cord injury management is in great need. Here we review a stem cell based tissue engineering approach under preclinical or clinical development for spinal cord injury, with a focus on promoting functional recovery after SCI, aiming to provide some beneficial suggestion on stem cell based tissue engineering design.

Being a great threat to human health, with no permanent cure yet, better treatment and further research in cancer are inevitable. Nanoparticle drug delivery systems (NDDSs), especially pH-sensitive NDDSs, such as lipid-based, polymeric, and mesoporous silica nanoparticles have played a significant role in cancer treatments. Further, three-dimensional (3D) cell cultures models, which include tumor spheroid models, microfluidic systems, and matrix/scaffolds-based 3D tumor, better mimic the tumor microenvironment than the conventional two-dimensional cultures, making it possible to better understand the disease while serving as a useful in vitro model for future research. The present review mainly focuses on such 3D cell cultures and drug delivery systems that are applied in cancer research and treatments.

Semiconductor quantum dots (QDs) are a new kind of biological fluorescence material, which has many advantages, such as broad excitation spectra, tunable emission spectra and good photostability. In the field of biomedical detection, the problems encountered in the traditional organic dye-based biomedical detections, such as short fluorescence lifetime and failure to simultaneous excitation of multiple colors, can be solved by using QDs. Water-soluble QDs combined with specific bio-molecules can label targeting bio-compound, which is useful in bio-molecule detection, cell labeling, tissue imaging, and can be used in fluorescence resonance energy transfer (FRET) technology. Combining QDs and protein chip technology to develop a new technology to detect multiple kinds of tumor markers will be one of the promising clinical applications of QDs with greater sensitivity, specificity, rapidity and convenience.

Quantum dots, as a new kind of biological fluorescence material, have properties superior to the traditional organic dyes. In the recent decade, researches about the application of quantum dots in biomedicine have made great progress. Tumor markers have vital importance in the diagnosis and treatment of carcinoma; however, they are not widely used for lack of specificity and sensitivity. Researches about applications of quantum dots in the detection of tumor markers are centralized in three aspects, namely the detection of serum/plasma tumor markers, the detection of tissue and cell tumor markers (such as molecular imaging of cell and tissue), and the detection of tumor in vivo animals. A combination of quantum dots and flow cytometry technique for developing a new technique to detect multiple kinds of tumor markers at the same time with greater sensitivity, specificity, rapidity and convenience may have the potential for clinical use of quantum dots.