TGF‐β1‐activated type 2 dendritic cells promote wound healing and induce fibroblasts to express tenascin c following corneal full‐thickness hydrogel transplantation

We showed previously that 1‐ethyl‐3‐(3‐dimethylamino‐propyl)‐carbodiimide hydrochloride (EDC) cross‐linked recombinant human collagen III hydrogels promoted stable regeneration of the human cornea (continued nerve and stromal cell repopulation) for over 4 years. However, as EDC cross linking kinetics were difficult to control, we additionally tested a sterically bulky carbodiimide. Here, we compared the effects of two carbodiimide cross linkers—bulky, aromatic N‐cyclohexyl‐N0‐(2‐morpholinoethyl)‐carbodiimide (CMC), and nonbulky EDC—in a mouse corneal graft model. Murine corneas undergoing full‐thickness implantation with these gels became opaque due to dense retro‐corneal membranes (RCM). Corneal epithelial cytokeratin 12 and alpha smooth muscle actin indicative of functional tissue regeneration and wound contraction were observed in RCM surrounding both hydrogel types. However, quantitatively different levels of infiltrating CD11c⁺ dendritic cells (DC) were found, suggesting a hydrogel‐specific innate immune response. More DC infiltrated the stroma surrounding EDC‐N‐hydroxysuccinimide (NHS) hydrogels concurrently with higher fibrosis‐associated tenascin c expression. The opposite was true for CMC‐NHS gels that had previously been shown to be more tolerising to DC. In vitro studies showed that DC cultured with transforming growth factor β1 (TGF‐β1) induced fibroblasts to secrete more tenascin c than those cultured with lipopolysaccharide and this effect was blocked by TGF‐β1 neutralisation. Furthermore, tenascin c staining was found in 40‐ to 50μm long membrane nanotubes formed in fibroblast/DC cocultures. We suggest that TGF‐β1 alternatively activated (tolerising) DC regulate fibroblast‐mediated tenascin c secretion, possibly via local production of TGF‐β1 in early wound contraction, and that this is indirectly modulated by different hydrogel chemistries.     

The extracellular matrix enriched with membrane metalloendopeptidase and insulin‐degrading enzyme suppresses the deposition of amyloid‐beta peptide in Alzheimer's disease cell models

Amyloid plaque is a typical feature of Alzheimer's disease (AD) and is one of the targets for AD therapy. Membrane metalloendopeptidase (MME) and insulin‐degrading enzyme (IDE) are two types of proteases that could cleave beta‐amyloid (Aβ) peptides generated by neuron cells of AD patients. Extracellular matrix (ECM) plays a crucial role in regulating tissue‐specific functions and is an ideal biomaterial for tissue repair. In this study, we extracted the liquid ECM enriched with collagen‐binding‐domain‐fused IDE or MME from human foreskin fibroblast cells. We found that these ECM biomaterials reduced the aggregation of Aβ peptides, prevented the formation of amyloid plaques, and also suppressed phosphorylation of Tau protein in AD cell models. Overall, our research provides a novel ECM biomaterial that can be potentially used for AD therapy.     

2003-2012年护理学高被引论文学术特征分析及启示

目的：为护理学期刊编辑选题、组稿,提升期刊质量和学术影响力提供参考。方法：运用文献计量学方法,从期刊、发表栏目、主题、研究方法、基金资助5方面进行描述性统计分析。结果：护理学高被引论文期刊、发表栏目、研究方法呈集中性分布,主题呈集中性和动态性分布,基金资助以院校、省级为主,省级基金资助比例高于国家级基金。结论：护理学期刊编辑应围绕研究热点展开选题,加强产生高被引论文栏目建设与组稿,积极挖掘优质稿源,提高国家级基金资助论文的刊出比例。     

RESECTION FOR RUPTURED DUODENAL VARICES SECONDARY TO PORTAL HYPERTENSION

Apatient complicated by gastrointestinal bleeding was treated successfully using resection of ruptured duodenal varies. The paper reviewed the literatures and introduced surgical procedures and its indications.     

New insights into the effects of biomaterial chemistry and topography on the morphology of kidney epithelial cells

Increasing incidence of renal pathology in the western world calls for innovative research for the development of cell‐based therapies such as a bioartificial kidney (BAK) device. To fulfil the multitude of kidney functions, the core component of the BAK is a living membrane consisting of a tight kidney cell monolayer with preserved functional organic ion transporters cultured on a polymeric membrane surface. This membrane, on one side, is in contact with blood and therefore should have excellent blood compatibility, whereas the other side should facilitate functional monolayer formation. This work investigated the effect of membrane chemistry and surface topography on kidney epithelial cells to improve the formation of a functional monolayer. To achieve this, microtopographies were fabricated with high resolution and reproducibility on polystyrene films and on polyethersulfone‐polyvinyl pyrrolidone (PES‐PVP) porous membranes. A conditionally immortalized proximal tubule epithelial cell line (ciPTEC) was cultured on both, and subsequently, the cell morphology and monolayer formation were assessed. Our results showed that L‐dopamine coating of the PES‐PVP was sufficient to support ciPTEC monolayer formation. The polystyrene topographies with large features were able to align the cells in various patterns without significantly disruption of monolayer formation; however, the PES‐PVP topographies with large features disrupted the monolayer. In contrast, the PES‐PVP membranes with small features and with large spacing supported well the ciPTEC monolayer formation. In addition, the topographical PES‐PVP membranes were compatible as a substrate membrane to measure organic cation transporter activity in Transwell® systems. Copyright © 2016 John Wiley & Sons, Ltd.     

Tissue-engineered cartilage with inducible and tunable immunomodulatory properties

The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis.     

Sugar‐Derived Poly(β‐thioester)s as a Biomedical Scaffold

The monomer isosorbide diacrylate (iSDA) and commercially available dithiols allowed access to a range of biosourced, degradable polymers. Altering the dithiol identity significantly affected the glass transition T_gs of the polymer products; however, polymers did not exhibit T_gs above room temperature. Incorporating the comonomer N,N′‐methylene bisacrylamide provided mechanical reinforcement through hydrogen bonding, resulting in soft, pliable materials. Differential scannin calorimetry (DSC) and variable‐temperature fourier‐transform infrared (FTIR) spectroscopy indicated that increases in mechanical integrity resulted from hydrogen bonding. Dynamic mechanical analysis (DMA) revealed materials that exhibited suitable moduli and service windows at body temperature. Biological evaluation demonstrated favorable cytotoxicity and cell attachment, rendering these materials potential candidates as novel scaffold materials for tissue growth.     

Influence of the stiffness of three-dimensional alginate/collagen-I interpenetrating networks on fibroblast biology

Wound dressing biomaterials are increasingly being designed to incorporate bioactive molecules to promote healing, but the impact of matrix mechanical properties on the biology of resident cells orchestrating skin repair and regeneration remains to be fully understood. This study investigated whether tuning the stiffness of a model wound dressing biomaterial could control the behavior of dermal fibroblasts. Fully interpenetrating networks (IPNs) of collagen-I and alginate were fabricated to enable gel stiffness to be tuned independently of gel architecture, polymer concentration or adhesion ligand density. Three-dimensional cultures of dermal fibroblasts encapsulated within matrices of different stiffness were shown to promote dramatically different cell morphologies, and enhanced stiffness resulted in upregulation of key-mediators of inflammation such as IL-10 and COX-2. These findings suggest that simply modulating the matrix mechanical properties of a given wound dressing biomaterial deposited at the wound site could regulate the progression of wound healing.     

Collagen-Based Biomaterials for Tissue Engineering Applications

Collagen is the most widely distributed class of proteins in the human body. The use of collagen-based biomaterials in the field of tissue engineering applications has been intensively growing over the past decades. Multiple cross-linking methods were investigated and different combinations with other biopolymers were explored in order to improve tissue function. Collagen possesses a major advantage in being biodegradable, biocompatible, easily available and highly versatile. However, since collagen is a protein, it remains difficult to sterilize without alterations to its structure. This review presents a comprehensive overview of the various applications of collagen-based biomaterials developed for tissue engineering, aimed at providing a functional material for use in regenerative medicine from the laboratory bench to the patient bedside.