Vapor construction and modification of stem cell-laden multicomponent scaffolds for regenerative therapeutics.

Tissue engineering based on the combined use of isolated cells, scaffolds, and growth factors is widely used; however, the manufacture of cell-preloaded scaffolds faces challenges. Herein, we fabricated a multicomponent scaffold with multiple component accommodations, including bioactive molecules (BMs), such as fibroblast growth factor-2 (FGF-2) and l-ascorbic acid 2-phosphate (A2-P), and living cells of human adipose-derived stem cells (hASCs), within one scaffold construct. We report an innovative fabrication process based on vapor-phased construction using iced templates for vapor sublimation.

Accurate prediction of acute pancreatitis severity based on genome-wide cell free DNA methylation profiles.

Background: Patients with severe acute pancreatitis (SAP) have a high mortality, thus early diagnosis and interventions are critical for improving survival. However, conventional tests are limited in acute pancreatitis (AP) stratification. We aimed to assess AP severity by integrating the informative clinical measurements with cell free DNA (cfDNA) methylation markers.

[Hydrogen-rich water improves progressive sperm motility in rats by reducing oxidative stress and upregulating CLDN3 and SRD5A2 expressions].

Objective: To investigate the protective effect of long-term consumption of hydrogen-rich water (HRW) on the percentage of progressively motile sperm (PMS) in male rats.

Methods: Twenty normal healthy male SD rats were equally randomized into an HRW and a control group, the former given HRW (1.2 ppm) and the latter normal saline, both intragastrically at 2 ml/d for 9 months.

Parylene-Based Porous Scaffold with Functionalized Encapsulation of Platelet-Rich Plasma and Living Stem Cells for Tissue Engineering Applications.

A scaffold was fabricated to synergistically encapsulate living human adipose-derived stem cells (hASCs) and platelet-rich plasma (PRP) based on a vapor-phase sublimation and deposition process. During the process, ice templates were prepared using sterile water as the solvent and were used to accommodate the sensitive living cells and PRP molecules. Under controlled processing conditions, the ice templates underwent vapor sublimation to evaporate water molecules, while at the same time, vapor-phase deposition of poly--xylylene (Parylene, USP Class VI highly biocompatible) occurred to replace the templates, and the final construction yielded a scaffold with Parylene as the matrix, with simultaneously encapsulated living hASCs and PRP molecules.

Exploring prognostic indicators in the pathological images of hepatocellular carcinoma based on deep learning.

Objective: Tumour pathology contains rich information, including tissue structure and cell morphology, that reflects disease progression and patient survival. However, phenotypic information is subtle and complex, making the discovery of prognostic indicators from pathological images challenging.

Design: An interpretable, weakly supervised deep learning framework incorporating prior knowledge was proposed to analyse hepatocellular carcinoma (HCC) and explore new prognostic phenotypes on pathological whole-slide images (WSIs) from the Zhongshan cohort of 1125 HCC patients (2451 WSIs) and TCGA cohort of 320 HCC patients (320 WSIs).

Synergistically Enhanced Wound Healing of a Vapor-Constructed Porous Scaffold.

In this study, a porous, three-dimensional material of parylene (poly--xylylene) incorporating keratin was fabricated. As an FDA-approved material, parylene is highly stable and biocompatible. Keratin is an abundant natural material that can enhance cell adhesion and wound healing.

Nucleophilic Substitution of gem-Difluoroalkenes with TMSNu Promoted by Catalytic Amounts of CsCO.

The efficient and practical nucleophilic cyanation and trifluoromethylation with appropriate trimethylsilyl nucleophiles were developed. Catalytic amounts of cheap and nontoxic CsCO were used to maintain a sufficiently high concentration of nucleophilic anion (CN or CF) which could begin the catalytic cycle. The present methodologies provide diverse functionalized monofluoroalkenes bearing a cyano and trifluoromethyl group with excellent to moderate stereoselectivities.

Clickable and Photo-Erasable Surface Functionalities by Using Vapor-Deposited Polymer Coatings.

A prospective design for interface properties is enabled to perform precise functionalization, erasure capability for existing properties, reactivation of surface functionality to a second divergent property. A vapor-deposited, 2-nitro-5-(prop-2-yn-1-yloxy)methylbenzyl carbamate-functionalized poly--xylylene coating is synthesized in this study to realize such tasks by offering the accessibility of the azide/alkyne click reaction, an integrated photochemical decomposition/cleavage moiety, and the reactivation sites of amines behind the cleavage that allow the installation of a second surface function. With the benefits from the mild processing conditions used for the coatings and the rapid response of the photochemical reaction, the creation of sophisticated interface properties and localized chemical compositions was elegantly demonstrated with a hybrid functionality including a confined hydrophlic/hydrophobic wetting property and/or a cell adherent/repellent platform on such a coating surface.

Defined cell adhesion for silicon-based implant materials by using vapor-deposited functional coatings.

The field of implantable electronics relies on using silicon materials due to the merits of a well-established fabrication process and favorable properties; of particular interest is the surface modification of such materials. In the present study, we introduce a surface modification technique based on coatings of functionalized Parylene on silicon substrates, where the modified layers provide a defined cell adhesion capability for the resultant silicon materials/devices. Functionalization of Parylene was achieved during a one-step chemical vapor deposition (CVD) polymerization process, forming NHS ester-functionalized Parylene, and subsequent RGD attachment was enabled via a conjugation reaction between the NHS ester and amine groups.

Synthesis of β-Alkyl 2-Hydroxychalcones by Rhodium-Catalyzed Coupling of N-Phenoxyacetamides and Nonterminal Propargyl Alcohols.

An efficient rhodium-catalyzed coupling of N-phenoxyacetamides and nonterminal propargyl alcohols has been developed. A series of β-Alkyl 2-hydroxychalcones bearing diverse functional groups were obtained with excellent regio- and stereoselectivity, and the desired chalcones could then be converted to triazole and chromene smoothly.

Vapor sublimation and deposition to build porous particles and composites.

The vapor deposition of polymers on regular stationary substrates is widely known to form uniform thin films. Here we report porous polymer particles with sizes controllable down to the nanometer scale can be produced using a fabrication process based on chemical vapor deposition (CVD) on a dynamic substrate, i.e.

Surface modification: activation and deactivation of osteogenic differentiation based on detachable growth factor protein.

An advanced material interface is modified by using a substrate-independent coating of detachable poly-para-xylylene, enabling dynamical control of the immobilization and detachment of biomolecules, and a previously installed biological function is deactivated or tuned with reduced activity. The induction of osteogenesis activity, and subsequent deactivation of such osteogenesis activity, is demonstrated.

Topologically Controlled Cell Differentiation Based on Vapor-Deposited Polymer Coatings.

In addition to the widely adopted method of controlling cell attachment for cell patterning, pattern formation via cell proliferation and differentiation is demonstrated using precisely defined interface chemistry and spatial topology. The interface platform is created using a maleimide-functionalized parylene coating (maleimide-PPX) that provides two routes for controlled conjugation accessibility, including the maleimide-thiol coupling reaction and the thiol-ene click reaction, with a high reaction specificity under mild conditions. The coating technology is a prime tool for the immobilization of sensitive molecules, such as growth factor proteins.

Stepwise and Programmable Cell Differentiation Pathways of Controlled Functional Biointerfaces.

An advanced control of biomaterial surfaces was created to enable the stepwise and switchable activities of the immobilized growth factor (GF) proteins for a programmed manipulation over cell differentiation pathways. The GF protein was immobilized on an advanced vapor-based coating of poly[(4-2-amide-2'-amine-dithiobisethyl--xylylene)--(-xylylene)], and the equipped disulfide exchange mechanism of the coating enables the detachment and/or the displacement of the previously installed GF to reinstall a second GF protein. In this study, the controlled immobilization and displacement of the fibroblast growth factor (FGF-2) and bone morphogenetic protein (BMP-2) were demonstrated on cell culture substrates, and the resulting surfaces provided a programmable induction of cellular responses in proliferation and osteogenesis toward the cultured murine preosteoblasts (MC3T3-E1).

Controlling multi-function of biomaterials interfaces based on multiple and competing adsorption of functional proteins.

Multifunctional biomaterial surfaces can be created by controlling the competing adsorption of multiple proteins. To demonstrate this concept, bone morphogenetic protein 2 (BMP-2) and fibronectin were adsorbed to the hydrophobic surface of polychloro-para-xylylene. The resulting adsorption properties on the surface depended on the dimensional and steric characteristics of the selected protein molecule, the degree of denaturation of the adsorbed proteins, the associated adsorption of interphase water molecules within the protein layers, and the aggregation of proteins in a planar direction with respect to the adsorbent surface.

Vapor-based coatings for antibacterial and osteogenic functionalization and the immunological compatibility.

The immobilization of biofunctional molecules to biomaterial surfaces has enabled and expanded the versatility of currently available biomaterials to a wider range of applications. In addition, immobilized biomolecules offer modified surfaces that allow the use of smaller amounts of potentially harmful substances or prevent overdose, while the exhibited biological functions remain persistently effective. Surface concentrations of chlorhexidine (CHX) (1.

Multifunctional and Continuous Gradients of Biointerfaces Based on Dual Reverse Click Reactions.

Chemical or biological gradients that are composed of multifunctional and/or multidirectional guidance cues are of fundamental importance for prospective biomaterials and biointerfaces. As a proof of concept, a general modification approach for generating multifunctional and continuous gradients was realized via two controlled and reversed click reactions, namely, thermo-activated thiol-yne and copper-free alkyne and azide click reactions. The cell adhesion property of fibroblasts was guided in a gradient with an enhancement, showing that the PEG molecule and RGD peptide were countercurrently immobilized to form such reversed gradients (with negating of the cell adhesion property).

Fabrication of multipotent poly-para-xylylene particles in controlled nanoscopic dimensions.

In this study, poly-para-xylylene-based multifunctional nanoparticles (PPX-NPs) were fabricated. Based on the solubility characteristics determined for asymmetrically substituted poly-para-xylylenes in polar solvents, well-dispersed nanocolloids with a controllable size ranging from 50 to 800nm were produced in solution by the displacement of the solvent (water). These size ranges were found to have acceptable cellular compatibility through examinations of cultured 3T3 fibroblasts and adipose-derived stem cells treated with the PPX-NPs.

Switching the Biointerface of Displaceable Poly-p-xylylene Coatings.

A new class of functionalized poly-p-xylyene coating has been synthesized to provide switchable and displaceable surface properties for biomaterials. The switchability is achieved through a mechanism for detaching/attaching biomolecules and/or a mechanism through which the programmed restoration of functions or their replacement by other functions can be carried out. This advanced version of poly-p-xylylene comprises an integrated disulfide moiety within the functional side group, and the switching phenomenon between the immobilized functional molecules is triggered by the redox thiol-disulfide interchange reaction.

Expression of group IIA phospholipase A2 is an independent predictor of favorable outcome for patients with gastric cancer.

Growing evidence suggests that phospholipase A2 (PLA2) plays a pivotal role in tumorigenesis in human gastrointestinal cancer. One of the well-studied isoforms of PLA2, group IIA PLA2 (PLA2G2A), appears to exert its protumorigenic or antitumorigenic effects in a tissue-specific manner. The present study was designed to determine the expression profile and prognostic value of PLA2G2A in gastric cancer in a large Chinese cohort.

Reduced group IVA phospholipase A2 expression is associated with unfavorable outcome for patients with gastric cancer.

Arachidonic acid metabolic pathway has been implicated in the inflammation-associated tumorigenesis of gastrointestinal cancers. As the rate-limiting enzyme of arachidonic acid production, group IVA phospholipase A2 (PLA2G4A) is hypothesized to play a fundamental role in gastric tumorigenesis as well as cyclooxygenase-2 (COX-2). However, little is known about the expression and role of PLA2G4A in gastric cancer, and the association of PLA2G4A with COX-2 remains to be elucidated.

Expression profile and prognostic role of sex hormone receptors in gastric cancer.

Background: Increasing interest has been devoted to the expression and possible role of sex hormone receptors in gastric cancer, but most of these findings are controversial. In the present study, the expression profile of sex hormone receptors in gastric cancer and their clinicopathological and prognostic value were determined in a large Chinese cohort.

Methods: The mRNA and protein expression of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), progesterone receptor (PR), and androgen receptor (AR) in primary gastric tumors and corresponding adjacent normal tissues from 60 and 866 Chinese gastric cancer patients was detected by real-time quantitative PCR and immunohistochemistry method, respectively.

Interleukin-8, a promising predictor for prognosis of pancreatic cancer.

Aim: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer.

Methods: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochemistry in pancreatic cancer and chronic pancreatitis samples. Enzyme-linked immunosorbent assay was used to detect the serum IL-8 levels in pancreatic cancer patients.