抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Additive manufacturing (AM) alias 3D printing translates computer-aided design (CAD) virtual 3D models into physical objects. By digital slicing of CAD, 3D scan, or tomography data, AM builds objects layer by layer without the need for molds or machining. AM enables decentralized fabrication of customized objects on demand by exploiting digital information storage and retrieval via the Internet. The ongoing transition from rapid prototyping to rapid manufacturing prompts new challenges for mechanical engineers and materials scientists alike. Because polymers are by far the most utilized class of materials for AM, this Review focuses on polymer processing and the development of polymers and advanced polymer systems specifically for AM. AM techniques covered include vat photopolymerization (stereolithography), powder bed fusion (SLS), material and binder jetting (inkjet and aerosol 3D printing), sheet lamination (LOM), extrusion (FDM, 3D dispensing, 3D fiber deposition, and 3D plotting), and 3D bioprinting....

Polymers for 3D Printing and Customized Additive Manufacturing

BACKGROUND Hydrogels are formed through the cross-linking of hydrophilic polymer chains within an aqueous microenvironment. The gelation can be achieved through a variety of mechanisms, spanning physical entanglement of polymer chains, electrostatic interactions, and covalent chemical cross-linking. The water-rich nature of hydrogels makes them broadly applicable to many areas, including tissue engineering, drug delivery, soft electronics, and actuators. Conventional hydrogels usually possess limited mechanical strength and are prone to permanent breakage. The lack of desired dynamic cues and structural complexity within the hydrogels has further limited their functions. Broadened applications of hydrogels, however, require advanced engineering of parameters such as mechanics and spatiotemporal presentation of active or bioactive moieties, as well as manipulation of multiscale shape, structure, and architecture. ADVANCES Hydrogels with substantially improved physicochemical properties have been enabled by rational design at the molecular level and control over multiscale architecture. For example, formulations that combine permanent polymer networks with reversibly bonding chains for energy dissipation show strong toughness and stretchability. Similar strategies may also substantially enhance the bonding affinity of hydrogels at interfaces with solids by covalently anchoring the polymer networks of tough hydrogels onto solid surfaces. Shear-thinning hydrogels that feature reversible bonds impart a fluidic nature upon application of shear forces and return back to their gel states once the forces are released. Self-healing hydrogels based on nanomaterial hybridization, electrostatic interactions, and slide-ring configurations exhibit excellent abilities in spontaneously healing themselves after damages. Additionally, harnessing techniques that can dynamically and precisely configure hydrogels have resulted in flexibility to regulate their architecture, activity, and functionality. Dynamic modulations of polymer chain physics and chemistry can lead to temporal alteration of hydrogel structures in a programmed manner. Three-dimensional printing enables architectural control of hydrogels at high precision, with a potential to further integrate elements that enable change of hydrogel configurations along prescribed paths. OUTLOOK We envision the continuation of innovation in new bioorthogonal chemistries for making hydrogels, enabling their fabrication in the presence of biological species without impairing cellular or biomolecule functions. We also foresee opportunities in the further development of more sophisticated fabrication methods that allow better-controlled hydrogel architecture across multiple length scales. In addition, technologies that precisely regulate the physicochemical properties of hydrogels in spatiotemporally controlled manners are crucial in controlling their dynamics, such as degradation and dynamic presentation of biomolecules. We believe that the fabrication of hydrogels should be coupled with end applications in a feedback loop in order to achieve optimal designs through iterations. In the end, it is the combination of multiscale constituents and complementary strategies that will enable new applications of this important class of materials.

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Advances in engineering hydrogels

We demonstrate the additive manufacturing of complex three-dimensional (3D) biological structures using soft protein and polysaccharide hydrogels that are challenging or impossible to create using traditional fabrication approaches. These structures are built by embedding the printed hydrogel within a secondary hydrogel that serves as a temporary, thermoreversible, and biocompatible support. This process, termed freeform reversible embedding of suspended hydrogels, enables 3D printing of hydrated materials with an elastic modulus <500 kPa including alginate, collagen, and fibrin. Computer-aided design models of 3D optical, computed tomography, and magnetic resonance imaging data were 3D printed at a resolution of ~200 μm and at low cost by leveraging open-source hardware and software tools. Proof-of-concept structures based on femurs, branched coronary arteries, trabeculated embryonic hearts, and human brains were mechanically robust and recreated complex 3D internal and external anatomical architectures.

Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels.

3D bioprinting for engineering complex tissues.

Additive manufacturing processes such as 3D printing use time-consuming, stepwise layer-by-layer approaches to object fabrication. We demonstrate the continuous generation of monolithic polymeric parts up to tens of centimeters in size with feature resolution below 100 micrometers. Continuous liquid interface production is achieved with an oxygen-permeable window below the ultraviolet image projection plane, which creates a "dead zone" (persistent liquid interface) where photopolymerization is inhibited between the window and the polymerizing part. We delineate critical control parameters and show that complex solid parts can be drawn out of the resin at rates of hundreds of millimeters per hour. These print speeds allow parts to be produced in minutes instead of hours.

http://science.sciencemag.org/content/sci/347/6228/1349.full.pdf

Continuous liquid interface production of 3D objects

A sustained effort to develop and commercialize a practical radical addition route to amine functional polymers (AFPs) resulted, after almost 20 years, in the successful completion of a world scale monomer plant to produce N-vinylformamide (NVF). NVF is readily polymerized and its polymers are easily hydrolyzed to reactive and atom economical polyvinylamine (PVAm) or its salts. This highlight touches on work by many companies, but focuses on efforts at Air Products and Chemicals, tracing the origins, rational, challenges, technical and commercial advances, and failures. Practical routes to new AFPs, copolymers, and derivatives across the entire molecular weight range (MW 106) were achieved. NVF offers access to multiple water soluble, water dispersible, and nonwater soluble polymer markets, including papermaking additives and coatings, water treatment polymers, enhanced oil recovery polymers, radiation cure monomers, stabilizers, dispersing agents, surfactants, and crosslinkers. Lessons learned along the road to commercializing major new chemical technologies are also highlighted. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2257–2283, 2010

https://onlinelibrary.wiley.com/doi/pdf/10.1002/pola.23992

Polyvinylamine at last

A build plate unit (400) for a three-dimensional printer includes a build plate (410) having an optically transparent member comprising a flexible, gas permeable, optically transparent sheet (414) having upper and lower opposing sides, wherein the flexible sheet upper side defines the build surface; and a flexible, gas permeable or impermeable, optically transparent base layer (412) on the lower side of the flexible sheet opposite the build region, wherein the build plate i s configured to permit gas flow to the build surface.

Three-dimensional printing with flexible build plates

A method of forming a three-dimensional object, comprising: providing a carrier (18, 418) and an optically transparent member having a build surface, said carrier (18, 418) and said build surface defining a build region therebetween; filling said build region with a polymerizable liquid, continuously or intermittently irradiating said build region with light through said optically transparent member to form a solid polymer from said polymerizable liquid, continuously or intermittently advancing (e.g., sequentially or concurrently with said irradiating step) said carrier (18, 418) away from said build surface to form said three-dimensional object from said solid polymer, said optically transparent member comprising a flexible layer (414, 514, 614) having upper and lower opposing sides, wherein the flexible layer (414, 514, 614) upper side defines the build region, the method further comprising forming a region of reduced pressure adjacent the flexible layer (414, 514, 614) lower side.

Three-dimensional printing with reduced pressure build plate unit

A method of forming the body portion of a three-dimensional object (17) from a polymerizable liquid (16) is carried out by a process including advancing a carrier (18) for the object away from a build surface while irradiating a build region between the carrier and build surface in a pattern of advancing and irradiating defined by an operating mode. The body portion has a plurality of contiguous segments, with the irradiating carried out in sequentially presented slices of exposure. Each slice having a pattern that corresponds to a segment of said body portion. Each pattern includesg regions of greater irradiation and regions of lesser irradiation (e.g., within the perimeter of each pattern). The method includes consecutively changing, for at least a portion of the forming of said three- dimensional object, the pattern between consecutive slices in a sequence of sequentially presented patterns of exposure that facilitates the flow of the polymerizable liquid to the build surface.

Robert Pinschmidt

Papers

Continuous liquid interface production of 3D objects

Polyvinylamine at last

Three-dimensional printing with flexible build plates

Three-dimensional printing with reduced pressure build plate unit

Continuous liquid interface production with sequential patterned exposure