Get a grip: integrins in cell-biomaterial interactions

Integrin adhesion receptors have emerged as central regulators of cell–biomaterial interactions. This opinion paper discusses how integrins control cellular and host responses to biomaterials and new strategies to manipulate these adhesive interactions in order to elicit specific cellular responses.     

Biomimetic model of skeletal muscle isometric contraction: II. A phenomenological model of the skeletal muscle excitation-contraction coupling process

This paper describes a new macroscopic, phenomenological model of the skeletal muscle excitation-contraction coupling process, as represented by four principal and consecutive compartments (biophysical, biochemical, and biomechanical phases) characteristic of isometric excitation-contraction coupling in mammalian skeletal muscle, and coupled by a system of simultaneous, first-order linear ordinary differential equations. The model is based upon biological compartmental transport kinetics and irreversible thermodynamic energy transformation, and represents a distinct improvement over other biomimetic models. The model was derived using physiological parameter data published in the literature, and validated using .     

Biomimetic phototherapy in cancer treatment: from synthesis to application

Phototherapy, with minimally invasive and cosmetic effect, has received considerable attention and been widely studied in cancer treatment, especially in biomaterials field. However, most nanomaterials applied for the delivery of phototherapy agents are usually recognized by the immune system or cleared by liver and kidney, thus hindering their clinical applications. To overcome these limitations, bionic technology stands out by virtue of its low antigenicity and targeting properties, including membrane bionics and bionic enzymes. In this review, we will summarize the up-to-date progress in the development of biomimetic camouflage-based nanomaterials for phototherapy, from synthesis to application, and their future in cancer treatment.     

Engineering functional anisotropy in fibrocartilage neotissues

The knee meniscus, intervertebral disc, and temporomandibular joint (TMJ) disc all possess complex geometric shapes and anisotropic matrix organization. While these characteristics are imperative for proper tissue function, they are seldom recapitulated following injury or disease. Thus, this study's objective was to engineer fibrocartilages that capture both gross and molecular structural features of native tissues. Self-assembled TMJ discs were selected as the model system, as the disc exhibits a unique biconcave shape and functional anisotropy. To drive anisotropy, 50:50 co-cultures of meniscus cells and articular chondrocytes were grown in biconcave, TMJ-shaped molds and treated with two exogenous stimuli: biomechanical (BM) stimulation via passive axial compression and bioactive agent (BA) stimulation via chondroitinase-ABC and transforming growth factor-β1. BM + BA synergistically increased Col/WW, Young's modulus, and ultimate tensile strength 5.8-fold, 14.7-fold, and 13.8-fold that of controls, respectively; it also promoted collagen fibril alignment akin to native tissue. Finite element analysis found BM stimulation to create direction-dependent strains within the neotissue, suggesting shape plays an essential role toward driving in vitro anisotropic neotissue development. Methods used in this study offer insight on the ability to achieve physiologic anisotropy in biomaterials through the strategic application of spatial, biomechanical, and biochemical cues.     

Modulated regeneration of acid-etched human tooth enamel by a functionalized dendrimer that is an analog of amelogenin

In the bioinspired repair process of tooth enamel, it is important to simultaneously mimic the organic-matrix-induced biomineralization and increase the binding strength at the remineralization interface. In this work, a fourth-generation polyamidoamine dendrimer (PAMAM) is modified by dimethyl phosphate to obtain phosphate-terminated dendrimer (PAMAM-PO₃H₂) since it has a similar dimensional scale and peripheral functionalities to that of amelogenin, which plays important role in the natural development process of enamel. Its phosphate group has stronger affinity for calcium ion than carboxyl group and can simultaneously provide strong hydroxyapatite (HA)-binding capability. The MTT assay demonstrates the low cytotoxicity of PAMAM-PO₃H₂. Adsorption tests indicate that PAMAM-PO₃H₂ can be tightly adsorbed on the human tooth enamel. Scanning electron microscopy and X-ray diffraction are used to analyze the remineralization process. After being incubated in artificial saliva for 3 weeks, there is a newly generated HA layer of 11.23 μm thickness on the acid-etched tooth enamel treated by PAMAM-PO₃H₂, while the thickness for the carboxyl-terminated one (PAMAM-COOH) is only 6.02 μm. PAMAM-PO₃H₂ can regulate the remineralization process to form ordered new crystals oriented along the Z-axis and produce an enamel prism-like structure that is similar to that of natural tooth enamel. The animal experiment also demonstrates that PAMAM-PO₃H₂ can induce significant HA regeneration in the oral cavity of rats. Thus PAMAM-PO₃H₂ shows great potential as a biomimetic restorative material for human tooth enamel.     

Chemical and physical properties of regenerative medicine materials controlling stem cell fate

Abstract

Regenerative medicine is a multidisciplinary field utilizing the potential of stem cells and the regenerative capability of the body to restore, maintain, or enhance tissue and organ functions. Stem cells are unspecialized cells that can self-renew but also differentiate into several somatic cells when subjected the appropriate environmental cues. The ability to reliably direct stem cell fate would provide tremendous potential for basic research and clinical therapies. Proper tissue function and regeneration rely on the spatial and temporal control of biophysical and biochemical cues, including soluble molecules, cell–cell contacts, cell–extracellular matrix contacts, and physical forces. The mechanisms involved remain poorly understood. This review focuses on the stem cell–extracellular matrix interactions by summarizing the observations of the effects of material variables (such as overall architecture, surface topography, charge, ζ-potential, surface energy, and elastic modulus) on the stem cell fate. It also deals with the mechanisms underlying the effects of these extrinsic, material variables. Insight in the environmental interactions of the stem cells is crucial for the development of new material-based approaches for cell culture experiments and future experimental and clinical regenerative medicine applications.     

A fluorophore-tagged RGD peptide to control endothelial cell adhesion to micropatterned surfaces

The long-term patency rates of vascular grafts and stents are limited by the lack of surface endothelialisation of the implanted materials. We have previously reported that GRGDS and WQPPRARI peptide micropatterns increase the endothelialisation of prosthetic materials in vitro. To investigate the mechanisms by which the peptide micropatterns affect endothelial cell adhesion and proliferation, a TAMRA fluorophore-tagged RGD peptide was designed. Live cell imaging revealed that the micropatterned surfaces led to directional cell spreading dependent on the location of the RGD-TAMRA spots. Focal adhesions formed within 3 h on the micropatterned surfaces near RGD-TAMRA spot edges, as expected for cell regions experiencing high tension. Similar levels of focal adhesion kinase phosphorylation were observed after 3 h on the micropatterned surfaces and on surfaces treated with RGD-TAMRA alone, suggesting that partial RGD surface coverage is sufficient to elicit integrin signaling. Lastly, endothelial cell expansion was achieved in serum-free conditions on gelatin-coated, RGD-TAMRA treated or micropatterned surfaces. These results show that these peptide micropatterns mainly impacted cell adhesion kinetics rather than cell proliferation. This insight will be useful for the optimization of micropatterning strategies to improve vascular biomaterials.     

自组装法仿生骨材料的制备及性能分析

目的研究利用自组装法制备的纳米羟基磷灰石／胶原（HA／COL）复合物的理化特性和生物学特性。方法采用自组装法制备出HA／COL复合物,通过傅里叶红外光谱仪、透射电镜、X射线粉末衍射仪分析HA／COL复合物的理化特性;采用MTT法及扫描显微镜分析HA／COL复合物的生物学特性。结果HA／COL复合物微观结构与自然骨相似,胶原与HA之间产生了化学键合,晶粒尺度在纳米范围内,细胞毒性为0—1级,细胞在其表面生长状态良好。结论自组装法制备的仿生HA／COL复合物骨材料,具有与天然骨相似的组成成分和微观结构,并具有良好的生物相容性,是一种理想的人工骨支架材料。     

Biomimetic coating of magnesium alloy for enhanced corrosion resistance and calcium phosphate deposition

Degradable metals have been suggested as biomaterials with revolutionary potential for bone-related therapies. Of these candidate metals, magnesium alloys appear to be particularly attractive candidates because of their non-toxicity and outstanding mechanical properties. Despite their having been widely studied as orthopedic implants for bone replacement/regeneration, their undesirably rapid corrosion rate under physiological conditions has limited their actual clinical application. This study reports the use of a novel biomimetic peptide coating for Mg alloys to improve the alloy corrosion resistance. A 3DSS biomimetic peptide is designed based on the highly acidic, bioactive bone and dentin extracellular matrix protein, phosphophoryn. Surface characterization techniques (scanning electron microscopy, energy dispersive X-ray spectroscopy and diffuse-reflectance infrared spectroscopy) confirmed the feasibility of coating the biomimetic 3DSS peptide onto Mg alloy AZ31B. The 3DSS peptide was also used as a template for calcium phosphate deposition on the surface of the alloy. The 3DSS biomimetic peptide coating presented a protective role of AZ31B in both hydrogen evolution and electrochemical corrosion tests.     

玉米蛋白3-D多孔支架材料仿生矿化的初步研究

为了提高玉米蛋白的骨诱导性和骨结合性,以促进其在骨组织工程领域中的应用,将玉米蛋白多孔支架材料浸泡于5倍模拟体液(5×SBF)中,尝试在不同的条件下对玉米蛋白多孔支架材料表面进行仿生矿化。通过场发射扫描电镜(SEM)观察仿生矿化后多孔支架材料各个表面的形貌,能谱(EDS)计算出钙磷比(Ca/P)比。在5倍模拟体液中浸泡后,材料各表面均形成了分布和尺寸相对均匀的微米级(2~10 um)颗粒。其钙磷比接近羟基磷灰石,可以认为获得了比较理想的玉米蛋白-羟基磷灰石多孔支架复合材料。