[Effect of skin autograft with different thickness on the transdifferentiation of fibroblasts after deep partial thickness burn in rats].

OBJECTIVE: To investigate the effect of thin split-thickness skin, inter-mediate thickness skin and full-thickness skin autograft on the differentiation of fibroblasts into myofibroblasts in rats after deep partial thickness burn. METHODS: A total of 40 SD rats were divided randomly into two groups (Group A & Group B, n = 20 each). In Group A, tissue samples were collected at Day 2 after skin-grafting while Day 7 in Group B. In each group, every rat was scalded to cause deep partial thickness wound with an area of 10% of total body surface. The wounds received eschar shaving instantly coupled with skin-autograft, covering with thin split-thickness skin, inter-mediate thickness skin and full-thickness skin respectively. Meanwhile the control wound on the same rat was scalded only. Then the expression of α-SMA was detected by immunohistochemistry in each wound. And the numbers of myofibroblasts (α-SMA positive cells) and fibroblasts (negative cells) were counted to calculate the conversion ratio of myofibroblasts. RESULTS: In Group A, the conversion ratios of myofibroblasts of control, thin split-thickness skin autograft, inter-mediate thickness skin and full-thickness skin groups were (76.3 ± 3.3)%, (69.8 ± 1.6)%, (57.5 ± 1.6)% and (44.7 ± 1.7)% respectively. In Group B, the ratios were (72.9 ± 6.1)%, (63.6 ± 4.7)%, (50.2 ± 1.6)% and (32.3 ± 1.2)% respectively. The ratio was higher in control group than that in any other one (P < 0.01). There was statistic difference between thin split-thickness skin, inter-mediate thickness skin and full-thickness skin autograft groups (P < 0.05). CONCLUSION: A direct association may exist between the conversion ratio of myofibroblasts and the application of skin-grafting in rats after deep partial thickness scalding. It is probably related with varying degrees of scar contracture in the long-term.

Wood-Inspired Cement with High Strength and Multifunctionality.

Taking lessons from nature offers an increasing promise toward improved performance in man-made materials. Here new cement materials with unidirectionally porous architectures are developed by replicating the designs of natural wood using a simplified ice-templating technique in light of the retention of ice-templated architectures by utilizing the self-hardening nature of cement. The wood-like cement exhibits higher strengths at equal densities than other porous cement-based materials along with unique multifunctional properties, including effective thermal insulation at the transverse profile, controllable water permeability along the vertical direction, and the easy adjustment to be water repulsive by hydrophobic treatment. The strengths are quantitatively interpreted by discerning the effects of differing types of pores using an equivalent element approach. The simultaneous achievement of high strength and multifunctionality makes the wood-like cement promising for applications as new building materials, and verifies the effectiveness of wood-mimetic designs in creating new high-performance materials. The simple fabrication procedure by omitting the freeze-drying treatment can also promote a better efficiency of ice-templating technique for the mass production in engineering and may be extended to other material systems.

3D printed Mg-NiTi interpenetrating-phase composites with high strength, damping capacity, and energy absorption efficiency.

It is of significance, but still remains a key challenge, to simultaneously enhance the strength and damping capacities in metals, as these two properties are often mutually exclusive. Here, we provide a multidesign strategy for defeating such a conflict by developing a Mg-NiTi composite with a bicontinuous interpenetrating-phase architecture through infiltration of magnesium melt into three-dimensionally printed Nitinol scaffold. The composite exhibits a unique combination of mechanical properties with improved strengths at ambient to elevated temperatures, remarkable damage tolerance, good damping capacities at differing amplitudes, and exceptional energy absorption efficiency, which is unprecedented for magnesium materials. The shape and strength after deformation can even be largely recovered by heat treatment. This study offers a new perspective for the structural and biomedical applications of magnesium.

Nature-Inspired Nacre-Like Composites Combining Human Tooth-Matching Elasticity and Hardness with Exceptional Damage Tolerance.

Making replacements for the human body similar to natural tissue offers significant advantages but remains a key challenge. This is pertinent for synthetic dental materials, which rarely reproduce the actual properties of human teeth and generally demonstrate relatively poor damage tolerance. Here new bioinspired ceramic-polymer composites with nacre-mimetic lamellar and brick-and-mortar architectures are reported, which resemble, respectively, human dentin and enamel in hardness, stiffness, and strength and exhibit exceptional fracture toughness. These composites are additionally distinguished by outstanding machinability, energy-dissipating capability under cyclic loading, and diminished abrasion to antagonist teeth. The underlying design principles and toughening mechanisms of these materials are elucidated in terms of their distinct architectures. It is demonstrated that these composites are promising candidates for dental applications, such as new-generation tooth replacements. Finally, it is believed that this notion of bioinspired design of new materials with unprecedented biologically comparable properties can be extended to a wide range of material systems for improved mechanical performance.

Multiscale designs of the chitinous nanocomposite of beetle horn towards an enhanced biomechanical functionality.

Operating mainly as a type of weapon, the beetle horn develops an impressive mechanical efficiency based on chitinous materials to maximize the injury to opponent and simultaneously minimize the damage to itself and underlying brain under stringent loading conditions. Here the cephalic horn of the beetle Allomyrina dichotoma is probed using multiscale characterization combined with finite element simulations to explore the origins of its biomechanical functionality from the perspective of materials science. The horn is revealed to be highly regulated from the macroscopic shape, geometry, and connection with the body to the meso- and microscopic architecture, moisture content, and chemical and structural characteristics. Varying kinds of gradients are integrated at all length-scales. Such designs are demonstrated to benefit the mechanical performance by mitigating stress concentrations, retarding crack propagation, and modulating local properties to better adapt to stress. Enhanced rigidity, robustness and stability are additionally generated from the constrained flexibility endowed by the nanocomposite plywood structure through the reorientation of chitin nanofibrils within the proteinaceous matrix. These findings shed light on the intriguing materials-design strategies of nature in creating synergy of offence and persistence. They may even offer inspiration for the synthesis of high-performance materials and structures, in particular beams to resist bending and torsion.

[Effects of Chinese fir litter cover on its seedling emergence and early growth]. / 杉木凋落物覆盖对自身幼苗出土和早期生长的影响.

Litter accumulation can strongly affect seedling emergence and early growth through both physical and chemical mechanisms, and can further influence natural regeneration. Chinese fir (Cunninghamia lanceolata) is one of the most important afforestation tree species. Its natural regeneration is poor, possibly due to the thick leaf accumulation inhibiting seedling emergence and growth. We used natural and plastic litter to study the effects of Chinese fir litter on its own seedling emergence and early growth, as well as to assess whether the effect was physical or chemical. In this experiment, two litter types (natural and plastic litter) and four different litter amounts (control, 0 g·m-2; low, 200 g·m-2; medium, 400 g·m-2; high, 800 g·m-2) were used. The results showed that compared to the control (0 g·m-2), low litter amount (200 g·m-2) exerted a slight positive effect on seedling emergence, whereas high litter amount (800 g·m-2) significantly reduced the seedling emergence and survival rate in the case of both natural and plastic litter. With increasing litter amount, root length of seedlings decreased and stem length increased. The highest and lowest root mass, leaf mass, and total mass of seedlings were observed for the low and high litter amount, respectively, in the case of both natural and plastic litter. The root:shoot ratio of seedlings decreased with the increasing litter amount for both natural and plastic litter. The photosynthesis:non-photosynthesis biomass ratio of the seedlings was higher under all litter cover treatments, compared to that in the control. Because the effect of the same amounts of the natural and plastic litter on seedling emergence and early growth did not differ, the litter layer's short-term influence was primarily physical. As the litter cover increased, the initial slight positive effects on seedling emergence and early growth could shift to inhibitory effects. Moreover, to penetrate the thick litter layer, Chinese fir seedlings allocated more resources toward stems and aboveground growth. This study provided evidence for litter amount being a key ecological factor that affects the seedling development and subsequent natural regeneration of Chinese fir.

Hydration-induced nano- to micro-scale self-recovery of the tooth enamel of the giant panda.

The tooth enamel of vertebrates comprises a hyper-mineralized bioceramic, but is distinguished by an exceptional durability to resist impact and wear throughout the lifetime of organisms; however, enamels exhibit a low resistance to the initiation of large-scale cracks comparable to that of geological minerals based on fracture mechanics. Here we reveal that the tooth enamel, specifically from the giant panda, is capable of developing durability through counteracting the early stage of damage by partially recovering its innate geometry and structure at nano- to micro- length-scales autonomously. Such an attribute results essentially from the unique architecture of tooth enamel, specifically the vertical alignment of nano-scale mineral fibers and micro-scale prisms within a water-responsive organic-rich matrix, and can lead to a decrease in the dimension of indent damage in enamel introduced by indentation. Hydration plays an effective role in promoting the recovery process and improving the indentation fracture toughness of enamel (by ∼73%), at a minor cost of micro-hardness (by ∼5%), as compared to the dehydrated state. The nano-scale mechanisms that are responsible for the recovery deformation, specifically the reorientation and rearrangement of mineral fragments and the inter- and intra-prismatic sliding between constituents that are closely related to the viscoelasticity of organic matrix, are examined and analyzed with respect to the structure of tooth enamel. Our study sheds new light on the strategies underlying Nature's design of durable ceramics which could be translated into man-made systems in developing high-performance ceramic materials. STATEMENT OF SIGNIFICANCE: Tooth enamel plays a critical role in the function of teeth by providing a hard surface layer to resist wear/impact throughout the lifetime of organisms; however, such enamel exhibits a remarkably low resistance to the initiation of large-scale cracks, of hundreds of micrometers or more, comparable to that of geological minerals. Here we reveal that tooth enamel, specifically that of the giant panda, is capable of partially recovering its geometry and structure to counteract the early stages of damage at nano- to micro-scale dimensions autonomously. Such an attribute results essentially from the architecture of enamel but is markedly enhanced by hydration. Our work discerns a series of mechanisms that lead to the deformation and recovery of enamel and identifies a unique source of durability in the enamel to accomplish this function. The ingenious design of tooth enamel may inspire the development of new durable ceramic materials in man-made systems.

Enhanced protective role in materials with gradient structural orientations: Lessons from Nature.

UNLABELLED: Living organisms are adept at resisting contact deformation and damage by assembling protective surfaces with spatially varied mechanical properties, i.e., by creating functionally graded materials. Such gradients, together with multiple length-scale hierarchical structures, represent the two prime characteristics of many biological materials to be translated into engineering design. Here, we examine one design motif from a variety of biological tissues and materials where site-specific mechanical properties are generated for enhanced protection by adopting gradients in structural orientation over multiple length-scales, without manipulation of composition or microstructural dimension. Quantitative correlations are established between the structural orientations and local mechanical properties, such as stiffness, strength and fracture resistance; based on such gradients, the underlying mechanisms for the enhanced protective role of these materials are clarified. Theoretical analysis is presented and corroborated through numerical simulations of the indentation behavior of composites with distinct orientations. The design strategy of such bioinspired gradients is outlined in terms of the geometry of constituents. This study may offer a feasible approach towards generating functionally graded mechanical properties in synthetic materials for improved contact damage resistance. STATEMENT OF SIGNIFICANCE: Living organisms are adept at resisting contact damage by assembling protective surfaces with spatially varied mechanical properties, i.e., by creating functionally-graded materials. Such gradients, together with multiple length-scale hierarchical structures, represent the prime characteristics of many biological materials. Here, we examine one design motif from a variety of biological tissues where site-specific mechanical properties are generated for enhanced protection by adopting gradients in structural orientation at multiple length-scales, without changes in composition or microstructural dimension. The design strategy of such bioinspired gradients is outlined in terms of the geometry of constituents. This study may offer a feasible approach towards generating functionally-graded mechanical properties in synthetic materials for improved damage resistance.

Intrinsic hierarchical structural imperfections in a natural ceramic of bivalve shell with distinctly graded properties.

Despite the extensive investigation on the structure of natural biological materials, insufficient attention has been paid to the structural imperfections by which the mechanical properties of synthetic materials are dominated. In this study, the structure of bivalve Saxidomus purpuratus shell has been systematically characterized quantitatively on multiple length scales from millimeter to sub-nanometer. It is revealed that hierarchical imperfections are intrinsically involved in the crossed-lamellar structure of the shell despite its periodically packed platelets. In particular, various favorable characters which are always pursued in synthetic materials, e.g. nanotwins and low-angle misorientations, have been incorporated herein. The possible contributions of these imperfections to mechanical properties are further discussed. It is suggested that the imperfections may serve as structural adaptations, rather than detrimental defects in the real sense, to help improve the mechanical properties of natural biological materials. This study may aid in understanding the optimizing strategies of structure and properties designed by nature, and accordingly, provide inspiration for the design of synthetic materials.

MicroRNA-146a modulates TGF-ß1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4.

During wound healing and tissue repair the dermal fibroblast-to-myofibroblast transdifferentiation plays an important role, transforming growth factor-ß1 (TGF-ß1) is considered to be the main stimuli factor of transdifferentiation. MicroRNAs (miRNAs) have recently emerged as key post-transcriptional regulators of gene expression. The involvement of miRNAs and their roles in TGF-ß1-induced myofibroblast transdifferentiation remains to be determined in detail. The current study found that the expression of miR-146a was upregulated in human dermal fibroblasts cells in response to TGF-ß1 stimulation in dose-dependent manner by quantitative RT-PCR. Bioinformatic analyses predict that signaling effectors mothers against decapentaplegic protein 4 (SMAD4) is a miR-146a target gene. Luciferase assay demonstrated that miR-146a mimics suppressed SMAD4 3'-UTR reporter construct activity. Furthermore, miR-146a overexpression in dermal fibroblast did not decrease target mRNA levels, but significantly reduced target protein expression. In addition, dermal fibroblasts transfected with miR-146a mimics exhibited attenuated TGF-ß1 -induced α-smooth muscle actin (α-SMA) expression compared with the control. This study demonstrated that miR-146a may function as a novel negative regulator to modulate myofibroblast transdifferentiation during TGF-ß1 induction by targeting SMAD4.

[The effect of RhoA/Rho kinase signal pathway on TGF-beta1-induced phenotypic differentiation of human dermal fibroblasts].

OBJECTIVE: To examine the effect of RhoA/Rho kinase signal pathway on TGF-beta1-induced phenotypic differentiation of human dermal fibroblasts. METHODS: The 4th generation of primary cultured human dermal fibroblasts were stimulated with TGF-beta1, (10 ng/ml). The expression of alpha-SMA was detected after treatment with TGF-beta1, for 0, 3, 6, and 24 h. The expression of alpha-SMA was also detected after treatment with different concentration of TGF-beta1 (0, 2, 10, 50 ng/ml). Then the human dermal fibroblasts (4th generation) were stimulated with TGF-beta1, (10 ng/ml) after being treated with the RhoA/Rho kinase signaling pathway inhibitor Y-27632 (10 umol/ml). The fibroblasts were treated with nothing as sham control, or with Y-27632 (10 umol/L) only as negative control group, or with TGF-beta1 (10 ng/ml) only as positive control group. The expression of alpha-SMA was detected in all the groups. Protein expression was analyzed with ANOVA statistical method. RESULTS: alpha-SMA expression in fibroblasts with 10 ng/ml TGF-beta1 stimulation for 0, 3, 6, 24 h was 1.0, 1.9 0.2, 2.1 +/- 0. 1, 3. 1 +/- 0.1, respectively. Alpha-SMA expression in 24 h group was significantly higher than that in other three groups (n = 4, P < 0.05). alpha-SMA expression in human dermal fibroblasts after stimulation with different concentration of TGF-beta1 (0, 2, 10, 50 ng/ml) was 1.0, 1.4 +/- 0.2, 3.2 + 0.1, 3.1 +/- 0.2, respectively. alpha-SMA expression in 10 ng/ ml group was significantly higher than that in 2 ng/ml group and control group (n = 4, P < 0.05). There was no statistical difference in alpha-SMA expression between 10 ng/ml group and 50 ng/ml group (n = 4, P > 0.05). With both Y-27632 (10 micromol/L) and TGF-beta1 stimulation, the cell phenotype differentiation was inhibited. Alpha-SMA expression in experimental group (1.2 +/- 0.2) was significantly reduced, when compared with that in positive control group (2.9 +/- 0.1) (n = 5, P < 0.05). There was no significant difference (n = 5, P > 0.05) in alpha-SMA expression between control group (1.0) and negative control group (1.1 +/- 0.1). CONCLUSIONS: RhoA/Rho kinase signaling pathway should be involved in TGF-beta1-induced phenotypic differentiation of human dermal fibroblasts.