Study of Cell Behaviors on Anodized TiO_2 Nanotube Arrays with Coexisting Multi-Size Diameters

It has been revealed that the different morphologies of anodized TiO_2 nanotubes, especially nanotube diameters, triggered different cell behaviors. However, the influence of TiO_2 nanotubes with coexisting multi-size diameters on cell behaviors is seldom reported. In this work, coexisting four-diameter TiO_2 nanotube samples, namely,one single substrate with the integration of four different nanotube diameters(60, 150, 250, and 350 nm), were prepared by repeated anodization. The boundaries between two different diameter regions show well-organized structure without obvious difference in height. The adhesion behaviors of MC3T3-E1 cells on the coexisting fourdiameter TiO_2 nanotube arrays were investigated. The results exhibit a significant difference of cell density between smaller diameters(60 and 150 nm) and larger diameters(250 and 350 nm) within 24 h incubation with the coexistence of different diameters, which is totally different from that on the single-diameter TiO_2 nanotube arrays. The coexistence of four different diameters does not change greatly the cell morphologies compared with the singlediameter nanotubes. The findings in this work are expected to offer further understanding of the interaction between cells and materials.

Research of a novel biodegradable surgical staple made of high purity magnesium

Surgical staples made of pure titanium and titanium alloys are widely used in gastrointestinal anastomosis.However the Ti staple cannot be absorbed in human body and produce artifacts on computed tomography(CT)and other imaging examination,and cause the risk of incorrect diagnosis.The bioabsorbable staple made from polymers that can degrade in human body environment,is an alternative.In the present study,biodegradable high purity magnesium staples were developed for gastric anastomosis.U-shape staples with two different interior angles,namely original 90
and modified 100
,were designed.Finite element analysis(FEA)showed that the residual stress concentrated on the arc part when the original staple was closed to B-shape,while it concentrated on the feet for the modified staple after closure.The in vitro tests indicated that the arc part of the original staple ruptured firstly after 7 days immersion,whereas the modified one kept intact,demonstrating residual stress greatly affected the corrosion behavior of the HP-Mg staples.The in vivo implantation showed good biocompatibility of the modified Mg staples,without inflammatory reaction 9 weeks post-operation.The Mg staples kept good closure to the Anastomosis,no leaking and bleeding were found,and the staples exhibited no fracture or severe corrosion cracks during the degradation.

High-purity magnesium pin enhances bone consolidation in distraction osteogenesis via regulating Ptch protein activating Hedgehog-alternative Wnt signaling

Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability,osteogenic effects,and biocompatibility.Magnesium has been proven to promote distraction osteogenesis.However,its mechanism of promoting distraction osteogenesis is not thoroughly studied.In this work,a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis.Mechanical test,radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time.Further RNA sequencing investigation found that alternative Wnt signaling was activated.In further bioinformatics analysis,it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway.We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein.In conclusion,HP Mg implants have the potential to enhance bone consolidation in the DO application,and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.

Site-Dependent Osseointegration of Biodegradable High-Purity Magnesium for Orthopedic Implants in Femoral Shaft and Femoral Condyle of New Zealand Rabbits

Magnesium （Mg） has been widely accepted as osteoconductive biomaterial, but osseointegration of Mg device at different implantation sites is still unclear. In the present study, high-purity magnesium （HP Mg） pins were implanted into femoral shaft and condyle of New Zealand rabbits concurrently. 2, 8, 12 and 16 weeks after surgery, rabbit femurs were harvested for micro-computed tomography （micro-CT） scanning and subsequent histological examinations. HP Mg pins were retrieved for scanning electron microscope and energy dispersive spectrum （SEM/EDS） analyses. HP Mg pins at both implantation sites performed stable corrosion with mineral deposition and bone incorporation on surface. However, difference in distribution of contact osteogenesis centers and biological properties of peri-implant bone tissues was detected between femoral shaft and femoral condyle. In femoral condyle, contact osteogenesis centers originated from both periosteum and cancellous bones and the whole HP Mg pin was encapsuled in trabecular bone at 16 weeks. Meanwhile, bone volume to total bone volume （BV/TV） and bone mineral density （BMD） of peri-implant bone tissues were above those of normal bone tissues. In femoral shaft, contact osteogenesis centers were only from periosteum and direct bone contact was confined in cortical bone, while BV/TV and BMD kept lower than normal. Furthermore, new formation of peri-implant bone tissues was more active in femoral condyle than in femoral shaft at 16 weeks. Therefore, although HP Mg performed good biocompatibility and corrosion behavior in vivo, its bioadaption of osseointegration at different implantations sites should be taken into consideration. Bone metaphysic was suitable for Mg devices where peri-implant bone tissues regenerated rapidly and the biological properties were close to normal bone tissues.

Comparative Study about Degradation of High-purity Magnesium Screw in Intact Femoral Intracondyle and in Fixation of Femoral Intracondylar Fracture

Bone screws encounter complex mechanical environment in fracture fixation of weight-bearing bone.In the present study, high-purity magnesium（HP Mg） screws were applied in fixation of rabbit femoral intracondylar fracture with 3 mm gap. In the control group, HP Mg screws of the same design were implanted at corresponding position of contralateral leg. At 4, 8 and 16 weeks after surgery, retrieved femurs went through micro-computed tomography（micro-CT） scanning and hard tissue processing. Under mechanical stress involved in fracture fixation, bending of screw bolt was observed at the portion exposed to facture gap at 4 weeks. Then local corrosion at the same portion was detected 16 weeks after surgery,which indicated the accumulation effect of mechanical stress on Mg corrosion. HP Mg screws in the fracture group had no significant difference with the control group in screw volume, surface area, surfaceto-volume ratio（S/V）. And peri-implant bone volume/tissues volume（BV/TV） and bone volume density（BMD） in the fracture group was comparable to that in the control group. Furthermore, histological analysis showed new formed bone tissues in fracture gap and fracture healing 16 weeks after surgery. Under mechanical stress, HP Mg screw suffered bolt bending and local corrosion at the portion exposed to fracture gap. But it had no influence on the integral corrosion behaviors, osseointegration of HP Mg screw and the fracture healing. Therefore, HP Mg screws possessed good potential in fracture fixation of weightbearing bones.

Hydrogen-bonding regulated supramolecular chirality with controllable biostability

The regulation of natural helical nanostructures is principally supported and actuated by hydrogen bonds(H-bonds)formed from hydrogen-bonding groups(peptide bonds and base pairs)to realize biological activities and specific biofunctional transformations.However,studying the role of H-bonding patterns on the handedness of supramolecular assemblies is still challenging,since supramolecular assemblies will be disassembled or destabilized with slightly varying H-bonding groups for most supramolecules.To circumvent this issue,herein,two types of self-assembled C2-symmetric phenylalanine derivatives differed by a single H-bonding group(ester or amide)are systematically designed for deciphering the role of H-bonding pattern on the chirality of supramolecular assemblies and their related biostability.Opposite handedness nanofibrous structures with tailorable diameter and helical pitch are achieved with the transition from ester to amide groups in the gelators.Experimental and theoretical evidence suggests that helical orientation of ester-containing gelators ascribes to intermolecular H-bonds.In contrast,the helical direction for the amide-counterparts is mainly due to intra-and intermolecular H-bonds.Moreover,these H-bonding groups greatly influence their stability,as revealed by in vitro and in vivo degradation experiments and the left-handed assemblies are more stable than the right-handed ones.Thus,the study offers a feasible model to have valuable insight into understanding the role of H-bonding patterns in biological folding.

Bio-inspired chiral self-assemblies promoted neuronal differentiation of retinal progenitor cells through activation of metabolic pathway

Retinal degeneration is a main class of ocular diseases.So far,retinal progenitor cell(RPC)transplantation has been the most potential therapy for it,in which promoting RPCs neuronal differentiation remains an unmet challenge.To address this issue,innovatively designed L/D-phenylalanine based chiral nanofibers(LPG and DPG)are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation.qPCR,western blot,and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation,whereas left-handed LPG nanofibers decrease this effect.These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4(RBP4,a key protein in the retinoic acid(RA)metabolic pathway).The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers.

Chirality Transfer in Supramolecular Co-assembled Fibrous Material Enabling the Visual Recognition of Sucrose

Molecular recognition of simple sugars is crucial due to their essential roles in most living organisms.However,it remains extremely challenging to achieve a visual recognition of simple sugars like sucrose in water media under physiological conditions.In this article,the visual recognition of sucrose is accomplished by a chiral supramolecular hydrogel formation through the co-assembly of a two-component fibrous solution(l-phenylalanine based gelator co-diaminopyridine,LDAP)and sucrose.H-bonding between the amino group of LDAP and the hydroxyl group of sucrose facilitates the gelation by loading sucrose into the LDAP solution.The formed hydrogel showed an amplified inversion of circular dichroism(CD)signals as compared to the corresponding LDAP solution.In addition,the effective chirality transfer was accompanied by a bathochromic shift in UV-Vis and FL spectra of the gel.Such a simple and straightforward chiral co-assembled strategy to visually recognize sucrose will have the potential use of smart gelators in saccharides separation and proteomics to be further applied in medical diagnostics and cell imaging.

Biphenyl-Induced Superhelix in L-Phenylalanine-Based Supramolecular Self-Assembly with Dynamic Morphology Transitions

Dynamic transitions of supramolecular assemblies between lower-order structures and higher-order superhelical structures(e.g.,double-helical DNA,helical biopolymers)are of vital importance in many physiological processes,but still remain a great challenge to be realized in artificially assembled systems.Herein,a novel biphenyl central core symmetrically coupled with phenylalanine groups drives the construction of the dynamic superhelix.