A porous poly(lactic-co-glycolic acid) scaffold induces innervation in a rabbit model of disc degeneration following annular injury

BACKGROUND： A degradable poly（lactic-co-glycolic acid） （PLGA） scaffold has been used to construct a degradable porous scaffold. This template can simulate the in vivo microenvironment and promote tissue formation. OBJECTIVE： To observe the histopathological changes during degeneration and regeneration of the intervertebral disc, and to analyze the effects of a PLGA scaffold on nerve fiber ingrowth into the lesion in vivo. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed at the Orthopaedic Laboratory, Clinic Medical Research Institution, Sir Run Run Shaw Hospital, Zhejiang University, from December 2007 to July 2008. MATERIALS： PLGA （China Textile Academy）; growth-associated protein-43 （Life-span, USA）; and protein gene product 9.5 antibody （AbD, United Kingdom） were used in this study. METHODS： Three consecutive segments of the intervertebral disc of thirty-two healthy adult male New Zealand rabbits were exposed, comprising L3-4, L4-5 and L5-6. Experimental intervertebral disc （L4-5 and L5-6） models were established by two different methods. In the test （trephine ＋ scaffold） group, a 5-mm deep hole was drilled into the annulus fibrosus using a 3-mm diameter trephine, and the PLGA scaffold was implanted into the hole. In the acupuncture group, the remaining experimental intervertebral disc annulus fibrosus was damaged using a 16G needle at a depth of 5 mm. The L3-4 disc served as a control. MAIN OUTCOME MEASURES： Intervertebral disc degeneration was assessed using radiography, magnetic resonance imaging, and histological examination at various time points post-surgery. Nerve fiber ingrowth into the degenerated intervertebral disc was observed using immunohistochemical staining for growth-associated protein-43 and protein gene product 9.5. RESULTS： Compared with the normal controls, the heights of the damaged intervertebral discs were decreased, and T2 signal intensity was decreased in the test and acupuncture groups 2 weeks post-surgery. Intervertebral disc degeneration was faster in the test group than in the acupuncture group. PLGA was coated with newly formed tissue, gradually degraded, and absorbed, and could induce tissue ingrowth deep into the annulus fibrosus. Results of immunohistochemical staining showed that nerve fibers were distributed in newly formed tissue in the test group, and in the superficial layer or surrounding scar tissue in the acupuncture group. CONCLUSION： A porous PLGA scaffold provides an important biological channel to induce nerve fiber ingrowth deep into the degenerated intervertebral disc.

A reactive oxygen species-responsive hydrogel encapsulated with bone marrow derived stem cells promotes repair and regeneration of spinal cord injury

Spinal cord injury(SCI)is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes,such as excessive reactive oxygen species(ROS)produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment,leading to the widespread apoptosis of the neuron cells,glial and oligodendroctyes.In this study,a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells(BMSCs),which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment.The hydrogel could effectively encapsulate BMSCs,and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS,attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α),resulting in a reduced cell apoptosis in the spinal cord tissue.The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation,and improved the neurogenesis of the spinal cord tissue,and thus distinctly enhanced the motor functional recovery of SCI rats.Our work provides a combinational strategy against ROS-mediated oxidative stress,with potential applications not only in SCI,but also in other central nervous system diseases with similar pathological conditions.

Reactive oxygen species-scavenging nanoparticles coated with chondroitin sulfate protect cartilage against osteoarthritis in vivo

Osteoarthritis(OA)is a prevalent chronic inflammatory disease in joints.Current interventions confront systemic toxicity and insufficient bioavailability.The unbalanced microenvironment of OA joints mainly fosters over-expressed reactive oxygen species(ROS),extracellular matrix disintegration,and apoptosis of chondrocytes.In this study,a kind of ROS-scavenging,biodegradable and drug-free nanoparticles(PP NPs)were constructed by the crosslinking of poly(propylene fumarate)(PPF)and ROS-scavenging poly(thioketal)(PTK).The high content of PTK and high crosslinking density of PPF and PTK innovatively endowed the NPs with slow degradation and prolonged ROS-elimination ability.The NPs were further surface-modified with chondroitin sulfate(CS),one of the dietary supplements for osteoarthritis.The intrinsic properties of resultant PP-CS NPs were excavated in vitro and in vivo.The PP-CS NPs could desirably consume 1,10-diphenyl-2-picrylhydrazyl(DPPH)radicals without toxicity to RAW264.7 cells in vitro.With an average diameter of~300 nm,the PP-CS NPs could be intra-articular administrated in OA rats and showed prolonged joint retention time,allowing only one injection per month.Moreover,the PP-CS NPs possessed a prolonged ROS depletion and M2 macrophage induction effect,down-regulated inflammatory cytokines,and reduced glycosaminoglycans loss.Consequently,the PP-CS NPs protected articular surface erosion,inhibited uneven cartilage matrix,and attenuated OA progression.

Recent advances in cell imaging and cytotoxicity of intracellular stimuli-responsive nanomaterials

The stimuli-responsive nanomaterials are gaining more and more interest in the biological field,including cell imaging and biosensing etc. Nanomaterials in response to the bio-relevant stimuli(i.e., p H, enzymes and other bioactive molecules) can be utilized to enhance imaging(i.e., optical imaging, MRI, and multi-mode imaging) sensitivity via disease site-specific delivery and controlled release, which helps to diagnose cancer at an early stage or to monitor progression during treatment. In the triggered responsive process, smart nanomaterials undergo changes in physiochemical properties that can cause cytotoxicity or influence on cell functions due to the interactions between nanomaterials and cells. In order to promote the design and fabrication of effective platforms for therapeutics and diagnostics, special attention should be paid to these effects. By taking the advantages of intracellular stimuli, the controlled self-assembly in living cells can be achieved, which has been used for various in situ detections and insights into biological self-assembly. In this review, the recent advances in cell imaging, cytotoxicity and self-assembly of intracellular stimuli-responsive nanomaterials are summarized. Some principles for the further design and applications of intracellular stimuli-responsive nanomaterials and future perspectives are discussed.

Adaptable hydrogel with reversible linkages for regenerative medicine:Dynamic mechanical microenvironment for cells

Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility.It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues.Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix.The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows.First,we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry.Next,we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate,including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling.Finally,we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine.We conclude by discussing the limitations and challenges for adaptable hydrogel,and we present perspectives for future studies.

Biomedical polymers: synthesis, properties, and applications

Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.

Dexamethasone-loaded ROS-responsive poly(thioketal)nanoparticles suppress inflammation and oxidative stress of acute lung injury

Acute lung injury(ALI)is associated with excessive inflammatory response,leading to acute respiratory distress syndrome(ARDS)without timely treatment.A fewer effective drugs are available currently to treat the ALI/ARDS.Herein,a therapeutic nanoplatform with reactive oxygen species(ROS)-responsiveness was developed for the regulation of inflammation.Dexamethasone acetate(Dex)was encapsulated into poly(thioketal)polymers to form polymeric nanoparticles(NPs)(PTKNPs@Dex).The NPs were composed of poly(1,4-phenyleneacetonedimethylene thioketal)(PPADT)and polythioketal urethane(PTKU),in which the thioketal bonds could be cleaved by the high level of ROS at the ALI site.The PTKNPs@Dex could accumulate in the pulmonary inflammatory sites and release the encapsulated payloads rapidly,leading to the decreased ROS level,less generation of pro-inflammatory cytokines,and reduced lung injury and mortality of mice.RNA sequencing(RNA-seq)analysis showed that the therapeutic efficacy of the NPs was associated with the modulation of many immune and inflammation-linked pathways.These findings provide a newly developed nanoplatform for the efficient treatment of ALI/ARDS.

Bone tissue regeneration:The role of finely tuned pore architecture of bioactive scaffolds before clinical translation

Spatial dimension of pores and interconnection in macroporous scaffolds is of particular importance in facilitating endogenous cell migration and bone tissue ingrowth.However,it is still a challenge to widely tune structure parameters of scaffolds by conventional methods because of inevitable pore geometrical deformation and poor pore interconnectivity.Here,the long-term in vivo biological performances of nonstoichiometric bioceramic scaffolds with different pore dimensions were assessed in critical-size femoral bone defect model.The 6%Mg-substituted wollastonite(CSi-Mg6)powders were prepared via wet-chemical precipitation and the scaffolds elaborately printed by ceramic stereolithography,displaying designed constant pore strut and tailorable pore height(200,320,450,600μm),were investigated thoroughly in the bone regeneration process.Together with detailed structural stability and mechanical properties were collaboratively outlined.BothμCT and histological analyses indicated that bone tissue ingrowth was retarded in 200μm scaffolds in the whole stage(2-16 weeks)but the 320μm scaffolds showed appreciable bone tissue in the center of porous constructs at 6-10 weeks and matured bone tissue were uniformly invaded in the whole pore networks at 16 weeks.Interestingly,the neo-tissue ingrowth was facilitated in the 450μm and 600μm scaffolds after 2 weeks and higher extent of bone regeneration and remodeling at the later stage.These new findings provide critical information on how engineered porous architecture impact bone regeneration in vivo.Simultaneously,this study shows important implications for optimizing the porous scaffolds design by advanced additive manufacture technique to match the clinical translation with high performance.

Doxorubicin-conjugated pH-responsive gold nanorods for combined photothermal therapy and chemotherapy of cancer

Cancer chemotherapy can be hindered by drug resistance which leads to lower drug efficiency.Here,we have developed a drug delivery system that tethers doxorubicin to the surface of gold nanorods via a pHsensitive linkage(AuNRs@DOX),for a combined photothermal and chemical therapy for cancer.First,AuNRs@DOX is ingested by HepG2 liver cancer cells.After endocytosis,the acidic pH triggers the release of doxorubicin,which leads to chemotherapeutic effects.The gold nanorods are not only carriers of DOX,but also photothermal conversion agents.In the presence of an 808 nm near-infrared laser,AuNRs@DOX significantly enhance the cytotoxicity of doxorubicin via the photothermal effect,which induces elevated apoptosis of hepG2 cancer cells,leading to better therapeutic effects in vitro and in vivo.

Induced migration of endothelial cells into 3D scaffolds by chemoattractants secreted by pro-inflammatory macrophages in situ

Cell migration in scaffolds plays a crucial role in tissue regeneration,which can better mimic cell behaviors in vivo.In this study,a novel model has been proposed on controlling 3D cell migration in porous collagen-chitosan scaffolds with various pore structures under the stimulation of inflammatory cells to mimic the angiogenesis process.Endothelial cells(ECs)cultured atop the scaffolds in the Transwell molds which were placed into a well of a 24-well culture plate were promoted to migrate into the scaffolds by chemoattractants such as vascular endothelial growth factor(VEGF)and tumor necrosis factor-alpha(TNF-α)secreted by the pro-inflammatory macrophages incubated in the well culture plate.The phenotype of macrophages was mediated by 50 ng/ml interferongamma(IFN-c)and different concentrations of lipopolysaccharide(LPS,150–300 ng/ml).The cell migration depth had a positive correlation with LPS concentration,and thereby the TNF-a concentration.The ECs migrated easier to a deeper zone of the scaffolds prepared at10C(187 lm in pore diameter)than that at20C(108 lm in pore diameter)as well.The method provides a useful strategy to study the 3D cell migration,and is helpful to reveal the vascularization process during wound healing in the long run.

The Dynamic Inflammatory Tissue Microenvironment:Signality and Disease Therapy by Biomaterials

Tissue regeneration is an active multiplex process involving the dynamic inflammatory microenvironment.Under a normal physiological framework,inflammation is necessary for the systematic immunity including tissue repair and regeneration as well as returning to homeostasis.Inflammatory cellular response and metabolic mechanisms play key roles in the well-orchestrated tissue regeneration.If this response is dysregulated,it becomes chronic,which in turn causes progressive fibrosis,improper repair,and autoimmune disorders,ultimately leading to organ failure and death.Therefore,understanding of the complex inflammatory multiple player responses and their cellular metabolisms facilitates the latest insights and brings novel therapeutic methods for early diseases and modern health challenges.This review discusses the recent advances in molecular interactions of immune cells,controlled shift of pro-to anti-inflammation,reparative inflammatory metabolisms in tissue regeneration,controlling of an unfavorable microenvironment,dysregulated inflammatory diseases,and emerging therapeutic strategies including the use of biomaterials,which expand therapeutic views and briefly denote important gaps that are still prevailing.

Gold nanoparticles with surface-anchored chiral poly（acryloyI-L（D）-valine） induce differential response on mesenchymal stem cell osteogenesis

Chirality is one of the most distinctive biochemical signatures of life, and plays crucial roles in maintaining normal functions of living cells or organisms. Pioneering work from another group has demonstrated the dependency of cell differentiation on the chirality of nano-coated substrates, but the effect of the chiral surface of nanoparticles on stem cell fates has not been investigated. In this study, the influence of molecular chiral poly（acryloyl-L（D）-valine） （L（D）- PAV）-anchored gold nanoparticles （L（D）-PAV-AuNPs） on the differentiation of mesenchymal stem cells （MSCs） was investigated. Though osteogenic differentiation of MSCs was not affected by D-PAV-AuNPs, it was significantly promoted by L-PAV-AuNPs in terms of calcium deposition, alkaline phosphatase （ALP） activity, and expression of collagen type I and osteocalcin （OCN） at both mRNA and protein levels. L-PAV-AuNPs could activate the P38 mitogen-activated protein kinase （MAPK） pathway, and may exert mechanical stress on MSCs because of high amounts of internalization. These results provide new insights on surface chirality at the nanoscale as a direct regulator to guide the differentiation of MSCs, and the use of these nanomaterials for strategic regenerative medicine.

In situ assembly of fibrinogen/hyaluronic acid hydrogel via knob-hole interaction for 3D cellular engineering

Hyaluronic acid(HA)-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability.However,the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the biocompatibility.Inspired by the crosslinking mechanism of fibrin gel,a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA(knob-g-HA)in this study.The knob-grafted HA was synthesized by coupling knob peptides(GPRPAAC,a mimic peptide of fibrin knob A)to HA via Michael addition.Then the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of 1.2.The rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50,100 and 200 mg/mL were evaluated,and it was found that the dynamic storage moduli(G0)were higher than the loss moduli(G00)over the whole frequency range for all the groups.The SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/MA-HA hydrogels.Correspondingly,a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA hydrogel.Finally,the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation test.All these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering.

Spheroids of Endothelial Cells and Vascular Smooth Muscle Cells Promote Cell Migration in Hyaluronic Acid and Fibrinogen Composite Hydrogels

Cell migration plays a pivotal role in many pathological and physiological processes.So far,most of the studies have been focused on 2-dimensional cell adhesion and migration.Herein,the migration behaviors of cell spheroids in 3D hydrogels obtained by polymerization of methacrylated hyaluronic acid(HA-MA)and fibrinogen(Fg)with different ratios were studied.The Fg could be released to the medium gradually along with time prolongation,achieving the dynamic change of hydrogel structures and properties.Three types of cell spheroids,i.e.,endothelial cell(EC),smooth muscle cell(SMC),and EC-SMC spheroids,were prepared with 10,000 cells in each,whose diameters were about 343,108,and 224μm,respectively.The composite hydrogels with an intermediate ratio of Fg allowed the fastest 3D migration of cell spheroids.The ECs-SMCs migrated longest up to 3200μm at day 14,whereas the SMC spheroids migrated slowest with a distance of only~400μm at the same period of time.The addition of free RGD or anti-CD44 could significantly reduce the migration distance,revealing that the cell-substrate interactions take the major roles and the migration is mesenchymal dependent.Moreover,addition of anti-N-cadherin and MMP inhibitors also slowed down the migration rate,demonstrating that the degradation of hydrogels and cell-cell interactions are also largely involved in the cell migration.RT-PCR measurement showed that expression of genes related to cell adhesion and antiapoptosis,and angiogenesis was all upregulated in the EC-SMC spheroids than single EC or SMC spheroids,suggesting that the use of composite cell spheroids is more promising to promote cell-substrate interactions and maintenance of cell functions.

Adsorption of plasma proteins and fibronectin on poly(hydroxylethyl methacrylate) brushes of different thickness and their relationship with adhesion and migration of vascular smooth muscle cells

The surface-grafted poly(hydroxylethyl methacrylate)(PHEMA)molecules were demonstrated to show a brush state regardless of their molecular length(molecular weight).Adsorption of proteins from 10%fetal bovine serum(FBS),fibronectin(Fn)and bovine serum albumin(BSA)was quantified by ellipsometry,revealing that the amounts of FBS and Fn decreased monotonously along with the increase of PHEMA thickness,whereas not detectable for BSA when the PHEMA thickness was larger than 6 nm.Radio immunoassay found that the adsorption of Fn from 10%FBS had no significant difference regardless of the PHEMA thickness.However,ELISA results showed that the Arg-Gly-Asp(RGD)activity of adsorbed Fn decreased with the increase of PHEMA thickness.By comparison of cellular behaviors of vascular smooth muscle cells(VSMCs)being cultured in vitro in the normal serum-containing medium and the Fn-depleted serum-containing medium,the significant role of Fn on modulating the adhesion and migration of VSMCs was verified.Taking account all the results,the Fn adsorption model and its role on linking the biomaterials surface to the VSMCs behaviors are proposed.

Polyelectrolyte Multilayer Patterns Created by Capillary Force and Their Impact on Cell Migration

Cell migration plays a crucial role in a variety of physiological and pathological processes.In this study a method of capillary force lithography was used to treat poly(sodium 4-styrenesulfonate) (PSS)/poly(diallyldimethylammonium) chloride (PDADMAC) multilayers with a PDMS stamp before or after etching by NaC1 solution,yielding physical patterns with various features such as double thin lines,double strips,meniscus-shaped ridges,and high ridges.The ridge height is controllable in the range of 25 and 1100 nm.Migration of smooth muscle cells (SMCs) was restrained by the double-line patterns in a ridge height-dependent manner.By contrast,the mobility of SMCs was controlled by both the hydration ratio of the multilayers and the pattern features.

Micropatterns and peptide gradient on the inner surface of a guidance conduit synergistically promotes nerve regeneration in vivo

Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo.However,they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far.In this study,a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly(D,L-lactide-co-caprolactone)(PLCL)guidance conduit and its advantages in regeneration of peripheral nerve in vivo.After linear ridges/grooves of 20/40μm in width are created on the PLCL film,its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups,which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde.The Schwann cells are better aligned along with the stripes,and show a faster migration rate toward the region of higher peptide density.Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate,function recovery and microstructures,and reduction of fibrosis in muscle tissues.Moreover,this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization in vivo.

Migration of endothelial cells into photo-responsive hydrogels with tunable modulus under the presence of pro-inflammatory macrophages

Cell migration in three-dimensional environment is extremely important for tissue regeneration and other biological processes.In this work,a model system was developed to study how endothelial cells(ECs)migrate into photo-responsive hydrogels under the presence of pro-inflammatory macrophages.The hydrogel was synthesized from hyaluronic acid grafted with coumarin and methacrylate moieties by both carbon–carbon covalent linking and coumarin dimerization under UV irradiation at 365 nm.The structure of the hydrogel was conveniently modulated by UV irradiation at 254nm to decompose the coumarin dimers,leading to the significant decrease of modulus and increase of swelling ratio and mesh size.Under the presence of M1 macrophages,ECs were induced to migrate into the hydrogels with a different degree.A significant larger net displacement of ECs was found in the softer hydrogel obtained by irradiation with UV at 254nm than in the stiffer original one at day 7.

A tarsus construct of a novel branched polyethylene with good elasticity for eyelid reconstruction in vivo

Branched polyethylene(B-PE)elastomer was investigated for its potential medical application as a tarsus construct.The in vitro results showed that the B-PE and processed B-PE films or scaffolds did not exhibit noticeable cytotoxicity to the NIH3T3 fibroblasts and human vascular endothelial cells(ECs).The B-PE scaffolds with a pore size of 280–480 mm were prepared by using a gelatin porogen-leaching method.The porous scaffolds implanted subcutaneously in rats exhibited mild inflammatory response,collagen deposition and fast fibrovascularization,suggesting their good biocompatibility.Quantitative real-time PCR analysis showed low expression of pro-inflammatory genes and up-regulated expressions of collagen deposition and vascularization-related genes,validating the results of historical evaluation in a molecular level.The B-PE scaffolds and Medpor controls were transplanted in rabbits with eyelid defects.The B-PE scaffolds exhibited a similar elastic modulus and provided desirable repair effects with mild fibrous capsulation,less eyelid deformities,and were well integrated with the fibrovascular tissue compared with the Medpor controls.

Fabrication of Pyrene and Tetraphenylethylene Nanostructures by a Hydrolysis-Assisted Co-Assembly

The poly(allylamine hydrochloride)-g-pyrene-tetraphenylethylene(PAH-g-Py-g-TPE)copolymers with different ratios of Py and TPE are synthesized by grafting 1-pyrenecarboxaldehyde(Py-CHO)and tetraphenylethylene-carboxaldehyde(TPE-CHO)to PAH via a Schiff base reaction in methanol.The PAH-g-Py-g-TPE forms spherical micelles in water regardless of the ratios of Py and TPE,which can transform into different nanostructures after being incubated in pH 0 and pH 2 solutions,respectively.These nanomaterials including nanoparticles(NPs),nano-rods(NRs),nanotubes(NTs)and nanoribbons(NBs)are composed of Py-CHO and TPE-CHO with different ratios,and emit fluorescence with colors different from the pure Py NRs and NTs,and TPE NPs.