Water-soluble Initiator Research Articles

Perspective on Water-Soluble Two-Photon Initiator for Two-Photon Polymerization.

Two-photon polymerization (TPP) as an unparalleled technology empowers the rapid prototyping of customized three-dimensional (3D) micro/nanostructures, garnering noticeable interest in tissue engineering, drug delivery, and regenerative medicine. These applications have a high requirement on the biocompatibility and integrity of 3D structures. Therefore, it is important to develop two-photon initiator with good water-solubility, initiation efficiency, and biocompatibility. Here, we share our insights into the development of a water-soluble two-photon initiator (WTPI) and applications from the material and manufacturing perspective. We highlight the nonlinear optical properties and the synthesis of WTPI through three pathways. Then we further demonstrate the applications of the TPP technique in the aqueous phase in the fields of tissue engineering, 4D printing, and ceramic manufacturing. Finally, a general conclusion and outlook are provided for the future development and application of WTPI.

Impact of polyethylene nanoplastics on human intestinal cells

Polyethylene (PE) is one of the most widely used plastics in the world. Its degradation leads to the production of small particles including microplastics and nanoplastics (NPs). Plastic particles’ presence poses a health risk. The aim of this work was to investigate the toxicity of two model surfactant-free PE NPs prepared by polymerization of ethylene from cationic and anionic water-soluble initiators on human cell lines Caco-2 and HT29-MTX. After physicochemical characterization, their acute and subacute toxicity profile, including cytotoxicity, oxidative stress, and genotoxicity, was evaluated on both cell lines. Results showed a size increase of PE NPs in culture medium. Zeta potential values close to −10 mV were no longer dependent on the initiator charge after adsorption of serum components in culture medium. However, the cellular toxicity of the cationic and anionic PE NPs was very different. A time-and-concentration dependent cytotoxic, oxidative, and genotoxic effects on Caco-2 cells were only observed for PE NPs prepared with cationic initiators. No toxicity was observed on HT29-MTX, likely due to the protective mucus layer. Genotoxicity correlated with oxidative stress of some PE NPs on Caco-2 cells was observed from a concentration of 0.1 mg.mL−1 after 48-h exposure.

Physicochemical Effects of PEG Content in Alginate-based Double Network Hydrogels as Hybrid Scaffolds

This study aims to prepare a double-network hydrogel as hybrid networks bearing both natural and synthetic polymers to obtain scaffolds with increased swelling capacity and tunable mechanical and morphological properties. Physically cross-linked alginate hydrogel was reinforced with various ratios of Poly(ethylene glycol) (PEG) polymers which were chemically gellated via UV light exposure with a water soluble initiator. Physicochemical properties of the resulting hydrogels were systematically investigated via Fourier-transform infrared (FT-IR) spectroscopy for chemical composition and Scanning Electron Microscopy (SEM) for their morphological features like porosity. Furthermore, the effect of PEG amount in the final hydrogel (10, 20 and 40%) on swelling capacity was evaluated as well as the rheological properties. Prepared double-network hydrogels were demonstrated to be composed of both natural alginate polymer and synthetic PEG chains in FT-IR spectrum. Although 10%PEG containing hydrogel was not significantly different in terms of swelling capacity from the alginate hydrogel alone, increasing PEG amount seems to have improved the swelling ability. Comparative reological studies presented that introducing covalently cross-linked PEG network into alginate one increased crosspoint of storage and loss moduli almost 12 times more providing a stiffer scaffold. Increasing PEG content decreased the pore size on SEM images, indicating more crosslinking points in hydrogel structure.

Hollow particles synthesized by water-soluble and oil-soluble initiators and the mechanism of incorporating an oil-soluble initiator

Monodisperse polystyrene particles were first synthesized by soap-free emulsion polymerization to enhance the monodispersity of hollow particles. Thereafter, the polystyrene particles were immersed in an aqueous solution of 2,2′-azobis(2-methylbutyronitrile) (V-59) to allow the particles to absorb V-59 while maintaining their monodispersity. Thermogravimetric measurements using p-styrenesulfonic acid sodium salt revealed that this absorption occurred not through electrostatic interactions but through hydrophobic ones. Subsequently, the TEOS sol-gel reaction was performed on the polystyrene particle surface to create a silica shell with the help of N-vinyl acetoamide. Finally, the synthesized particles were heated to induce the decomposition reaction of V-59 (which emits nitrogen gas) in the particles, thereby creating a hollow structure as the gas stayed in the particle. These procedures enabled the synthesis of monodisperse hollow particles.

22 nm Resolution Achieved by Femtosecond Laser Two-Photon Polymerization of a Hyaluronic Acid Vinyl Ester Hydrogel.

Three-dimensional (3D) bioinspired hydrogels have played an important role in tissue engineering, owing to their advantage of excellent biocompatibility. Here, the two-photon polymerization (TPP) of a 3D hydrogel with high precision has been investigated, using the precursor with hyaluronic acid vinyl ester (HAVE) as the biocompatibility hydrogel monomer, 3,3'-((((1E,1'E)-(2-oxocyclopentane-1,3-diylidene) bis(methanylylidene)) bis(4,1-phenylene)) bis(methylazanediyl))dipropanoate as the water-soluble initiator, and dl-dithiothreitol (DTT) as the click-chemistry cross-linker. The TPP properties of the HAVE precursors have been comprehensively investigated by adjusting the solubility and the formulation of the photoresist. The feature line width of 22 nm has been obtained at a processing laser threshold of 3.67 mW, and the 3D hydrogel scaffold structures have been fabricated. Furthermore, the average value of Young's modulus is 94 kPa for the 3D hydrogel, and cell biocompatibility has been demonstrated. This study would provide high potential for achieving a 3D hydrogel scaffold with highly precise configuration in tissue engineering and biomedicine.

Synthesis of biocompatible BSA-GMA and two-photon polymerization of 3D hydrogels with free radical type I photoinitiator.

Although the development of three-dimensional (3D) printing technology is growing rapidly in the biomedical field, it remains a challenge to achieve arbitrary 3D structures with high resolution and high efficiency. Protein hydrogels fabricated by two- photon polymerization (TPP) have excellent mechanical properties, high precision, and 3D architecture. However, a large number of the amino acid group in bovine serum albumin (BSA) would be consumed when the protein-based hydrogels use dyes of free radical type II photoinitiators. In this study, we use glycidyl methacrylate (GMA) to modify BSA molecules to obtain a series of BSA-GMA materials, allowing the protein material to be two-photon polymerized with a water-soluble free radical type I photoinitiator. The precisely controllable 3D structure of the BSA-GMA hydrogel was fabricated by adjusting the concentration of the precursor solution, the degree of methacrylation, and the processing parameters of the TPP technique. Importantly, BSA-GMA materials are free of acidic hazardous substances. Meanwhile, the water-soluble initiator lithium phenyl (2,4,6-trimethylbenzoyl) phosphite (LAP) allows TPP on the vinyl group of the GMA chain and thus without consuming its amino acid group. The as-prepared BSA-GMA hydrogel structure exhibits excellent autofluorescence imaging, pH responsiveness, and biocompatibility, which would provide new avenues for potential applications in tissue engineering and biomedical fields to meet specific biological requirements.

One-pot generation of gold-polymer hybrid nanoparticles using a miniemulsion reactor system

We investigated one-pot synthesis of gold nanoparticles (AuNPs) and AuNPs-polymer hybrid nanoparticles in a water-in-oil (W/O) miniemulsion. Water nanodroplets were dispersed as a reactor in cyclohexane using dimethicone as a surfactant. First, we intended to generate AuNPs in water nanodroplets, which contained HAuCl4 with a mixture of 1-vinylpyrrolidone (VP) and N,N’-methylenebisacrylamide (MBAAm). Several AuNPs with the size of approximately 10–20 nm were generated in each nanodroplet via reduction of AuCl4- by dimethicone. On the other hand, AuNPs was scarcely generated in water nanodroplets containing HAuCl4 with 2-hydroxyethyl methacrylate (HEMA). Next, we carried out polymerization in water nanodroplets to encapsulate AuNPs into polymer nanoparticles. Several AuNPs were encapsulated within polymer particles by copolymerization of VP and MBAAm with an oil-soluble initiator (V-601), and some AuNPs were present in the oil phase. The encapsulation efficiency of AuNPs was 34%. The encapsulation efficiency of AuNPs was dramatically increased by increasing the concentration of the initiator. The same result was obtained by increasing the concentration of the crosslinker due to rapid gelation of nanodroplets. On the other hand, monodisperse particles could be obtained by polymerization of HEMA using a water-soluble initiator (V-65). After polymerization for 5 d at 65ºC, the color of the suspension changed from opaque blue to blue purple and the encapsulation efficiency of AuNPs (5–20 nm) increased to 99 wt%. The average number of AuNPs encapsulated in a PHEMA nanoparticle increased from 1.5 to 4.6 particle. Furthermore, the size of AuNPs could be tuned by increasing the HAuCl4 concentration, and the corresponding color of the suspensions such as blue, purple, and red could be observed. The number and location of AuNPs in polymer nanoparticles could also be tuned by additives such as L-histidine and polyvinylpyrrolidone. By drop-casting the obtained hybrid nanoparticles, we could obtain gold-polymer hybrid films where AuNPs were evenly distributed within a film. The films exhibited different colors corresponding to their LSPR of AuNPs.

One-Step Synthesis of Self-Stratification Core-Shell Latex for Antimicrobial Coating

Herein, we describe a one-step method for synthesizing cationic acrylate-based core-shell latex (CACS latex), which is used to prepare architectural coatings with excellent antimicrobial properties. Firstly, a polymerizable water-soluble quaternary ammonium salt (QAS-BN) was synthesized using 2-(Dimethylamine) ethyl methacrylate (DMAEMA) and benzyl bromide by the Hoffman alkylation reaction. Then QAS-BN, butyl acrylate (BA), methyl methacrylate (MMA), and vinyltriethoxysilane (VTES) as reactants and 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AIBA) as a water-soluble initiator were used to synthesize the CACS latex. The effect of the QAS-BN dosage on the properties of the emulsion and latex film was systematically investigated. The TGA results showed that using QAS-BN reduced the latex film's initial degradation temperature but improved its thermal stability. In the transmission electron microscopy (TEM) photographs, the self-stratification of latex particles with a high dosage of QAS-BN was observed, forming a core-shell structure of latex particles. The DSC, TGA, XPS, SEM, and performance tests confirmed the core-shell structure of the latex particles. The relationship between the formation of the core-shell structure and the content of QAS-BN was proved. The formation of the core-shell structure was due to the preferential reaction of water-soluble monomers in the aqueous phase, which led to the aggregation of hydrophilic groups, resulting in the formation of soft-core and hard-shell latex particles. However, the water resistance of the films formed by CACS latex was greatly reduced. We introduced a p-chloromethyl styrene and n-hexane diamine (p-CMS/EDA) crosslinking system, effectively improving the water resistance in this study. Finally, the antimicrobial coating was prepared with a CACS emulsion of 7 wt.% QAS-BN and 2 wt.% p-CMS/EDA. The antibacterial activity rates of this antimicrobial coating against E. coli and S. aureus were 99.99%. The antiviral activity rates against H3N2, HCoV-229E, and EV71 were 99.4%, 99.2%, and 97.9%, respectively. This study provides a novel idea for the morphological design of latex particles. A new architectural coating with broad-spectrum antimicrobial properties was obtained, which has important public health and safety applications.

Low-toxic, fluorescent labeled and size-controlled graphene oxide quantum dots@polystyrene nanospheres as reference material for quantitative determination and in vivo tracing

Polystyrene (PS) is selected as a representative nanoplastic and persistent pollutant for its difficult degradation and wide application. The environmental risk assessment of PS is obstructed by the toxic dye-based fluorescent PS, which false positives could be induced by the leakage of dye. For high biocompatibility, low toxicity, hydrophilicity, good water dispersibility, strong fluorescent stability, graphene oxide quantum dots (o-CQDs) are selected and embedded into PS microspheres, i.e., o-CQDs@PS, by microemulsion polymerization and denoted as CPS. Meanwhile, the sizes of CPS, e.g., 100, 150, and 200 nm, could be controlled by optimizing the type and number of water-soluble initiators. The anti-interference, low toxicity, and in vivo fluorescent tracing of CPS are proven by the coexistence of metals (including Fe2+, Fe3+, K+, Ba2+, Al3+, Zn2+, Mg2+, Ca2+, and Na+) on the fluorescence intensity of CPS, the growth of Chlorella pyrenoidosa and Artemia cysts as aquatic phytoplankton and zooplankton cultured with CPS, and the transfer of CPS from water into brine shrimp. In the concentration range of 0.1–100 mg/L, CPS can be quantitatively determined, which is suitable for coastal water and wastewater treatment plants. Therefore, CPS with standard size is suitable as reference material of PS.

Anti-tumor and antioxidant activity of kaempferol-3-O-alpha-L-rhamnoside (Afzelin) isolated from Pithecellobium dulce leaves

BackgroundPithecellobium dulce (Roxb.), an evergreen medium-sized, spiny tree which have vast nutritional values and widely used in ayurvedic medicines and home remedies. The plant has also been a rich source of biologically active compounds. The present study was designed to isolate pure compound from ethyl acetate fraction of methanol extract of leaves and to know the efficacy as antioxidant as well as its anti-tumor activity on Ehrlich ascites carcinoma cell (EAC). MethodsThe leaves were extracted with methanol and fractionated with different solvents. The isolation of the compound was carried out by column chromatography from ethyl acetate fraction (EAF) and structure was revealed by 1H-NMR and 13C NMR. The antioxidant activity was investigated by the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals as well as the inhibition of oxidative damage of pUC19 plasmid DNA, hemolysis and lipid peroxidation induced by a water-soluble free radical initiator 2,2’-azo (2-asmidinopropane) dihydrochloride (AAPH) in human erythrocytes. In vivo anti-tumor activity of the compound was also evaluated by determining the viable tumor cell count, hematological profiles of experimental mice along with observing morphological changes of EAC cells by fluorescence microscope.ResultsThe isolated compound kaempferol-3-O-alpha-L-rhamnoside effectively inhibited AAPH induced oxidation in DNA and human erythrocyte model and lipid per oxidation as well as a stronger DPPH radical scavenging activity. In anti-tumor assay, at a dose of 50 mg/kg body weight exhibit about 70.89 ± 6.62% EAC cell growth inhibition, whereas standard anticancer drug vincristine showed 77.84 ± 6.69% growth inhibition.ConclusionThe compound may have a great importance as a therapeutic agent in preventing oxidative damage of biomolecules and therapeutic use in chemotherapy.

Poly (L-phenylalanine-paired ionic liquid) as halogen-free heterogeneous nanocatalyst toward regiospecific 1,3-dipolar cycloaddition reaction

Although amino acid-paired ionic liquids (IL [AA]) have attracted considerable attention due to their environmental-friendly nature and providing abundant catalytic active sites, polymerized eco-friendly ILs have been rarely reported. Herein, we introduce a novel polymerized L-phenylalanine-paired ionic liquid (PIL [Phe]), synthesized in a new smart manner, as a promising heterogeneous nanocatalyst for regiospecific 1,3-dipolar cycloaddition reaction. For this purpose, new polymerizable ionic liquid (3-(3-aminopropyl)-1-vinylimidazolium (L)-2-amino-3-phenylpropanoate ([AVIm][Phe])) was designed and constructed as a halogen-free multifunctional monomer. The successful fabrication of chiral IL was approved by different techniques including 1H NMR, FT-IR, and elemental analysis. Next, a green precipitation polymerization approach was applied using a water-soluble initiator under mild conditions. Co3O4@PIL [Phe] was synthesized by in situ copolymerization of the [AVIm][Phe] with ethyleneglycoldimethacrylate (EGDMA) (as non-ionic cross-linker) supported on magnetic Co3O4@MPS. The obtained data reveal that the supported polymerized form of [AVIm][Phe] is more efficient due to the formation of a porous structure with high-specific surface area (235.5 m2/ g) and a cross-linked network with high thermal stability (35% weight loss around 600 °C). In the following, the proposed Co3O4@PIL [Phe] nanostructure was applied as a magnetic catalyst toward the preparation of new and reported pyrrolidinyldispirooxindoles; and it displayed accelerated mass transfer due to its large pore volume (0.85 cm3/ g), and numerous accessible active sites. Consequently, a range of pharmaceutical dispirobisoxindole scaffolds with broad structural diversity were readily obtained in excellent yields (>92%) and high regioselectivity under environmental conditions.

Janus particles by simplified RAFT-based emulsion polymerization process for polymer coating

We describe a simplified method to synthesize film forming polymer Janus particles by phase separation during RAFT-based free radical emulsion polymerization. Fully crosslinked snowman- or football-shaped polystyrene Janus particles (PSJPs) were first produced in a one-step batch process using amphiphilic triblock macro-RAFT copolymers as stabilizers. Such particles were in turn employed as seeds in a continuous emulsion polymerization in which a monomer mixture of methyl methacrylate (MMA) and butyl acrylate (BA) (1/1 by weight) was constantly injected into the reaction in the presence of a water soluble initiator. The added monomers wetted seed particle surface and their polymerization led to formations of 93-nm film forming single- or two-headed Janus particles. The resulted latex was successfully used to disperse and encapsulate solid calcite extender.Graphical abstract

Encapsulation of cellulose nanocrystals into acrylic latex particles via miniemulsion polymerization

Cellulose nanocrystals (CNCs) show promise for enhancing properties of waterborne latexes and coatings. Miniemulsion polymerization is a promising route to obtaining well-controlled latex distributions sufficient to encapsulate CNCs in the monomer phase. Here, we demonstrate the first miniemulsion polymerization resulting in encapsulation of CNCs that incorporates costabilizer, water soluble initiator, and comonomer mixtures, aspects that are important for practical implementation. CNCs were added to the monomer phase as either unmodified (umCNC) or one of two functionalized forms: modified with isocyanatoethyl methacrylate (mCNC, containing a polymerizable vinyl group) or grafted with butyl acrylate/methyl methacrylate copolymer (gmCNC). The gmCNCs were incorporated successfully into acrylic particles. In contrast, the umCNCs were located outside the formed latex particles. Interestingly, the mCNCs coagulated during the polymerization, highlighting the challenge of utilizing polar and reactive acryloyl CNC surface modifiers that lead to migration from the droplet phase.

Self-Stabilizing Encapsulation through Fast Interfacial Polymerization of Ethyl α-Cyanoacrylate: From Emulsions to Microcapsule Dispersions

Herein, fast interfacial polymerization (FIP) of highly reactive ethyl α-cyanoacrylate (ECA) monomers triggered by water-soluble initiators is demonstrated as a brand new method for instantly provi...

Design and fabrication of novel polymerized dual nature ionic liquid as highly effective catalyst for regioselective synthesis of monospiro derivatives

Poly (ionic liquid)s (PILs) are promising candidates in catalytic transformations; however, hyper cross-linked poly ionic liquids have been rarely reported in catalysis field. In this study, we developed a novel hyper cross-linked PIL (HCPIL) as an effective heterogeneous catalyst for regioselective synthesis of monospiro compounds. For this purpose, a new polymerizable ionic liquid (1-(2-methacryloyloxy)ethyl)-3-vinylimidazolium bromide ([MEVIm]Br)) was designed and synthesized with two different natures; that is, ionic monomer and cross-linker agent. The successful construction of dual nature ionic liquid (IL) was confirmed by analytical techniques such as 1H NMR, 13C NMR, elemental, and FTIR. Next, magnetic HCPIL was fabricated using copolymerization of the prepared IL with N,N-methylenebisacrylamide (MBAA) in the presence of a water soluble initiator (4,4‘-azobis(4-cyanopentanoic acid)) supported on vinyl functionalized Co3O4 nanoparticles (NPs). The results illustrated that the polymerization of ILs and covalent binding onto the magnetic support improved the thermal stability (from 75 to 33% weight loss around 450 °C), reusability, catalytic activity, and generated porous structure. Accordingly, the proposed magnetic Co3O4@p[MEVIm]Br composite was investigated as a heterogeneous catalyst for the ultrasound-assisted synthesis of new and known spirooxindole-2-azapyrrolizidines and spiro-2-amino-4H-pyran-oxindoles; and it showed accelerated mass transfer owing to its great porosity, high surface area (170.0 m2/g), and abundant accessible active sites. The applied scalable catalytic protocol has integrated the rules of an ideal biology-oriented synthesis and organic synthesis to access a spiro heterocyclic skeleton. Easy work-up, high regioselectivity, excellent yields (>90%), short reaction time (6–12 min), and green reaction media are the other advantages of the proposed synthetic method.

Functionalization of the Fine Al2O3 Abrasive by the Polyacrylamide Deposition

In order to enhance the dispersion stability of ultra-fine Al2O3 powder in aqueous media, the alumina particles were modified with silane coupling agent KH570 at first, and then 2,2'-Azobis(2-amidinopropane) dihydrochloride (AIBA) was anchored onto the modified Al2O3 to initiate the graft polymerization of acrylamide monomer (AM), and PAM/Al2O3 composite particles were obtained finally. The structure and dispersion property of Al2O3 composite particles were characterized by XPS, FTIR, laser particle size analyzer, micro electrophoresis apparatus, SEM and spectrophotometer. The results indicated that the attained composite abrasive when water-soluble azo initiator was added at 40 ℃ showed good dispersion stability in aqueous media with PAM as shell and Al2O3 as core. Compared with unmodified Al2O3, the reunion phenomenon of grafting polymerization modified Al2O3 powder was improved by AM, the D50 of the modified particles reduced. The isoelectric point (IEP) of the grafting modified particles migrated, and the zeta potential of the modified particles reached to the maximum value when the pH was 9. After PAM/Al2O3 abrasive polished, the surface roughness of NiP/Al hard disk surface was obviously reduced.

Macromolecular Chain Structure Regulation of AN–MA–IA Aqueous Copolymerization with a Water-Soluble Azo Initiator AIBA

Macromolecular Chain Structure Regulation of AN–MA–IA Aqueous Copolymerization with a Water-Soluble Azo Initiator AIBA

On the mechanism of acrylamide emulsion polymerization with the participation of its dimers

The role of both dimeric and monomeric forms of acrylamide monomer in the process of polymerization in emulsions initiated by different type of initiators was discussed and the reasons for the reaction order with respect to monomer greater than unity were elucidated for acrylamide free radical polymerization in emulsions. The emulsion polymerization mechanism of acrylamide is discussed separately for the processes initiated by water-soluble initiator and oil-soluble initiator. The main difference in two cases is the distribution of acrylamide and initiator in aqueous and toluene phases. In the case of using water-soluble initiator, the initiator and acrylamide are in the same phase, whereas the molecules of the initiator and acrylamide are distributed between different phases in the case of using oil-soluble initiator. As a result, the participation of the dimers in the process of acrylamide emulsion polymerization is more efficient for the system where water-soluble initiator is used. For that system, it is suggested that both dimers and monomers of acrylamide participate in the propagation reaction at relatively low concentrations of acrylamide, which explains the value of the reaction order with respect to monomer greater than unity.

A Theoretical Antioxidant Mechanism for Cytoprotective Effect of p-AcetamideSalicylate Derivatives against Free Radical Initiator AAPH in Human Erythrocytes

The molecular mechanism of cytoprotective effect on human erythrocytes of aminophenol and salicylates associated derivatives was related to their antioxidant capacity. The oxidative hemolysis induced by water-soluble free-radical initiator 2,2’-azobis-(2-amidine-propane)-dihydrochloride (AAPH) was inhibited by drug candidates named benzaminophen (BZL), salicytamide or 5-acetamide-salicylic acid (ASL), and salibenzamide or 5-benzamide-salicylic acid (BSL) when compared to their parents salicylic acid (SAC) and acetaminophen (ACP). Trolox (TLX) was the most powerful compound and used as positive control. BZL showed a potent effect followed by ACP > BSL > ASL. SAC did not show protective effect in any evaluated concentrations. These results are in accordance with the molecular mechanism by using theoretical calculation of single electron transfers (SET), hydrogen atom transfers (HAT), and sequential proton loss electron transfer (SPLET) by means of DFT/B3LYP/6-31++G(d,p) level of theory. [1,5] Hydrogen shift between carboxyl and phenol moieties and electronic properties related to pKa and other physicalchemical properties can be involved. The molecular association approach provides protective compounds more effective than SAC.

Two-photon polymerization nanolithography technology for fabrication of stimulus-responsive micro/nano-structures for biomedical applications

AbstractMicro/nano-fabrication technology via two-photon polymerization (TPP) nanolithography is a powerful and useful manufacturing tool that is capable of generating two dimensional (2D) to three dimensional (3D) arbitrary micro/nano-structures of various materials with a high spatial resolution. This technology has received tremendous interest in cell and tissue engineering and medical microdevices because of its remarkable fabrication capability for sophisticated structures from macro- to nano-scale, which are difficult to be achieved by traditional methods with limited microarchitecture controllability. To fabricate precisely designed 3D micro/nano-structures for biomedical applications via TPP nanolithography, the use of photoinitiators (PIs) and photoresists needs to be considered comprehensively and systematically. In this review, widely used commercially available PIs are first discussed, followed by elucidating synthesis strategies of water-soluble initiators for biomedical applications. In addition to the conventional photoresists, the distinctive properties of customized stimulus-responsive photoresists are discussed. Finally, current limitations and challenges in the material and fabrication aspects and an outlook for future prospects of TPP for biomedical applications based on different biocompatible photosensitive composites are discussed comprehensively. In all, this review provides a basic understanding of TPP technology and important roles of PIs and photoresists for fabricating high-precision stimulus-responsive micro/nano-structures for a wide range of biomedical applications.