Stimuli-responsive Polymers Research Articles

A stimuli-responsive in situ spray hydrogel co-loaded with naringenin and gentamicin for chronic wounds

Abstract The potentials held by stimuli-responsive polymers in wound dressing have led to the present research in formulating a hydrogel base formulation with polymers having pH and thermo-sensitivity. Thus, hyaluronic acid (pH-sensitive polymer), and Pluronic F-127 (thermo-sensitive polymer) with hydroxypropyl methylcellulose (mucoadhesive polymer) were incorporated to obtain an in situ hydrogel containing gentamicin and naringenin (NAR). The optimization of the stimuli-responsive formulation was performed by the Box–Behnken statistical design to acquire variable parameters that influence the gelling temperature and viscosity. Thermo-gravimetric analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy were performed to confirm the suitability of incorporating the selected polymers with drugs. The optimized formulations (blank and drug-loaded) were found to possess satisfactory characteristics of gelling temperatures (30–33°C), viscosities (174 ± 3 to 184 ± 4 cP), and mucoadhesive properties (0.29 ± 0.01 to 0.31 ± 0.01 N) with a spray diameter of 16.8 ± 1.4 to 18.9 ± 1.2 cm2 to facilitate the application at the wound environment. The in vitro drug release study depicted a sustained release profile over a time frame of 8 h with a cumulative release of 56.18 ± 4.59% NAR. The drug-containing in situ hydrogels showed superior potency by producing a larger zone of inhibition (2.03 ± 0.12 cm). Furthermore, a cytotoxicity study of the developed formulations in HaCaT cells revealed no toxicity of the drug-loaded formulations when compared to the blank hydrogel. These findings indicate the potential of the in situ hydrogel as an effective wound dressing for chronic wounds; however, additional investigation is needed for further implementation.

Skate Fin‐Mimetic Muscle‐Cartilage Structured Fabric Layer for Robust and Muti‐Function Actuation Systems

AbstractActuators based on stimuli‐responsive polymers (SRP) have great potential applications in soft robots, remote control, artificial muscle, etc., but their practical robustness is usually limited by mechanical strength and environmental tolerance. Inspired by the unique “muscle‐cartilage” structure of Skate fin, a general strategy is developed for improving the mechanical strength and environmental tolerance of SRP actuators by introducing a twill cotton fabric as the supporting cartilage. Besides, benefiting from the special twill pattern and micro‐nano substructure of the fabric layer, the prepared SRP actuator possesses anisotropic actuation and fast wet recovery, which further enriches its versatility. This SRP actuator can be extended to complicated actuation systems with programmable motion series or cyclic task execution by simply heat‐soldering or assembling with other functional components. The method provides an idea in simultaneously addressing the practical robustness and rich extensibility of SRP actuators, facilitating their application in complex environments or multi‐tasking scenarios.

Thermoplastic polyurethane-based shape memory polymers with potential biomedical application: The effect of TPU soft-segment on shape memory effect and cytocompatibility

Stimuli-responsive biocompatible polymer blends with adjustable properties are highly desirable for biomedical applications. It is crucial to meticulously consider the chemical structure and composition of each polymer to prepare a melt-miscible blend system that possesses desirable shape memory and cytocompatibility performance. Herein, we developed thermo-responsive SMPs by melt-blending Polycaprolactone (PCL) with two different Thermoplastic polyurethanes (TPU) composed of the same hard segment, but different soft segments derived from adipic acid polyester and polycaprolactone diols and the critical role of TPU chemical structure on the thermomechanical properties and biocompatibility of TPU-based SMPs were investigated and uncovered. Cyclic thermomechanical tests show that compared with adipic acid-based TPU/PCL blends, PCL diol-based TPU/PCL blends exhibit remarkable shape memory properties (Rf and Rr >90%) with the ability to start recovery at lower temperatures (∼45 °C), while the cytotoxicity and wettability studies implied higher biocompatibility and hydrophilicity of adipic acid-based TPU/PCL blends making them more favorable substrates for cell proliferation.

Research Progress on Stimulus-Responsive Polymer Nanocarriers for Cancer Treatment.

As drug carriers for cancer treatment, stimulus-responsive polymer nanomaterials are a major research focus. These nanocarriers respond to specific stimulus signals (e.g., pH, redox, hypoxia, enzymes, temperature, and light) to precisely control drug release, thereby improving drug uptake rates in cancer cells and reducing drug damage to normal cells. Therefore, we reviewed the research progress in the past 6 years and the mechanisms underpinning single and multiple stimulus-responsive polymer nanocarriers in tumour therapy. The advantages and disadvantages of various stimulus-responsive polymeric nanomaterials are summarised, and the future outlook is provided to provide a scientific and theoretical rationale for further research, development, and utilisation of stimulus-responsive nanocarriers.

Cellulose acetate for a humidity-responsive self-actuator bilayer composite

The use of stimuli-responsive polymers to produce environmentally responsive self-actuators continues to rise. Highly hygroscopic materials are attracting great interest for the design of humidity-responsive self-actuators. In this context, bilayer composites, formed by the coupling of a hygroscopic layer with a non-hygroscopic one, are relevant as they allow for the response to be tuned through the design of the composite layers. Therefore, the meticulous material characterization and the definition of descriptive models of their hygroscopic behavior are the primary steps towards the development of humidity-responsive self-actuators. This study is aimed at measuring and predicting the response of a bilayer composite made of a hygroscopic material layer and a layer of a non-hygroscopic material when subjected to changes in environmental humidity levels, to be used as a humidity-responsive self-actuator. A cellulose acetate was used as the hygroscopic material. Predictions for the induced hygroscopic deformation in the bilayer composite, based on two-physics finite element simulations, are compared to experimental measurements.

A review of thermoresponsive drug delivery systems based on LCST/UCST polymer nanofibers

Drug delivery systems and thermoresponsive polymers are garnering more interest due to technological advancement. The synthesis, characteristics, and uses of stimuli-responsive polymers in drug delivery systems are discussed in this paper. LCST and UCST polymers, two subtypes of thermoresponsive polymers, are also discussed, along with their processes and biomedical applications. The paper also discusses the use of conventional nanofibers and stimuli-responsive nanofibers for drug delivery systems and the most recent developments in electrospinning technology. The article also analyses the difficulties facing drug delivery systems today. This paper makes the case that novel electrospinning technologies must be developed in addition to further research into drug delivery systems based on UCST polymers with strong biocompatibility and biodegradability.

4D Printing in Biomedical Engineering: Advancements, Challenges, and Future Directions.

4D printing has emerged as a transformative technology in the field of biomedical engineering, offering the potential for dynamic, stimuli-responsive structures with applications in tissue engineering, drug delivery, medical devices, and diagnostics. This review paper provides a comprehensive analysis of the advancements, challenges, and future directions of 4D printing in biomedical engineering. We discuss the development of smart materials, including stimuli-responsive polymers, shape-memory materials, and bio-inks, as well as the various fabrication techniques employed, such as direct-write assembly, stereolithography, and multi-material jetting. Despite the promising advances, several challenges persist, including material limitations related to biocompatibility, mechanical properties, and degradation rates; fabrication complexities arising from the integration of multiple materials, resolution and accuracy, and scalability; and regulatory and ethical considerations surrounding safety and efficacy. As we explore the future directions for 4D printing, we emphasise the need for material innovations, fabrication advancements, and emerging applications such as personalised medicine, nanomedicine, and bioelectronic devices. Interdisciplinary research and collaboration between material science, biology, engineering, regulatory agencies, and industry are essential for overcoming challenges and realising the full potential of 4D printing in the biomedical engineering landscape.

Redox-Triggered Activation of Heavy-Atom-Free Photosensitizer and Implications in Targeted Photodynamic Therapy.

A strategy for a redox-activatable heavy-atom-free photosensitizer (PS) based on thiolated naphthalimide has been demonstrated. The PS exhibits excellent reactive oxygen species (ROS) generation in the monomeric state. However, when encapsulated in a disulfide containing bioreducible amphiphilic triblock copolymer aggregate (polymersome), the PS exhibits aggregation in the confined hydrophobic environment, which results in a smaller exciton exchange rate between the singlet and triplet excited states (TDDFT studies), and consequently, the ROS generation ability of the PS was almost fully diminished. Such a PS (in the dormant state)-loaded redox-responsive polymersome showed excellent cellular uptake and intracellular release of the PS in its active form, which enabled cell killing upon light irradiation due to ROS generation. In a control experiment involving aggregates of a similar block copolymer, but lacking the bioreducible disulfide linkage, no intracellular reactivation of the PS was noticed, highlighting the importance of stimuli-responsive polymer assemblies in the area of targeted photodynamic therapy.

Solvent-Free High-Temperature Capillary Stamping of Stimuli-Responsive Polymers: Wettability Management by Orthogonal Substrate Functionalization

Solvent-Free High-Temperature Capillary Stamping of Stimuli-Responsive Polymers: Wettability Management by Orthogonal Substrate Functionalization

Polysaccharide-Based Formulations for the Treatment of Diabetic Wounds: A Review

This article highlights recent progress in the development of polysaccharide-based formulations for the treatment of diabetic wounds. Wound healing is generally slower in diabetic patients than in non-diabetic individuals, which can be complicated into cellulitis, gangrene and foot abscess. Here, the influence of diabetes on the wound healing process and the potential effects of polysaccharide-based formulations on wounds associated with diabetes mellitus are described. Polysaccharides are excellent candidates for effective skin repair due to the characteristics of biodegradability, biocompatibility, and non-toxicity. Common polysaccharides employed in the development of diabetic wound care include cellulose, hyaluronic acid, and alginate. In addition, novel polysaccharides for diabetic wound care have been extracted from natural materials used for traditional medicine, such as Ganoderma lucidum, Periplaneta americana, and psyllium seed husk. Several strategies have been adopted, including crosslinking, grafting, quaternation, nanoformulation, and polymeric composites, to improve the physicochemical and mechanical attributes of polysaccharide-based formulations. These properties are crucial to the wound healing process by facilitating wound closure via accelerated re-epithelialization and collagen synthesis, as well as maintaining an optimal moist environment while minimizing the risk of infection and scar formation. The roles of stimuli-responsive polymers, controlled-release formulations, and bioactive polysaccharides in facilitating diabetic wound healing are also discussed.

Stimuli-Responsive π-Conjugated Polymers Showing Solid-State Emission Based on Boron-Fused Azomethine Complexes with NNO-Tridentate Ligands.

We report stimuli-responsive luminescent π-conjugated polymers involving the boron-fused azomethine (BAm) structure with the NNO-tridentate ligands and demonstrate their application to film-type sensors. The acid-responsive properties of the polymers are provided by the free lone-pair electrons of the nitrogen atom on the BAm unit. The polymer films showed red shifts in emission wavelengths under acid vapor, and the responses were reversible and corresponded to deprotonation. Furthermore, owing to environmental sensitivity in the film state, unique luminescent color changes were observed. The bilayer films of the BAm polymer coated by poly(n-butyl methacrylate) exhibited vapochromic luminescence with gradual blue shifts (orange → yellow → green) by vapor annealing with chloroform depending on the exposure time. We demonstrated that these changes were applicable for evaluating solvent-vapor permeability of target membranes. This study shows that nitrogen substitution into existing organic compounds is effective for creating stimuli-responsive materials.

Stimuli-Responsive Polymer Nanoprobes Intended for Fluorescence-Guided Surgery of Malignant Head-and-Neck Tumors and Metastases.

Nano-sized carriers are widely studied as suitable candidates for the advanced delivery of various bioactive molecules such as drugs and diagnostics. Herein, the development of long-circulating stimuli-responsive polymer nanoprobes tailored for the fluorescently-guided surgery of solid tumors is reported. Nanoprobes are designed as long-circulating nanosystems preferably accumulated in solid tumors due to the Enhanced permeability and retention effect, so they act as a tumor microenvironment-sensitive activatable diagnostic. This study designs polymer probes differing in the structure of the spacer between the polymer carrier and Cy7 by employing pH-sensitive spacers, oligopeptide spacers susceptible to cathepsin B-catalyzed enzymatic hydrolysis, and non-degradable control spacer. Increased accumulation of the nanoprobes in the tumor tissue coupled with stimuli-sensitive release behavior and subsequent activation of the fluorescent signal upon dye release facilitated favorable tumor-to-background ratio, a key feature for fluorescence-guided surgery. The probes show excellent diagnostic potential for the surgical removal of intraperitoneal metastasis and orthotopic head and neck tumors with very high efficacy and accuracy. In addition, the combination of macroscopic resection followed by fluorescence-guided surgery using developed probes enable the identification and resection of most of the CAL33 intraperitoneal metastases with total tumor burden reduced to 97.2%.

Recombinant Multi-l-Arginyl-Poly-l-Aspartate (Cyanophycin) as an Emerging Biomaterial.

Multi-l-arginyl-poly-l-aspartate (MAPA) is a non-ribosomal polypeptide which synthesis is directed by cyanophycin synthetase, and its production can be achieved using recombinant microorganisms carrying the cphA gene. Along its poly-aspartate backbone, arginine or lysine links to each aspartate via an isopeptide bond. MAPA is a zwitterionic polyelectrolyte full of charged carboxylic, amine, and guanidino groups. In aqueous solution, MAPA exhibits dual thermal and pH responses similar to those stimuli-responsive polymers. Being biocompatible, the films containing MAPA can support cell proliferation and elicits minimal immune response in macrophages. Dipeptides from MAPA after enzymatic treatments can provide nutritional benefits. In light of the increasing interest in MAPA, this article focuses on the recent discovery of the function of cyanophycin synthetase and the potentials of MAPA as a biomaterial.

Development and Optimization of Novel Drug Delivery Systems for Targeted Therapy: An Analytical Perspective

A promising strategy in the realm of pharmaceutical research is the creation and improvement of new drug delivery systems for targeted therapy. Targeted therapy tries to deliver therapeutic medicines to cells or tissues selectively, reducing systemic side effects and increasing treatment effectiveness. To improve the targeting capacities of drug delivery systems, several ways have been investigated. These include using ligands, antibodies, peptides, or nanoparticles to recognize and bind to target cells or tissues in a targeted manner. The development of nanoparticles with distinctive physicochemical properties that can more precisely and effectively encapsulate and distribute medicinal medicines to target areas is another result of breakthroughs in nanotechnology. The stability, drug loading capacity, release kinetics, and biocompatibility of drug delivery systems have all been improved with the help of optimization techniques. A controlled-release system that reacts to triggers, such as pH, temperature, or enzyme activity, has been developed because of the incorporation of smart materials, such as stimuli-responsive polymers and nanogels. These developments offer hope for the treatment of numerous illnesses, including as cancer, cardiovascular problems, and neurodegenerative issues, by improving medicine efficacy and reducing side effects. To transfer these novel techniques into practical applications and enhance patient outcomes, more study and cooperation amongst multidisciplinary teams are required.

Effect of heterocyclic substituents on the thermo/pH/CO2-responsiveness of multistimuli-responsive homopolymers

A series of novel thermo/pH/CO2-triple responsive homopolymers were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. These homopolymers contain ethoxy groups, and the end substituents are pyrrolidine, piperidine, N-methylpiperazine, morpholine and thiomorpholine, respectively. The effects of different heterocyclic substituents on the responsiveness of temperature, pH and CO2 were studied. For temperature-response, it was found that the lower critical solution temperature (LCST)-type cloud point (CP) temperature decreased as the number of carbon atoms increases, while the solubility of the polymers changed greatly with the introduction of oxygen, nitrogen and sulfur atoms. And the CP of the polymers can be adjusted by molecular weight, concentration and salt. Furthermore, some of these polymers present upper critical solution temperature (UCST) behavior in alcohols. For pH-response, the initial pH of the polymer solution is different, their critical pH changed accordingly, and is affected by temperature; in addition, changing the pH of solution can also affect the CP. For CO2-response, all of the polymers were completely soluble after pumping with CO2, and their LCST behavior recovered after N2 was pumped in, but there was a gap with the initial CP. The study of these properties reveals the influence of different heterocyclic substituents on the responsiveness of polymers, which is of great significance for understanding the stimulation response properties of polymers and provides ideas for the design of new stimuli-responsive polymers.

Shape-Stabilized Monolithic Composite for Switchable Stiffness Based on Cellulose and Poly(stearyl methacrylate)

Stiffness-changing materials (SCMs) have recently attracted attention because their mechanical strength can be changed in response to external stimuli. Although the stiffness of SCMs can be adjusted considerably, these materials do not necessarily possess sufficient mechanical robustness in their soft state, thereby limiting their practical applicability. In this study, a stimuli-responsive polymer was incorporated into a porous supporting material to fabricate SCMs with high structural stability. Poly(stearyl methacrylate) (PSMA) was utilized as the responsive domain owing to the phase-changing behavior of its long alkyl side chain. A cellulose monolith (CM) was selected as the support owing to its outstanding chemical and physical stability despite its high porosity. The PSMA-modified CM (PSMA-CM) exhibited clearly detectable stiffness changes in response to temperature as a result of melting and crystallization of the PSMA domain. The Young’s modulus of PSMA-CM at 60 °C was half as large as that at 20 °C. Furthermore, during cyclic compressive loading–unloading tests, PSMA-CM displayed good shape recoverability, and the changes in its thermoresponsive stiffness were highly repeatable owing to both the stability of CM and the reversible responsive properties of PSMA. In addition, as opposed to CM, the stiffness of PSMA-CM decreased as the polarity of the surrounding solvent decreased. This result indicates that PSMA was composited not only onto the surface but also into the interior of the CM skeletal backbone. PSMA clearly reflects the variable stiffness of the monolith derived from the PSMA domain without impeding the dimensional stability of the material.

Effects of Steam Sterilization on the Properties of Stimuli-Responsive Polymer-Based Hydrogels.

Hydrogels based on stimuli-responsive polymers can change their characteristics in response to small variations in environmental conditions, such as temperature, pH, and ionic strength, among others. In the case of some routes of administration, such as ophthalmic and parenteral, the formulations must meet specific requirements, namely sterility. Therefore, it is essential to study the effect of the sterilization method on the integrity of smart gel systems. Thus, this work aimed to study the effect of steam sterilization (121 °C, 15 min) on the properties of hydrogels based on the following stimuli-responsive polymers: Carbopol® 940, Pluronic® F-127, and sodium alginate. The properties of the prepared hydrogels-pH, texture, rheological behavior, and sol-gel phase transition-were evaluated to compare and identify the differences between sterilized and non-sterilized hydrogels. The influence of steam sterilization on physicochemical stability was also investigated by Fourier-transform infrared spectroscopy and differential scanning calorimetry. The results of this study showed that the Carbopol® 940 hydrogel was the one that suffered fewer changes in the studied properties after sterilization. By contrast, sterilization was found to cause slight changes in the Pluronic® F-127 hydrogel regarding gelation temperature/time, as well as a considerable decrease in the viscosity of the sodium alginate hydrogel. There were no considerable differences in the chemical and physical characteristics of the hydrogels after steam sterilization. It is possible to conclude that steam sterilization is suitable for Carbopol® 940 hydrogels. Contrarily, this technique does not seem adequate for the sterilization of alginate or Pluronic® F-127 hydrogels, as it could considerably alter their properties.

NIR Laser Irradiation-Controlled Docetaxel Release from Nanodiamond Decorated with Temperature Stimuli Responsive Polymer Containing PAMAM Dendrimer

NIR Laser Irradiation-Controlled Docetaxel Release from Nanodiamond Decorated with Temperature Stimuli Responsive Polymer Containing PAMAM Dendrimer

Tailoring Hydrogen-Bonding Strategy for Sequence-Dependent and Thermo/pH Dual-Responsive Clusteroluminescence.

Rational design of monomer sequence for desired properties is challenging. This study investigates the effect of monomer distribution of double hydrophilic copolymers (DHCs) with electron-rich units on cluster triggered emission (CTE) capacity. By means of combining latent monomer strategy, reversible addition fragmentation chain transfer (RAFT) polymerization and selective hydrolysis technology, the random, pseudo di-block and the gradient DHCs consisting of pH-responsive polyacrylic acid (PAA) segments and thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) segments were successfully synthesized in a controlled manner. Moreover, the gradient DHCs showed a tremendously increased luminescent intensity due to the distinct hydrogen-bonding interaction compared to random and pseudo di-block DHCs. To the best of our knowledge, this is the first reported the direct correlation between luminescent intensity and sequence structure of non-conjugated polymer. Meanwhile, thermo and pH dual-responsive clusteroluminescence could be easily performed. This work demonstrates a novel and facile method to tailor the hydrogen-bonding for the stimuli-responsive light-emitting polymers.

APPLİCATİON OF THE SİLK SMART MATERİALS İN BİOMEDİCAL

The development of natural polymers into intelligent materials with exceptional functions and properties always involves the integration of both organic and inorganic components. Scientists would use ideas from nature to create the newest biomedical technology. Scientists have become more interested in the improvement of composite materials during the past few decades . A family of polymers known as "smart polymer materials" react to their surroundings and change their. Therefore, stimulus responsive polymers are those with specific physical or chemical properties. Depending on the physical state of polymer chains, the stimuli may include pH, salt, temperature, electric, magnetic, or optical field. These factors might cause a macroscopic response in materials. For tissue engineering, drug administration, gene therapy, and diagnostics, these intelligent biomaterial polymers serve as a "on-off" switch. This chapter's goal is to introduce readers to the fascinating world of silk-based smart polymers by outlining the present state of research in the subject as well as its potential for use in medical applications. Keywords: smart materials, biomedical technology, natural polymers