Shape-Memory Polymers Hallmarks and Their Biomedical Applications in the Form of Nanofibers.

Shape-Memory Polymers (SMPs) are considered a kind of smart material able to modify size, shape, stiffness and strain in response to different external (heat, electric and magnetic field, water or light) stimuli including the physiologic ones such as pH, body temperature and ions concentration. The ability of SMPs is to memorize their original shape before triggered exposure and after deformation, in the absence of the stimulus, and to recover their original shape without any help. SMPs nanofibers (SMPNs) have been increasingly investigated for biomedical applications due to nanofiber's favorable properties such as high surface area per volume unit, high porosity, small diameter, low density, desirable fiber orientation and nanoarchitecture mimicking native Extra Cellular Matrix (ECM). This review focuses on the main properties of SMPs, their classification and shape-memory effects. Moreover, advantages in the use of SMPNs and different biomedical application fields are reported and discussed.

Stimuli-Responsive Drug Delivery Systems for the Diagnosis and Therapy of Lung Cancer.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Numerous drugs have been developed to treat lung cancer patients in recent years, whereas most of these drugs have undesirable adverse effects due to nonspecific distribution in the body. To address this problem, stimuli-responsive drug delivery systems are imparted with unique characteristics and specifically deliver loaded drugs at lung cancer tissues on the basis of internal tumor microenvironment or external stimuli. This review summarized recent studies focusing on the smart carriers that could respond to light, ultrasound, pH, or enzyme, and provided a promising strategy for lung cancer therapy.

Influence of shape-memory stent grafts on local aortic compliance.

The effect of repair techniques on the biomechanics of the aorta is poorly understood, resulting in significant levels of postoperative complications for patients worldwide. This study presents a computational analysis of the influence of Nitinol-based devices on the biomechanical performance of a healthy patient-specific human aorta. Simulations reveal that Nitinol stent-grafts stretch the artery wall so that collagen is stretched to a straightened high-stiffness configuration. The high-compliance regime (HCR) associated with low diastolic lumen pressure is eliminated, and the artery operates in a low-compliance regime (LCR) throughout the entire cardiac cycle. The slope of the lumen pressure-area curve for the LCR post-implantation is almost identical to that of the native vessel during systole. This negligible change from the native LCR slope occurs because the stent-graft increases its diameter from the crimped configuration during deployment so that it reaches a low-stiffness unloading plateau. The effective radial stiffness of the implant along this unloading plateau is negligible compared to the stiffness of the artery wall. Provided the Nitinol device unloads sufficiently during deployment to the unloading plateau, the degree of oversizing has a negligible effect on the pressure-area response of the vessel, as each device exerts approximately the same radial force, the slope of which is negligible compared to the LCR slope of the native artery. We show that 10% oversizing based on the observed diastolic diameter in the mid descending thoracic aorta results in a complete loss of contact between the device and the wall during systole, which could lead to an endoleak and stent migration. 20% oversizing reaches the Dacron enforced area limit (DEAL) during the pulse pressure and results in an effective zero-compliance in the later portion of systole.

Bifunctional Smart Hydrogel Dressing with Strain Sensitivity and NIR-Responsive Performance.

Smart response hydrogel has a broad application prospect in human health real-time monitoring due to its responses to a variety of stimuli. In this study, we developed a novel smart hydrogel dressing based on conductive MXene nanosheets and a temperature-sensitive PNIPAm polymer. γ-Methacryloxypropyltrimethoxysilane (KH570) was selected to functionalize the surface of MXene further to improve the interface compatibility between MXene and PNIPAm. Our prepared K-M/PNIPAm hydrogel was found to have a strain-sensitive property, as well as a respond to NIR phase change and volume change. When applied as a strain flexible sensor, this K-M/PNIPAm hydrogel exhibited a high strain sensitivity with a gauge factor (GF) of 4.491, a broad working strain range of ≈250%, a fast response of ∼160 ms, and good cycle stability (i.e., 3000 s at 20% strain). Besides, this K-M/PNIPAm hydrogel can be used as an efficient NIR light-controlled drug release carrier to achieve on-demand drug release. This work paved the way for the application of smart response hydrogel in human health real-time monitoring and NIR-controlled drug release functions.

NIR as a "trigger switch" for rapid phase change, on-demand release, and photothermal synergistic antibacterial treatment with chitosan-based temperature-sensitive hydrogel.

Temperature-sensitive hydrogels have shown good performances as wound dressing owing to their ability to fill wounds in the liquid state and to release drugs in a solid state. However, their treatment efficiency is restricted by the phase transition time. In this study, we developed a photothermal synergistic chitosan-based temperature-sensitive hydrogel, h-EGF-CS/ß-GP-MPDA@Cip, with the unique properties of rapid phase transition and drug release under near-infrared light (NIR). High antibacterial efficiency was achieved when we covered infected mice wounds with hydrogels. The local high temperature produced under NIR illumination not only accelerated the formation of a porous gel to release the loaded drug on-demand, but also dissolved bacteria, achieving synergistic anti-bacterial treatment. In addition, the healing cycle of wounds could be significantly shortened by adding human epidermal growth factor (h-EGF) in the hydrogel. Overall, the developed temperature-sensitive hydrogel could utilise NIR as a "trigger switch" for on-demand drug release and photothermal-enhanced antibacterial treatment during the rapid phase change process.

Carbohydrate-based films containing pH-sensitive red barberry anthocyanins: Application as biodegradable smart food packaging materials.

A novel pH-sensitive colorimetric film was prepared based on immobilizing red barberry anthocyanins (RBAs) within composite chitin nanofiber (CNF) and methylcellulose (MC) matrices. The incorporation of CNFs and RBAs improved their mechanical properties, moisture resistance, and UV-vis screening properties. Moreover, the RBAs could be used as colorimetric indicators to detect food spoilage because they are sensitive to changes in pH and ammonia gas production. The RBA-halochromic indicator changed from reddish/crimson → pink → yellow with increasing pH, and from pink → yellow with increasing ammonia vapor concentration. Furthermore, the smart films possessed good antioxidant and antimicrobial activity owing to the presence of the RBAs and CNFs. Finally, the validity of the indicator to monitor the freshness/spoilage of a model food (fish) was demonstrated. Overall, this study shows that active/smart films can be assembled from food grade ingredients that can protect and monitor the freshness of products, like meat and fish.

Photosensitive hydrogels: from structure, mechanisms, design to bioapplications.

Hydrogel is a smart material with a three-dimensional network structure and has been widely used in various fields due to its good biodegradability, biocompatibility, and modification. Photosensitive hydrogel is a smart hydrogel, and its amenability to remote, precise control, and flexible and convenient regulation of stimulating factors make it an ideal candidate for use in fields such as biological materials, drug carriers, and sensors. In this review, we discuss the structure, mechanisms, design principles, and bioapplications of photosensitive hydrogels as developed in recent years. Finally, their potential for development and potential future challenges are outlined.

Biofunctionalized chondrogenic shape-memory ternary scaffolds for efficient cell-free cartilage regeneration.

Cartilage defect repair remains a great clinical challenge due to the limited self-regeneration capacity of cartilage tissue. Surgical treatment of injured cartilage is rather difficult due to the narrow space in the articular cavity and irregular defect area. Herein, we designed and fabricated chondrogenic and physiological-temperature-triggered shape-memory ternary scaffolds for cell-free cartilage repair, where the poly (glycerol sebacate) (PGS) networks ensured elasticity and shape recovery, crystallized poly (1,3-propylene sebacate) (PPS) acted as switchable phase, and immobilized bioactive kartogenin (KGN) endowed the scaffolds with chondrogenic capacity. The resultant scaffolds exhibited shape-memory properties with shape-memory fixed ratio of 98% and recovered ratio of 97% at 37°C for PPS/PGS/KGN-100, indicating a good potential for minimally invasive implantation. The scaffolds gradually degraded in Dulbecco's phosphate-buffered saline and released KGN up to 12 weeks in vitro. In addition, the scaffolds promoted chondrogenic differentiation while inhibiting osteogenic differentiation of bone marrow-derived mesenchymal stem cells in a concentration-dependent manner and cartilage regeneration in full-thickness defects of rat femoropatellar groove for 12 weeks. Consequently, the PPS/PGS/KGN-100 scaffolds stimulated the formation of an overlying layer of neocartilage mimicking the characteristic architecture of native articular cartilage even in the absence of exogenous growth factors and seeded cells. This study provides much inspiration for future research on cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: There are two crucial challenges for cartilage defect repair: the lack of self-regeneration capacity of cartilage tissue and difficult scaffold implantation via traditional open surgery due to space-limited joints. Herein, bioactive body-temperature-responsive shape memory scaffolds are designed to simultaneously address the challenges. The scaffolds can be readily implanted by minimally invasive approach and recover by body-temperature of patient. The integration of kartogenin endows scaffolds the bioactivity, leading to the first example of bulk shape-memory scaffolds for cell-free cartilage repair. These characteristics make the scaffolds advantageous for clinical translation. Moreover, our developed material is easy to be functionalized due to the presence of extensive free hydroxyl groups and provides a versatile platform to design diverse functional shape memory biomaterials.

A programmable, fast-fixing, osteo-regenerative, biomechanically robust bone screw.

The use of a screw for repairing defected bones is limited by the dilemma between stiffness, bioactivity and internal fixation ability in current products. For polymer bone screw, it is difficult to achieve the bone stiffness and osteo-induction. Polymer composites may enhance bioactivity and mechanical properties but sacrifice the shape memory properties enormously. Herein, we fabricated a programmable bone screw which is composed of shape memory polyurethane, hydroxyapatite and arginylglycylaspartic acid to resolve the above problem. This composite has significantly improved mechanical and shape-memory properties with a modulus of 250 MPa, a shape fixity ratio of ~90% and a shape recovery ratio of ~96%. Moreover, shape fixity and recovery ratios of the produced SMPC screw in the simulative biological condition were respectively ~80% and ~82%. The produced screw could quickly recover to its original shape in vitro within 20 s leading to easy internal fixation. Additionally, the composite could support mesenchymal stem cell survival, proliferation and osteogenic differentiation in vitro tests. It also promoted tissue growth and showed beneficial mechanical compatibility after implantation into a rabbit femoral intracondyle for 12 weeks with little inflammation. Such bone screw exhibited a fast-fixing, tightened fitting, enhanced supporting and boosted bioactivity simultaneously in the defective bone, which provides a solution to the long-standing problem for bone repairing. We envision that our composite material will provide valuable insights into the development of a new generation of bone screws with good fixation and osteogenic properties. STATEMENT OF SIGNIFICANCE: The main obstacles to a wider use of a bone screw are unsatisfied stiffness, inflammatory response and screw loosening issues. Herein, we report a programmable screw with mechanically robust, bioactive and fast-fixing performances. The shape memory polymer composite takes advantage of the component in the natural bone and possesses a stable bush-like structure inside through the covalent bonding, and thus achieve significantly improved mechanical and memory properties. Based on its shape memory effect, the produced screw was proved to offer a recovery force to surroundings and promote the bone regeneration effectively. Therefore, the composite realizes our expectations on functions through structure design and paves a practical and effective way for the development of a new generation of bone screws.

Smart textiles in wound care: functionalization of cotton/PET blends with antimicrobial nanocapsules.

Management of infected wounds is one of the most costly procedures in the health care sector. Burn wounds are of significant importance due to the high infection risk that can possibly lead to severe consequences such as sepsis. Because antibiotic wound treatments have caused increasing antibiotic resistance in bacteria, there is currently a strong need for alternative strategies. Therefore, we developed new antimicrobial wound dressings consisting of pH-responsive human serum albumin/silk fibroin nanocapsules immobilized onto cotton/polyethylene terephthalate (PET) blends loaded with eugenol, which is an antimicrobial phenylpropanoid. Ultrasound-assisted production of eugenol-loaded nanocapsules resulted in particle sizes (hydrodynamic radii) between 319.73 ± 17.50 and 574.00 ± 92.76 nm and zeta potentials ranging from -10.39 ± 1.99 mV to -12.11 ± 0.59 mV. Because recent discoveries have indicated that the sweat glands contribute to wound reepithelialisation, release studies of eugenol were conducted in different artificial sweat formulas that varied in pH. Formulations containing 10% silk fibroin with lower degradation degree exhibited the highest release of 41% at pH 6.0. After immobilization, the functionalized cotton/PET blends were able to inhibit 81% of Staphylococcus aureus and 33% of Escherichia coli growth. Particle uniformity, silk fibroin concentration, and high surface-area-to-volume ratio of the produced nanocapsules were identified as the contributing factors leading to high antimicrobial activities against both strains. Therefore, the production of antimicrobial textiles using nanocapsules loaded with an active natural compound that will not contribute to antibiotic resistance is seen as a potential future alternative to commercially available antiseptic wound dressings.

Enzymatically triggered shape memory polymers.

Cytocompatible shape memory polymers activated by thermal or photothermal triggers have been developed and established as powerful "smart material" platforms for both basic and translational research. Shape memory polymers (SMPs) that could be triggered directly by biological activity have not, in contrast, been reported. The goal of this study was to develop an SMP that responds directly to enzymatic activity and can do so under isothermal cell culture conditions. To achieve this goal, we designed an SMP with a shape fixing component, poly(ε-caprolactone) (PCL), that is vulnerable to enzymatic degradation and a shape memory component, Pellethane, that is enzymatically stable - as the shape fixing component undergoes enzymatically-catalyzed degradation, the SMP returns to its original, programmed shape. We quantitatively and qualitatively analyzed material properties, shape memory performance, and cytocompatibility of the enzymatically-catalyzed shape memory response. The results demonstrate enzymatic recovery, as contraction of tensile specimens, using bulk enzymatic degradation experiments and show that shape recovery is achieved by degradation of the PCL shape-fixing phase. The results further showed that both the materials and the process of enzymatic shape recovery are cytocompatible. Thus, the SMP design reported here represents both an enzyme responsive material capable of applying a programmed shape change or direct mechanical force and an SMP that could respond directly to biological activity. STATEMENT OF SIGNIFICANCE: Cytocompatible shape memory polymers activated by thermal or photothermal triggers have become powerful "smart material" platforms for basic and translational research. Shape memory polymers that could be triggered directly by biological activity have not, in contrast, been reported. Here we report an enzymatically triggered shape memory polymer that changes its shape isothermally in response to enzymatic activity. We successfully demonstrate enzymatic recovery using bulk enzymatic degradation experiments and show that shape recovery is achieved by degradation of the shape-fixing phase. We further show that both the materials and the process of enzymatic shape recovery are cytocompatible. This new shape memory polymer design can be anticipated to enable new applications in basic and applied materials science as a stimulus responsive material.

A biodegradable functional water-responsive shape memory polymer for biomedical applications.

Shape memory polymers (SMPs) have exhibited great potential in biomedical applications. However, the typical triggers of shape recovery such as heat, UV light, and electricity may be harmful to humans. Accordingly, water-responsive SMPs have become significant, especially for in vivo applications, due to the intrinsic biocompatibility and ready availability of water. However, the reported water-responsive SMPs are limited and relatively complicated. Here, we design a new water-responsive SMP, poly(butanetetrol fumarate) (PBF); the properties of PBF could be modulated by curing. The cured PBF scaffolds exhibited high shape recovery and fixity rates (>95%). PBF showed good biodegradability, and it could support the attachment, viability and alkaline phosphatase activity of osteoblasts. Furthermore, PBF could be readily functionalized via pendant hydroxyl groups, which was demonstrated by the immobilization and controlled release of bone morphogenetic protein 2. We expect that PBF will be useful for various biomedical applications including water-responsive scaffolds, sensors or actuators.